Org React. 1985,33, 247 and references cited therein), base (see Danheiser, R. L.; Martinez- Davila, C.; Morin, J. M. J. Org. Chem. 1980,45, 1340-1341. Danheiser, R. L.; Bronson, J. L.; Okano, K. J. Am Chem. Soc. 1985,107, 4579-4581) and light (see Jorgensen, M. J.; Heathcock, C. H. J. Am. Chem. Soc. 1965,87, 5264).

Natural products and the starting reactants from which synthetic natural products might be synthesised are not generally suited to reactive manipulation at high temperatures. Existing processes for the synthetic production of natural products based on cyclopentenes is thus constrained by the reaction conditions.

The present invention is concerned with an alternative to known methods of producing cyclopentenols.

SUMMARY OF THE INVENTION The present invention concerns the base-catalysed C3-C5 ring expansion of cyclopropanes to cyclopentenols. The process of the invention produces cyclopentenols in high yield and excellent diastereoselectivity.

Therefore according the a first aspect of the present invention there is provided a process for the production of cyclopentenols (2) from cyclopropanes including the steps of reacting a cyclopropane of the type (1) shown above together with a base in the presence of tetrahydrofuran, according to Scheme 1, wherein RI, R2 and R3 may be the same or different and are each a hydrogen atom, an alkyl radical, an alkenyl radical, an allynyl radical, a cycloalkyl radical, an aralkyl radical, an aryl radical, an alkoxy radical, alkenyloxy radical, an alkoxy carbonyl radical, alkenyloxycarbonyl radical, alkylthio radical, or alkenylthio radical.

Scheme 1 The reaction of Scheme 1 may be conducted at ambient temperatures and is thus suited to the reactive manipulation of natural products or reactants easily degraded at higher temperatures.

Preferably, the base is selected from the group consisting of alkali metal hydrides and hydroxides and alkali metal alkyl silazanes. In a preferred embodiment the base is lithium hexamethyldisilazane.

Scheme 2

The cyclopropane starting material is a P-ketocyclopropylcarboxylate and may be used as a racemic mixture or as an optically pure compound. Where an optically pure starting material is required the relevant cyclopropane starting material may be prepared by the reaction of 1,2- dioxines and stabilized phosphorus ylides as shown in Scheme 2 (Avery, T. A.; Haselgrove, T.

D.; Rathbone, T. J.; Taylor, D. K.; Tiekink, E. R. T. J. Chem. Soc. Chem. Comm. 1998,333.

Avery, T. D.; Taylor, D. K.; Tiekink, E. R. T. J. Org. Chem. 2000,65, 5531-5546).

It has been established that the preferred p-ketocyclopropylcarboxylate starting compound can be generated by the use of bulky ylides, LiBr and the adoption of dilute solutions.

DESCRIPTION OF THE PREFERRED EMBODIMENT A variety of cyclopentenols were prepared using (3-keto-cyclopropanes with various bases.

The results are tabulated in table 1 giving yields for various reaction products identified from the reaction R2 R F 0 ,, R, g , R, + oH + v o 1 3 8 5 isareriza jl t' 0 \ f F z, F 6

Scheme 3 The first base tested with cyclopropanes of type 1 was sodium hydride (Table 1, entries 1,4 and 9). Although a small amount of the ring-closed cyclopentenol 3 was found in each case, the major product were the trans ring-opened products 5 and 6. When a mixture of 3a and 5a

was allowed to react with an additional portion of sodium hydride, no increase in 3a was observed. Instead 5a rearranged to the more thermodynamically stable styryl isomer 6.

The isolation of the trans ring-opened products 5b and 5c indicated competitive cis and trans ring-opening. Of the two product enolates 7a and 7b, only cis 7a could undergo an intramolecular aldol yielding the observed cyclopentenol, Scheme 3. Higher temperatures failed to cleanly afford cyclopentenol (entry 2) whilst changing counter ions from sodium to lithium using lithium hydride gave a multi component reaction mixture.

Table 1. The Reaction of ß-keto-cyclopropanes with base.

