J. CHEM. soc PERKIN TRANS. I 1991 Rhodium Carbenoid Mediated Cyclisations. Part 7.' Synthesis and Coupling Reactions of 2-Substituted 3-Oxooxepanes Martin J. Davies, Christopher J. Moody"? and Roger J. Taylor Department of Chemistry, Imperial College of Science, Technology and Medicine, London SW7 2A Y, UK A range of 2-substituted oxepanes 3 has been prepared from 6-lactones via rhodium(ii) acetate catalysed cyclisation of the intermediate diazo alcohols 2. The phenylsulphonyloxepane 3e and the oxepane phosphonate 3f are versatile substrates for further elaboration, and are readily converted into substituted oxepanes 12-14. The introduction of substituents into the 2-position (anomeric position) of cyclic ethers is an important synthetic goal, and in recent years many solutions to this problem in 5-and 6- membered rings have been advanced.2 In continuation of our work on the synthesis and reactions of 7-membered ring ether^,^ we have investigated the preparation of 3-oxooxepanes con- taining functional groups at the 2-position, that are suitable for further elaboration, and we now report our results in full.4 Results and Discussion The route to 2-functionalised oxepanes is based on our previously reported novel 2-step ring expansion of 6-lactones.3b In its original form, the reaction sequence involved the ring opening of the lactone 1 with ethyl lithiodiazoacetate, followed by rhodium( 11) acetate catalysed cyclisation of the resulting diazo alcohol 2 (Z = C0,Et) to give, by formal OH insertion, 3-oxooxepane 2-esters 3 (Z = C0,Et) (Scheme 1).Although 1 2 3 Z = S02Ph. PO(OEt)2 Scheme 1 Rrcigenfs: i, Z(Li)C=N,, THF, low temp.; ii, ZCH,Li, THF, -78 "C; then LDA (1 equiv.); Me3SiC1(2 equiv.); iii, MsN,, Et,N; iv, 0.5 M HCI, THF; v, cat. Rh,(OAc),, benzene, reflux ethyl lithiodiazoacetate is the most frequently used and the most readily accessible diazo anion, a small range of other diazo compounds have been successfully metallated. Therefore, we attempted the ring opening of 6-lactones 1 with a range of diazo anions. The organolithiums derived by deprotonation of t-butyl diazoacetate."' diazoacetone 'and trimethylsilyldiazomethane using butyllithium or lithium diisopropylamide (LDA) reacted readily with 6-valerolactone and undecanoic acid 6-lactone to give the diazo alcohols 2a4 (Table 1 and Scheme l), although in the latter case the trimethylsilyl group was lost on work-up.Use of triethylsilyldiazomethane also gave the diazo alcohol 2d, the bulkier silyl group still being lost on work-up. We were also interested in the preparation, and OH insertion reactions of %-diazo P-keto sulphones, and phosphonates. lo However. attempted deprotonation of phenylsulphonyldiazo- methane '' using either LDA or butyllithium at -90 OC resulted only in decomposition of the substrate. Diethyl diazomet hylphosphonate, '' however, was readily lithiated, and although the lithium species is known to react with aldehydes and ketone^.^.'^ we were unable to isolate any products from Table 1 Preparation and cyclisation of diazo alcohols 2 213 R Z a H C0,Bu' b C C,5H13 H COZBU' Ac d e C,H,, C6H13 Me,Si(H) SOzPh f C6HI3 PO(OEt), g H PO(OIt), Yield 2 (x) Yield 3 (%) 87 48-56 67 64 26 62 32 56 40 73 56 54 62 52 its reaction with 6-valerolactone.Therefore, an alternative approach to diazo sulphones and phosphonates was used (Scheme 1). The 6-lactone was ring opened using the anions derived from methyl phenyl sulphone or diethyl methylphos- phonate, and the diazo group was introduced subsequently by diazo transfer, originally using toluene-4-sulphonyl a~ide,~ although methanesulphonyl azide l4 was found to be a superior reagent for these transformations, giving cleaner reactions and higher yields. However, the ring opening of lactones with anions such as diethyl lithiomethylphosphonate is not straightforward, since the product P-keto compounds are more acidic than the substrates from which they are derived.Therefore, a modi- fication developed by Dietrich and Hoffmann lS was used. In this one-pot procedure, the &-lactone was added to the anion (formed using butyllithium as base), followed by the addition of one equivalent of LDA, and quenching with an excess of trimethylsilyl chloride. The resulting trimethylsilyl enol ether was readily hydrolysed on work-up, and the crude product was immediately treated under diazo transfer conditions, before final acidic cleavage of the trimethylsilyl ether. Using this method the overall yields of the diazo alcohols 2e, 2f and 2g were 40, 56 and 62%, respectively.When heated in boiling benzene in the presence of a catalytic amount of rhodium(1r) acetate, the diazo alcohols 2 underwent rhodium carbenoid mediated cyclisation by a formal intramolecular OH insertion, and gave the 3-0x0-oxepanes 3 in good yield (Table 1). Like the corresponding methyl and ethyl e~ters,~~?~' the t-butyl esters 3a and 3b existed as a mixture of keto and enol forms in solution, whereas the 2-acetyloxepane 3c was completely enolised. On the other hand, the sulphone 3e and the phosphonates 3f and 3g existed exclusively in the keto form as evidenced by their 'H NMR spectra, and NOE spectroscopy established the stereochemistry of the sulphone 3e.Thus pre-irradiation of the singlet at 6 4.67 (2-H) resulted in enhancement of the multiplet at 6 3.18 (7-H). t Present address: Department of Chemistry, Loughborough University of Technology, Loughborough, Leics., LE11 3TU, UK. 2 J. CHEM. SOC. PERKIN TRANS. 