Process for preparation of tetrahydrothiophene derivatives Description The present invention relates to a process for the preparation of tetrahydrothiophene derivatives of formula I

wherein

R ¹ is halomethyl;

each R ² is independently H, halogen, CN, N ₃ , NO ₂ , SCN, SF ₅ , C ₁ -C ₆ -alkyl, C ₃ -C ₈ -cycloalkyl, C2-C6-alkenyl, C2-C6-alkynyl, which groups are unsubstituted, partially or fully halogenated and/or substituted by one or more same or different R ⁸ ,

Si(R ¹² )3, OR ⁹ , S(O)nR ⁹ , NR ^10a R ^10b ,

phenyl which may be partially or fully substituted by R ¹¹ , and a 3- to 10-membered satura- ted, partially or fully unsaturated heteromonocyclic or heterobicyclic ring containing 1, 2, 3 or 4 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or substitu- ted by one or more same or different R ¹¹ , preferably the unsubstituted or substituted HET; n is 0, 1, or 2;

R ³ halogen, OH, C1-C6-alkoxy, C1-C6-haloalkoxy, C3-C6-alkenyloxy, C3-C6-haloalkenyloxy, C3- C6-alkynyloxy, C3-C6-haloalkynyloxy, C3-C6-cycloalkyloxy, C3-C6-halocycloalkyloxy, OS(O) _n -C ₁ -C ₄ -alkyl, heterocyclyloxy, or hetaryloxy which groups are unsubstituted or par- tially or fully substituted by R ⁸ ;

G ¹ , G ² , G ³ and G ⁴ are each independently selected from N and CR ⁴ , with the proviso that at most two of G ¹ , G ² , G ³ , and G ⁴ are N;

each R ⁴ is independently selected from the meanings mentioned for R ² ,

or two R ⁴ bonded to adjacent carbon atoms may form a five- or sixmembered saturated, par- tially or fully unsaturated carbocyclic ring, or

R ⁴ bonded to carbon atoms in position G ² or G ⁴ form a bond to the chain *-Q-Z- in group A ⁴ ; A is a group A ¹ , A ² , A ³ , A ⁴ , or A ⁵ ; wherein

A ¹ is C(=W)Y, wherein

W is O, or S;

Y is H, N(R ⁵ )R ⁶ , or OR ⁹ ;

A ² is CR ^7a R ^7b NR ²¹ C(=O)R ²² ; wherein

R ²¹ is H, C ₁ -C ₃ -alkyl, C ₂ -C ₃ -alkenyl, C ₂ -C ₃ -alkynyl, C ₁ -C ₃ -alkoxymethyl, or CH ₂ CN; R ²² is H, C ₁ -C ₆ -alkyl-(R ⁸¹ ) _n , C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -haloalkyl-R ⁸¹ , C ₂ -C ₆ -alkenyl, C ₂ - C6-haloalkenyl, C2-C6-alkynyl, C2-C6-haloalkynyl, C3-C6-cycloalkyl, C3-C6- cycloalkyl-CN, C3-C6-halocycloalkyl, N(R ⁴³ )R ⁴⁵ , C(=O)N(R ⁴³ )R ⁴⁴ , CH=NOR ⁴⁶ ; phenyl, or HET which rings are unsubstituted or partially or fully substituted by R ^A ; wherein R ⁸¹ is OH, CN, C ₃ -C ₆ -cycloalkyl which is unsubstituted or substituted by CN or halomethyl, C3-C6-halocycloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, SO _n -C ₁ -C ₆ -alkyl, SO _n -C ₁ -C ₆ -haloalkyl, C(=O)N(R ⁴³ )R ⁴⁴ ; phenyl and HET, which rings are unsubstituted or partially or fully substituted by R ¹⁶ ; and A ³ is a 3-, 4-, 5-, 6- or 7-membered saturated, partially or fully unsaturated heteromono- cyclic ring containing 1, 2, 3, or 4 heteroatoms N, O, and/or S as ring members, or is a 8-, 9- or 10-membered saturated, partially or fully unsaturated heterobicyclic ring containing 1, 2, 3, or 4 heteroatoms N, O, and/or S as ring members,

which ring may be substituted by one or more same or different R ¹¹ ;

A ⁴ is

wherein # denotes the bond of group A, and % denotes the bond to G ² or G ⁴ ;

Q-Z is %–CH2-O-*,‘%-CH2-S(O)n-*, or %–C(=O)-O-*, wherein % marks the bond of Q to phenyl, and * the bond of Z to azetidin; and

R ^A4 is H or C(=O)R ^4A , wherein

R ^4A is H, C1-C6-alkyl, C1-C6-haloalkyl, C2-C6-alkenyl, C2-C6-haloalkenyl, C2- C6-alkynyl, C2-C6-haloalkynyl, which aliphatic groups are unsubstituted or substituted by one or more radicals R ⁴¹ ; C ₃ -C ₆ -cycloalkyl, C ₃ -C ₆ -halo- cycloalkyl which cyclic groups are unsubstituted or substituted by one or more radicals R ⁴² ; C(=O)N(R ⁴³ )R ⁴⁴ , N(R ⁴³ )R ⁴⁵ , CH=NOR ⁴⁶ ; phenyl, het- erocycle, or hetaryl which rings are unsubstituted or partially or fully sub- stituted by R ^A ;

R ⁴¹ is independently OH, cyano, C1-C6-alkoxy, C1-C6-haloalkoxy, S(O)n-C1- C6-alkyl, S(O)n-C1-C6-haloalkyl, C(=O)N(R ⁴³ )R ⁴⁴ , C3-C6-cycloalkyl, or C3- C ₆ -halocycloalkyl which cycles are unsubstitued or substituted by one or more R ⁴¹¹ ; or

phenyl, heterocycle or hetaryl HET which rings are unsubstitued or par- tially or fully substituted by R ^A ;

R ⁴¹¹ is independently OH, cyano, C ₁ -C ₂ -alkyl, or C ₁ -C ₂ -haloalkyl; R ⁴³ is H, or C1-C6-alkyl,

R ⁴⁴ is H, C1-C6-alkyl, C1-C6-haloalkyl, C2-C6-alkenyl, C2-C6-haloalkenyl, C2- C ₆ -alkynyl, C ₂ -C ₆ -haloalkynyl, or C ₃ -C ₆ -cycloalkyl, C ₃ -C ₆ -halocycloalkyl, C3-C6-cycloalkylmethyl, or C3-C6-halocycloalkylmethyl which rings are unsubstituted or substituted by a cyano;

R ⁴⁵ H, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₂ -C ₄ -alkenyl, C ₂ -C ₄ -alkynyl, CH ₂ -CN, C ₃ -C ₆ -cycloalkyl, C ₃ -C ₆ -halocycloalkyl, C ₃ -C ₆ -cycloalkylmethyl, C ₃ -C ₆ - halocycloalkylmethyl, phenyl and hetaryl HET which aromatic rings are unsubstituted or partially or fully substituted by R ^A ;

R ⁴² C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, or a group as defined for R ⁴¹ ;

R ⁴⁶ is independently H, C1-C6-alkyl, or C1-C6-haloalkyl;

R ^A is independently selected from halogen, cyano, NO2, C1-C4-alkyl, C1-C4- haloalkyl, C ₂ -C ₄ -alkenyl, C ₂ -C ₄ -haloalkenyl, C ₂ -C ₄ -alkynyl, C ₂ -C ₄ -haloal- kynyl, C ₃ -C ₆ -cycloalkyl, C ₃ -C ₆ -halocycloalkyl, C ₁ -C ₄ -alkoxy, C ₁ -C ₄ -haloal- koxy, S(O)n-C1-C4- alkyl, S(O)n-C1-C4-haloalkyl, C1-C4-alkylcarbonyl, C1- C ₄ -haloalkylcarbonyl, C(=O)N(R ⁴³ )R ⁴⁴ ; or

two R ^A present on the same carbon atom of a saturated or partially saturated ring may form together =O or =S; or

two R ^A present on the same S or SO ring member of a heterocyclic ring may together form a group =N(C ₁ -C ₆ -alkyl), =NO(C ₁ -C ₆ -alkyl), =NN(H)(C ₁ -C ₆ - alkyl) or =NN(C ₁ -C ₆ -alkyl) ₂ ;

A ⁵ is halogen, or OSO2R ⁹ ;

R ⁵ is H, CN, C ₁ -C ₁₀ -alkyl, C ₃ -C ₈ -cycloalkyl, C ₂ -C ₁₀ -alkenyl, C ₂ -C ₁₀ -alkynyl, which groups are unsubstituted, partially or fully halogenated and/or substituted by one or more same or dif- ferent R ⁸ ;

or S(O) _n R ⁹ , or C(=O)R ⁸ ;

each R ⁶ is independently selected from the meanings mentioned for R ² ;

or R ⁵ and R ⁶ , together with the nitrogen atom to which they are bound, form a 3- to 8-membered saturated, partially or fully unsaturated heterocyclic ring, which ring may contain 1, 2, 3 or 4 heteroatoms O, S, N, C=O and/or C=S as ring members, which heterocyclic ring is un- substituted or partially or fully substituted by same or different halogen, CN, C ₁ -C ₆ -alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C1-C6-alkylthio, C1-C6-haloalkylthio, C3- C ₈ -cycloalkyl, C ₃ -C ₈ -halocycloalkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -haloalkenyl, C ₂ -C ₆ -alkynyl, C ₂ -C ₆ - haloalkynyl, which groups are unsubstituted, or partially or fully substituted by same or dif- ferent R ⁸ , or phenyl which may be partially or fully substituted by R ¹¹ ;

or R ⁵ and R ⁶ together form a group =C(R ⁸ )2, =S(O)m(R ⁹ )2, =NR ^10a , or =NOR ⁹ ;

R ^7a , R ^7b are each independently H, halogen, CN, C ₁ -C ₆ -alkyl, C ₃ -C ₈ -cycloalkyl, C ₂ -C ₆ -alkenyl, or C ₂ -C ₆ -alkynyl, which groups are unsubstituted, partially or fully halogenated and/or sub- stituted by same or different R ⁸ ;

each R ⁸ is independently CN, N ₃ , NO ₂ , SCN, SF ₅ , C ₃ -C ₈ -cycloalkyl, C ₃ -C ₈ -halocycloalkyl, wherein the carbon chains may be substituted by one or more R ¹³ ;

