Chemistry of ketene acetals. Part 9. A simple lsquo;one-potrsquo; synthesis of 4-hydroxy-delta;-lactones and 5,6-dihydro-2-pyrones from 1,1-dimethoxypropene and beta;-oxy aldehydes

摘要

J. CHEM. SOC. PERKIN TRANS. I 1988 Chemistry of Ketene Acetals. Part 9.t A Simple 'One-Pot' Synthesis of 4-Hydroxy-Wactones and 5,6-Dihydro-2-pyrones from 1,I -Dimethoxypropene and p-Oxy Aldehydes Rob G. Hofstraat, Jos Lange, Hans W. Scheeren," and Rutger J. F. Nivard Laboratory of Organic Chemistry, Catholic University, Toernooiveld, 6525ED Nijmegen, The Netherlands Protected j3-oxy aldehydes react easily with 1,I -dimethoxypropene (la) in the presence of ZnCI, to give 2,2-dimethoxyoxetanes. Hydrolysis of these oxetanes and deprotection of the latent hydroxy function in a one-pot procedure gives 4-hydroxy-amp;lactones in moderate to good yields. Starting with p-oxy aldehydes having an a-branched side chain and defined stereochemistry, amp;lactones with completely defined stereochemistry can be synthesized.Dehydration of the hydroxy lactones with concentrated sulphuric acid gives easy access to 5,6-dihydro-2-pyrones. The usefulness of this route is demonstrated in the synthesis of a simple, optically active 5,6-dihydro-2-pyrone (37). amp;Lactones are versatile, synthetic intermediates and are widespread in Nature; y-lactones occur preferentially in plants and 6-lactones in animal products.' Some amp;lactones are significant in insect behaviour and recently there has been a lot of synthetic effort concerning the synthesis of these phero- mones.3-5 However, general synthetic routes to 6-lactones are relatively scarce and most syntheses that have been published use strongly basic conditions and yield 5,6-dihydro-2- pyr~nes.~-~A relatively mild, basic method was presented by Giese et ul.," who used radical C-C bond formation as the critical step.Paterson et ul." used the Lewis acid-catalysed reaction of ketene bis-trimethylsilyl acetals with a-chloro sulphides as the key reaction. However, the products of the latter procedure were also transformed into 5,6-dihydro-2- pyrones in order to reduce the number of diastereoisomeric products. In previous work l2 we showed that hydroxy substituted y-lactones can easily be obtained from ketene acetals (1) and a-oxygenated aldehydes or ketones (Scheme 1,n = 0, X = Ac). In order to extend this strategy we undertook an investigation into +R' MeC=C(OMe12 iii. iv3 R3 Scheme 1.Reagents: i, cat; ii, H,Of; iii, deprotection of 0-X;iv, Hf; v, dehydration the synthetic applications of reactions between P-oxygenated carbonyl compounds and ketene acetals (1). These would give access to 4-hydroxy-S-lactone derivatives. Elimination of the 4-hydroxy function might then allow the synthesis of substituted 5,6-dihydro-2-pyrones (Scheme 1, n = 1). t Part 8. R. G. Hofstraat, H. W. Scheeren, and R. J. F. Nivard, J. Chem. Soc., Perkin Trans. 1, 1985, 561. We now present a mild, acidic route to 4-hydroxy-3-methyl-6-lactones and their corresponding 5,6-dihydro-2-pyrones based on readily available P-oxygenated aldehydes and ketene acetals. Synthesis of P-Oxygenated Aldehydes.-First, we conc-entrated on the synthesis of P-hydroxy aldehydes since we expected P-hydroxy ketones lacking an activating a-substituent to be unreactive.13 Since P-hydroxy aldehydes are very labile compounds, readily dehydrating to the corresponding a,p- unsaturated aldehydes, most synthetic routes provide p-hydroxy aldehydes in a protected form.The protection of the hydroxy group is, moreover, necessary, in order to avoid reaction between the free hydroxy group and the ketene acetal (1). Two methods are known to us which deliver directly protected compounds in a one-step synthesis. Tsumara et aZ.I4 described the synthesis of 3-acetoxypropanal (2) from propenal, acetic acid, and barium acetate uia a Michael addition reaction. Reaction of propenal under the described conditions gave compound (2) in an overall yield of 43 after careful distillation.A further study of the method showed not only that sodium acetate could be used instead of barium acetate but also that the formyloxy-and propionyloxy-analogues of compound (2) could be similarly prepared from formic acid and propionic acid, respectively. This method enabled us to synthesize 3-acetoxybutanal(3) and the P-acetoxy ketone (4), in yields of 5 and 5amp;54, respectively. 