1 1991 The phenylsulphonyloxepane 3e and the oxepane phos- phonate 3f are ideal substrates for further elaboration. Thus treatment of the phenylsulphonyloxepane 3e with sodium amalgam in methanol containing sodium dihydrogen phos- phate led to very slow desulphonylation, though the product appeared to have ring opened, and was not the expected oxepane 3d. However, the P-keto sulphone 3e was readily desulphonylated using tributyltin hydride and gave 7-hexyl- oxepan-3-one 3d in 73% yield.The ketone group in 3e was stereoselectively reduced using sodium borohydride and cerium(rrr) chloride to give the crystalline all-cis-alcohol 4 in excellent yield. In the absence of cerium(r1r) chloride the yield was lower, although the diastereoselectivity was the same. High diastereoselectivity in the sodium borohydride reduction of acyclic P-keto sulphones has been noted previously. l7 The stereochemistry of the alcohol 4 was confirmed by NOE spectroscopy in which pre-irradiation of the singlet at 6 4.36 (2-H) caused an enhancement of the multiplet at 6 3.37 (7-H) and the triplet at 6 4.75 (3-H). Pre-irradiation of the latter signal also caused a strong enhancement of the singlet at 6 4.36.* The alcohol 4 was converted into a number of derivatives 510 by conventional means (Scheme 2).Of these derivatives, the acetate C6H13 AO' 3eI ii 3d 5 R =AC ix * C6H13 Q,,,,, 11 4R=H 5R=Ac x or xil8 6 R =CH20Me b; R =CH =CHPh 7 R =SiMe3 I-C\fOSiEt38 R=SiEt3 C; R =2-fuvl n Fig. 1 X-Ray crystal structure of 7-hexyl-2-phenylsulphonyloxepan-3-01 4 under conditions similar to those reported for 6-membered ring ethers. Thus radical alkylation of 8 with allyl(tributy1)tin in the presence of tributyltin triflate 2c gave the trisubstituted oxepane 12 (76%) (Scheme 2). Similarly, reaction with phenylmagnesium bromide in the presence of zinc bromide 2b gave the oxepane 13 (70%). The stereochemistry of the 2,3,7-trisubstituted oxepane 12 is assigned on the basis of its NMR spectrum and on literature precedent.2' Similarly, the major (ca.3: 1) oxepane 13 has its 2- and 7-substituents trans to one another. On the other hand, the phosphonate 3f could be used directly, and underwent smooth Wadsworth-Emmons reaction with a range of aldehydes to give the oxepanes 14 in good yield (Scheme 3). The reaction gives largely (>90%) one geometrical i A 3f 14 a; R =Ph vii9 R =SiMe2Bu' 10 R= MS viii 5 underwent the expected elimination reaction on treatment with base to give the vinyl sulphone 11 in high yield. Attempts to carry out Julia reactions with aldehydes on the P-keto sulphone 3e were unsuccessful, presumably because the derived anion is too stable.We also attempted to couple the vinyl sulphone 11 with Grignard reagents in the presence of iron(1rr) or nickel(I1) acetylacetonate, *again without success. Although the P-keto sulphone 3e could not be utilised directly in coupling reactions, the phenylsulphonyl group in the all-cis protected alcohol 8 could be displaced by carbon nucleophiles *The stereochemistry was further confirmed by X-ray crystallography (Fig. I). Details can be obtained from Dr. D. J. Williams, Department of Chemistry, Imperial College. d; R =Bu'Me&iO(CH& Scheme 3 Reugents: i, NaH, THF; RCHO Experimental For general points, see refs. 3a and 36. In addition, all J values are in Hz. Preparation of Diazo Alcohols t-Butyl 2-Diazo-7-hydroxy-3-oxoheptanoate2a.-t-Butyl di-azoacetate (0.750 g, 5.25 mmol) was added dropwise to a solution of LDA (5.25 mmol) in THF (30 ml) at -90 "C.After 15 min at -90°C, 6-valerolactone (5.00 mmol, 0.501 g) was added dropwise over 5 min. After 15 min at -90 OC, the solution was warmed to -77 "C for 4.5 h. Acetic acid (0.3 ml) was added, and the mixture allowed to warm to 0 "C before the addition of water and extraction into dichloromethane. The J. CHEM. soc. PERKIN TRANS. 1 1991 crude product was purified by chromatography to give the title compound2a (1.06g, 87%) as a pale yellow oil (Found: C, 54.6; H, 7.7;N, 1 1.4.C H 8N204 requires C, 54.5;H, 7.5;N, 11.6%); v,,,(film)/cm 3421, 2133, 1713, 1655, 1315 and 1135;6,(250 MHz; CDCl,) 1.52 (9 H, s, Bu'), 1.5s1.80 (4 H, m), 1.90(1 H, s, OH), 2.84 (2 H, t, J 7.1, CH,CO) and 3.64 (2 H, t, J 6.4, CH20); m/z(FAB; glycerol) 243(MH'), 225, 187, 169, 141,99 and 57. t-Butyl 2-Diazo-7-hydroxy-3-oxotridecanoate2b.-To a solution of t-butyl diazoacetate (2.6g, 18mmol) and undecanoic acid 6-lactone (3.17ml, 3.04g, 16 mmol) in THF (80ml) at -78 "C under nitrogen was added uia a catheter a cooled solution of LDA [prepared from diisopropylamine (2.57ml, 1.85g, 18mmol) and butyllithium (1.6mol dmP3; 11.41ml, 0.018 mol)] in THF (60 ml).The reaction mixture was stirred at -78"C for 4h, after which acetic acid (2.06ml, 2.16g, 36mmol) was added and the solution allowed to warm to room temperature. The mixture was diluted with water (20ml) and extracted with dichloromethane (3 x 50 ml) and the combined organic extracts were washed with water (50 ml) and brine (50 ml), dried (Na2S04) and evaporated.The residue purified by column chromatography on silica (light petroleum-ther) gave the titlecompound2b (3.5g, 67%) as a yellow oil (Found: C, 62.6; H, 9.5;N,8.3.C17H30N204requires C, 62.55;H, 9.3;N,8.6%); v,,,(film)/cm-' 3410, 2930, 2131, 1714, 1655, 1371 and 1091; 6,(270 MHz; CDC13) 0.85[3 H, -t, J 10,Me(CH,),], 1.24-1.50 and 1.60-1.95(15H, 2m), 1.54(9H, s, Bu'0,C) 2.72-2.95 (2 H, m, 4-CH2) and 3.54-3.65(1 H, m, 7-CH); m/z 298 (M' -N2), 242,224, 197 and 99. 3-Diazo-8-h~~droxyoctane-2,4-dione solution of LDA 2c.-A (2.38mmol) in THF (5 ml) was added dropwise to a solution of diazoacetone (200mg, 2.38mmol) and 6-valerolactone (238 mg, 2.38mmol) in THF (10ml) at -92 "C.The solution was stirred at -90 "C for 0.5 h followed by 4.5h at -75 "C, before the addition of acetic acid (0.15ml). Aqueous work-up and purification of the residue by chromatography gave the title compound 2c (114 mg, 26%) as a yellow oil (Found: M+, 184.0844.C8H,2N2O3 requires M, 184.0848);v,,,(film)/cm-' 3419, 2130, 1662, 1367 and 1299;6,(250 MHz; CDCl,) 1.43-1.56(2H, m), 1.56-1.70(2H, m), 2.33(3 H, s, COMe), 2.66 (2 H, t, J 6.9, CH,CO), 2.66(1 H, br, OH) and 3.53(2H, t, J 5.8, CH20); mjz 184 (M+), 166, 156, 138, 126, 100,85,55 and 43. 