Entrya 2 R1 R2 R3 Base Temp Yieldb 3 8 5 6 1 a Ph Ph CO21-Ad NaH RT a 18 (23) -a-35 (77) 2'a Ph Ph CO21-Ad LiOH 110 a 38-a-8 3 a Ph Ph CO21-Ad LHMDS RT a 83 - - - 4d b Ph Me CO2Bu'NaH RT b- (23)-b- (77)- 5d b Ph Me CO2Bu'LHMDS-78 b- (6)-b- (94)- 6 b Ph Me CO-Bu'LHMDS RT b 78 7 c Ph Ph CO2Bu'LHMDS RT c 80 - - - 8 d Ph H CO21-Ad LHMDS RT d 85--- 9 e n-Pr n-Pr CO2Bu'NaH RT e -d(10) - c 59 (90) - 10 e n-Pr n-Pr CO2Bu'LHMDS RT e 84 - - - I I f Ph Ph CN LHMDS RT f 45--- b Ph Me CO2But KHMDS RT b 80 (86) 8 (14)

a Typically reactions were performed on a 50mg scale by addition of a solution of cyclopropane in THF or ether to 1.5-2. 0 equivalents of base in THF and worked up after 15 mins. b Yield refers to isolated product. Parentheses indicate product ratio determined by 1H NMR. c Reaction time was 3 hours. d Isolation not attempted. e Reaction performed in a 4: 1 ether/toluene mixture (toluene was present from the solution of base).

The first base tested with cyclopropanes of type 2 was sodium hydride (Table 1, entries 1,4 and 9). Although a small amount of the ring-closed cyclopentenol 3 was found in each case, the major product was the trans ring-opened products 5 and 6. When a mixture of 3a and 5a was allowed to react with an additional portion of sodium hydride, no increase in 3a was observed. Instead 5a rearranged to the more thermodynamically stable styryl isomer 6.

The isolation of the trans ring-opened products 5b and 5c indicated competitive cis and trans ring-opening. Of the two product enolates 7a and 7b, only cis 7a could undergo an intramolecular aldol yielding the observed cyclopentenol, Scheme 3. Higher temperatures failed to cleanly afford cyclopentenol (entry 2) whilst changing counter ions from sodium to lithium using lithium hydride gave a multi component reaction mixture.

As two cyclopropyl keto-enolates are possible, it was thought that each enolate could lead to the formation of a specific ring-opened geometric isomer. Lithium hexamethyldisilazide (LHMDS) gives exclusively Z-ketoenolates at-72° C. The reaction of 2b with LHMDS at- 78°C gave nearly exclusively trans ring-opening (entry 5), however, the addition of 2b to 1.5 equivalents of LHMDS in THF at 25° afforded cyclopentenol 3b in 78% yield (entry 6). The order of addition was found to be important, as the dropwise addition of base to cyclopropane reduced the yield to only 17%.

This optimised methodology was then applied to a series of cyclopropanes with various substitution patterns (entries 3,6-8, 10-12). All cyclopropanes with bulky ester groups afforded high yields of cyclopentenols ; most of the products being highly crystalline. Entry 11 demonstrates that the reaction is applicable with electron acceptors other than ester groups.

Stereochemistry was assigned on the basis of the 2D ROESY NMR spectra and all products were found to have trans stereochemistry between groups attached to C-1 and C-5 of the cyclopentenol ring. Further evidence for the conserved syn relationship between the group attached to Cl and the OH on C2 of the cyclopentene ring comes from the x-ray structure of cyclopentenol 3d.

The reaction of 2b with potassium hexamethyldisilazide (KHMDS) in toluene/ether yielded two cyclopentenol products (entry 12) arising from competing transition states in the intramolecular aldol addition. The structure of the minor isomer 8 was deduced by 2D IH NMR. Attempts at increasing the yield of cyclopentenol 8 by performing the reaction in toluene were unsuccessful as the yield of cyclopentenol decreased in favour of the trans ring- opened product 5b.

General Experimental 'H and 13C NMR was performed using a Varian Gemini-200, Bruker ACP-300 or a Varian Innova-600 spectrometer operating at 200,300 and 600 MHz respectively for'H and 50,75 and 150 MHz for 13C in CDC13.'H NMR were referenced to internal trimethylsilane (8 0.00).