Si(R ¹² )3, OR ⁹ , OSO2R ⁹ , S(O)nR ⁹ , N(R ^10a )R ^10b , C(=O)N(R ^10a )R ^10b , C(=S)N(R ^10a )R ^10b , C(=O)OR ⁹ , CH=NOR ⁹ ,

phenyl, which is unsubstituted or partially or fully substituted by same or different R ¹⁶ , or a 3-, 4-, 5-, 6- or 7-membered saturated, partially or fully unsaturated heterocyclic ring comprising 1, 2 or 3 heteroatoms N, O, and/or S as ring members, which ring is unsubsti- tuted or partially or fully substituted by same or different R ¹⁶ , or

two R ⁸ present on the same carbon atom of an alkyl, alkenyl, alkynyl or cycloalkyl group together form a group =O, =C(R ¹³ )2; =S; =S(O)m(R ¹⁵ )2, =S(O)mR ¹⁵ N(R ^14a )R ^14b , =NR ^10a , =NOR ⁹ ; or =NN(R ^10a )R ^10b ; or

two radicals R ⁸ , together with the carbon atoms of the alkyl, alkenyl, alkynyl or cycloalkyl group which they are bonded to, form a 3-, 4-, 5-, 6-, 7- or 8-membered saturated or par- tially unsaturated carbocyclic or heterocyclic ring, which heterocyclic ring comprises 1, 2, 3 or 4 heteroatoms N, O, and/or S as ring members, and which ring is unsubstituted, or partially or fully substituted by same or different R ¹⁶ ; and R ⁸ as a substituent on a cycloalkyl ring may additionally be C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C2-C6-alkenyl, C2-C6-haloalkenyl, C2-C6-alkynyl, and C2-C6-haloalkynyl, which groups are unsubstituted, or partially or fully substituted by same or different R ¹³ ; and

R ⁸ in the groups C(=O)R ⁸ and =C(R ⁸ ) ₂ may additionally be H, halogen, C ₁ -C ₆ -alkyl, C ₁ -C ₆ - haloalkyl, C2-C6-alkenyl, C2-C6-haloalkenyl, C2-C6-alkynyl, or C2-C6-haloalkynyl, which groups are unsubstituted, or partially or fully substituted by same or different R ¹³ ;

each R ⁹ is independently H, CN, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₃ -C ₈ -cycloalkyl, C ₃ -C ₈ -cycloal- kyl-C ₁ -C ₄ -alkyl-, C ₃ -C ₈ -halocycloalkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -haloalkenyl, C ₂ -C ₆ -alkynyl, or C2-C6-haloalkynyl, which groups are unsubstituted, or partially or fully substituted by same or different R ¹³ , or

C ₁ -C ₆ -alkyl-C(=O)OR ¹⁵ , C ₁ -C ₆ -alkyl-C(=O)N(R ^14a )R ^14b , C ₁ -C ₆ -alkyl-C(=S)N(R ^14a )R ^14b , C1-C6-alkyl-C(=NR ¹⁴ )N(R ^14a )R ^14b , Si(R ¹² )3, S(O)nR ¹⁵ , S(O)nN(R ^14a )R ^14b , N(R ^10a )R ^10b , N=C(R ¹³ ) ₂ , C(=O)R ¹³ , C(=O)N(R ^14a )R ^14b , C(=S)N(R ^14a )R ^14b , C(=O)OR ¹⁵ , or

phenyl, which is unsubstituted, or partially or fully substituted by R ¹⁶ ; and

a 3- to 7-membered saturated, partially or fully unsaturated heterocyclic ring comprising 1, 2 or 3 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or par- tially or fully substituted by same or different R ¹⁶ ; and

R ⁹ in the groups S(O) _n R ⁹ and OSO ₂ R ⁹ may additionally be C ₁ -C ₆ -alkoxy, or C ₁ -C ₆ -haloalk- oxy;

R ^10a , R ^10b are independently from one another H, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₃ -C ₈ -cycloal- kyl, C ₃ -C ₈ -halocycloalkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -haloalkenyl, C ₂ -C ₆ -alkynyl, C ₂ -C ₆ -haloalky- nyl, which groups are unsubstituted, or partially or fully substituted by same or different R ¹³ ;

C ₁ -C ₆ -alkyl-C(=O)OR ¹⁵ , C ₁ -C ₆ -alkyl-C(=O)N(R ^14a )R ^14b , C ₁ -C ₆ -alkyl-C(=S)N(R ^14a )R ^14b , C ₁ -C ₆ -alkyl-C(=NR ¹⁴ )N(R ^14a )R ^14b , C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -haloalkoxy, C ₁ -C ₆ -alkylthio, C ₁ -C ₆ - haloalkylthio, S(O)nR ¹⁵ , S(O)nN(R ^14a )R ^14b , C(=O)R ¹³ , C(=O)OR ¹⁵ , C(=O)N(R ^14a )R ^14b , C(=S)R ¹³ , C(=S)SR ¹⁵ , C(=S)N(R ^14a )R ^14b , C(=NR ¹⁴ )R ¹³ ;

phenyl, which is unsubstituted, or partially or fully substituted by same or different R ¹⁶ ; and a 3-, 4-, 5-, 6- or 7-membered saturated, partially or fully unsaturated heterocyclic ring comprising 1, 2, 3 or 4 heteroatoms N, O, and/or S as ring members, which ring is unsub- stituted, or partially or fully substituted by same or different R ¹⁶ , preferably unsubstituted or substituted HET; or

R ^10a and R ^10b together with the nitrogen atom they are bonded to form a 3- to 8-membered saturated, partially or fully unsaturated heterocyclic ring, which ring may additionally con- tain one or two heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or partially or fully substituted by same or different halogen, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C1-C6-alkylthio, C1-C6-haloalkylthio, C3-C8-cycloalkyl, C3- C ₈ -halocycloalkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -haloalkenyl, C ₂ -C ₆ -alkynyl, C ₂ -C ₆ -haloalkynyl, phe- nyl which may be partially or fully substituted by R ¹⁶ , and a 3-, 4-, 5-, 6,- or 7-membered saturated, partially or fully unsaturated heterocyclic ring comprising 1, 2 or 3 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or partially or fully substituted by same or different R ¹⁶ ; or

R ^10a and R ^10b together form a group =C(R ¹³ )2, =S(O)m(R ¹⁵ )2, =S(O)mR ¹⁵ N(R ^14a )R ^14b , =NR ¹⁴ , or =NOR ¹⁵ ; R ¹¹ is halogen, CN, N ₃ , NO ₂ , SCN, SF ₅ , C ₁ -C ₁₀ -alkyl, C ₃ -C ₈ -cycloalkyl, C ₂ -C ₁₀ -alkenyl, C ₂ -C ₁₀ - alkynyl, which groups are unsubstituted, partially or fully halogenated, and/or may be sub- stituted by same or different R ⁸ , or

OR ⁹ , NR ^10a R ^10b , S(O) _n R ⁹ , Si(R ¹² ) ₃ ;

phenyl, which is unsubstituted, or partially or fully substituted by same or different R ¹⁶ ; and a 3- to 7-membered saturated, partially or fully unsaturated aromatic heterocyclic ring comprising 1, 2, 3, or 4 heteroatoms N, O, and/or S as ring members, which ring is unsub- stituted, or partially or fully substituted by same or different R ¹⁶ ; or

two R ¹¹ present on the same ring carbon atom of an unsaturated or partially unsaturated heterocyclic ring may together form a group =O, =C(R ¹³ ) ₂ , =S, =S(O) _m (R ¹⁵ ) ₂ ,

=S(O) _m R ¹⁵ N(R ^14a )R ^14b , =NR ¹⁴ , =NOR ¹⁵ , or =NN(R ^14a )R ^14b ;

or two R ¹¹ bound on adjacent ring atoms form together with the ring atoms to which they are bound a saturated 3- to 9-membered ring, which ring may contain 1 or 2 heteroatoms O, S, N, and/or NR ¹⁴ , and/or 1 or 2 groups C=O, C=S, C=NR ¹⁴ as ring members, and which ring is unsubstituted, or partially or fully substituted by same or different halogen, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C1-C6-alkylthio, C1-C6-haloal- kylthio, C ₃ -C ₈ -cycloalkyl, C ₃ -C ₈ -halocycloalkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -haloalkenyl, C ₂ -C ₆ -al- kynyl, C ₂ -C ₆ -haloalkynyl, phenyl which may be partially or fully substituted by same or dif- ferent R ¹⁶ , and a 3- to 7-membered saturated, partially or fully unsaturated heterocyclic ring containing 1, 2, or 3 heteroatoms N, O, and/or S as ring members, which ring is un- substituted, or partially or fully substituted by same or different R ¹⁶ ;

each R ¹² is independently C1-C4-alkyl and phenyl, which is unsubstituted, or partially or fully substituted by same or different C1-C4-alkyl;

each R ¹³ is independently CN, NO ₂ , OH, SH, SCN, SF ₅ , C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -haloalkoxy, SO _n - C ₁ -C ₆ -alkyl, SO _n -C ₁ -C ₆ -haloalkyl, Si(R ¹² ) ₃ , -C(=O)N(R ^14a )R ^14b ,

C3-C8-cycloalkyl which is unsubstituted, partially or fully halogenated or substituted by 1 or 2 same or different C ₁ -C ₄ -alkyl, C ₃ -C ₄ -cycloalkyl, C ₁ -C ₄ -alkoxy, C ₁ -C ₄ -haloalkoxy and/or oxo; phenyl, benzyl, phenoxy, where the phenyl moiety may be substituted by one or more same or different R ¹⁶ ; and a 3- to 7-membered saturated, partially or fully unsatu- rated heterocyclic ring containing 1, 2, or 3 heteroatoms N, O, and/or S, as ring members, which ring is unsubstituted, or partially or fully substituted by same or different R ¹⁶ ; or two R ¹³ present on the same carbon atom of an alkyl, alkenyl, alkynyl or cycloalkyl group may together be =O, =CH(C1-C4-alkyl), =C(C1-C4-alkyl)C1-C4-alkyl, =N(C1-C6-alkyl) or =NO(C ₁ -C ₆ -alkyl); and

R ¹³ as a substituent of a cycloalkyl ring may additionally be C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl or C2-C6-alkynyl, which groups are unsubstituted, partially or fully halogenated, or substituted by 1 or 2 CN, C3-C4-cycloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, and oxo; and

R ¹³ in groups =C(R ¹³ ) ₂ , N=C(R ¹³ ) ₂ , C(=O)R ¹³ , C(=S)R ¹³ , and C(=NR ¹⁴ )R ¹³ may additionally be H, halogen, C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, or C ₂ -C ₆ -alkynyl, which groups are unsubsti- tuted, partially or fully halogenated, or substituted by 1 or 2 CN, C3-C4-cycloalkyl, C1-C4- alkoxy, C ₁ -C ₄ -haloalkoxy, and oxo;

each R ¹⁴ is independently H, CN, C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -haloalkoxy, SO _n -C ₁ -C ₆ -alkyl, SO _n -C ₁ - C6-haloalkyl, Si(R ¹² )3; C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, which groups are unsubstituted, partially or fully halogenated, or substituted by 1 or 2 CN, C1-C4-alkoxy, C1-C4-haloalkoxy, SOn-C1-C4-al- kyl, C ₃ -C ₆ -cycloalkyl which is unsubstituted or substituted by 1 or 2 substituents halogen and CN;

and oxo;