1-Diazo-6-hydroxydodecan-2-one2d.-Butyllithium (1.9ml, 3.00mmol) was added dropwise to a standardised solution of trimethylsilyldiazomethane in ether (1.50ml, 3.0mmol), diluted with THF (15 ml) at -65 "C.The solution was stirred for 20 min before the dropwise addition of undecanoic acid &-lactone (498mg, 2.70mmol). After 3h at -70"C, acetic acid (0.17ml, 3.0mmol) was added. The reaction mixture was warmed to 0 "C, diluted with water and rapidly extracted with ether. The crude product was purified by chromatography on neutral alumina, to give the title compound2d (198mg, 32%) as a low melting yellow solid, m.p. 30-33 "C (Found: M', 198.1625. C12H2,N202-N, requires M, 198.1620); v,,,(film)/cm-'3319, 3083, 2105, 1634, 1377, 1130 and 1087; 6,(250 MHz; CDCl,) 0.88(3 H, t, J7,CH,), 1.15-1.60 (12 H, m), 1.62-1.85 (3H, m), 2.36 (2 H, -t, J 7, CH,CO), 3.58(1 H, m, CHO) and 5.26(1 H, br, CHN); m/z 198 (M+ -N,), 185, 167, 156, 141, 113,84and 55.1-Diazo-6-hydroxy-1-phenylsulphonyldodecan-2-one2e.--To a solution of methyl phenyl sulphone (3.0g, 19mmol) in THF (25ml) at -78 "C under nitrogen was added dropwise over 5 min butyllithium (1.6mol dm-,; 12 ml, 19 mmol). After the resulting yellow anion solution had been stirred for 30 min, undecanoic acid 6-lactone (3.6ml, 3.5g, 19mmol) in THF (5ml) was added. The solution was stirred for 1 h at -78"C and then allowed to warm to 0°C; it was then maintained at this temperature for a further 2h before being recooled to -78 "C LDA [prepared from diisopropylamine (2.65ml, 1.9g, 19 mmol) and butyllithium (1.6rnol drn-,; 12ml, 19 mmol)] in THF (25ml) was added uiaa catheter and stirred for a further 30 min.Chlorotrimethylsilane (4.79ml, 4.1g, 38 mmol) was added and the solution allowed to come to room temperature overnight, whereupon saturated aqueous ammonium chloride (50 ml) was added. The mixture was extracted with ether (2 x 100ml) and the ethereal solution was washed with brine (100ml), dried (Na,SO,) and evaporated to give the crude p-keto sulphone intermediate. This was immediately subjected to diazo transfer using methanesulphonyl azide (2.39g, 20mmol) and triethylamine (7.9ml, 5.7g, 57 mmol) in ethanol (40ml). After 60h at room temperature, the residue taken up in ether (300ml), and the solution washed with water (2 x 100ml) and brine (100ml), dried (Na,SO,) and evaporated. The residue was purified by column chromatography on silica (light petroleum+ther) to give 1-diazo-1-phenylsulphonyl-6-trimethyl-siloxydodecan-2-one (4.18 g, 49%) as a yellow oil, v,,, (film)/cm-' 2112, 1668, 1448, 1344, 1250, 1178, 1157, 1086, 841 and 724; 6,(60 MHz; CDC1,) 0.08 (9 H, s), 0.50-1.65 (17 H, m), 2.38(2H, t, J6,CH,CO), 3.10-3.50(1 H, m, CHO) and 7.03-7.98(5 H, m, ArH); m/z 423 (M+ -Me), 397, 395, 379, 351, 327,297,281,273,187and 73.This oil was dissolved in THF (40 ml) and hydrochloric acid (0.5mol dm-,; 20ml) was added slowly. The mixture was stirred for 5 min, after which standard work-up as above and recrystallisation (light petroleum+ther) gave the titlecompound 2e (2.8g, 81%) as colourless needle crystals, m.p. 77-78"C (Found: C, 59.0;H, 7.1;N, 7.7.c18H&2o4S requires C, 59.0; H, 7.2;N, 7.7%); v,,,(melt)/cm-' 3436, 2114, 1667, 1448, 1337, 1155and 725; 6,(250 MHz; CDCl,) 0.88(3H, t, J6.7,Me), 1.16-1.57(13 H, m), 1.57-1.83 (2 H, m), 2.60 (2 H, t, J 7.1,CH,CO), 3.43-3.57(1 H, m, CHOH), 7.54-7.73(3H, m, ArH) and 7.98(2 H, -dd, J6.7,1,ArH); m/z 320 (M+ -N,), 281,274, 253,211, 197,125,99and 77.Diethyl (1-Diazo-6-hydroxy-3-oxododecyl)phosphonate 2f.-To a solution of diethyl methyl phosphonate (6.0g, 39.4 mmol) in THF at -78 "C under nitrogen was added butyllithium (1.6mol dm-3; 24.6ml, 39.4mmol) and the solution stirred for 30min. Undecanoic acid 6-lactone (3.40ml, 3.29g, 17.8mmol) in THF (5 ml) was added over 5 min and the solution allowed to warm to 0 "C.Stirring was continued for 2h after which the solution was recooled to -78"Cand a solution of LDA [prepared from diisopropylamine (2.76ml, 1.99g, 19.7 mmol) and butyllithium (1.6mol drn-,; 12.6ml, 19.7mmol)] in THF (20ml) was added viaa catheter. After a further 30min at -78"C, chlorotrimethylsilane (7.47ml, 6.38g, 59.1mmol) was added, and the solution allowed to warm to room temperature overnight. Saturated aqueous ammonium chloride (50 ml) was added, and the solution extracted with ether (2 x 200ml). The ethereal extracts were washed with brine (100 ml), dried (Na,SO,), and evaporated to give crude diethyl (2-0~0-6- trimethylsiloxydodecyl)phosphonate, (v,,, 1719 cm-'), which was dissolved in dichloromethane (1 3ml) and triethylamine (13 ml).Methanesulphonyl azide (2.38g, 19.7mmol) was added and the mixture stirred at room temperature for 48h, whereupon it was diluted with dichloromethane (100ml), washed with water (2 x 50 ml) and brine (50 ml), dried (Na,SO,) and evaporated. The residue was purified by column chromatography on silica (ether) to give diethyl(1-diazo-2-oxo-6-trimethylsiloxydodecyl)-phosphonate (4.42 g, 57%) as a yellow oil; v,,,(film)/cm-' 2121, 1661,1370,1250,1022,973and 841; 6,(250 MHz; CDCl,) 0.08 (9H, s), 0.85(3H, t, J6.7,Me), 1.04-1.80 (20 H, m), 2.53 (2 H, t, J 7.1, CH,CO), 3.58 (1 H, quin, J 5.5, CHO) and 3.96-4.27 (4 H, m, POCH,); m/z 419 (M+ -Me), 408,393,318,269, 179 and 73. To a solution of this diazo compound in THF (50 ml) was added hydrochloric acid (0.5 mol drn-,; 20 ml).After being stirred for 5 rnin at room temperature, the solution was diluted with water (200 ml) and extracted with dichloromethane (2 x 100 ml) and the organic extracts were washed with brine (100 ml), dried (Na2S04) and evaporated. The residue was purified by passage through a short silica gel column (ether) to give the title compound 2f (3.62 g, 98%) as a clear oil (Found: M', 334.1907. C,,H3,N,0,P -N, requires M, 334.1909); vmax(film)/cm-' 3487, 2121, 1658, 1369, 1262, 1018 and 975; 6,(250 MHz; CDC1,) 0.88 (3 H, t, J 6.7 Me), 1.19-1.57 (18 H, m), 1.76 (2 H, quin, J 7.2), 1.95 (I H, br, OH), 2.462.72 (2 H, m, CH2CO), 3.57 (1 H, m, CHOH) and 4.014.31 (4 H, m, CH20); m/z 334 (M' -N2), 318, 316, 277, 220, 194, 179 and 65.Diethyl ( 1-Diaio-6-hq,dro.