2- Methylpropenal was, however, entirely unreactive under these conditions. The low yield in the case of (3) and the non-reactivity of the methyl substituted propenal probably reflect the greater stability of a disubstituted over a monosubstituted double bond. 0-COMeI R'MeC=C(OMe), R2-CH-CH2-C -R II 0 =(1)a;~' H (2) R2 = R3 = H b;R' = Me (3) R2 = Me, R3 = H (4)R2 = H.R3 = Me OSiMe,I Ph-CH-CH-C H 0 I Et (5) J. CHEM. SOC. PERKIN TRANS. I 1988 Table 1. I R2peox R5 R' R2xx"eOH R5R2CH-CH(R5)-CHO Ketene R2 R5 X acetal R' R2 R5 Yield" R2 R5 Yield" (2) H H Ac (la) (21) H H (3) Me H Ac (la) (5) Ph Et SiMe, (la)(15) Ph Me CH(Me)OEt (la) (28) H Ph (15) Ph Me CH(Me)OEt (lb) (31) Me Ph (16) c-Hex Me CH(Me)OEt (la) (29) H c-Hex (17) Pr' Me CH(Me)OEt (la) (30) H Pr' (35) Me H CH(Me)OEt (la) " Yield in based on the aldehyde. 'Diastereoisomeric mixture. 'One diastereoisomer. H Me Me Me Me 50 61' 12' 4v 44' (22) H (25) Me (27) Ph (37) Me H H Et H 30 28 70' 38 Yamamoto and co-workers l5 described a synthesis of p-0-x silyloxy ketones from benzaldehyde or substituted benzalde- I hydes.Although the scope of this reaction is limited with respect R2-CH-CH-C02Me to the starting aldehydes, it is still an attractive method since it delivers the products in a single step from the readily available tie silyl enol ethers of ketones. By this route, benzaldehyde and the silyl enol ether of butanal in acetonitrile were pressurised in the (6) R2 = Ph. X=H (7) R2 = c-Hex, X=Hpresence of ZnC1, to 12 kbar for 96 h at 50"C to give a mixture containing ca. 75 of the I)-silyloxy aldehyde (5). Bulb-to-bulb (8) R2 = Pri, X=H distillation afforded compound (5) in a yield of 3amp;35 based (9) R2 = Ph. X = CH(Me1OEton benzaldehyde, as a 1 :1 diastereoisomeric mixture.Attempts (10) R2 = c-Hex, X = CH(Me)OEtto synthesize an analogue of (5) using cinnamaldehyde as the starting compound failed. (11) R2 = Pti, X = CH(Me1OEt Since both direct methods had drawbacks, Tsumara's being 0-C(Me OEtof limited scope and Yamamoto's leading to 1:1 diastereoiso- -v meric mixtures, we investigated others. R2-CH-CH-CH-R4 Four more laborious methods of potentially broader scope for the synthesis of (protected) P-hydroxy aldehydes have been Me published. First, the imine anion route as originally conceived by Wittig and co-workers l6 and second, an approach based on (121 R2 = Ph. R4 = CH20H the chemistry of dihydrothiazoles as pursued by Meyerset af." (131 R2 = c-Hex. R' = CH20H In our hands both these methods failed as a convenient syn- (14) R2 = Pri, R4 = CH,OH thesis of P-hydroxy aldehydes when we used simple aldehydes as (151 R2 = Ph, R' = CHO starting compounds.* The third method for the synthesis of P-(161 R2 = c-Hex.R4 = CHOoxygenated aldehydes is based on the selective reduction of suitable, protected P-hydroxy esters as for instance demon- (171 R2 = Pri, R4 = CHO strated by Corey et all8 The fourth method is based on 1,3- dithiane chemistry as developed by Masamune and co-The pure threo compound (6)was isolated by crystallisation workers. g from light petroleum22 of a 3: 1 threo-erythro rnixture.,l We have concentrated on the third method since stereo- Compounds (7) and (8) were obtained as 19:l threo-erythro selective methods for the synthesis of P-hydroxy esters have mixtures and were used without further purification.The recently been described by us and A priori, the use hydroxy function was protected as an acetal with ethyl vinyl This functionality of these compounds implies the synthesis of amp;-lactones with ether according to the method of T~fariello.'