C ₃ -C ₈ -cycloalkyl which is unsubstituted, or partially or fully halogenated or substituted by 1 or 2 CN, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy, C ₁ -C ₄ -haloalkoxy, SO _n -C ₁ -C ₆ -alkyl, C ₃ -C ₄ -cycloalkyl, C ₃ -C ₄ -cycloalkyl-C ₁ -C ₄ -alkyl-, which groups are unsubstituted, or substituted by 1 or 2 sub- stituents selected from halogen and CN;

phenyl, benzyl, pyridyl, phenoxy, which cyclic moieties are unsubstituted, or substituted by one or more same or different halogen, CN, NO ₂ , C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alk- oxy, C1-C6-haloalkoxy, C1-C6-alkylthio, C1-C6-haloalkylthio, C2-C4-alkenyl, C2-C4-haloal- kenyl, C ₂ -C ₄ -alkynyl, C ₂ -C ₄ -haloalkynyl, C ₃ -C ₆ -cycloalkyl, C ₃ -C ₆ -halocycloalkyl, and C ₁ -C ₆ - alkoxycarbonyl; and a 3-, 4-, 5- or 6-membered saturated, partially or fully unsaturated heterocyclic ring comprising 1, 2 or 3 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or partially or fully substituted by same or different R ¹⁶ ;

R ^14a and R ^14b independently of each other, have one of the meanings given for R ¹⁴ ; or R ^14a and R ^14b , together with the nitrogen atom to which they are bound, form a 3- to 7- membered saturated, partially, or fully unsaturated heterocyclic ring, wherein the ring may additionally contain 1 or 2 heteroatoms N, O, and/or S as ring members, which ring is un- substituted, or partially or fully substituted by same or different halogen, C ₁ -C ₄ -alkyl, C ₁ - C4-haloalkyl, C1-C4-alkoxy, or C1-C4-haloalkoxy; or

R ^14a and R ¹⁴ or R ^14b and R ¹⁴ , together with the nitrogen atoms to which they are bound in the group C(=NR ¹⁴ )N(R ^14a )R ^14b , form a 3- to 7-membered partially, or fully unsaturated heterocyclic ring, wherein the ring may additionally contain 1 or 2 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or partially or fully substituted by same or different halogen, C ₁ -C ₄ -haloalkyl, C ₁ -C ₄ -alkoxy, or C ₁ -C ₄ -haloalkoxy;

each R ¹⁵ is independently H, CN, Si(R ¹² ) ₃

C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, which groups are unsubstituted, partially or fully halogenated, or substituted by 1 or 2 radicals C3-C4-cycloalkyl, C1-C4-alkoxy, C1-C4-haloal- koxy, SO _n -C ₁ -C ₆ -alkyl, or oxo;

C ₃ -C ₈ -cycloalkyl which is unsubstituted, partially or fully halogenated or substituted by 1 or 2 radicals C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, SOn-C1-C6-alkyl, or oxo;

phenyl, benzyl, pyridyl, and phenoxy, which rings are unsubstituted, partially or fully halo- genated, or substituted by 1, 2 or 3 substituents C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, or (C1-C6-alkoxy)carbonyl;

each R ¹⁶ is independently halogen, NO ₂ , CN, OH, SH, C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -haloalkoxy, SO _n - C ₁ -C ₆ -alkyl, SO _n -C ₁ -C ₆ -haloalkyl, C ₁ -C ₄ -alkylcarbonyl, C ₁ -C ₄ -haloalkylcarbonyl, C ₁ -C ₄ - alkoxycarbonyl, C1-C4-haloalkoxycarbonyl, aminocarbonyl, C1-C4-alkylaminocarbonyl, di- (C ₁ -C ₄ -alkyl)-aminocarbonyl, Si(R ¹² ) ₃ ;

C ₁ -C ₆ -alkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -alkynyl, which groups are unsubstituted, partially or fully halogenated, or substituted by 1 or 2 radicals CN, C3-C4-cycloalkyl, C1-C4-alkoxy, C1-C4- haloalkoxy, or oxo; C ₃ -C ₈ -cycloalkyl which is unsubstituted, partially or fully halogenated or substituted by 1 or 2 radicals CN, C1-C4-alkyl, C3-C4-cycloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, or oxo;

phenyl, benzyl, pyridyl and phenoxy, which rings are unsubstituted, partially or fully halo- genated, or substituted by 1, 2 or 3 substituents C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₁ -C ₆ -alkoxy, C1-C6-haloalkoxy, or (C1-C6-alkoxy)carbonyl; or

two R ¹⁶ present together on the same atom of an unsaturated or partially unsaturated ring may be =O, =S, =N(C ₁ -C ₆ -alkyl), =NO-C ₁ -C ₆ -alkyl, =CH(C ₁ -C ₄ -alkyl), or =C(C ₁ -C ₄ -alkyl) ₂ ; or

two R ¹⁶ on two adjacent carbon atoms form together with the carbon atoms they are bonded to a 4- to 8-membered saturated, partially or fully unsaturated ring, wherein the ring may contain 1 or 2 heteroatoms N, O, and/or S as ring members, which ring is unsub- stituted, or partially or fully substituted by same or different halogen, C1-C4-alkyl, C1-C4- haloalkyl, C ₁ -C ₄ -alkoxy, or C ₁ -C ₄ -haloalkoxy;

each n is independently 0, 1, or 2; and

each m is independently 0, or 1; by reacting an α,β-unsaturated compound of formula II,

wherein the varia bles have the meanings given for formula I, with a thioglycolate of formula III,

wherein R ³ has the meaning given for formula I, in the presence of a catalyst.

Compounds of formula I are valuable intermediates for the preparation of active compounds of formula IV, wherein the variables are as defined in general and preferred embodiments for for- mula I. These dihydrothiophene compounds are generally known from WO 2014/072480, and WO 2016/102490.

However, fluorinated compounds of formula IV cannot be prepared in good yield by the pro- cesses disclosed in WO 2016/102490. Objective task for the present invention therefore is providing an economical, industrially applicable manufacturing process for fluorinated com- pounds of formula I, and to the active compounds of formual IV. This task is achieved by the process defined in the outset. The presence of a catalyst as defined herein in the reaction of compounds II and III ensures a quick and complete transformation at moderate temperatures. The reaction of compounds of formula II and compounds of formula III is carried out at temper- atures of from -20°C to 100°C, preferably from 0°C to 40°C, in an inert solvent such as ethers, such as tetrahydrofurane (THF), diethyl ether, and dioxane, or toluene, in the presence of or- ganic bases, for example tertiary amines, such as diisopropylethylamine (DIPEA), trimethyla- mine, triethylamine, and N-methylpiperidine, pyridine, substituted pyridines, such as collidine, lutidine and 4-dimethylaminopyridine, and also bicyclic amines, or inorganic bases such as al- kali metal and alkaline earth metal oxides, such as Li ₂ O, Na ₂ O, CaO, and MgO, in the presence of a catalyst, which is selected from lewis acids, and urea and thiourea derivatives. Lewis acids are preferably alkali metal halides, such as LiBr, LiI, LiCl, LiF, NaBr, NaI, NaCl, NaF, KBr, KI, KF, KCl, CsBr, CsI, CsCl, CsF; or BF ₃ , AlCl ₃ , FeCl ₃ , ZnCl ₄ , TiCl ₄ , ZnCl ₂ ,

SiCl(CH3)3, Cl3SiH, SiCl4, BF3 ^OC2H5, SiF4, (C2H5)3SiNTf2, (CH3)3SiClO4, TiCl4, SnCl4,

SiCl(CH ₃ ) ₃ , Cl ₃ SiH, SiCl ₄ , BF ₃ ^OC ₂ H ₅ , SiF ₄ , [(C ₂ H ₅ ) ₃ Si(toluene)][B(C ₆ F ₅ ) ₄ ], AgNTf ₂ , Me ₃ SiOTf, (CH ₃ ) ₃ SiNTf ₂ , (C ₂ H ₅ ) ₃ SiNTf ₂ , (CH ₃ ) ₃ SiClO ₄ , TiCl ₄ , SnCl ₄ , [PCH ₃ (C ₆ F ₅ ) ₄ ][I], or [Ph ₃ PCH ₂ C ₆ F ₅ ][Cl], preferably SiCl(CH3)3, Cl3SiH, SiCl4, BF3 ^OC2H5, SiF4, (C2H5)3SiNTf2, (CH3)3SiClO4, TiCl4, or SnCl ₄ , (c.f. WO 2015/169723). Preferred lewis acids are alkali metal halides, which are particu- larly selected from LiBr, LiCl, NaBr, and KBr.

Urea and thiourea derivatives are of formula V

wherein

R ⁵¹ is phenyl substituted by one or more OCF3, CF3, NO2, F, and OCH3; preferably CF3; R ⁵² CH2CH2N(CH3)2;

W is O, or S, preferably S. The lewis acid is used in 2 to 3, preferably 2 to 2.5, particularly about 2.2 mol equivalents of compound II. The urea derivative is used in 0.01 to 0.5, preferably 0.1 to 0.5, particularly about 0.1 mol equivalents of compound II. The starting materials are generally reacted with one an- other in equimolar amounts. In terms of yield, it may be advantageous to employ an excess of III, based on II. Compounds of formula II can be obtained by condensation of a ketone of formula VI with an acetyl compound of formula VII

This transformation is usually carried out at temperatures of from 0°C to +150°C, preferably from 20°C to +120°C, in an inert solvent, in the presence of a base (cf. WO 2016/102490). Suitable solvents are aliphatic hydrocarbons such as pentane, hexane, cyclohexane, and pet- rol ether, aromatic hydrocarbons such as toluene, o-, m-, and p-xylene, halogenated hydrocar- bons such as CH ₂ Cl ₂ , CHCl ₃ , dichloroethane and chlorobenzene, ethers such as diethyl ether, diisopropylether, tert.-butylmethyl ether, 1,4-dioxane, anisole, and THF, nitrils such as acetoni- trile, and propionitrile, alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, and tert.-butanol, preferably aliphatic hydrocarbons or halogenated hydrocarbons such as di- chloroethane. It is also possible to use mixtures of the solvents mentioned. Suitable bases are, in general, inorganic compounds, such as alkali metal and alkaline earth metal hydroxides, such as LiOH, NaOH, KOH and Ca(OH)2, alkali metal and alkaline earth metal oxides, such as Li ₂ O, Na ₂ O, CaO, and MgO, alkali metal and alkaline earth metal hydri- des, such as LiH, NaH, KH and CaH ₂ , alkali metal and alkaline earth metal carbonates, such as Li2CO3, K2CO3 and CaCO3, and also alkali metal bicarbonates, such as NaHCO3, moreover or- ganic bases, for example tertiary amines, such as N(CH ₃ ) ₃ , N(C ₂ H ₅ ) ₃ , DIPEA and N-methylpi- peridine, pyridine, substituted pyridines, such as collidine, lutidine and 4-dimethylaminopyridine, and also bicyclic amines. Particular preference is given to alkali metal and alkaline earth metal carbonates and organic bases, especially sodium or potassium carbonate and triethylamine. The bases are generally employed in catalytic amounts; however, they can also be used in equimolar amounts, in excess or, if appropriate, as solvent. It is also possible to use mixtures of the bases mentioned.