~y-2-o.~ohe-~yl)phosphonate 2g.-To a solution of diethyl methylphosphonate (6 g, 39.4 mmol) in THF (40 ml) at -78 "C under nitrogen was added dropwise over 10 rnin butyllithium (1.6 mol drnp3; 24.6 ml, 39.4 mmol). The mixture was stirred for 30 min after which valerolactone (1.83 ml, 1.97 g, 19.7 mmol) in THF (4 ml) was added and the solution allowed to come to 0°C. After being stirred for a further 3 h, the solution was recooled to -78 "C and a solution of LDA [prepared as above, 19.7ml in THF (20 ml)] was added uia a catheter. After 30 min, chlorotrimethylsilane (7.47 ml, 6.38 g, 59.1 mmol) was added, and the solution allowed to warm to room temperature overnight. Work-up as previously gave crude diethyl (2-0x0-6-trimethylsiloxyhexyl)phosphonatewhich was dissolved in dichloromethane (13 ml) and triethylamine (1 3 ml).Methanesulphonyl azide (2.38 g, 19.7 ml) was added and the mixture stirred at room temperature for 48 h. It was then diluted with dichloromethane (100 ml), washed with water (2 x 50 ml) and brine (50 ml), dried (Na,SO,) and evaporated. The residue was purified by column chromatography on silica (ether) to give diethyl (1-diazo-2-oxo-6-trimethylsiloxyhexyl)phosphonate (5.14 g, 75";) as a yellow oil. This oil was immediately dissolved in THF (60 ml), and hydrochloric acid (0.5mol dm-,; 25 ml) was added. After being stirred at room temperature for 5 min, the mixture was diluted with water (300 ml) and extracted with dichloromethane (2 x 200 ml), and the organic extracts were washed with brine (100 ml), dried (Na2S04) and evaporated.The residue was purified by passage through a short silica gel column (ether) to give the title compound 2g (2.4 g, 83%) as a viscous yellow oil (Found: C, 43.1; H, 6.9; N, 10.1. CloH,,N,O,P requires C, 43.2; H, 6.9; N, 10.13)); v,,,(film)/cm-' 3412, 2938, 2122, 1657, 1020 and 799; 6,(270 MHz; CDCl,) 1.35 [6 H, t, J 10, (OCH,CH,),], 1.5G1.62 and 1.68-1.80 (4 H, 2 m, 4-CH2 and 5-CH2), 1.97 (1 H, br s, OH), 2.60 (2 H, t, J 10, 6-CH2), 3.58-3.67 (2 H, m, 3-CH2)and 4.12-4.28(4H,m,(OCH,CH3),);m/z(C.I.,NH,)2.96(M++ NH,), 268 (M' -N, +NH,), 251,235 and 189. Preparation qf 2-Substituted 3-Oxooxepanes by Rhodium(1i) Acetate Catalysed Cyclisution qf Diazo A lcohols t-Butyl 3-Oxooxepane-2-carbo.~~vlate3a.-A solution of the diazo alcohol 2a (979 mg, 4.04 mmol) in benzene (9 ml) was added dropwise to a suspension of dirhodium tetraacetate (8.1 mg, 0.45 mol"/,) in benzene (CAUTION) (51 ml) at reflux over 13 min.After 3 min at reflux the reaction mixture was cooled, filtered, evaporated and the residue distilled to give the title compound3a (420 mg, 48%) as a clear oil, b.p. 9G95 "C at 0.03 mmHg (Found: C, 61.5; H, 8.6. C H requires C, 61.7; H, 8.5%)); v,,,(film)/cm-' 3475, 1746, 171 8, 1652, 1621, 1370, 1326, J. CHEM. SOC. PERKIN TRANS. 1 1991 1275, 1248 and 1153; 6,(250 MHz; CDCl,) 1.42 (9 H, s, But, keto), 1.48 (9 H, s, But, enol), 1.50-1.98 (4 H, m, keto/enol), 2.4G 2.54 (2 + 1 H, m, CH2C0 enol and HCHCO keto), 2.85 (1 H, dt, J 11.7, 2.5, HCHCO, keto), 3.42 (1 H, ddd, J 12.0, 9.7, 2.4, CHO, keto), 3.71 (2 H, t, J 5.1, CH,O, enol), 4.22 (1 H, ddt, J 13.0, 3.8, 1.4, CHO, keto), 4.31 (1 H, s, CHCO, keto) and 10.97 (1 H, s, OH); ca.10% enol form; 6,(62.9 MHz; CDCI,) 22.6 (enol), 23.5, 27.7, 28.2 (enol), 30.7, 3 1.80 (enol), 33.1 (enol), 41.5, 72.3, 72.9 (enol), 81.6 (enol), 82.4, 86.8, 165.4 and 208.1; mjz 214 (M'), 158, 140, 113, 101 and 57. t-Butyl 7-Hexyl-3-o.voo.~epane-2-c.arho.vylate3b.-To a sol- ution of dirhodium tetraacetate (38 mg, 0.086 mmol) in dry benzene (260 ml) under nitrogen at reflux was added dropwise over 10 rnin the diazo alcohol 2b (3.5 g, 0.01 mol) in dry benzene (CAUTION) (100 ml). Heating was continued for a further 5 min, after which the solution allowed to cool.It was then filtered through Celite, the Celite washed with benzene (50 ml) and the combined organic filtrates were evaporated. The residue was passed through a short silica gel column (light petroleum-ether) and further purified by Kugelrohr distillation to give the titlt. c*ornpound3b (1.9 g, 64"/,,),b.p. 120 "C at 0.2 mmHg (Found: C, 68.4; H, 10.2. C17H3004requires C, 68.4; H, lO.lq,); v,,,(film)/cm-' 2932, 1743, 1720, 1651, 1622, 1369, 1326, 1248, 1157 and 844; 6,(270 MHz; CDCl,) 0.80-0.90 [3 H, m, Mc>(CH,),, keto and enol], 1.44 and 1.50 (9 H, 2s, But, keto, axial and equatorial), 1.55 (9 H, s, Bu', enol), 1.22-2.01 (14 H, m), 2.19-2.32 (1 H, dd, 16, 5, 4-CHH, enol), 2.36-2.49 (1 H, dd, J 13, 5, 4-CHH, keto).2.59-2.80 (1 H, m, 4-CHH, keto), 2.87-3.01 (1 H,dt, J 16,2.5,4-CNH,enol), 3.17-3.30(1 H, m,7-CH), 4.29 and 4.58 (1 H, 2s, 2-CH, keto, axial and equatorial) and 1 1.15 (1 H, s, OH, enol), ca. 503, enol form; mi; 298 (M'), 242, 197, 167, 149,99 and 57. t-Butj.1 3-( t-But~~ldinieth~~lsilo.~q~~-7-he.~q~l-4,5,6,7-t~~trah~~~ro-o.~c.pinc.-2-carbo.~q,lat~~.