~ defined stereochemistry at the 5-and 6-position. Thus, threo p-appeared to be perfectly stable under the applied reaction hydroxy esters (6)-(8) were chosen as the starting compounds. conditions. Reduction of these esters gives aldehydes with an a-branched Reduction of the ester function in (9) with di-isobutyl- side-chain. Previous results suggested that reaction with a aluminium hydride (DIBAH) in dichloromethane at -78 "C ketene acetal should give a threo configuration around the 3- according to the method of Keck et gave a mixture and 4-positions of the product after hydrolysis.'l Hence, 6-containing starting material, the corresponding alcohol (12), lactones with entirely defined stereochemistry might be and little of the desired aldehyde.? Scolastico and co-workers 24c synthesized. showed that reduction of an ester to the alcohol using LiAlH, followed by a Collins oxidation to afford the aldehyde delivers slightly better yields than selective reduction of the ester with * Hydrolysis according to the method of Dauben 16' of the P-hydroxy DIBAH at -90 "C.Hence, we decided to circumvent the imine obtained from 2-methylpropanal and N-ethylidenecyclohexyl- DIBAH reduction.amine resulted in a mixture of the starting hydroxy imine and the or$-unsaturated aldehyde. By following the method of Meyers using butanal, we could isolate the MOM-protected P-hydroxy aldehyde, 7 Careful investigation of the literature indicated that reduction of an albeit in very low yield (ca. 10);reduction of the dihydrothiazole to the ester with DIBAH is a delicate reaction, for which various solvents, e.g. thiazolidine with aluminium amalgam appeared in our hands not to be hexane, toluene, dichloromethane and various reaction tempera-straightforward. tures, e.g. -78 "C, -90 "C, -100 "C are used; see ref. 24. J. CHEM. SOC. PERKIN TRANS. I 1988 Reduction of compounds (9)--(11) with LiAIH, in ether was straightforward and gave the alcohols (12)-(14) in good yield.Oxidation of the alcohols to aldehydes (15)-(17) was investigated with the alcohol (12) both by a modification of the Collins oxidation 26 and by the dimethyl sulphoxide (DMS0)-oxalyl chloride oxidation as described by Swern." Both methods gave the desired aldehyde (15) but since the Swern oxidation is easier to perform and gives slightly better yields we continued to use it. Aldehydes (15)-(17) were obtained in good yield via this method. Synthesis of 4- Hydroxy-6-lactones and 5,6-Dihydro-2-pyrones.-The protected aldehydes thus obtained were con- verted with the ketene acetals (la) and (lb) into 4-hydroxy lactones and 5,6-dihydropyrones (see Scheme 1) and a survey of the results is given in Table 1.A ZnCl, catalysed reaction of compound (2) with the ketene acetal (la) in acetonitrile and at room temperature gave, instead of the expected products, rapid dimerisation of (la): probably ZnC1, catalyses the elimination of acetic acid from (2), and (la) dimerises readily under the influence of protonic acids. How- ever, using bornyloxyaluminium dichloride (BAD) 28 and dichloromethane at low temperature, compound (2) was converted into a product which, when isolated at room temperature in the presence of the catalyst, appeared to be the 2,2-dimethoxytetrahydropyran (19): its 'H n.m.r. spectrum H I MeCO-0-CH2-C H2-C -0 Me#OMe H OMe (18) 0-COMe OH I I R2-CH-CH2-C -CH-C02Me R 2 OH M eg R ''3 Me (20) R2 = R3 = H (21) R2 H (23) R2 = Me, R3= H (24) R2 = Me R2aMe (221 R2 = H (25) R2 = Me showed no signals characteristic of 3-H in 2,2-dialkoxyoxetanes in the range 2.5-2.9 p.p.m.14 The formation of compound (19) may be explained by a shift of the acetoxy group, as already noted in the reactions of analogous a-acetoxy aldehydes 28c with compound (la) (Scheme 2).However, hydrolysis of the crude reaction product at -10"C in a two-phase system, dichloro- methane-water, gave compound (20) in good yield as an 8: 1 threo-erythro mixture, indicating that the oxetane (18) is the initially formed product. Although compound (20) could be obtained analytically pure in small amounts via bulb-to-bulb distillation, purification is rather tricky since elimination of acetic acid and subsequent dehydration during distillation is a substantial problem. Consequently, in a further experiment we pursued the reaction route with the crude product (85-90).2317 OMe OMe I .I 0-COMe 0-C-OMe 0-COMe 0-+C-OMe LI II 7 1 I1 C H 2-C H 2-C- C-H CH2-CH2-C-C-H II II H Me H Me 11 OMeOMe 0' MeCO-7 +?