3C NMR were referenced to CDC13 (8 77.0). Multiplicities are assigned as s: singlet, d: doublet, t: triplet, q: quartet, p: pentet, and br: broad denotes broadened signals. All coupling constants are reported in Hz.

IR Spectra were recorded using a Perkin Elmer spectrometer BX FT-IR system as either nujol mulls or in the neat form as denoted. Melting points were determined on a Reichert hot stage apparatus and are uncorrected. Mass spectra were acquired using a VG ZAB 2HF spectrometer and HRMS were performed by the Organic Mass Spectrometry Facility, Central Science Laboratory, University of Tasmania. Microanalysis was performed at the University of Otago.

Thin layer chromatography was performed using Merck silica gel 60 F254 aluminium backed silica sheets. Flash chromatography were performed using Merck silica gel 60 (230-400 mesh). Et20 and THF were distilled from sodium/benzophenone ketyl. All cyclopropanes were prepared using the protocol outlined in reference 5.

2-(2-oxo-2-phenylethyl)-3-phenylcyclopropyl cyanide 2f. To a solution of 3,6-diphenyl-3, 6- dihydro-1, 2-dioxine (100 mg, 0.41 mmol) ) in dichloromethane (9 ml) was added LiBr (37 mg, 0.50 mmol), 2- (l, 1, 1-triphenyl-X5-phosphanylidene) acetonitrile (152 mg, 0.50 mmol), and Co (II) Salen (5 mg) and the reaction left to stir for 1 week at ambient temperature. The mixture was evaporated and product purified by flash chromatography to give a colourless oil (35 mg, 32%); Rf 0.25 (80: 20, hexane: ethyl acetate); IR (neat) 3085,3060, 3029,1668, 1598,1450 cm-1 ; 1H NMR (CDCl3, 600 MHz) 8 1.80 (dd, J= 8.4, 4.8 Hz, 1H), 2.10 (ddd, J= 6.0, 6.0, 4.8 Hz, 1H), 2.35 (dd, J = 6.0, 4.8 Hz, 1H), 3.24 (dd, J = 18.6, 6.0 Hz, 1H), 3.42 (dd, J= 18.6, 6.0 Hz, 1H), 7.15-7. 25 (m, 5H), 7.40 (m, 2H), 7.52 (m, 1H), 7.93 (m, 2H); 13C NMR (CDC13,150 MHz) 8 11.7, 21.6, 31.5, 39.4, 119.3, 126.9, 127.5, 128.0, 128.1, 128.6, 128.7, 128.8, 129.3, 133.6, 136.2, 137.1, 197.1 (one aromatic signal masked). MS m/z (%) 261 (M+, 20), 120 (21), 105 (100), 77 (62), 51 (21).

() 1-Adamantyl (lS, 2R, 5R)-2-hydroxy-2, 5-diphenyl-3-cyclopentene-l-carboxylate 3a. To a stirred solution of hexamethyldisilazane (25 mg, 0.16 mmol) in THF (2 ml) was added methyl lithium (0.11 ml, 1.4 M, 0.16 mmol) in Et20 and stirring continued for 10 mins. 1- Adamantyl 2- (2-oxo-2-phenylethyl)-3-phenylcyclopropane-l-carboxylate 2a (42 mg, 0.10 mmol) in THF (2 ml) was added dropwise over 2 mins and the reaction mixture stirred for a further 15 mins. The reaction was quenched with methanol (0.5 ml) then volatiles removed in vacuo. The product was purified by flash chromatography (dichloromethane) then recrystallized from hot hexane to give colourless crystals (35 mg, 83%); mp = 180-182°C (hexane/ethyl acetate); Rf 0. 30 (dichloromethane); IR (nujol): 3430,1696, 1248, 1184 cm01; 'H NMR (600 MHz) 8 1.61 (m, 6H), 2.06 (m, 6H), 2.11 (br s, 3H), 3.05 (d, J = 9 Hz, 1H), 3.41 (br s, 1H), 4.54 (ddd, J = 9.0, 2.4, 1.8 Hz, 1H), 5.98 (dd, J = 5.4, 2.4 Hz, 1H), 6.15 (dd, J = 5.4, 1.8 Hz, 1H), 7.22-7. 25 (m, 4H), 7.26-7. 37 (m, 4H), 7.50-7. 52 (m, 2H); 13C NMR (75 MHz) # 30. 7,36. 1,41. 2,52. 5,65. 8,81. 7,86. 6,125. 4,126. 9,127. 0,127. 5,128. 0,128. 6, 136.5, 137.9, 142.8, 145. 6, 171.8 ; MS (EI) nilz (%): 414 (10), 396 (20), 352 (40), 135 (100); Anal. Calcd for C26H3003 : C, 81.12 ; H, 7.29 ; Found: C, 81.35 ; H, 7.50.