~To a solution of the oxepane 3b (200 mg, 0.67 mmol) in dry dichloromethane (10 ml) was added triethylamine (0.23 ml, 169 mg, 1.67 mmol), t-butyldimethylsilyl trifluoromethanesulphonate (0.35 ml, 408 mg, 1.54 mmol), and the reaction mixture stirred under nitrogen at room tem-perature for 1 h.The solution was diluted with dichloro- methane (20 ml), washed with saturated aqueous sodium hydrogen carbonate (10 ml) and brine (10 ml), dried (Na,SO,) and evaporated. The residue was purified by rapid column chromatography on silica (light petroleum-ether) to give the title compound (254 mg, 92",,) as a colourless oil (Found: C, 66.9; H, 11.05. C2,H4,SiO4 requires C, 66.9; H, 10.75"/,); v,,,(film)~cm-' 2930, 2859, 1698, 1610, 1472, 1240, 839 and 789; 6,(270 MHz; CDCl,) 0.14 and 0.15 (6 H, 2s, SiMr2Bu'),0.89 [3 H, -t, J 10, Me(CH,),], 0.96 and 0.98 (18 H, 2s, SiMe,Bu' and C02But), 1.21-1.92 (14 H, m), 2.09-2.18 (1 H, dd, J 14, 8, 4-CHH),2.73-2.86(1 H, -dt,Jl4,2.5,4-CHH)and3.3&3.42(1 H, m, 7-CH); m/z 413 (M' + H), 257,189,147,73 and 28.2-Acet),loxepan-3-o~e[Enol Form] 3c.-A solution of the diazo alcohol 2c (87.9 mg, 0.477 mmol) in benzene (7 ml) was added dropwise to a suspension of dirhodium tetraacetate (3 mg) in benzene (CAUTION) (15 ml) at reflux over 5 min. After 2 rnin at reflux the suspension was cooled, filtered and evaporated, and the residue purified by chromatography to give the title compound 3c (46.4 mg, 627;) as a clear oil, b.p. 130 "C at 0.25 mmHg (Found: M', 156.0783. C8HI2O3 requires M, 156.0786); vn,ax(film)/cm-l2700, 1736w, 17 11w, 1596, 1435, 1300 and 873; 6,(250 MHz; CDC1,) 1.70 (2 H, quin, J 5.5, CH2CH2CO),1.87 (2 H, quin, J 5.4, CH2CH20), 2.10 (3 H, s, COMe), 2.59 (2 H, C'LI. t, J 6.2, CH,CO), 3.81 (2 H, t, J 7.1, CH20)and 13.97 (1 H, s, OH); mjz 156 (M'), 155, 129,101,83, 55 and 43.J. CHEM. SOC. PERKIN TRANS. 1 1991 7-He.uylo.uc.pan-3-one 3d.-A solution of the diazo alcohol 2d (99 mg, 0.44 mmol) in benzene (5 ml) was added dropwise to a suspension of dirhodium tetraacetate (3 mg) in benzene (CAUTION) (20 ml) at reflux over 3 min. After 1 rnin at reflux, the reaction mixture was cooled, filtered and evaporated, and the residue purified by chromatography on Florisll to give the title compound 3d (49 mg, 56%) as a clear oil, b.p. 150 "C at 0.2 mmHg (Found: C, 72.9; H, 11.4. CI2H2,O2 requires C, 72.7; H, 1 1.2%); v,,,(film)/cm-' 1714, 1456, 1332, 1127 and 11 10; 6,(250 MHz; CDCI,) 0.83 (3 H, t, J 6.7, CH,), 1.13-1.70 (12 H, m), 1.77-2.00 (2 H, m), 2.43 (1 H, -dd, J 12.5, 5.8, CH,CO), 2.86 (1 H, dt, J 12.2, 2.5, CH2CO), 3.17 (1 H, -t, J8.9, CH2CHO), 3.88 (1 H, d, J 18.3 Hz, OCH,CO) and 4.23 (1 H, d, J 18.3, OCH,CO): mi': 198 (M+), 166, 124, 113,98,84,55 and 41.7-H~~.u~~l-2-phenylsulphonyloxepan-3-one3e.-A solution of the diazo alcohol 2e (270 mg, 0.794 mmol) in benzene (7 ml) was added to a suspension of dirhodium tetraacetate (4 mg) in benzene (CAUTION) (30 ml) at reflux over 7 min. After 5 rnin at reflux, the suspension was cooled, filtered and evaporated and the residue subjected to chromatography to give the title compound 3e (182 mg, 73%) as white needles, m.p. 60-62 "C (ether-hexane) (Found: Mt, 338.1558. C18H2604S requires M, 338.1 552); v,,,(melt)/cm-' 1722, 1449, 1131, 1083, 758, 721 and 688; 6,(250 MHz;CDC1,) 0.83 (3 H, t, J6.7, Me), 0.90-1.85 (12 H, m), 1.85-2.04 (2 H, m), 2.49 (1 H, dd, J 11.1, 5.4, CH,CO), 2.86 (I H, ddd..J 13.4, 8.9, 2.2, CH,CO), 3.12-3.25 (1 H, m, CH,CHO). 4.67 (1 H, s, CHS), 7.48-7.62 (2 H, m, ArH), 5.62- 7.71 (1 H, m, ArH) and 7.93 (2 H, -dd, J6.7; 1, ArH); m/z 338 (M'), 197, 143, 125,95,69,55 and 41. Diethj71 7-Hexyl-3-oxooxepan-2-ylphosphonate3f.-A sol-ution of the diazo alcohol 2f (140 mg, 0.39 mmol) in benzene (7 ml) was added to a suspension of dirhodium tetraacetate (4 mg) in benzene (CAUTION) (15 ml) at reflux over 5 min. After 20 min at reflux, the reaction mixture was cooled, filtered and evaporated and the residue purified by chromatography to give the title compound 3f (70 mg, 54%) as a clear oil, b.p.160- 165 "C at 0.25 mmHg (Found: C, 57.6; H, 9.6. C16H3105P requires C, 57.5; H, 9.4%); v,,,(film)/cm-' 3473, 1715, 1632, 1259, 11 18, 1055 and 1025; 6,(250 MHz; CDCl,) 0.85 (3 H, t, J 6.7, Me), 1.18 -1.84 (18 H, m), 1.89-2.04 (2 H, m), 2.44 (1 H, dd, J 15.0, 6.2, HCHCO), 3.02-3.20 (2 H, m, HCHCO and CH,CHO) and 4.094.28 (5 H, m, CH,CH, and CHP); m/z 334(M+), 167,139, lll,84and41. Diethyl 3-Oxooxepan-2-ylphosphonate 3g.-To a solution of dirhodium tetraacetate (14 mg, 31 pmol) in dry benzene (CAUTION) (120 ml) at reflux under nitrogen was added dropwise over 5 min a solution of the diazo alcohol 2g (870 mg, 3.1 mmol) in dry benzene (50 ml). When addition was complete, heating was continued for a further 20 min. The solution was then cooled, filtered through Celite, the Celite washed with further benzene (50 ml), and the combined benzene washings were evaporated.The residue was purified by column chromatography on silica (ether) to give the title compound 3g (401 mg, 52":;) as a colourless oil (Found: C, 48.1; H, 7.6. C ,H P requires C, 48.0; H, 7.7%); v,,,(film)/cm-' 2938, 1714,1259, 1024 and 961; 6,(270 MHz; CDCl,) 1.28-1.38 (6 H, m, (OCH,CH,),, 1.40-2.05 (6 H, m), 3.04-3.14 (1 H, ddd, J 16, 13.5, 5, 4-CMH), 3.25-3.36 (1 H, -ddd, J 16, 13.5, 3), 4.15- 4.27 [4 H, m (OCH,CH,),] and 4.354.44 (1 H, m, 2-CH); m/z 250 (M+), 167,138,111,55 and 29. Reuctiom of'7-Hexyl-2-phenylsulphonyloxepan-3-one3e 7- Hexyloxc.pan-3-one 3d.-A solution of the sulphone 3e (200 mg, 0.59 mmol) and tributyltin hydride (0.635 ml, 687 mg, 2.36 mmol) in toluene (6 ml) under nitrogen was heated to reflux.AIBN (192 mg, 1.17 mmol) was added in four equal portions at intervals of 4-5 min. When addition was complete. heating was continued for a further 20 min. On cooling, the toluene was evaporated at reduced pressure, and the column chromatograph column chromatography on silica (hexane-ether) to give 7- hexyloxepan-3-one 3d (85 mg, 73%) as a colourless oil, the spectroscopic properties of which corresponded with those already reported. 