-OMeI -I Me CH.,-CHq-C-C-H I cl I0-COMe H Me Scheme 2. Saponification of the protecting acetoxy group and the methyl ester of compound (20) with 30 KOH proceeded with little elimination of the acetoxy group, and careful acidification with 30 sulphuric acid to pH 2 gave the 4-hydroxy-6- lactone (21) (75-80) together with a very little of the 5,6-dihydropyrone (22). Reaction of compound (3) with ketene acetal (la) under the same conditions as used in the reaction of (2) gave compound (23) in good yield.Since the crude product was sufficiently pure (ca.90), the deprotection was carried out without purification. After acidification (30 sulphuric acid) a mixture containing compounds (24) and (25) in a ca. 1:1 ratio was isolated. Since (24) could not be obtained completely free from (25), the mixture was dehydrated with sulphuric acid at 0 "C to give (25) in 55-60 yield after work-up and bulb-to-bulb distillation. Analogously, (21) afforded (22) in similar yield. As expected, compound (4) failed to react with compound (la) both in refluxing acetonitrile and with ZnC1, catalysis. Since reaction of the diastereoisomeric mixture (5) with (la) and subsequent hydrolysis2' gave a complex mixture of 6- lactones (26), dehydration was carried out directly in a Dean- Stark apparatus with benzene and toluene-p-sulphonic acid to give the 5,6-dihydropyrone (27) as a 1 :1 diastereoisomeric mixture 60 yield based on (5).Reaction of the pure threo aldehyde (15) and the almost (95) pure threo aldehydes (16) and (17) with (la) in acetonitrile with ZnC1, catalysis and at room temperature gave the corresponding 2,2-dimethoxyoxetanes which were not isolated but directly hydrolysed ' to the 4-hydroxy-6-lactones phxxMepEt hqMe Et OH (26) (27) Mebsol;bsol;" n M e" OH (28) R' s Ph (291 R' I c-Hex (301 R' = Pti using THF and hydrochloric acid (18) (Scheme 1, n = 1, R3 = H, R5 = Me). In this way compounds (15) and (16)gave a 4 :1 diastereoisomeric mixture of F-lactones.Crystallization of the lactones from hexane-thy1 acetate in the case of (16) afforded the major diastereoisomer (29) pure and in moderate yield. The main product from (15), the lactone (28), was obtained as a solid 4: 1 mixture of diastereoisomers. Reaction of the aldehyde (17) with (la) and subsequent hydrolysis gave the main diastereoisomer (30) by purification by m.p.1.c. from the 3: 1 reaction mixture of diastereoisomers. Compound (15) reacted with (lb) in acetonitrile at 50deg;C in the presence of ZnC1, to give, after hydrolysis and crystallization, (31) in low yield. The low yield of (31) compared with (28) possibly arises as a result of the lower reactivity of (lb) relative to (la).Structural assignments for the major isomers (28), (29), (30), and (31) were based on 'H n.m.r. spectral results; they are in agreement with the stereochemical expectations based on oxetane f~rmation.~' For all these lactones the (-10 Hz) 5-H,6- H coupling constants indicate a trans axial disposition of these protons. This corresponds with the threo configuration present in the preceding aldehydes. The small 4-H, 5-H coupling constants for the lactones (28), (29), and (30) point to a cis equatorial disposition for 4-H. For the lactone (31) 4-H is expected to have a trans axial disposition as a result of strong coupling with 5-H (J4,5 -10 Hz). Finally the small coupling constants for 3-H,4-H in the lactones (28), (29), and (30) allow no discrimination between a trans equatorial or a cis axial position for 3-H.On account of the expected stereochemistry in the reaction of the aldehydes (15), (16), and (17) with (la) the major diastereoisomers of (28), (29), and (30) should have a threo configuration * at C-3 and C-4. Consequently, 3-H should have a trans equatorial disposition. The observed steric relationship between 4-H and 5-H can be rationalised in terms of complexation of zinc chloride with the aldehyde oxygen and the oxygen of the P-oxy substituent in compounds (15), (16), and (17). As illustrated in (I), formation of the most stable trans oxetanes from such aldehydes and (la) is Me favoured from the Re side of the aldehydes.For the reaction of the ketene acetal (lb), having two methyl groups, it appears from models that oxetane formation from the Re side is less favourable than from the Si side since it leads to strong steric interaction between a methyl group of the ketene acetal and the bulky R2 group. The oxetane formation with the ketene acetal (lb) is more difficult and needs stronger reaction conditions. Synthesis of a Chiral 5,6-Dihydro-2-pyrone.