() tert-Butyl (lS, 2R, 5R)-2-hydroxy-5-methyl-2-phenyl-3-cyclopentene carboxylate 3b.

The reaction of LHMDS (0.5 mmol) in Et2O (2.5 ml) with tert-butyl 2- (2-oxo-2-phenylethyl)- 3-methylcyclopropane-1-carboxylate 2b (95 mg, 0.34 mmol) as per 3a gave colourless crystals (74 mg, 78%); mp = 85-87°C ; Rf 0.25 (dichloromethane); IR (nujol): 3423,1711, 1184,1086 cm-1 ;'H NMR (300 MHz) 8 1.20 (d, J = 7.0 Hz, 3H), 2.41 (s, 9H), 2.65 (d, J = 7.4 Hz, 3H), 3.32 (dddq, J = 7.4, 7.0, 2.5, 1.8 Hz, 1H), 3.75 (br s, 1H), 5.76 (dd, J = 5.6, 2.5 Hz, 1H), 5.98 (dd, J = 5.6, 1.9 Hz, 1H), 7.25-7. 27 (m, 1H), 7.32-7. 37 (m, 2H), 7.43-7. 46 (m, 2H); 3C NMR (75 MHz) 8 19.4, 28.0, 42.1, 64.0, 81.4, 86.5, 125.2, 126.8, 127.9, 134.2, 139.9, 146.1, 172.3 ; MS (EI) m/z (%): 273 (M+, 3), 257 (100), 201 (50); Anal. Calcd for C17H2203 : C, 74.42 ; H, 8.08 ; Found: C, 74.53 ; H, 8.12 () tert-Butyl (1S, 2R, 5R)-2-hydroxy-2, 5-diphenyl-3-cyclopentene-1-carboxylate 3c. The reaction of LHMDS (2.67 mmol) in THF (10 ml) with tert-butyl 2- (2-oxo-2-phenylethyl)-3- phenylcyclopropane-1-carboxylate 2c (600 mg, 1.78 mmol) in THF (10 ml) as per 3a gave colourless crystals (481 mg, 80%); mp = 127-128°C (hexane); Rf 0.26 (dichloromethane); IR (nujol): 3450,1707, 1251,1160 cm'' ; 1H NMR (300 MHz) 8 1.35 (s, 9H), 3.06 (d, J = 7. 7, 1H), 3.37 (br s, 1H), 4.56 (ddd, J= 7.7, 2.5, 1.9 Hz, 1H), 5.99 (dd, J= 5.8, 2.5 Hz, 1H), 6.17 (dd, J = 5.8, 1.9 Hz, 1H), 7.21-7. 39 (m, 8H), 7.50-7. 53 (m, 2H) ; 13C NMR (75 MHz) 8 28.0, 52.4, 65.9, 81.5, 86.7, 125.3, 126.8, 127.0, 127.3, 128.0, 128.6, 136.5, 137.9, 142.7, 145.5, 171.3 ; MS (EI) m/z (%): 336 (M+, trace), 318 (12), 280 (30), 218 (100); Anal. Calcd for C22H2403 : C, 78.54 ; H, 7.19 ; Found: C, 78.58 ; H, 7.15.