7-Hexyl-2-phenylsulphonyloxepan-3-ol4.--To a solution of the P-keto sulphone 3e (400 mg, 1.18 mmol) in methanol (3 ml) at room temperature was added cerium trichloride heptahydrate (448 mg, 1.20 mmol), followed by sodium borohydride (45 mg, 1.20 mmol).After being stirred for 5 min. the suspension was acidified to pH 2 using 0.5~hydrochloric acid, diluted with water (10 mi) and extracted with ether (2 x 50 ml). The ethereal extracts were dried (Na,SO,) and evaporated, and the resulting solid residue was recrystallised from hexane+ther to give the title compound 4 (392 mg, 97%) as colourless needles, m.p. 82-83 "C (Found: C, 63.7; H, 8.45. C1 ,H,,O,S requires C, 63.5; H, 8.3%); v,,,(CHCl,)/cm-' 3310, 2959, 1600, 1459, 1219 and 1041; 6,(250 MHz; CDCl,) 0.89 [3 H, t, J 10, Me(CH,),], 1.06-1.35 (8 H, m), 1.39-2.04 (8 H, m), 2.70 (1 H, br s, OH), 3.37-3.48 (1 H, m, 7-CH), 4.36 (1 H, s, 2-CH), 4.75 (1 H, -t, J4, 3-CH), 7.5Ck7.70 and 7.94-8.00 (5 H, 2m, ArH); m/z 341 (Mf + H), 276, 246, 227, 199, 163, 143, 95 and 55.3-Aceto.xy-7-hexyl-2-phenylsulphonyloxepane5.--To a sol-ution of the alcohol 4 (195 mg, 0.57 mmol) in pyridine (2 ml) at room temperature under nitrogen was added acetic anhydride (81 pl, 88 mg, 0.86 mmol) and 4-(dimethy1amino)pyridine. After being stirred for 12 h, the reaction mixture was diluted with ether (20 ml), washed with water (20 ml), saturated aqueous copper sulphate (20 ml), water (20 ml) and brine (20 ml), dried (MgSO,) and evaporated. The resulting solid residue was recrystallised from ether-light petroleum (b.p. 60-80 "C) to give the title compound 5 (196 mg, 89%) as a colourless solid, m.p. 96-98 "C (Found: C, 62.6; H, 8.0. C,OH,,O,S requires C, 62.8; H, 7.9%); v,,,(CHCl,)/cm-' 2932, 2861, 1739, 1596, 1238, 914 and 866; 6,(270 MHz; CDCl,) 0.88 [3 H, t, J 10, Me(CH,),], l.l(b1.50 and 1.52-2.05 (16 H, 2m), 1.88 (3 H, s, OCOCH3), 3.32-3.40 (1 H, m, 7-CH), 4.49 (1 H, d, J 2, 2- CH), 5.665.75 (1 H, dt, J 6, 2, 3-CH) and 7.50-7.68 and 7.89- 7.99 (5 H, 2m, ArH); m/z 322 (M' -AcOH), 279, 241, 198, 181, 163,97 and 43.7-Hexyl-2-phenylsulphonyl-4,5,6,7-tetruhydroo.u~~pin~~11.-To a solution of the acetoxy sulphone 5 (96.5 mg, 0.25 mmol) in dry dioxane (15 ml) under nitrogen was added powdered sodium hydroxide (40 mg, 1 mmol). The mixture was stirred at room temperature for 16 h after which it was diluted with water (20 ml) and extracted with ether (2 x 30 ml). The ethereal extracts were dried (MgSO,) and evaporated, and the residue was purified by column chromatography on silica (light petroleum-ether) to give the title compound 11 (75 mg, 92x) as a colourless oil (Found: C, 67.3; H, 8.4.C18H260,S requires C, 67.0; H, 8.1%); ~,,,(film)/cm-l 2927, 1650, 1586, 1324, 1159, 1062 and 755; 6,(270 MHz; CDCl,) 0.88 [3 H, t, J 10, Me(CH,),], 1.1Ck2.96 (14 H, m), 2.17-2.44 (2 H, m, 4-CH2), 3.44-3.54(1H,m,7-CH),6.51-6.61(1H,dd,J14,6,3-CH),7.5& 7.65 and 7.89-7.95 (5 H, 2m, ArH); m/z 322 (Mf), 197, 181, 143, 125,83,69 and 55. 7-Hexyl-3-(methoxymethoxy)-2-phenylsulphonyloxepune6.-To a solution of the alcohol 4 (14.9 mg, 0.44 mmol) in dry dichloromethane (2.5 ml) under nitrogen was added chloro- methyl methyl ether (1 ml, 106 mg, 1.3 mmol) and di-isopropylethylamine (0.46 ml, 340 mg, 2.6 mmol).The solution was stirred at room temperature for 12 h after which the dichloromethane was evaporated and ether (20 ml) was added. The ether solution was washed with water (2 x 20 ml) and brine (20 ml), dried (MgSO,) and evaporated and the residue purified by column chromatography on silica (light petroleum- ether) to give the title compound 6 (1 10 mg, 65%) as a colourless solid, m.p. 53-55 "C (ether-light petroleum) (Found: C, 62.8; H, 8.5. C2,,H3,0,S requires C, 62.5; H, 8.4%); v,,,(CHCl,)/cm-' 2931, 1586, 1448, 1153, 1040 and 689; 6,(270 MHz; CDCl,) 0.90 [3 H, t, J 10, Me(CH,),], 1.10-2.00 (16 H, m), 3.17- 3.27 (1 H, m, 7-CH), 3.40 (3 H, s, OCH,), 4.42 (1 H, d, J 2, 2-CH), 4.584.67 (1 H, m, 3-CH), 4.64 and 4.83 (2 H, 2 dd, J 25, 8, OCH,OCH,) and 7.50-7.67 and 7.94-8.00 (5 H, 2m, ArH); mjz 353 (M' -CH,O), 323,273,257,169 and 45.7-Hexyl-2-phenylsulphonyl-3-(trimethylsilox~)oxepun~7.-To a solution of the alcohol 4 (72 mg, 0.21 mmol) in dry dichloromethane (1.5 ml) under nitrogen was added sequen- tially trimethylsilyl chloride (42 p1, 34 mg, 0.34 mmol), triethylamine (47 pl, 34 mg, 0.34 mmol) and 4-(dimethyl- amino)pyridine (1 crystal). After being stirred for 1 h at room temperature, the reaction mixture was diluted with dichloro- methane (25 ml), washed with water (20 ml) and brine (20 ml), dried (Na,SO,) and evaporated. The residue was purified by column chromatography on silica (light petroleum-ether) to give the title compound 7 (80 mg, 70%) as a colourless oil (Found: C, 61.2; H, 8.5.C21H3604SSi requires C, 61.1; H, 8.873; v,,,(film)/cm-' 2931, 1601, 1308, 1251, 844 and 689; 6,(270 MHz; CDCI,) 0.15 (9 H, s, SiMe,), 0.84 [3 H, t, J 10, Me(CH,),], 1.07-1.38 and 1.42-2.00 (16 H, 2m), 3.1s3.20 (1 H, m, 7-CH), 4.36 (1 H, d, J 2, 2-CH), 4.7W.78 (1 H, dt, J 6, 2, 3-CH), 7.45-7.63 and 7.90-8.00 (5 H, 2m, ArH); m/z 412 (M'), 397,271, 199,163,129 and 73. 7-Hexyl-2-phenylsulphonyl-3-(triethylsiloxy)oxepane8.