-Finally we attempted the synthesis of optically active 5,6-dihydro-2- pyrones starting with a chiral P-hydroxy ester. Recently, Seebach and co-workers 28 described an enantioselective * It has been demonstrated that under the applied reaction conditions aldehydes having an a-branched side chain can be selectively converted into trans oxetanes with (la).These trans oxetanes yield rhreo p-hydroxy esters after hydrolysis. See ref. 22. J. CHEM. SOC. PERKIN TRANS. I 1988 preparation of S-( + )-P-hydroxy esters from the corresponding P-keto esters by yeast reduction. We followed this method using the keto butyrate (32).Yeast reduction gave the optically active alcohol (33), as described, in a yield of 61 and with an e.e. of 84 +36.6 (c 4.5, CHCl,). Protection with ethyl vinyl ether and subsequent reduction with LiAlH, gave the protected diol (34) in good yield. Oxidation of (34)with DMSO and oxalyl chloride proceeded well and gave the aldehyde (35) in a yield of 75 based on (33). Reaction of (35) with (la) in acetonitrile at room temperature with ZnC1, catalysis was complete within 0.5 h.The product of this reaction was not isolated but directly hydrolysed with THF and hydrochloric acid (18) to give the 4-hydroxy lactone (36). This was dehydrated, without purification, with di-isopropyl ether and 0 OH-II Me-C--CH,-CO,Et Me-CH-CH2-C0,Et S (+I (32I (331 Q -CH( Me IOEt M e-CH-CH2-RL S (+I (31) RL = CH,OH (35) RL = CHO toluene-p-sulphonic acid in a Dean-Stark apparatus to give a crude product containing ca. 50 of (37). It was isolated in a moderate yield after m.p.1.c. purification using cyclohexane- ethyl acetate (3:l). The specific rotation a;' was +160deg; (c 0.81, CHCl,); the 'H n.m.r. spectrum of (37) in the presence of an optically active shift reagent Eu(hfc), showed an e.e.of 8amp;85. Although the method needs to be optimized, the synthesis of (37) shows that the route described has considerable potential in that the chirality present in the starting P-hydroxy ester is maintained during the formation of a 5,6-dihydro-2- pyrone (37). Experimental General Methods.--'H N.m.r. spectra were recorded on a Varian T60 Mz,a Hitachi Perkin-Elmer R-24B 60 Mz or a Bruker WH90 Mz spectrometer and for compounds (a),(29), and (30) a Bruker WM 500 Mz spectrometer, using CCl, or CDCl, with THS as internal reference. Mass spectra were measured with a Varian SM1-B double focussing mass spectrometer or with a VG 7070E mass spectrometer. Elemental analyses were performed by Mr.P. van Galen (Microanalytical Department of our University). Other general methods were described previously. 13b*21 Compounds (7)-49) were syn-thesized as reported.,' The silyl enol ether of butanal was prepared as described by House et aZ.,29 b.p. 42-52"C/70 mmHg (lit.,29 52-42 "C/75 mmHg). J. CHEM. SOC. PERKIN TRANS. I 1988 3-Acetoxypropanal (2).-A mixture of propenal (56 g, 1.0 mol), glacial acetic acid (120 g, 2.0 mol), and sodium acetate (8.2 g, 0.1 mol) was stirred at room temperature for 16 h after which most of the residual acetic acid was removed under reduced pressure. The remaining oil was treated with ether (100 ml), the precipitate (sodium acetate) filtered off, and the filtrate concentrated under reduced pressure. The remaining oil was distilled at low pressure, to yield the title compound (2) (50.2 g, 4373, b.p.354OoC/0.5 mmHg; GH(CCl,) 1.98 (3 H, s, OCOMe), 2.67 (2 H, d t, J6 and 1.5 Hz, 2-H), 4.22 (2 H, t, J6 Hz, 3-H), and 9.60 (1 H, t, J 1.5 Hz, 1-H). 3-Acetoxybutanal(3).-A mixture of but-2-enal(70 g, 1 .O mol),glacial acetic acid (1 20 g, 2.0 rnol), and sodium acetate (8.2 g, 0.1 mol) was stirred at 50deg;C for 72 h. After cooling to room temperature the reaction mixture was treated as described for compound (2) to yield the title compound (3)(6.5 g, 5), b.p. 45- 50 OC/O.4 mmHg; 6H(cc14) 1.30 (3 H, d, J 6 Hz, 4-H), 1.95 (3 H, s, OCOMe), 2.56 (2 H, d t, J 6 and 1.5 Hz, 2-H), 5.20 (1 H, br sextet, J 6 Hz, 3-H), and 9.52 (1 H, t, J 1.5 Hz, 1-H).2-Ethyl-3-phenyl-3-trimethylsilyloxypropan-l-al(5).