() 1-Adamantyl (1S, 2R)-2-hydroxy-2-phenyl-3-cyclopentene carboxylate 3d. The reaction of LHMDS (0.22 mmol) in Et20 (2 ml) and 1-Adamantyl 2- (2-oxo-2- phenylethyl) cyclopropane-l-carboxylate 2d (50mg, 0.15 mmol) in Et20 (2 ml) as per 3a gave colourless rods (43 mg, 85%); mp = 142-143°C (hexane); Rf 0.28 (dichloromethane); IR (nujol): 3423,1711, 1184,1086 cm'' ; 1H NMR (600 MHz) 8 1.64 (br s, 6H), 2.08-2. 14 (m,

6H), 2.14 (br s, 3H), 2.67 (dddd, J = 17.0, 8.6, 2.4, 1.8 Hz, 1H), 2.92 (dddd, J= 17.0, 7.0, 2.4, 2.2 Hz, 1H), 3.17 (dd, J = 8.6, 7.0 Hz, 1H) 3.47 (br s, 1H), 5.80 (ddd, J= 5.8, 2.4, 1.8 Hz, 1H), 6.12 (ddd, J = 5.8, 2.4, 2.2 Hz, 1H), 6.91-7. 31 (m, 1H), 7.33-7. 43 (m, 2H), 7.43-7. 47 (m, 2H); 13C NMR (75 MHz) 8 30.7, 34.7, 36.1, 41.3, 55.6, 81.4, 86.2, 125.2, 126.8, 127.9, 133.6, 136.0, 146.0, 172.2 ; MS (EI) m/z (%): 338 (M+, 20), 320 (10), 135 (100); Anal. Calcd for C22H2603 : C, 78. 07; H, 7.74 ; Found: C, 78.13 ; H, 7.58.

() tert-Butyl (1S, 2R, 5R)-2-hydroxy-2, 5-dipropyl-3-cyclopentene carboxylate 3e. The reaction of LHMDS (0.35 mmol) in Et20 (2 ml) and tert-butyl 2- (2-oxopentyl)-3-propyl-l- cyclopropanecarboxylate 2e (50 mg, 0.19 mmol) in Et20 (2 ml) as per 3a gave a colourless oil (42 mg, 84%); Rf0. 40 (dichloromethane); IR (neat): 3483,2959, 1717,1458, 1368 cm-1 ;'H NMR (300 MHz) 8 0.91 (t, J = 7.2 Hz, 3H), 0.94 (t, J = 7.4 Hz, 3H), 1.20-1. 50 (m, 6H), 1.44 (s, 9H), 2.47 (d, J = 8. 8,1H), 2.54 (br s, 1H), 3.17 (m, 1H), 5.61 (dd, J= 5.6, 2.5 Hz, 1H), 5.79 (dd, J = 5.6, 2.5 Hz, 1H) ; 13C NMR (75 MHz) 8 14.1, 14.5, 17.8, 20.8, 28.1, 37.2, 43.0, 47.4, 58.2, 80.9, 86.1, 134.2, 137.0, 172.8 ; MS (EI) m/z (%): 251 (M+-OH, 10), 195 (20), 169 (50), 151 (70); Anal. Calcd for Cl6HZgO3 : C, 71.6 ; H, 10.51 ; Found: C, 71.55 ; H, 10.25.

() (lR, 2R, 5R)-2-Hydroxy-2, 5-diphenyl-3-cyclopentene-1-carbonitrile 3f. The reaction of LHMDS (. 12 mmol) in THF (1 ml) and 2- (2-oxo-2-phenylethyl)-3-phenylcyclopropyl cyanide 2f (22 mg, . 08 mmol) in THF (1 ml) as per 3a gave colourless plates (10 mg, 45%); mp = 145- 146°C (hexane/dichloromethane); Rf0. 40 (dichloromethane); IR (nujol) 3429,2924, 2251, 1124,1052 cm'' ; 1H NMR (300 MHz) 8 2.47 (s, 1H), 3.65 (d, J = 8.7 Hz, 1H), 4.32 (d, J = 8.7 Hz, 1H), 6.22-6. 27 (m, 2H), 7.31-7. 54 (m, 1OH) ; 13C NMR (75 MHz) 8 50.1, 52.5, 85.8, 116.8, 124.7, 128.1, 128.3, 128.5, 128.8, 128.8 135.9, 136.0, 138.2, 143.3 ; MS (EI) mlz (%) : 261 (M+) (20), 233 (10), 43 (100); Anal. Calcd for CisHON : C, 82.73 ; H, 5.78 ; N, 5.35 ; Found: C, 82.70 ; H, 6.05 ; N, 5.43.