-To a solution of the alcohol 4 (300 mg, 0.88 mmol) in dry dichloromethane (1 5 ml) under nitrogen was added 2,6-dimethylpyridine (0.154 ml, 142 mg, 1.32 mmol) and triethylsilyl trifluoromethanesulphonate (0.279 ml, 326 mg, 1.24 mmol).After being stirred at room temperature for 30 min, the reaction mixture was diluted with dichloromethane (30 ml), washed with saturated aqueous sodium hydrogen carbonate (20 ml), water (20 ml) and brine (20 ml), dried (Na,SO,) and evaporated. The residue was purified by column chromatography on silica (light petroleum-ether) to give the title compound 8 (240 mg, 61%) as a low-melting colourless solid, m.p. 31-34 "C (Found: C, 63.3; H, 9.4. C2,H,,04SSi requires C, 63.4; H, 9.373; v,,,(melt)/cm-' 2931, 1599, 1308, 1251, 1084 and 688; 6,(270 MHz; CDC1,) 0.5 [6 H, q, J 8, OSi(CH,CH,),], 0.83 [3 H, t, J 10, Me(CH,),], 0.95 (9 H, t, J 8, OSi(CH,CH,), 1.04-1.35 and 1.40-1.95 (16 H, 2m), 3.00-3.11 (1 H, 7-CH), 4.33 (1 H, d J 2, 2- CH), 4.744.83 (1 H, m, 3-CH) and 7.46-7.65 and 7.91-8.00 (5 H, 2m, ArH); mjz 425 (M' -C,H,), 375,283,227, 163,95,55 and 41.3-( t- Butyldimethylsilo~xy)-7-he.xyl-2-phenylsulphonyloxepune 9.-A solution of the alcohol 4 (150 mg, 0.44 mmol) in dry dichloromethane (0.5 ml) was added to a solution of 2,6-(0.102 ml, 95 mg, 0.88 mmol) and t-butyldimethylsilyl trifluoro-methanesulphonate (0.152 ml, 174 mg, 0.66 mmol) in dry dichloromethane (0.5 ml) under nitrogen. After being stirred at room temperature for 24 h, work-up as above gave the title compound 9 (55 mg, 27%) as a colourless solid, m.p. 51-53 "C (Found: M +,313.2566. C2,H,,0,SSi -C6H,02S requires M, 3 13.2563); vmax(melt)/cm-' 2929, 1463, 1254, 1084, 837 and 688; 6,(270 MHz; CDCl,) 0.10 and 0.19 (6 H, 2s, SiMe,Bu'), 0.84 J.CHEM. SOC. PERKIN TRANS. 1 1991 [3 H, t, J 10, Me(CH,),], 0.93 (9 H, s, Bu'), 0.94-1.88 (16 H, m), 2.93-3.05 (1 H, m, 7-CH), 4.30 (1 H, d, J 2, 2-CH), 4.75-5.83 (1 H, m, 3-CH), 7.45-7.55 and 7.92-8.00 (5 H, 2m, ArH); m/z 455 (Mf),397,313,297,283,255, 199 and 73. 7-Hexy1-3-(methylsulphonyloxy)-2-phenylsuIphonyloxepane 10.-To a solution of the alcohol 4 (67 mg, 0.197 mmol) in pyridine (0.5 ml) was added methanesulphonyl chloride (23 pl, 34 mg, 0.29 mmol) and a crystal of 4-(dimethy1amino)pyridine. The solution was stirred under nitrogen at room temperature for 24 h after which it was diluted with water (20 ml) and the aqueous layer extracted with dichloromethane (2 x 20 ml). The organic extracts were washed with saturated aqueous copper sulphate (20 ml) and brine (20 ml), dried (Na,SO,) and evaporated.The solid residue recrystallised from ether-hexane to give the title compound 10 (86 mg, 96%) as a colourless solid, m.p. 140-142 "c(Found: C, 54.3; H, 7.3. Cl,H,,06S, requires C, 54.5; H, 7.2%); v,,,(CCl,)/cm-' 2950, 1583, 1470, 1160 and 720; 6,(270 MHz; CDCI,) 0.88 [3 H, t, J 10, Me(CH,),], 1.04-1.35 (10 H, m), 1.45-1.75 (4 H, m), 1.85-2.06 (2 H, m), 3.1s3.15 (1 H, m, 7-CH), 3.15 (3 H, s, CH,SO,O), 4.42 (1 H, d, J 2,2-CH), 5.57-5.64 (1 H, m, 3-CH), 7.55-7.74 and 7.95-8.00 (5 H, 2m, ArH); m/z 277 (Mf -PhSO,H), 245,181,163,125 and 97. 7-Hexyl-2-(prop-1-enyl)-3-triethylsiloxyoxepane12.-To a solution of the oxepane 8 (118 mg, 0.26 mmol) and allyl- tributy1)tin (161 p1, 172 mg, 0.52 mmol) in benzene (CAUTION) (3 ml) at 60°C under nitrogen was added a solution of tributyltin trifluoromethanesulphonate (34 mg, 78 pmol) in benzene (0.5 ml).The solution was heated to reflux for 24 h, after which it was cooled and the benzene removed at reduced pressure. The residue was purified by column chroma- tography on silica (light petroleum-ther 30: 1) to give the title compound 12 (70 mg, 76%) as a colourless oil (Found: M', 354.2987. C2 1H4202Si requires M, 354.2954); v,,,(film)/cm-' 2931,1642,1459, 1084 and 813; 6,(270 MHz; CDCI,) 0.54-0.65 [6 H, q, J 10, Si(CH,CH,),], 0.88 [3 H, m, Me(CH,),], 0.95 [9 H, t, J 10, Si(CH,CH,),], 1.18-1.56 and 1.60-2.17 (18 H, 2m), 3.39-3.45 and 3.47-3.58 (3 H, m, 2-CH, 3-CH and 7-CH), 5.00-5.14 (2 H, m, CH=CH,) and 5.8G5.96 (1 H, m, CH,CHCH,); m/z 354 (M'), 325,313,255,227, 154, 103 and 87.7-Hexyl-2-phenyl-3-(triethylsilo.xy)oxepune13.-To a solu-tion of zinc bromide (1.0 mol dm-, in THF; 204 pl, 0.24 mmol) in tetrahydrofuran (0.8ml) at room temperature under nitrogen was added phenylmagnesium bromide (2.0 mol dmP3 in THF; 170 p1, 34 mmol). After the mixture had been stirred for 30 min a solution of the oxepane 8 (76 mg, 0.17 mmol) in tetrahydrofuran (0.8 ml) was added and the solution stirred overnight. It was then diluted with water (5 ml) and extracted with ether (2 x 20 ml). The ethereal extracts were washed with brine (20 ml), dried (Na,SO,) and evaporated and the residue purified by column chromatography on silica (light petroleum- ether) to give the title compound 13(46 mg, 70%) as a colourless oil (Found: M', 361.2562.C2,H,,02Si -C2H5 requires M, 36 1.2563); v,,,(film)/cm-' 2930, 1604, 1452, 1239, 1097 and 739; 6,(270 MHz; CDC1,) 0.20-0.35 [6 H, m, Si (CH,CH,),], 0.74 [9 H, t, J 10, Si(CH,CH,),, 0.9M.95 [3 H, m, Me(CH,),], 1.05-1.35 and 1.4&2.00(16 H, 2m), 3.65-3.75 (2 H, m, 3-CH and 7-CH), 4.28 (1 H, d, J 10,2-CH, trans-isomer), 4.50 (1 H, d, J 2.7, 2-CH, cis-isomer), 7.15-7.35 (5 H, m, ArH), ca. 3:l trans:cis; m/z 390 (M'), 375,361,255,152,103 and 75. Reactions of Diethyl 7- Ht.x.~~l-3-oxooxepan-2-ylphosphonute3f 2-Benzylidenc-7-he.xyloxepan-3-one14a.-To a solution of the phosphonate 3f (83 mg, 0.27 mmol) in tetrahydrofuran (3 ml) at 0°C under nitrogen was added sodium hydride (60% as a J.CHEM. SOC. PERKIN TRANS. 1 1991 dispersion in oil; 15 mg, 0.30 mmol) and the solution stirred for 30 min. Benzaldehyde (30 p1,32 mg, 0.30 mmol) was added, and the reaction mixture allowed to come to room temperature. It was then stirred overnight, diluted with water and extracted into ether. The ether extracts were washed with brine, dried (Na,SO,), concentrated and the residue chromatographed to give the title compound 14a (50 mg, 73%) as a yellow oil (Found: C, 79.8; H, 8.85. C19H2602 requires C, 79.7; H, 9.15%); v,,,(film)/cm-' 2930, 1692, 1613, 1327, 1180, 694 and 525; 6,(270 MHz; CDC1,) 0.85 [3 H, t, J8 Hz, Me(CH,),], 1.13-1.42 and 1.6G2.09 (14 H, 2m), 2.55-2.66 (1 H, ddd, J 14, 10, 8.5, 4-CHH), 2.81-2.92 (1 H, ddd, J 14, 8, 2.5), 3.63-3.77 (1 H, m, 7-CH), 6.60 (1 H, s, WHPh) and 7.24-7.39 and 7.73-7.82 (5 H, 2m, ArH); m/z 286 (M'), 162,118,91,55,51 and 28.7-Hexyl-2-(3-phenylpropenylidene)oxepan-3-onel4b.