Starting materials of formulae II and III, resp. required for preparing the compounds I are com- mercially available or known from the literature (cf. WO 2015/128358, WO 2016/102490) or can be prepared as outlined above, or in accordance with the literature cited. Furthermore, the invention also relates to a process for the manufacture of compounds of for- mula IV starting from formula II compounds which are reacted with formula III compounds to yield compounds of formula I as outlined in the outset, which is then hydrolyzed to the carboxy- lic acid of formula VIII,

s rans orma on s usua y carre ou a empera ure rom - o , pre era y at 10°C to 50°C, in water and a base such as an alkali metal hydroxide such as KOH, NaOH, or preferably LiOH, in a solvent, such as THF, dioxane, or methanol, or an aqueous mixture thereof, preferably a THF-water mixture (c.f. WO 2015/169723).

Under these conditions, the ester group A being COOR ⁹ in formula I is hydrolysed to COOH in formula VIII.

Compounds o ormua can e prepare rom compoun s y e y ra ve ecarboxylation of compounds of formula VIII with reagents such as methyl sulphonyl chroride (CH ₃ SO ₂ Cl), or dineopentylacetal in a solvent such as dimethylsulfoxide (DMSO), DMF, or N-methylpyrrolidone (NMP), preferably in DMF. The reaction is carried out at temperature from 25°C to 250°C, pref- erably at 100°C to 150°C (c.f. WO 2014/072480). The reaction sequences from formula II to I, and VIII to IV, resp., are preferably carried out with compounds wherein group A is a group C(=W)OR ⁹ , particularly an ester group C(=O)OR ⁹ . In intermediate compounds R ⁹ usually is C ₁ -C ₄ -alkyl. Compounds IV, wherein A is a group A ¹ , correspond to formula IV.1. Such compounds, wherein W is O, can be prepared by reacting a compound IV wherein A is A ⁵ , which is Cl, Br, I, or OSO2- R ⁹ , and the other variables are as defined for formula IV (such compounds represent formula IV.5), with carbon monoxide in the presence of a Pd catalyst and an alcohol R ⁹ OH, wherein R ⁹ is C1-C4-alkyl or R ⁹ , to a compound of formula IV.1. Suitable Pd catalysts are for example those described in WO 2011/161130.

s es er . s en y royse o e respec ve car oxy c ac , w c s e reac e un er standard amidation conditions with an amine NHR ⁵ R ⁶ . Hydrolyzation can be carried out under standard conditions, e.g. under acidic conditions using for example hydrochloric acid, sulfuric acid or trifluoroacetic acid, or under basic conditions using for example an alkali metal hydrox- ide, such as LiOH, NaOH, or KOH. Amidation is preferably carried out by activation of the car- boxylic acids with oxalylchloride [(COCl)2] or thionylchloride (SOCl2) to the respective acid chlo- rides, followed by reaction with an amine NHR ⁵ R ⁶ . Alternatively, amidation is carried out in the presence of a coupling reagent. Suitable coupling reagent (activators) are well known and are for instance selected from carbodiimides, such as DCC (dicyclohexylcarbodiimide) and DIC (diisopropylcarbodiimide), benzotriazol derivatives, such as HATU (O-(7-azabenzotriazol-1-yl)- N,N,N',N'-tetramethyluronium hexafluorophosphate), HBTU ((O-benzotriazol-1-yl)-N,N,N',N'-tet- ramethyluronium hexafluorophosphate) and HCTU (1H-benzotriazolium-1-[bis(dimethylami- no)methylene]-5-chloro tetrafluoroborate) and phosphonium-derived activators, such as BOP ((benzotriazol-1-yloxy)-tris(dimethylamino)phosphonium hexafluorophosphate), Py-BOP ((ben- zotriazol-1-yloxy)-tripyrrolidinphosphonium hexafluorophosphate) and Py-BrOP (bromotripyrroli- dinphosphonium hexafluorophosphate). Generally, the activator is used in excess. The benzotri- azol and phosphonium coupling reagents are generally used in a basic medium.

Compounds IV.1, wherein W is S, can be prepared by reacting the corresponding oxo-com- pound (W is O) with Lawesson's reagent (c.f. Jesberger et al., Synthesis, 2003, 1929-1958). Solvents such as Hexamethylphosphoramide (HMPA) or THF at an elevated temperature such as 60°C to 100°C can be used. Preferred reaction conditions are THF at 65°C. Compounds I wherein A is a group A ² can be prepared by reacting a compound I wherein A is an aldehyde group CHO with NH2-NH-C(O)-NHR ²² . Suitable reaction conditions for this conden- sation reaction include heating in a solvent such as a lower alcohol under the influence of an acid (e.g. acetic acid or HCl), where the acid may be used in catalytic or equimolar amounts. Compounds I wherein A is a group A ² , wherein R ^7a and R ^7b are hydrogen, correspond to formula IV.2. Such compounds can be prepared by reducing an aldehyde IV.1 wherein Y is H (such al- dehyde represents formula IV.1a) for example with LAH (lithium aluminium hydride) or DIBAL-H (diisobutyl aluminium hydride) to a compound 20. This is then reacted in an S _N reaction with an amide NHR ²¹ C(O)R ²² , or, preferably with an amine NH2R ²¹ . In both cases, the OH group can first be converted into a better leaving group, e.g. into a sulfonate (for example mesylate, tosylate or a triflate group). In the second variant (reaction with an amine NH ₂ R ²¹ ) the resulting benzylic amine is then reacted with an acid R ²² -COOH or a derivative thereof, such as its acid chloride R ²² -COCl, in an amidation reaction. Starting from the carboxylic acid, amidation is preferably carried out by activation of the car- boxyl group with oxalylchloride [(COCl) ₂ ] or thionylchloride (SOCl ₂ ) to the respective acid chlo- rides, followed by reaction with the benzylic amine. Alternatively, amidation is carried out in the presence of a coupling reagent. Suitable coupling reagents (activators) are well known and are for instance selected from carbodiimides, such as DCC (dicyclohexylcarbodiimide) and DIC (di- isopropylcarbodiimide), benzotriazol derivatives, such as HATU (O-(7-azabenzotriazol-1-yl)- N,N,N',N'-tetramethyluronium hexafluorophosphate), HBTU ((O-benzotriazol-1-yl)-N,N,N',N'-tet- ramethyluronium hexafluorophosphate) and HCTU (1H-benzotriazolium-1-[bis(dimethylami- no)methylene]-5-chloro tetrafluoroborate) and phosphonium-derived activators, such as BOP ((benzotriazol-1-yloxy)-tris(dimethylamino)phosphonium hexafluorophosphate), Py-BOP ((ben- zotriazol-1-yloxy)-tripyrrolidinphosphonium hexafluorophosphate) and Py-BrOP (bromotripyrroli- dinphosphonium hexafluorophosphate). Generally, the activator is used in excess. The benzotri- azol and phosphonium coupling reagents are generally used in a basic medium. Compounds IV wherein A is a group A ² , represent formula IV.2. Such compounds wherein R ^7a is optionally substituted alkyl or optionally substituted cycloalkyl and R ^7b is H, can be prepared by subjecting a ketone 22, wherein R ^7a is optionally substituted C1-C6-alkyl or optionally substi- tuted C3-C8-cycloalkyl, to a reductive amination to yield compounds 21. Typical conditions for the reductive amination are: Reacting ketone 22 with an amine H ₂ NR ²¹ to yield the correspond- ing imine which is reduced to amine 21 with a reducing agent reagent such as NaBH ₃ CN. The reaction from ketone 22 to amine 21 may also be carried out as a one pot procedure.

The amine 21 is then r reof, such as its acid chloride R ²² -COCl, in an amidation reaction, as described above.

The ketone 22 is prepared from the aldehyde IV.1a which is reacted with a Grignard reagent R ^7a -MgHal, where Hal is Cl, Br or I, or an organolithium compound R ^7a -Li to obtain an alcohol of formul

For obtaining compounds in which R ^7a and R ^7b are optionally substituted alkyl, optionally sub- stituted cycloalkyl, optionally substituted alkenyl or optionally substituted alkynyl, carbonyl com- pounds such as 22, where R ^7a is optionally substituted C ₁ -C ₆ -alkyl, optionally substituted C ₃ -C ₈ - cycloalkyl, optionally substituted C2-C6-alkenyl or optionally substituted C2-C6-alkynyl, is reacted with a Grignard reagent R ^7b -MgHal, where Hal is Cl, Br or I, or an organolithium compound R ^7b - Li, where R ^7b is optionally substituted C ₁ -C ₆ -alkyl, optionally substituted C ₃ -C ₈ -cycloalkyl, option- ally substituted C2-C6-alkenyl or optionally substituted C2-C6-alkynyl, to obtain an alcohol of for- mula 24.

Alcohol 24 can then be converted into amine 25 via the corresponding azide (c.f. in Organic Let- ters, 2001, 3(20), 3145-3148.

If desired, this can be converted into compounds IV.2 by standard alkylation or acylation reac- tions.

Compounds IV.2, wherein R ^7a is optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl or CN and R ^7b is H, can be prepared by converting an aldehyde IV.1a into an imine 26 by reaction with an amine derivative NH2R, wherein R is tert-butyl sulfinyl, or, for preparing a compound with R ^7a being CN.