() (E) tert-Butyl 3-methyl-6-phenyl-6-oxo-4-hexenoate 5b. Colourless oil; Rf 0. 27 (dichloromethane); IR (neat): 2976,1727, 1671,1621, 1367,1156 cm-1 ; 1H NMR (300 MHz) 8 1.17 (d, J = 6.9 Hz, 3H), 1.43 (s, 9H), 2.32 (dd, J = 14.8, 7. 0 Hz, 1H), 2.40 (dd, J = 15.3, 7.0 Hz, 1H), 2.93 (dddq, J = 7.0, 7.0, 6.9, 6.9 Hz, 1H), 6.90 (d, J = 15.6 Hz, 1H) 6.98 (dd, J = 15.6, 6.9 Hz, 1H), 7.42-7. 61 (m, 3H), 7.90-7. 96 (m, 2H) ;'3C NMR (75 MHz) 8 19.2, 28.0, 33.8, 41.8, 80.7, 124.5, 128.5, 128.5, 132.6, 137.8, 152.5, 171.1, 190.9 ; MS (LSI) niz (%) : 275 (M+H, 15), 219 (100), 201 (40); HRMS of 5b (+H) CnH2303 : calcd, 275.1647 ; found 275.1650.

() (E) tert-Butyl 3-propyl-6-oxo-4-nonenoate 5c. Colourless oil; Rf 0.45 (dichloromethane); IR (neat): 2961,1729, 1673,1457, 1153 cm-1 1; 1H NMR (600 MHz) 8 0.89 (t, J = 7.2 Hz, 3H), 0.93 (t, J = 7.2 Hz, 3H), 1.20-1. 50 (m, 6H), 1.42 (s, 9H), 1.63 (tq, J = 7.2, 7.2 Hz, 2H), 2.24 (dd, J = 15, 8.4 Hz, 1H) 2.35 (d, J = 15,6. 0 Hz, 1H), 2.63-2. 67 (m, 1H), 6.09 (dd, J = 16,0. 8 Hz, 1H), 6.64 (dd, J = 16,9. 0 Hz, 1H) ;'3C NMR (75 MHz) # 13.7, 13.8, 17.6, 20.0, 28.0, 36.1, 38.9, 40.4, 42.1, 80.5, 130.1, 148.8, 171.0, 200.4 ; MS (LSI) m/z (%): 269 (M+H+, 5), 213 (100); HRMS of 5c Cl6H2903 : calcd, 269.2116 ; found 269.2103.

(E) 1-Adamantyl 3,6-diphenyl-6-oxo-3-hexenoate 6. Colourless oil; Rf0. 45 (dichloromethane); IR (neat): 3054,2912, 1722,1690, 1596,1445, 1253,1056 cm-1 ; 1H NMR (300 MHz) 8 1. 58-1. 59 (m, 6H), 2.00 (br s, 6H), 2.10 (br s, 3H), 3.48 (s, 2H), 3.98 (d, J = 6.6 Hz, 2H), 6.30 (d, J = 6.6 Hz, 1H) 7.24-7. 58 (m, 8H), 8.00-8. 03 (m, 2H) ; 13C NMR (75 MHz) 8 30.7, 36.1, 38.4, 38.8, 41.6, 81.1, 123.4, 126.2, 127.1, 128.2, 128.3, 128.6, 133.1, 136. 1, 136. 7, 142.0, 169.8, 197.3 ; MS (EI) m/z (%): 414 (M+, 30), 413 (100); HRMS of 6 C28H3003 : calcd, 414.2194 ; found, 414.2181.

(. ) tert-Butyl (lS, 2S, 5R)-2-hydroxy-5-methyl-2-phenyl-3-cyclopentene carboxylate 8. To a stirred solution of KHMDS (0.5 mmol) in Et2O (3 ml) and toluene (0.7 ml) was added tert- butyl 2-(2-oxo-2-phenylethyl)-3-methylcyclopropane-1-carboxylate 2b (95 mg, 0.34 mmol) in