-To a solution of the phosphonate 3f (53 mg, 0.173 mmol) in tetrahydrofuran (3 ml) at 0°C under nitrogen was added sodium hydride (100%; 5 mg, 0.208 mmol). The mixture was stirred for 30 min after which cinnamaldehyde (24 ~1, 25 mg, 0.190 mmol) was added and the solution allowed to warm to room temperature. The mixture was stirred for a further 6 h after which work-up and purification as above gave the title compound 14b (33 mg, 66%) as a pale yellow solid, m.p.7G81 "C (hexane-ether) (Found: M', 312.2089. C21H2802 requires M, 312.2089); v,,,(CHCl,)/cm-l 2934, 1678,1610, 1600,1582, 1327 and 1152; 6,(270 MHz; CDC1,) 0.88-0.99 [3 H, m, Me(CH,),, 1.28-1.51 and 1.5G2.03 (14 H, 2m), 2.59-2.68 (1 H, ddd, J 14,8, 1.5,4-CHH), 2.83-2.95 (1 H, dt, J 14,3.5,4-CHH), 3.62-3.70 (1 H, m, 7-CH), 6.78 (1 H, d, J 16, CH*CH=CHPh), 6.90 (1 H, d, J 19, CH-CH=CHPh) and 7.28-7.55 (6 H, m, CH-CH=CHPh and ArH); m/z 312 (M'), 206,144,115,55 and 41. 2-Furylidene-7-hexyloxepan-3-one14c.-To a solution of the phosphonate 3f (56 mg, 0.283 mmol) in tetrahydroduran (3 ml) at 0 "C under nitrogen was added sodium hydride (100"/; 6.5 mg, 0.274 mol). The mixture was stirred for 30 min after which 2-furfuraldehyde (30 p1,35 mg, 0.366 mmol) was added and the solution allowed to come to room temperature.The mixture was stirred overnight after which work-up and purification as above gave the title compound 14c (39 mg, 77%) as a pale yellow oil (Found: M+, 276.1725. C17H2403 requires M, 276.1725); v,,,(film)/cm-' 1687, 1610, 1328, 1283, 1012 and 740; 6,(270 MHz; CDC1,) 0.87 [3 H, t, J 10 Hz, Me(CH,),], 1.17-1.46 (8 H, m), 1.53-2.08 (6 H, m), 2.52-2.62 (1 H,ddd, J 14,8, 1.5,4-CHH), 2930, 1697,1630, 1471, 1327,1256,1103 and 837; 6,(270 MHz; CDC13) 0.05 (6 H, s, SiBu'MeJ, 0.87 (s, 9 H, SiBu'Me,), 0.85- 0.90 (3 H, m, Me(CH,),), 1.20-1.35 (8 H, m), 1.44-1.99 (8 H, m), 2.21-2.34 (2 H, dq, J 11,6, C==CHCH,CH,), 2.35-2.45 1 H, m, 4- CHH), 2.72-2.83 (1 H, dt, J 14, 3.5, 4-CHH), 3.37-3.48 (1 H, m, 7-CH), 3.62 (2 H, t, J 14, CH,CH,OSi) and 6.00 (1 H, t, J 13 Hz, C=CH); m/z 382 (M'), 325,281,197,157 and 75.Acknowledgements We thank the SERC for studentships (to R. J. T. and M. J. D.), the Royal Society of Chemistry for a Hickinbottom Fellowship (to C. J. M.), Mr. R. N. Sheppard for the NOE results, Dr. D. J. Williams for the X-ray crystal structure and Dr. J. A. Ballantine and his colleagues at the SERC Mass Spectrometry Service Centre, University College of Swansea. References 1 Part 6, C. J. Moody and R. J. Taylor, Tetrahedron,1990,46,6525. 2 (a) D. S. Brown, S. V. Ley and M. Bruno, Heterocycles, 1989, 28 (Special Issue No. 2), 773, and references therein; (b)D. S. Brown, M. Bruno, R.J. Davenport and S. V. Ley, Tetrahedron, 1989,45,4293; (c) G. E. Keck, E. J. Enholm and D. F. Kachensky, Tetrahedron Lett., 1984,25,1867; H. Kosugi, K. Tagami, A. Takahashi, H. Kanna and H. Uda, J. Chern.Soc., Perkin Trans. 1,1989,935;(d)S. V. Ley, B. Lygo, H. M. Organ and A. Wonnacott, Tetrahedron, 1985,41,3825. 3 (a)J. C. Heslin and C. J. Moody, J. Chem. Soc., Perkin Trans. 1,1988, 1417;(b) C. J. Moody and R. J. Taylor, J. Chem.Soc.,Perkin Trans. I, 1989, 721; (c) M. J. Davies, J. C. Heslin and C. J. Moody, J. Chern. SOC., Perkin Trans. 1, 1989,2473. 4 Preliminary communication, M. J. Davies, C. J. Moody and R. J. Taylor, Synfett.,1990, 93. 5 0.A. Kruglaya and N. S. Vyazankin, Russ.Chem. Rev., 1980,49,357. 6 M. Regitz, J. Hocker and A.Liedhegener, Org. Synth., Coll. Vol., 5, 179. 7 J. B. Hendrickson and W. A. Wolf, J. Org. Chern., 1968,33,3610. 8 M. Martin, Synth. Commun., 1983, 13, 809. 9 Triethylsilyldiazomethane was prepared in an analogous fashion to trimethylsilyldiazomethane (ref. 8), but see also G. S. Zaitseva, 0.P. Novikova, L. I. Livantsova and Y.I. Baukov, Zh. Obshch. Khim., 1988,58,1676. 10 For C-H insertion reactions of such diazo compounds in cyclopentanone synthesis, see: H. J. Monteiro, Tetrahedron Lett., 1987, 28, 3459; B. Corbel, D. Hernot, J. P. Haelters and G. Sturz, 1987,28,6605. 11 A. L. Fridman, Y. S. Andreichikov, L. F. Gein and V. L. Gein, J. Org. Chern.(USSR), 1977,12,457. (51 mg, 0.254 mmol) was added, and the solution allowed to 2469. come to room temperature. The mixture was stirred overnight after which work-up and purification as above gave the title compound 14d (36 mg, 80%) as a colourless oil (Found: M', 382.2903. C, H,,O $1 requires M, 382.2903); vmax(film)/cm-l 12 M. Regitz, A. Liedhegener, U. Eckstein, M. Martin and W. Anschutz, 2.75-2.89(1H, -dt,J14,3.5,4-CHH),3.68-3.79(1H,m,7-CH), Annafen,1971,748,207.6.44-6.47 (1 H, m, ArH), 6.65 (1 H, s, C==CH-),6.89 (1 H, d, J2, 13 J. R. Hawke, M. Guadliana and K. Desai, J. Org. Chem., 1982, 47, ArH) and 7.45 (1 H, d, J 1, ArH); m/z 276 (M+),258,201, 152, 5019; E. W. Colvin and B. J. Hamill, J. Chern.SOC.,Perkin Trans. 1, 108,81,55 and 41. 1977,869. 14 D. F. Taber, R. E. Ruckle and M. J. Hennesey, J. Org. Chern., 1986, 51, 4077. 2-(4-t-But~~~ldimethylsiloxybutylidene)-7-hexyloxepan-3-~~ne15 K. Dietrich and R. W. Hoffmann, Tetrahedron Lett., 1985, 26, 6325.14d.-To a solution of the phosphonate 3f (39 mg, 0.127 mmol) 16 A. B. Smith, K. J. Hale and J. P. McCauley, Tetrahedron Lett., 1989,in tetrahydrofuran (2 ml) at 0°C under nitrogen was added 30, 5579. sodium hydride (100%; 4.6 mg, 0.19 mmol). The mixture was 17 W. E. Truce and T. C. Klingler, J. Org. Chem., 1970,35, 1834. stirred for 30 min after which 4-(t-butyldimethylsiloxy)butanal 18 J.-L. Fabre, M. Julia and J.-N. Verpeaux, Tetrahedron Lett., 1982,23, Paper 0/03687K Received 10th August 1990 Accepted 5th September 1990