-ZnC12 (0.5 ml of a saturated solution in acetonitrile) was added to a mixture of benzaldehyde (1.90 g, 18 mmol) and 1-trimethylsilyloxybut-1-ene(3.20 g, 22 mmol) in acetonitrile (1.5 ml). The mixture was placed in a 7.5 ml Teflon ampoule, and acetonitrile (a few drops) was added to fill the ampoule completely. The closed ampoule was placed in a one-wall piston-in-cylinder high-pressure apparatus 30 and pressurised at 12 kbar and 50 "C for 96 h. After depressurising and cooling of the reaction mixture to room temperature triethylamine (TEA) (0.5 ml) was added and the solvent evaporated. Pentane (ca. 40 ml) was then added until a light precipitate formed. This was filtered off and the filtrate evaporated to give the crude product which upon bulb-to-bulb distillation afforded a (1 :1) diastereoisomeric mixture of the title compound (5) (1.55 g, 34), b.p.95-105 "C/0.6 mmHg (Found: M+ + 1, 251.1115; C,,H,,O,Si requires M + 1,251.1 108); m/z 251 (M + 1,1279, 235 (M -Me, 16), 205 (18), 180 (22), 179 M -CH(Et)CHO, 1001, 177 (18), and 161 (M -OSiMe,, 20); GH(CDC1,) 0.04 (9 H, br s, OSiMe,), 0.84 and 0.87 (3 H, 2 t, J9 Hz, Me), 1.16-2.00 2319 pure products as (1 :1) diastereoisomeric mixtures. The following compounds were prepared in this way. 3-(l-Ethoxyethoxy)-2-methyl-3-phenylpropan-1-01 (12) (7.2 g, 76), b.p. 100-1 10 "C/0.4 mmHg (Found: M+ + 1, 239.1652. C14H22O3 requires M + 1, 239.1647); mjz (c.i.) (M + 1, l), 221 (M -OH, 2), 193 (M -EtO, 3), 149 M -OCH(Me)-OEt, 401, 131 M -OCH(Me)OEt, -H20, 221, and 73 C(Me)OEt+, 1001; v,,,.(CHCl,) 3 600-3 300 (OH), 3 140- 2 860 (CH), 1 510-1 370 (CH), and 1 170-1 010 cm-' (CO); G,(CDCl,) 0.71 and 0.73 (3 H, 2d, J7 Hz, 2-Me), 0.93 and 1.22 (3 H, 2t, J 7 Hz, OCHMe), 1.24 and 1.31 (3 H, 2d, J 7 Hz, OCHMeOEt), 1.78 (1 H, br s, OH), 1.76-2.31 (1 H, m, 2-H), 2.99-3.98 (4 H, m, OCH,Me, 3-H), 4.22 and 4.45 (1 H, 2d, J 9 Hz, 1-H), 4.44 and 4.58 l H, 2q, J5 Hz, OCHMeOEt, and 7.31 (5 H, br s, Ph).3-Cyclohexyl-3-( 1 -ethoxyethoxy)-2-methylpropan-1-01 (13) (7.0 g, 72), b.p. 120-130 "C/0.5 mmHg (Found: M+ -OEt, 199.1699. C12H23O2 requires 199.1698); m/z(c.i.) 245 (M' + 1, l), 199 (M -OEt, 74), 155 M -OCH(Me)OEt, 1003, 153 (18), and 137 (30); v,,,.(CHCI,) 3 600-3 300 (OH), 3 020- 2 860 (CH), 148k-1 380 (CH), and 1 170-970 cm-' (CO); GH(CDC1,) 0.84-2.09 21 H, m, c-Hex-H, 2-H, 2-Me, OCH(Me)OCH,Me, 2.59 (1 H, br t, J 6 Hz, OH), 3.20-4.03 (5 H, m, 1-H, 3-H, OCH,Me), and 4.60 and 4.72 l H, 2q, J 5 Hz, OCH(Me)OEt .3-(l-Ethoxyethoxy)-2,4-dimethylpentan-1-01 (14) (5.95 g, 7373, b.p. 65-48 "C(0.5 mmHg (Found: M+ + 18, 222.2084. C11H,,O, requires M + 18, 222.2069); m/z (c.i., NH,) 222 (M + 18,673,176 (72), 159 (M -OEt, 81), 150 (loo), and 133 (32); v,,,.(NaCl) 3 610-3 160 (OH), 3 000-2 780 (CH), 1 450 (CH), 1 380 (CH), and 1 180-990 cm-' (CO);G,(CDCl,) 0.73-1.39 15 H, m, 2,4-Me, 5-H, CH(Me)OCH,MeJ, 1.56-2.09 (2 H, m, 2-H, 4-H), 2.49 (1 H, br s, OH), 3.21-3.73 (5 H, m, 1-H, 3- H, OCH,-Me), and 4.62 and 4.73 (1 H, 2q, J 6 Hz, OCHMe).Synthesis of the Aldehydes (15)--(17): General Procedure.- The aldehydes (15)--(17) were prepared as described by Swern et a1.,26 using DMSO and oxalyl chloride in dichloromethane; the procedure was executed on a 20 mmol scale. The following compounds were prepared in this way. 3-( 1 -Ethoxyethoxy)-2-rnethyl-3-phenylpropan-1 -a1 (15) (4.1 g, 8673, b.p. 100-1 10 OC/O.5 mmHg; m/z (c.i.) 221 (M -(2H,m,CH2Me),2.36-2.67(1H,m,2-H),4.86and5.04(1H,2 d, J7 and 5 Hz, 3-H), 7.32 (5 H, br s, Ph), and 9.65 and 9.69 (1 H, 2 d, J 3 and 4 Hz, 1-H). Synthesis of the Alcohols (12j-(14): General Procedure.- Trifluoroacetic acid (1 ml) was carefully added to a vigorously stirred mixture of ethyl vinyl ether (30 ml) and a P-hydroxy ester (40 mmol) cooled to 0 "C.The mixture was stirred at 0 "C for 2 h and then left at 5 "C for 16 h; TEA (7 ml) was then added and the excess of ethyl vinyl ether was evaporated. Di-isopropyl ether (100 ml) was added and the mixture was washed with water (2 x 30 ml) and brine (30 ml). The combined aqueous layers were extracted with di-isopropyl ether (25 ml) and the combined ethereal layers were dried (Na2S04). After evaporation of the solvent crude products were isolated 92 pure by g.c. The crude products were dissolved in dry ether (40 ml) and dropped into a suspension of LiAlH, (1.6 g, 42 mmol) in dry ether (200 ml) at room temperature. After the addition was complete the mixture was refluxed for 4 h and allowed to come to room temperature.The excess of LiAlH, was then destroyed carefully by addition of water (ca. 3 ml) and potassium hydroxide (15 solution; ca. 4 ml). The resulting suspension was filtered and the remaining salts were washed with ether (2 x 15 ml). The combined filtrates were dried (Na,SO,) and evaporated to yield the crude products which upon distillation via a short Vigreux column (10 x 1 cm) or bulb-to-bulb distillation afforded the Me, 2), 191 (M -OEt, 9), 147 M -OCH(Me)OEt, 591,135 (16), 119 (27), and 73 (100); v,,,~(CHCl,) 3 100-2 8 10 (CH), 1 730 (CO), 15amp;1370 (CH), and 1 170-1 ooo cm-' (co); 6,(CDC13) 0.86 and 0.87 (3 H, 2d, J7 Hz, 2-Me), 0.91 and 1.19 (3 H, 2t, J7 Hz, OCH,Me), 1.23 and 1.25 (3 H, 2 d, J7 Hz, OCHMe), 2.56 3.64 (3 H, m, 2-H, OCH,Me), 4.394.84 (2 H, m, 1-H, OCHMe), 7.31 (5 H, br s, Ph), and 9.83 (1 H, d, J3 Hz, CHO).3-Cyclohexyl-3-(l-ethoxyethoxy)-2-methylpropan-1-a1 (16) (3.95 g, 81), b.p. 100-1 10 "C/0.3 mmHg (Found: M+ -OEt, 197.1537. C12H2,0, requires 197.1542); m/z (ci, NH,) 260 (M + 18,4), 216 (ll), 215 (20), 214 (44), 198 (l3), 197 (A4-OEt, loo), 196 (15), 188 (ll), 170 (18), 153 A4-OCH-(Me)OEt, 311, and 73 (20); v,,,~(CHCl,) 3 010-2 810 (CH), 1725 (CO), 1450 (CH), and 1200-1070 cm-' (CO); 6,(CDC1,) 0.82-2.07 20 H, m, c-Hex-H, 2-Me, OCH-(Me)OCH,Me, 2.44-2.84 (1 H, m, 2-H), 3.33-3.76 (3 H, m, 1- H, OCH2Me),4.51-4.82 l H, m, OCH(Me), and 9.76 (1 H, d, J 2 Hz, CHO.3-(l-Ethoxyethoxy)-2,4-dimethylpentan-l-al(17)(3.0 g, 7479, b.p. 72-76"C/0.6 mmHg; (Found: M+ + 18, 220.193. Cll- H,,O, requires M + 18,220.191);m/z(ci, NH,) 220 (M + 18, 19), 174 (32), 157 (M -OEt, loo), 148 (36), and 131 (23); vmax.(CHC1,) 3 04amp;2 800 (CH), 2 710 (CH), 1720 (CO), 1460-1 380 (CH), and 1 130-1010 cm-' (co); 8H(CDC13) 0.761.40 15 H, m, 5-H, 2-Me, 4-Me, OCH(Me)OCH,Me, 1.53-2.05 (1 H, m,4-H), 2.42-2.82 (1 H,m, 2-H), 3.24-3.73 (3 H, m, 3-H, OCH,Me), 4.51-4.78 (1 H, m, OCHMe), and 9.73 (1 H, br d, J 1.8 Hz, CHO). Methyl 5-Acetoxy-3-hydroxy-2-methylpentanoate (20).-BAD (0.55~solution in ether; 1.0 ml) was added to a stirred mixture of compounds (2) (4.65 g, 40 mmol) and (la) (4.45 g, 44 mmol) in dry dichloromethane (15 ml) at -78 "C.After 30 min the mixture was allowed to warm to -10 "C when water (15 ml) was added. This mixture was stirred vigorously for 1 h at -10 "C and then allowed to come to room temperature. The dichloromethane layer was separated and the aqueous layer was extracted with dichloromethane (3 x 20 ml). The combined dichloromethane layers were dried (Na,SO,) and evaporated to yield a crude mixture containing ca. 90 of the title compound (20). Bulb-to-bulb distillation, using a container and receivers previously treated with base (TEA), afforded compound (20) as an 8: 1 diastereoisomeric mixture (6.9 g, 84), b.p. 90- 100 "C/0.5 mmHg (Found: C, 52.85; H, 7.9. C,H160, requires C, 52.93; H, 7.90); vmax,(CC14) 3 660-3 220 (OH), 3 010- 2 840 (CH), 1 750-1 710 (CO), 1450 and 1 380 (CH), and 1 235 cm-' (CO); 6H(cc14) (major isomer) 1.20 (3 H, d, J7 Hz, 2- Me), 1.73 (2 H, d t, J 6 and 6 Hz, 4-H), 2.05 (3 H, s, OCOMe), 2.30-2.77 (1 H, m, 2-H), 2.83 (1 H, br s, OH), 3.67 (3 H, br s, CO,Me), 3.95 (1 H, d t, J6 and 4 Hz, 3-H), and 4.18 (2 H, br t, J 6 Hz, 5-H).Tetrahydro-4-hydroxy-3-methyl-2-pyrone(21).-Compound (20) (4.1 g, 20 mmol) was added to a vigorously stirred solution of KOH (30 solution; 15 ml) and the mixture was stirred at room temperature for 16 h. It was then carefully acidified to pH 1 with sulphuric acid (30 solution; ca. 14 ml) and its temperature allowed to rise 30 "C. After almost complete evaporation of the water the resulting mixture was extracted with dichloromethane (5 x 30 ml).The combined dichloro- methane extracts were dried (Na,SO,) and evaporated to give a crude product which upon bulb-to-bulb distillation afforded the title compound (21) as an 8: 1 diastereoisomeric mixture (1.56 g, 60), b.p. 120-130 "C/0.3mmHg; m/z (ei) 130 (M', 5479,112 (M -H20,65), 102 (M -CO, 14), 74 (M -Camp;O, 25), and 71 (M -C0,Me 100); v,,,.(CHCl,) 3 600 (OH), 3 650-3 250 (OH), 3 010-2 850 (CH), 1 730 (CO), 1 400 (CH), and 1 280- 1080 cm-' (CO); GH(CDC1,) 1.30 and 1.36 (3 H, 2d, J 7 Hz, 3-Me), 1.58-2.71 (3 H, m, 5-H, 3-H),3.49 (1 H, br s, OH), 3.71- 3.94 (1 H, m, 4-H), and 4.09-4.64 (2 H, m, 6-H). 5,6-Dihydro-3-methyl-2-pyrone(22).