Et2O (1 ml). Purification by successive flash chromatography (dichloromethane) then recrystallization from hexane gave 3b (38 mg, 76%) and 8 as colourless crystals (4 mg, 8%); mp = 114-116°C ; Rf 0.25 (dichloromethane); IR (nujol): 3472,1686, 1162 cm- 1; 1H NMR (600 MHz) 8 1. 05 (s, 9H), 1.23 (d, J = 6.9 Hz, 3H), 2.66 (br s, 1H), 2.90 (d, J = 7.2 Hz, 3H), 3.32 (dddq, J = 7. 2,6. 9,2. 3,1. 9 Hz, 1H), 5.66 (dd, J = 5. 5,2. 3 Hz, 1H), 5. 88 (dd, J = 5. 5,1. 9 Hz, 1H), 7.19-7. 43 (m, 5H) ;'3C NMR (75 MHz) 8 20.3, 27.5, 41.7, 52.6, 67.9, 80.6, 88.9, 125.2, 127.2, 128.0, 135.4, 137.1, 141.6, 142.9, 170.3 ; MS (EI) m/z (%): 274 (M+, 3), 256 (3), 218 (100), 200 (25); HRMS of 8 C17H2203 : calcd, 274.1568 ; found, 274.1564.

(+/-) tert-Butyl 4-methyl-6-phenyl-6-oxo-2-hexenoate 11. White solid. mp = 35-38°C ; Rf 0.53 (80/20 hexane/ethyl acetate); IR (nujol): cm-1 ; 1H NMR (600 MHz) 8 1.14 (d, J = 6.6 Hz, 3H), 1.47 (s, 9H), 2.94-3. 12 (m, 4H), 5.78 (dd, J = 15.6, 1.5 Hz, 1H), 6.87 (dd, J = 15.6, 6.6 Hz, 1H), 7.44-7. 57 (m, 3H), 7.93-7. 96 (m, 2H) ; 13C NMR (75 MHz) 8 19.1, 28.1, 31.7, 44.2, 80.2, 121.7, 128.1, 128.6, 133.1, 137.0, 151.4, 166.1, 198.1 ; MS (EI) MHz (%): 274 (M+, 20), 218 (50), 200 (80), 157 (50), 104, (100); Anal. Calcd for C17H2203 : C, 74.40 ; H, 8.08 ; Found: C, 74.18, 7.89.

Crystallography for 3a Intensity data for a colourless block (0.08 x 0.24 x 0.29 mm) were collected at 173 K on a Rigaku AFC7R diffractometer employing Mo-Koc radiation (R 0.7107 A) and the o) : 20 scan technique such that #max was 27. 5°. Corrections were made for Lorentz and polarization effects (teXsan, Single Crystal Structure Analysis Software, Version 1.04 (1997), Molecular Structure Corporation, The Woodlands, TX, USA. ( but not for absorption. Of the 4260 reflections measured, 3811 were unique (Rint = 0. 051) and of these, 2372 satisfied the I 2. 0o (I) criterion.

Crystal data: C28H30O3, M = 414.5, monoclinic, P2,/n, a = 12.757 (4), b = 9.738 (3), c = 17.633 (5) Å, ß = 98.51 (2), V = 2166 (1) 3, Z = 4, Dx = 1.271 g eni-3,-Ka) = 0.81 cm-1, F (000) = 888,281 refined parameters, pmaX = 0.20 e -3.

The structure was solved by direct-methods (A. Altomare, M. C. Burla, M. Camalli, G. L.

Cascarano, C. Giacovazzo, A. Guagliardi, A. G. G. Moliterni, G. Polidori and R. Spagna, SIR97, J. Appl. Crystallogr. 32 (1999) 115) and refined by a full-matrix least-squares procedure based on F2 using all reflections (G. M. Sheldrick, SHELXL-97. Program for crystal structure refinement. University of Gttingen, Germany, 1997). The non-hydrogen atoms were refined with anisotropic displacement parameters and H atoms were included in the model at their calculated positions. A weighting scheme of the form w = 1/[62 (F) + 0. 0709P2 + 0. 365P], where P = (Fo2 + 2Fc2)/3, was employed and at convergence, final R = 0.096 and wR =0. 135 (all data); final R = 0.046 and wR = 0.114 (observed data).

The invention has been described by way of example. The examples are not, however, to be taken as limiting the scope of the invention in any way. Modifications and variations of the invention such as would be apparent to a skilled addressee are deemed to be within the scope of the invention.