This imine is then reacted with a compound X-R ^7a in an addition reaction. Suitable reagents are for example Si(CH3)3-CN or HCN for introducing CN as R ^7a , or Si(CH3)3-CF3 for introducing CF3 as R ^7a , or methyl magnesium bromide (CH3-MgBr) for introducing a methyl group as R ^7a . Suitable conditions are described, for example, in J. Am. Chem. Soc.2009, 3850-3851 and the references cited therein or in Chemistry - A European Journal 2009, 15, 11642-11659. R (tert- butylsulfinyl) can then be removed under acidic conditions, such as hydrochloric acid in metha- nol, to yield an amino group. The group C(O)R ²² can then be introduced as described above by acylating this amino group with an acid R ²² -COOH or a derivative thereof, such as its acid chlo- ride R ²² -COCl. Compounds I wherein A is a group A ² can be prepared by reacting a compound I wherein A is an aldehyde group CHO with NH ₂ -NH-C(O)-NHR ²² . Suitable reaction conditions for this conden- sation reaction include heating in a solvent such as a lower alcohol under the influence of an acid (e.g. acetic acid or HCl), where the acid may be used in catalytic or equimolar amounts. These reactions can be carried out in analogy to the methods described in WO 2011/161130 or in WO 2010/072781.

Compounds IV.1a can be prepared by reaction of a compound IV.5, in which A ⁵ is Cl, Br, I or OSO ₂ -R ⁹ , with carbon monoxide and a hydride source, such as triethylsilane, in the presence of a transition metal complex catalyst, preferably a palladium catalyst, to the aldehyde IV.1a. This reaction converts the starting group A ⁵ into a carbonyl group CHO. Compounds IV wherein A is A ³ represent formula IV.3. Such compounds can be prepared by standard ring coupling reactions. For example, compounds, wherein A ³ is an N-bound heterocy- clic ring can be prepared by reacting a compound IV.5 wherein A ⁵ is Cl, Br or I with the respec- tive ring A ³ -H (H being on the nitrogen ring atom to be coupled) under Ullmann coupling condi- tions, such as described, for example, in WO 2007/075459. Typically, copper(I) iodide or cop- per(I) oxide and a ligand such as 1,2-cyclohexyldiamine is used, c.f. Kanemasa et al., European Journal of Organic Chemistry, 2004, 695-709. If A' is F, the reaction is typically run in a polar aprotic solvent such as N,N-dimethylformamide, N,N-dimethylacetamide or N-methylpyrroli- done, and in the presence of an inorganic base such as sodium, potassium or cesium car- bonate.

Compounds, wherein A ³ is a C-bound heterocyclic ring can be prepared by reacting a com- pound I.1' wherein A' is Br or I with the boronic acid or ester A ³ -B(OR)2, wherein R is H or C1-C4- alkyl or the two R form together a C ₂ -C ₆ -alkylene bridge, e.g. -CH ₂ -CH ₂ - under Suzuki reaction conditions via Pd-catalyzed cross coupling, such as described, for example, in WO

2007/075459. A typical catalyst is tetrakis(triphenylphosphine)palladium(0). Solvents such as tetrahydrofuran, acetonitrile, diethyl ether and dioxane are suitable. The boronic acids A ³ - B(OH) ₂ are either commercially available or can be prepared by known methods. Other meth- ods for introduction of the heterocyclic groups A ³ are the Heck, Stille, Kumada and Buchwald- Hartwig coupling procedures; c.f. Tetrahedron, 2004, 60, 8991-9016. The reaction mixtures are worked up in a customary manner, for example by mixing with wa- ter, separating the phases and, if appropriate, chromatographic purification of the crude prod- ucts. Some of the intermediates and end products are obtained in the form of colorless or slightly brownish viscous oils which are purified or freed from volatile components under re- duced pressure and at moderately elevated temperature. If the intermediates and end products are obtained as solids, purification can also be carried out by recrystallization or digestion.

If individual compounds I cannot be obtained by the routes described above, they can be pre- pared by derivatization of other compounds I.

However, if the synthesis yields mixtures of isomers, a separation is generally not necessarily required since in some cases the individual isomers can be interconverted during work-up for use or during application (for example under the action of light, acids or bases). Such conver- sions may also take place after use, for example in the treatment of plants in the treated plant, or in the harmful fungus to be controlled. The organic moieties mentioned in the above definitions of the variables are - like the term hal- ogen - collective terms for individual listings of the individual group members. The prefix Cn-Cm indicates in each case the possible number of carbon atoms in the group.

The term“halogen” denotes in each case fluorine, bromine, chlorine or iodine, in particular flu- orine, chlorine or bromine.

The term“CN” denotes in each case cyano.

The term "alkyl" as used herein and in the alkyl moieties of alkylamino, alkylcarbonyl, alkylthio, alkylsulfinyl, alkylsulfonyl and alkoxyalkyl denotes in each case a straight-chain or branched al- kyl group having usually from 1 to 10 carbon atoms, frequently from 1 to 6 carbon atoms, prefer- ably 1 to 4 carbon atoms, more preferably from 1 to 3 carbon atoms. Examples of an alkyl group are methyl, ethyl, n-propyl, iso-propyl, n-butyl, 2-butyl, iso-butyl, tert-butyl, n-pentyl, 1-methyl- butyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, 1,1-dimethylpro- pyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-di- methylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dime- thylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methyl- propyl, and 1-ethyl-2-methylpropyl.

The term "haloalkyl" as used herein and in the haloalkyl moieties of haloalkylcarbonyl, haloalk- oxycarbonyl, haloalkylthio, haloalkylsulfonyl, haloalkylsulfinyl, haloalkoxy and haloalkoxyalkyl, denotes in each case a straight-chain or branched alkyl group having usually from 1 to 10 car- bon atoms, frequently from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, wherein the hydrogen atoms of this group are partially or totally replaced with halogen atoms. Preferred haloalkyl moieties are selected from C1-C4-haloalkyl, more preferably from C1-C3-haloalkyl or C ₁ -C ₂ -haloalkyl, in particular from C ₁ -C ₂ -fluoroalkyl such as fluoromethyl, difluoromethyl, trifluo- romethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, and the like.

The term "alkoxy" as used herein denotes in each case a straight-chain or branched alkyl group which is bonded via an oxygen atom and has usually from 1 to 10 carbon atoms, fre- quently from 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms. Examples of an alkoxy group are methoxy, ethoxy, n-propoxy, iso-propoxy, n-butyloxy, 2-butyloxy, iso-butyloxy, tert.-butyloxy, and the like.

The term "alkoxyalkyl" as used herein refers to alkyl usually comprising 1 to 10, frequently 1 to 4, preferably 1 to 2 carbon atoms, wherein 1 carbon atom carries an alkoxy radical usually com- prising 1 to 4, preferably 1 or 2 carbon atoms as defined above. Examples are CH2OCH3, CH ₂ -OC ₂ H ₅ , 2-(methoxy)ethyl, and 2-(ethoxy)ethyl.

The term "haloalkoxy" as used herein denotes in each case a straight-chain or branched alk- oxy group having from 1 to 10 carbon atoms, frequently from 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, wherein the hydrogen atoms of this group are partially or totally replaced with halogen atoms, in particular fluorine atoms. Preferred haloalkoxy moieties include C ₁ -C ₄ - haloalkoxy, in particular C1-C2-fluoroalkoxy, such as fluoromethoxy, difluoromethoxy, trifluoro- methoxy, 1-fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2-flu- oroethoxy, 2-chloro-2,2-difluoro-ethoxy, 2,2dichloro-2-fluorethoxy, 2,2,2-trichloroethoxy, penta- fluoroethoxy and the like.

The term "alkylthio" (S-alkyl) as used herein refers to a straight-chain or branched saturated alkyl group having 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms (C ₁ -C ₄ -alkylthio), more preferably 1 to 3 carbon atoms, which is attached via a sulfur atom.

The term "haloalkylthio" as used herein refers to an alkylthio group as mentioned above wherein the hydrogen atoms are partially or fully substituted by fluorine, chlorine, bromine and/or iodine.

The term "alkylsulfinyl" (S(=O)-C ₁ -C ₆ -alkyl), as used herein refers to a straight-chain or branched saturated alkyl group (as mentioned above) having 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms (C ₁ -C ₄ -alkylsulfinyl), more preferably 1 to 3 carbon atoms bonded through the sulfur atom of the sulfinyl group at any position in the alkyl group. The term "haloalkylsulfinyl" as used herein refers to an alkylsulfinyl group as mentioned above wherein the hydrogen atoms are partially or fully substituted by fluorine, chlorine, bromine and/or iodine.

The term "alkylsulfonyl" (S(=O) ₂ -alkyl) as used herein refers to a straight-chain or branched saturated alkyl group having 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms (C1-C4-alkyl- sulfonyl), preferably 1 to 3 carbon atoms, which is bonded via the sulfur atom of the sulfonyl group at any position in the alkyl group.

The term "haloalkylsulfonyl" as used herein refers to an alkylsulfonyl group as mentioned above wherein the hydrogen atoms are partially or fully substituted by fluorine, chlorine, bro- mine and/or iodine.

The term "alkylcarbonyl" refers to an alkyl group as defined above, which is bonded via the carbon atom of a carbonyl group (C=O) to the remainder of the molecule.

The term "haloalkylcarbonyl" refers to an alkylcarbonyl group as mentioned above, wherein the hydrogen atoms are partially or fully substituted by fluorine, chlorine, bromine and/or iodine. The term "alkoxycarbonyl" refers to an alkylcarbonyl group as defined above, which is bonded via an oxygen atom to the remainder of the molecule.

The term "haloalkoxycarbonyl” refers to an alkoxycarbonyl group as mentioned above, where- in the hydrogen atoms are partially or fully substituted by fluorine, chlorine, bromine and/or io- dine.

The term "alkenyl" as used herein denotes in each case a singly unsaturated hydrocarbon rad- ical having usually 2 to 10, frequently 2 to 6, preferably 2 to 4 carbon atoms, e.g. vinyl, allyl (2- propen-1-yl), 1-propen-1-yl, 2-propen-2-yl, methallyl (2-methylprop-2-en-1-yl), 2-buten-1-yl, 3- buten-1-yl, 2-penten-1-yl, 3-penten-1-yl, 4-penten-1-yl, 1-methylbut-2-en-1-yl, 2-ethylprop-2-en- 1-yl and the like.

The term "haloalkenyl" as used herein refers to an alkenyl group as defined above, wherein the hydrogen atoms are partially or totally replaced with halogen atoms.

The term "alkynyl" as used herein denotes in each case a singly unsaturated hydrocarbon rad- ical having usually 2 to 10, frequently 2 to 6, preferably 2 to 4 carbon atoms, e.g. ethynyl, pro- pargyl (2-propyn-1-yl), 1-propyn-1-yl, 1-methylprop-2-yn-1-yl), 2-butyn-1-yl, 3-butyn-1-yl, 1-pen- tyn-1-yl, 3-pentyn-1-yl, 4-pentyn-1-yl, 1-methylbut-2-yn-1-yl, 1-ethylprop-2-yn-1-yl and the like. The term "haloalkynyl" as used herein refers to an alkynyl group as defined above, wherein the hydrogen atoms are partially or totally replaced with halogen atoms.

The term "cycloalkyl" as used herein and in the cycloalkyl moieties of cycloalkoxy and cycloal- kylthio denotes in each case a monocyclic cycloaliphatic radical having usually from 3 to 10 or from 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl and cyclodecyl or cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. The term "halocycloalkyl" as used herein and in the halocycloalkyl moieties of halocycloalkoxy and halocycloalkylthio denotes in each case a monocyclic cycloaliphatic radical having usually from 3 to 10 C atoms or 3 to 6 C atoms, wherein at least one, e.g.1, 2, 3, 4 or 5 of the hydrogen atoms, are replaced by halogen, in particular by fluorine or chlorine. Examples are 1- and 2-fluo- rocyclopropyl, 1,2-, 2,2- and 2,3-difluorocyclopropyl, 1,2,2-trifluorocyclopropyl, 2,2,3,3-tetrafluo- rocyclpropyl, 1- and 2-chlorocyclopropyl, 1,2-, 2,2- and 2,3-dichlorocyclopropyl, 1,2,2-trichloro- cyclopropyl, 2,2,3,3-tetrachlorocyclpropyl, 1-,2- and 3-fluorocyclopentyl, 1,2-, 2,2-, 2,3-, 3,3-, 3,4-, 2,5-difluorocyclopentyl, 1-,2- and 3-chlorocyclopentyl, 1,2-, 2,2-, 2,3-, 3,3-, 3,4-, 2,5-dichlo- rocyclopentyl and the like.

The term "cycloalkenyl" as used herein and in the cycloalkenyl moieties of cycloalkenyloxy and cycloalkenylthio denotes in each case a monocyclic singly unsaturated non-aromatic radical ha- ving usually from 3 to 10, e.g.3 or 4 or from 5 to 10 carbon atoms, preferably from 3- to 8 car- bon atoms. Exemplary cycloalkenyl groups include cyclopropenyl, cycloheptenyl or cycloocte- nyl.

The term“halocycloalkenyl” as used herein and in the halocycloalkenyl moieties of halocyclo- alkenyloxy and halocycloalkenylthio denotes in each case a monocyclic singly unsaturated non- aromatic radical having usually from 3 to 10, e.g.3 or 4 or from 5 to 10 carbon atoms, preferably from 3- to 8 carbon atoms, wherein at least one, e.g.1, 2, 3, 4 or 5 of the hydrogen atoms, are replaced by halogen, in particular by fluorine or chlorine. Examples are 3,3-difluorocyclopropen- 1-yl and 3,3-dichlorocyclopropen-1-yl.

The term "cycloalkenylalkyl" refers to a cycloalkenyl group as defined above which is bonded via an alkylene group, such as a C ₁ -C ₅ -alkyl group or a C ₁ -C ₄ -alkyl group, in particular a meth- ylene group (= cycloalkenylmethyl), to the remainder of the molecule.

The term“carbocycle” or“carbocyclyl” includes in general a 3- to 12-membered, preferably a 3- to 8-membered or a 5- to 8-membered, more preferably a 5- or 6-membered mono-cyclic, non-aromatic ring comprising 3 to 12, preferably 3 to 8 or 5 to 8, more preferably 5 or 6 carbon atoms. Preferably, the term“carbocycle” covers cycloalkyl and cycloalkenyl groups as defined above.

The term "3-, 4-, 5-, 6-, 7-, 8-, 9- or 10-membered saturated, partially or fully unsaturated het- erocyclic ring containing 1, 2 or 3 (or 4) heteroatoms N, O, and/or S, as ring members" denotes a 3-, 4-, 5-, 6-, 7- or 8-membered saturated, partially unsaturated or fully unsaturated hetero- monocyclic ring or a 8-, 9- or 10-membered saturated, partially or fully unsaturated heterobicy- clic ring containing 1, 2 or 3 (or 4) heteroatoms which are selected from N, O, and S as ring members. Unsaturated rings contain at least one C-C and/or C-N and/or N-N double bond(s). Fully unsaturated rings contain as many conjugated C-C and/or C-N and/or N-N double bonds as allowed by the ring size. Fully unsaturated include aromatic heterocyclic rings. The heterocy- clic ring may be attached to the remainder of the molecule via a carbon ring member or via a ni- trogen ring member. Of course, the heterocyclic ring contains at least one carbon ring atom. If the ring contains more than one O ring atom, these are not adjacent. N and S ring atoms may be oxidized, if not mentioned otherwise. The oxidized ring atoms constitue an N-oxide, Sulfox- ide (SO), and a sulfone (SO ₂ ), resp., wherein the only the N- or S atom is a ring member.

Examples of a 3-, 4-, 5-, 6- or 7-membered saturated, partially or fully unsaturated heteromon- ocyclic ring include: Oxiranyl, thiiranyl, aziridinyl, oxetanyl, thietanyl, azetidinyl, tetrahydrofuran- 2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl, pyrrolidin-1-yl, pyrrolidin-2- yl, pyrrolidin-3-yl, pyrazolidin-1-yl, pyrazolidin-3-yl, pyrazolidin-4-yl, pyrazolidin-5-yl, imidazolidin- 1-yl, imidazolidin-2-yl, imidazolidin-4-yl, oxazolidin-2-yl, oxazolidin-3-yl, oxazolidin-4-yl, oxazoli- din-5-yl, isoxazolidin-2-yl, isoxazolidin-3-yl, isoxazolidin-4-yl, isoxazolidin-5-yl, thiazolidin-2-yl, thiazolidin-3-yl, thiazolidin-4-yl, thiazolidin-5-yl, isothiazolidin-2-yl, isothiazolidin-3-yl, isothiazoli- din-4-yl, isothiazolidin-5-yl, 1,2,4-oxadiazolidin-3-yl, 1,2,4-oxadiazolidin-5-yl, 1,2,4-thiadiazolidin- 3-yl, 1,2,4-thiadiazolidin-5-yl, 1,2,4-triazolidin-3-yl, 1,3,4-oxadiazolidin-2-yl, 1,3,4-thiadiazolidin- 2-yl, 1,3,4-triazolidin-1-yl, 1,3,4-triazolidin-2-yl, 2-tetrahydropyranyl, 4-tetrahydropyranyl, 1,3-di- oxan-5-yl, 1,4-dioxan-2-yl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, hexahydro- pyridazin-3-yl, hexahydropyridazin-4-yl, hexahydropyrimidin-2-yl, hexahydropyrimidin-4-yl, hexa- hydropyrimidin-5-yl, piperazin-1-yl, piperazin-2-yl, 1,3,5-hexahydrotriazin-1-yl, 1,3,5-hexahydro- triazin-2-yl and 1,2,4-hexahydrotriazin-3-yl, morpholin-2-yl, morpholin-3-yl, morpholin-4-yl, thio- morpholin-2-yl, thiomorpholin-3-yl, thiomorpholin-4-yl, 1-oxothiomorpholin-2-yl, 1-oxothiomor- pholin-3-yl, 1-oxothiomorpholin-4-yl, 1,1-dioxothiomorpholin-2-yl, 1,1-dioxothiomorpholin-3-yl, 1,1-dioxothiomorpholin-4-yl, azepan-1-, -2-, -3- or -4-yl, oxepan-2-, -3-, -4- or -5-yl, hexahydro- 1,3-diazepinyl, hexahydro-1,4-diazepinyl, hexahydro-1,3-oxazepinyl, hexahydro-1,4-oxazepinyl, hexahydro-1,3-dioxepinyl, hexahydro-1,4-dioxepinyl and the like. Examples of an 8-membered saturated heterocyclic ring include: oxocanyl, azocanyl, 1,2-, 1,3-, 1,4- and 1,5-diazocanyl and the like.

Examples of a 3-, 4-, 5-, 6- or 7-membered partially unsaturated heterocyclic ring (HET) in- clude: 2,3-dihydrofur-2-yl, 2,3-dihydrofur-3-yl, 2,4-dihydrofur-2-yl, 2,4-dihydrofur-3-yl, 2,3-dihy- drothien-2-yl, 2,3-dihydrothien-3-yl, 2,4-dihydrothien-2-yl, 2,4-dihydrothien-3-yl, 2-pyrrolin-2-yl, 2-pyrrolin-3-yl, 3-pyrrolin-2-yl, 3-pyrrolin-3-yl, 2-isoxazolin-3-yl, 3-isoxazolin-3-yl, 4-isoxazolin-3- yl, 2-isoxazolin-4-yl, 3-isoxazolin-4-yl, 4-isoxazolin-4-yl, 2-isoxazolin-5-yl, 3-isoxazolin-5-yl, 4- isoxazolin-5-yl, 2-isothiazolin-3-yl, 3-isothiazolin-3-yl, 4-isothiazolin-3-yl, 2-isothiazolin-4-yl, 3- isothiazolin-4-yl, 4-isothiazolin-4-yl, 2-isothiazolin-5-yl, 3-isothiazolin-5-yl, 4-isothiazolin-5-yl, 2,3- dihydropyrazol-1-yl, 2,3-dihydropyrazol-2-yl, 2,3-dihydropyrazol-3-yl, 2,3-dihydropyrazol-4-yl, 2,3-dihydropyrazol-5-yl, 3,4-dihydropyrazol-1-yl, 3,4-dihydropyrazol-3-yl, 3,4-dihydropyrazol-4- yl, 3,4-dihydropyrazol-5-yl, 4,5-dihydropyrazol-1-yl, 4,5-dihydropyrazol-3-yl, 4,5-dihydropyrazol- 4-yl, 4,5-dihydropyrazol-5-yl, 2,3-dihydrooxazol-2-yl, 2,3-dihydrooxazol-3-yl, 2,3-dihydrooxazol- 4-yl, 2,3-dihydrooxazol-5-yl, 3,4-dihydrooxazol-2-yl, 3,4-dihydrooxazol-3-yl, 3,4-dihydrooxazol-4- yl, 3,4-dihydrooxazol-5-yl, 3,4-dihydrooxazol-2-yl, 3,4-dihydrooxazol-3-yl, 3,4-dihydrooxazol-4- yl, 2-, 3-, 4-, 5- or 6-di- or tetrahydropyridinyl, 3-di- or tetrahydropyridazinyl, 4-di- or tetrahydro- pyridazinyl, 2-di- or tetrahydropyrimidinyl, 4-di- or tetrahydropyrimidinyl, 5-di- or tetrahydropyrim- idinyl, di- or tetrahydropyrazinyl, 1,3,5-di- or tetrahydrotriazin-2-yl, 1,2,4-di- or tetrahydrotriazin- 3-yl, 2,3,4,5-tetrahydro[1H]azepin-1-, -2-, -3-, -4-, -5-, -6- or -7-yl, 3,4,5,6-tetrahydro[2H]azepin- 2-, -3-, -4-, -5-, -6- or -7-yl, 2,3,4,7-tetrahydro[1H]azepin-1-, -2-, -3-, -4-, -5-, -6- or -7-yl,

2,3,6,7-tetrahydro[1H]azepin-1-, -2-, -3-, -4-, -5-, -6- or -7-yl, tetrahydrooxepinyl, such as 2,3,4,5-tetrahydro[1H]oxepin-2-, -3-, -4-, -5-, -6- or -7-yl, 2,3,4,7-tetrahydro[1H]oxepin-2-, -3-, -4- , -5-, -6- or -7-yl, 2,3,6,7-tetrahydro[1H]oxepin-2-, -3-, -4-, -5-, -6- or -7-yl, tetrahydro-1,3-diaze- pinyl, tetrahydro-1,4-diazepinyl, tetrahydro-1,3-oxazepinyl, tetrahydro-1,4-oxazepinyl, tetrahy- dro-1,3-dioxepinyl and tetrahydro-1,4-dioxepinyl. Examples of an 8-membered partially unsatu- rated heterocyclic ring include: dihydroazocinyl, tetrahydrazocinyl, hexahydroazocinyl and the like.

Examples for a 3-, 4-, 5-, 6- or 7-membered fully unsaturated (including aromatic) heterocyclic ring are 5- or 6-membered heteroaromatic rings (HET), such as 2-furyl, 3-furyl, 2-thienyl, 3-thi- enyl, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 1-pyrazolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 2-oxa- zolyl, 4-oxazolyl, 5-oxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 1-imidazolyl, 2-imidazolyl, 4-im- idazolyl, 1,3,4-triazol-1-yl, 1,3,4-triazol-2-yl, 1,2,4-triazol-1-yl, 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 1-oxopyridin-2-yl, 1-oxopyridin-3-yl, 1-oxopyridin-4-yl, 3-pyridazinyl, 4-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl and 2-pyrazinyl, and also homoaromatic radicals, such as 1H-aze- pine, 1H-[1,3]-diazepine and 1H-[1,4]-diazepine. Examples of an 8-membered fully unsaturated saturated heterocyclic ring include: azocinyl, 1,2-, 1,3-, 1,4- and 1,5-diazocinyl and the like. A group of preferred heterocycles (HET) is the following: 2-pyridyl (E-1), 3-pyridyl (E-2), 4-py- ridyl (E-3), 3-pyridazinyl (E-4), 4-pyrimidinyl (E-5), 2-pyrazinyl (E-6), 2-pyrimidinyl (E-7), thio- phen-2-yl (E-8), thiophen-3-yl (E-9), furan-2-yl (E-10), furan-3-yl (E-11), pyrazol-1-yl (E-12), and 1,2,4-triazol-1-yl (E-13); heterocycles E-1, E-2, E-7, E-12, and E-13 are particularly preferred, which rings E-1 to E-13 are unsubstituted or substituted by up to 3 same or different substitu- ents.

Another particulary preferred heterocycle are E-12, and E-13.

Preferred 3-, 4-, 5-, 6- or 7-membered saturated, partially or fully unsaturated heterocyclic rings comprising 1, 2 or 3 heteroatoms N, O, and/or S as ring members (HET) are in any posi- tions of formulae I and IV, the following: azetidin-3-yl (H-1), dioxin-6-yl (H-2), 1,3-dioxolan-2-yl (H-3), 1,1-dioxotetrahydrothiophen-3-yl (H-4), 1,1-dioxothietan-2-yl (H-5), 1,1-dioxothietan-3-yl (H-6), imidazol-2-yl (H-7), imidazol-4-yl (H-8), imidazol-5-yl (H-9), isothiazol-3-yl (H-10), isothia- zol-4-yl (H-11), isothiazol-5-yl (H-12), isoxazol-3-yl (H-13), isoxazol-4-yl (H-14), isoxazol-5-yl (H- 15), isoxazolidin-4-yl (H-16), oxazol-2-yl (H-17), oxazol-4-yl (H-18), oxazol-5-yl (H-19), oxethan- 3-yl (H-20), 3-oxoisoxazolidin-4-yl (H-21), 2-oxopyrrolidin-3-yl (H-22), 2-oxotetrahydrofuran-3-yl (H-23), [1,3,4]-thiadiazol-2-yl (H-24), [1,2,3]-thiadiazol-4-yl (H-25), [1,2,3]-thiadiazol-5-yl (H-26), thiazol-2-yl (H-27), thiazol-4-yl (H-28), thiazol-5-yl (H-29), thien-2-yl (H-30), thien-3-yl (H-31), thietan-2-yl (H-32), thietan-3-yl (H-33), 1-oxothietan-2-yl (H-34), 1-oxothietan-3-yl (H-35), 1-oxo- tetrahydrothiophen-3-yl (H-36), tetrahydrofuran-2-yl (H-37), tetrahydrofuran-3-yl (H-38), tetrahy- drothiophen-3-yl (H-39), pyrazin-2-yl (E-6), pyrazol-1-yl (E-12), pyrazol-3-yl (H-40), 2-pyridyl (E- 1), 3-pyridyl (E-2), 4-pyridyl (E-3), pyridazin-3-yl (E-4), pyridazin-4-yl (H-41), 2-pyrimidinyl (E-7), 4-pyrimidinyl (E-5), 5-pyrimidinyl (H-42), pyrrolidin-3-yl (H-43), and 1,2,4-triazol-1-yl (E-13). More preferred rings HET are the following: E-1, E-7, E-12, E-13, H-6, H-21, H-33, and H-35. Rings E-12, and E-13 are particularly preferred. With respect to the variables, the particularly preferred embodiments of intermediates and final products correspond to those of compounds of formula I.

In a particular embodiment, the variables of the compounds of formula I have the following meanings, these meanings, both on their own and in combination with one another, being par- ticular embodiments of the compounds of formula I. R ¹ is preferably fluoromethyl, particularly CF3. R ² is preferably halogen, halomethyl, halomethoxy, particularly F, Cl, Br, CF ₃ , or OCF ₃ . Particularly preferred is each one of the following combinations of R ^2a , R ^2b and R ^2c wherein R ^2a , R ^2b and R ^2c are selected from R ² , H, and F, and at least on of R ^2a , R ^2b and R ^2c is F. Each line of Table P denotes a substitution pattern of the phenyl ring (“P”) bearing the R ^2a , R ^2b and R ^2c moieties. A particularly preferred embodiment of compounds of formula I are those wherein the phenyl ring which is substituted by one F and R ² _n groups shows one of the following substi- tution pattern. P

Table P

Groups P-1, P-3, P-8, P-9, P-10, P-11, P-13, P-14, and P-17 are more preferred patterns in formula I and IV compounds. P-8 and P-9 is particularly preferred. R ³ is preferably C1-C6-alkoxy, particularly methoxy or ethoxy. The group

preferably represents a group G:

wherein # denotes the bond to the di- or tetrahydrothiophene ring;

wherein R ^4a and R ^4b together form with the C-atoms to which they are bonded, a five- or six- membered saturated carbo- or heterocyclic ring which may contain one or two heteroatoms which are preferably selected from oxygen and sulfur. Particularly preferred are the following chains, wherein“a”, and“b” denote the bonds to positions of R ^4a and R ^4b , resp.:

a-CH ₂ CH ₂ O-b, -CH ₂ OCH ₂ -, -OCH ₂ O-, a-CH ₂ CH ₂ S-b, -CH ₂ CH ₂ CH ₂ -, -CH ₂ CH ₂ CH ₂ CH ₂ -, and a-CH ₂ CH ₂ CH ₂ O-b; particularly preferred are -CH ₂ CH ₂ CH ₂ -, -CH ₂ CH ₂ CH ₂ CH ₂ -.

In a further embodiment R ^4a and R ^4b in group G are selected from R ⁴ as follows:

H, halogen, C1-C6-alkyl, C3-C8-cycloalkyl, C2-C6-alkenyl, and C2-C6-alkynyl. Particularly R4 ^a and R4 ^b have the following meanings:

R4 ^a is H, and CH3, and

R4 ^b is CH ₃ , halogen, halomethyl, C ₁ -C ₄ -alkoxy, and C ₁ -C ₄ -haloalkoxy. Most preferred is CH ₃ and halogen. In case A is A ⁴ then R ^4b is a bond to bridge -Q-Z- in group A ⁴ . One embodiment relates to compounds wherein A is A ¹ being C(=O)NR ⁵ R ⁶ . R ⁵ is preferably H, C1-C10-alkyl, C3-C8-cycloalkyl, C2-C10-alkenyl, C2-C10-alkynyl, which groups are unsubstituted, partially or fully halogenated and/or substituted by one or more same or dif- ferent R ⁸ , or C(=O)R ⁸ ; particularly R ⁵ is H. R ⁶ is preferably H, C1-C6-alkyl, C3-C8-cycloalkyl, C2-C6-alkenyl, C2-C6-alkynyl, which groups are unsubstituted, partially or fully halogenated and/or substituted by one or more same or dif- ferent R ⁸ , wherein R ⁸ is preferably S(O) _n R ⁹ and R ⁹ preferably is C ₁ -C ₆ -alkyl;

OR ⁹ ;

phenyl which may be partially or fully substituted by R ¹¹ ; and 3- to 10-membered saturated, partially or fully unsaturated heteromonocyclic or heterobicyclic ring containing 1, 2, 3 or 4 het- eroatoms N, O, and/or S as ring members, which ring is unsubstituted, or substituted by one or more same or different R ¹¹ , preferably a HET, which particularly is selected from E-1, E-7 and H-6, H-21, H-33 and H-35. Rings E-2 and E-7 are particularly preferred. HET is unsubstituted or substituted. Substitution of HET is preferably C ₁ -C ₄ -alkyl. R ⁸ is preferably C ₃ -C ₈ -cycloalkyl, C ₃ -C ₈ -halocycloalkyl, wherein the carbon chains may be sub- stituted by one or more radicals R ¹³ ;

two radicals R ⁸ , together with the carbon atoms of the alkyl, alkenyl, alkynyl or cycloalkyl group which they are bonded to, form a 3- to 8-membered saturated or partially unsaturated carbocy- clic or heterocyclic ring, which heterocyclic ring comprises 1, 2, 3 or 4 heteroatoms N, O, and/or S as ring members, and which ring is unsubstituted, or partially or fully substituted by same or different R ¹⁶ ; the heterocyclic ring preferably is selected from E-1, E-7, H-6, H-21, H-33, and H- 35, which is unsubstituted or substituted by R ¹⁶ , wherein R ¹⁶ is particularly C ₁ -C ₄ -alkyl. Another embodiment relates to compounds wherein A is A ¹ being COOR ⁹ . R ⁹ is preferably H, CN, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -haloalkyl, C ₃ -C ₈ -cycloalkyl, C ₃ -C ₈ -cycloalkyl-C ₁ -C ₄ - alkyl-, C ₃ -C ₈ -halocycloalkyl, C ₂ -C ₆ -alkenyl, C ₂ -C ₆ -haloalkenyl, C ₂ -C ₆ -alkynyl, or C ₂ -C ₆ -haloalky- nyl, which groups are unsubstituted, or partially or fully substituted by same or different R ¹³ , R ⁹ in the groups S(O) _n R ⁹ and OSO ₂ R ⁹ may additionally and preferably be C ₁ -C ₆ -alkoxy, or C ₁ - C ₆ -haloalkoxy; the group OSO ₂ R ⁹ is preferably a triflate, tosylate, or mesylate. Another embodiment relates to compounds wherein A is A ¹ being CHO. Another embodiment relates to compounds wherein A is A ² being CR ^7a R ^7b NR ⁵ R ⁶ . R ^7a and R ^7b are preferably H, C ₁ -C ₃ -alkyl or C ₁ -C ₃ -haloalyl, particularly R ^7a is H and R ^7b is H or C ₁ -C ₃ -alkyl. Another embodiment relates to compounds wherein A is A ³ being pyrazol-1-yl (E-12), and 1,2,4-triazol-1-yl (E-13), which rings are unsubstituted or substituted. In group A ⁴ Q-Z is preferably %–CH ₂ -O-*, %-CH ₂ -S(O) _n -*, or %–C(=O)-O-*.

Most preferred is %–CH2-O-* Another embodiment relates to compounds wherein A is A ⁴ being

wherein R ^A4 preferably is selected from H, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-haloalkyl, C3-C6-cy- cloalkyl, the groups being unsubstituted or substituted by S(O)n-C1-C4-alkyl, or S(O)n-C1-C4- haloalkyl. Examples

With appropriate modification of the starting materials, the procedures given in the synthesis de- scription were used to obtain further compounds I and IV. The compounds obtained in this man- ner are listed in the table that follows, together with physical data.

The products shown below were characterized by melting point determination, by NMR spec- troscopy or by the masses ([m/z]) or retention time (RT [min.]) determined by HPLC-MS or HPLC spectrometry.

HPLC-MS = high performance liquid chromatography-coupled mass spectrometry;

HPLC method: Phenomenex Kinetex 1.7 µm XB-C18100A; 50 x 2.1 mm; mobile phase:

A: water + 0.1% trifluoroacetic acid (TFA); B: acetonitrile; gradient: 5-100% B in 1.50 minutes; 100% B 0.25 min; flow: 0.8-1.0ml/min in 1.51 minutes at 60°C. MS: ESI positive, m/z 100-700. Example 1: Preparation of Methyl 7-[(Z)-3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-2- en- oyl]indane-4-carboxylate

Under N2 atmosphere, in a 100 ml single neck round bottom flask both 2.0g methyl 7-acetylin- dane-4-carboxylate and 4.8g 1-(3,5-dichloro-4-fluorophenyl)-2,2,2-trifluoroethanone in 25ml di- chloroethane was added with 1.7g K2CO3 and 1.2g trimethylamine. The reaction mixture was refluxed for 15 hrs. The reaction mixture was brought to 20-25°C and quenched with 40ml water and extracted with 50ml dichloromethane (DCM). The combined organic phases were dried over Na ₂ SO ₄ . Evaporation of the solvents under reduced pressure afforded the crude product which was purified by flash column chromatography on silica gel using (n-heptane : ethylacetate [EtOAc] 95:5) afforded 3.2 g of the title compound (80% yield) as a white solid.

1H NMR (300 MHz, CDCl ₃ ): δ/ppm = 7.85 (d, J = 8.1 Hz, 1H), 7.49 (d, J = 8.1 Hz, 1H), 7.31 (d, J = 1.5 Hz, 1H), 7.19 (d, J = 6.2 Hz, 2H), 3.92 (s, 3H), 3.24 (t, J = 7.6 Hz, 2H), 3.09 (t, J = 7.6 Hz, 2H), 2.07 (p, J = 7.7 Hz, 2H). Example 2: Preparation of Methyl 5-(3,5-dichloro-4-fluorophenyl)-3-hydroxy-3-(7-methoxy- carbonylindan-4-yl)-5-(trifluoromethyl)tetrahydrothiophene-2 -carboxylate (Formula I)

Under N2 atmosphere, to a stirred solution of 2.07g LiBr and 0.70g DIPEA in 100ml dry THF was added 1.27g ethyl thioglycolate and stirred for 5 minutes at 20-25°C. The resulting reaction mixture was cooled to 0°C and a solution of 5 g of the product from Example 1 in THF was added dropwise and the reaction mixture was allowed to warm to 20-25°C and left stirred over 5 hrs. The reaction mixture was then quenched with water and extracted with EtOAc. The com- bined organic phases were dried over Na ₂ SO ₄ . Evaporation of the solvents under reduced pres- sure afforded 5g of the crude title compound as a white solid.

1H NMR (300 MHz, CDCl3): δ/ppm = 7.83 (d, J = 8.3 Hz, 1H), 7.62 (d, J = 6.0 Hz, 2H), 7.38 (d, J = 8.3 Hz, 1H), 5.04 (s, 1H), 4.61 (s, 1H), 3.89 (s, 3H), 3.70 (s, 3H), 3.27 (t, J = 7.5 Hz, 2H), 3.22–3.02 (m, 2H), 2.97 (s, 2H), 2.22–2.00 (m, 2H). Example 3: Preparation of Methyl 5-(3,5-dichloro-4-fluorophenyl)-3-hydroxy-3-(7-methoxy- carbonylindan-4-yl)-5-(trifluoromethyl)tetrahydrothiophene-2 -carboxylate (Formula I)

100mg of the product from Example 1 with 12mg 1-[3,5-bis(trifluoromethyl)phenyl]-3-[2-dime- thylamino)ethyl]thiourea were stirred in toluene at 0°C.28mg methyl thioglycolate were added. The reaction mixture was allowed to warm to 20-25°C. After 12 hrs, the reaction mixture was quenched with water and extracted with EtOAc. The combined organic phases were dried over Na ₂ SO ₄ . Evaporation of the solvents under reduced pressure afforded the crude product which was purified by flash column chromatography on silica gel using (n-heptane : EtOAc-90:10) af- forded 120mg of the title compound (97% yield) as a white solid. Example 4: Preparation of 3-(7-carboxyindan-4-yl)-5-(3,5-dichloro-4-fluorophenyl)-3-hy droxy- 5-(trifluoromethyl)tetrahydrothiophene-2-carboxylic acid

4.0g of the crude product from Example 2 was added in a solution of 80ml THF : water (3:1) and 1.2g LiOHxH2O and allowed to stirred at 20-25°C for 20 hrs. Then the reaction mixture was quenched with water and the reaction mixture was acidified by 1N HCl to form white a suspen- sion, which was then extracted with EtOAc. The combined organic phases were dried over Na ₂ SO ₄ . Evaporation of the solvents under reduced pressure afforded 3.7g of the title com- pound as off white solid. Crude as such used for next step without purification.

1H NMR (300 MHz, CDCl ₃ ): δ/ppm = 7.87 (d, J = 8.3 Hz, 1H), 7.62 (d, J = 6.0 Hz, 1H), 7.43 (d, J = 8.4 Hz, 1H), 6.55 (brs, 1H), 5.11 (s, 1H), 4.43 (s, 1H), 4.12 (q, J = 7.2 Hz, 1H), 3.76 (s, 1H), 3.25 (t, J = 7.6 Hz, 2H), 3.17-3.06 (m, 1H), 2.98 (s, 1H), 2.15-2.00 (m, 2H), 1.92– 1.78 (m, 1H), 1.26 (t, J = 7.1 Hz, 1H). Example 5: Preparation of 7-[2-(3,5-dichloro-4-fluorophenyl)-2-(trifluoromethyl)-3H-th iophen-4- yl]indane-4-carboxylic acid

To a stirred solution of 3.7g of the product from Example 4 in 50ml pyridine at 0°C was added 1.57g methane sulfonyl chloride and allowed to warm to 20-25°C over 2 hrs. Then the reaction mixture was quenched with water and acidified by 1N HCl while the reaction mixture was cooled to 0°C, which was then extracted with EtOAc. The combined organic phases were dried over Na ₂ SO ₄ . Evaporation of the solvents under reduced pressure afforded 3.5g of the crude product as off white solid.0.8g of the crude product thus obtained were heated in 10ml DMF for 3 hrs at 100°C. Then the reaction mixture was quenched with water and extracted with EtOAc. The combined organic phases were dried over Na ₂ SO ₄ . Evaporation of the solvents under reduced pressure afforded the crude product which was purified by flash column chromatography on sil- ica gel using (n-heptane:EtOAc 95:5) afforded 0.56g of the title compound (98% yield) as a white solid. ¹ H NMR (300 MHz, DMSO-d ₆ ): δ/ppm = 12.78 (s, 1H), 7.83 (d, J = 6.2 Hz, 2H), 7.73 (d, J = 8.1 Hz, 1H), 7.33 (d, J = 8.2 Hz, 1H), 6.81 (s, 1H), 3.98 (s, 2H), 3.18 (hept, J = 8.9, 7.8 Hz, 2H), 2.96 (td, J = 7.3, 3.7 Hz, 2H), 1.99 (qt, J = 8.2, 5.0 Hz, 2H). Example 6: Preparation of 7-[2-(3,5-dichloro-4-fluoro-phenyl)-2-(trifluoromethyl)-3H-t hiophen- 4-yl]-N-[(4R)-2-ethyl-3-oxo-isoxazolidin-4-yl]indane-4-carbo xamide (Formula IV)

To a mixture of 2.8g of the product from Step 4 and 1.17 g of (4R)-4-amino-2-ethyl-isoxazoli- din-3-one hydrochloride in 60ml DMF was added 2.27g DIPEA and stirred at 20-25°C for 5 min. To this reaction mixture 2.68g HATU were added and stirred at 20-25°C for 3 hrs. Then the re- action mixture was quenched with water, the resulting solid was filtered and washed with pen- tane and filtered off. The obtained solid was dissolved in DCM and dried over Na ₂ SO ₄ . Evapora- tion of the solvent under reduced pressure afforded the crude product which was purified by flash column chromatography on silica gel to yield 3.2g of the title compound (92% yield) as a white solid.