-Compound (21) (1.3 g, 10 mmol) was added dropwise to concentrated sulphuric acid (5.0 g) at 0 "C to give after 10 min a dark brown mixture which was stirred for 45 min.It was then poured onto ice (50 g) and carefully neutralised with sodium hydrogen carbonate (8.5 g). Dichloromethane (20 ml) was added and the organic layer was separated. The aqueous layer was extracted with dichlorometh- ane (2 x 20 ml) and the combined dichloromethane layers were dried (Na,SO,) and evaporated. Bulb-to-bulb distillation afforded the title compound (22) (0.71 g, 56), b.p. 42-44 "C/2 mmHg; m/z (ei) 112 (M, loo), 97 (M -Me, 5), 84 (M -CO, 18), and 68 (M -C02, 11); vmax.(CC14) 3 040-2 880 (CH), 1 730 (CO), 1470-1 360 (CH), and 1 130 cm-' (CO); G,(CDCl,) 1.91 (3 H, q, J2 Hz, 3-Me), 2.21-2.61 (2 H, m, 5-H),4.35 (2 H, t, J 6 Hz, 6-H), and 6.61 (1 H, m, 4-H).(25).-BAD (0.55~5,6-Dihydro-3,6-dimethyl-2-pyrone solu-tion in ether; 0.5 ml) was added to a stirred mixture of compounds (3) (2.0 g, 15.4 mmol) and (la) (1.75 g, 17 mmol) in dichloromethane (5 ml) at -78 "C and the mixture was stirred for 30 min. It was then treated as described for compound (20). After work-up the product was directly saponified, cyclised, and dehydrated as described for compounds (21) and (22), J. CHEM. SOC. PERKIN TRANS. I 1988 respectively, without purification of the intermediate products. After final work-up the crude product (750 mg) was purified by bulb-to-bulb distillation to yield the title compound (25) (610 mg, 28), b.p. 75-90 "C/ 0.6 mmHg (lit.,4 55-60 "C/0.2 mmHg, m.p. 31-33 "C) (Found: C, 65.85; H, 8.1.Calc. for C,H,,02: C, 66.65; H, 7.99); m/z (ei.) 126 (M+,85), 111 (M -Me, lo), 82 (M -CO,, loo), and 54 (25); vmax.(CCI,) 3 010-2 810 (CH), 1 720 (CO), 1 380-1 330 (C=C), and 1 250 and 1 120 cm-' (CO); amp;,(CDCI,) 1.41 (3 H, d, J 6 Hz, 6-Me), 1.91 (3 H, q, J 1.8 Hz, 3-Me), 2.20-2.40 (2 H, m, 5-H), 4.52 (1 H, br sextet, J 6 Hz, 6-H), and 6.47-6.64 (1 H, m, 4-H). 5-Ethyl- 5,6-dihydro- 3 -meth yl-6-phen yl- 2-pyrone (27).-ZnC1 ,(saturated solution in acetonitrile; 0.5 ml) was added to a stirred mixture of compounds (5) (1.15 g, 4.6 mmol) and (la) (1.65 g, 16 mmol) in acetonitrile (5 ml) at room temperature. The mixture was stirred for 2 h and work-up was performed as previously described.21 Toluene (100 ml) and toluene-p-sulphuric acid (ca.100 mg) were added to the crude product and the mixture was refluxed for 16 h in a Dean-Stark apparatus. After cooling, the mixture was extracted with water (2 x 25 ml) and brine (25 ml). The combined aqueous layers were extracted with toluene (25 ml) and the combined organic layers were dried (Na,SO,), and evaporated to yield a crude product (1.4 g). M.p.1.c. of a part of the crude product (500 mg) using silica gel and hexane- di-isopropyl ether (5:3) afforded a 1:1 diastereoisomeric mixture of the title compound (27) (250 mg, 70), b.p. 125- 145"C/0.4 mmHg (Found: M+ + 1, 217.1231. C14H160, requires M + 1, 217.1228); m/z (ci) 217 (M + 1, loo), 199 (M -17, 24), 171 (M -45, 13), 139 (M -Ph, 16), and 110 (M -Ph, -Et, 30); vmax.(CC14) 3 100-2 840 (CH), 1725 (CO), 1610-1480 (CH), and 1280-1 200 cm-' (CO); 6,- (CDCl,) 0.68-1.53 (5 H, m, Et), 1.99 (3 H, q, J 1.5 Hz, Me), 2.27-2.82(1 H,m,5-H),5.09and5.58(lH,2d,JlOand4Hz,6-H), 6.56 and 6.87 (1 H, 2dq, J2.5 and 1.5 Hz, J6 and 1.5 Hz, 4- H), and 7.36 (5 H, br s, Ph).Synthesis of 4-Hydroxy-3-methyl-6-lactones (28)-(30): General Procedure.-ZnCI, (saturated solution in acetonitrile; 0.5 ml) was added to a stirred mixture of the appropriate alde- hyde, (15)-(17), (2 mmol) and ketene acetal (la) (310 mg, 3 mmol) in acetonitrile (1 ml) at room temperature. The mixture was stirred for 1 h and TEA (0.5 ml) and THF (15 ml) were added. The mixture was cooled to -78 "C and a solution of toluene-p-sulphonic acid (15 mg) in MeOH (1.5 ml) was added.The mixture was kept at -78 "C for 0.5 h and then allowed to warm to room temperature. Hydrochloric acid (18.5 solution; 10 ml) was added and the mixture was stirred for 36 h. Brine (20 ml) was then added and the ethereal layer was separated. The aqueous layer was extracted with ether (4 x 25 ml) and the combined ethereal layers were washed with brine (25 ml), dried (Na,SO,), and evaporated. The resulting faint yellow oils in the case of compounds (28) and (29) contained a 4:l diastereo- isomeric mixture of amp;lactones according to capillary g.c. Crystallisation from hexane-di-isopropyl ether-ethyl acetate afforded the major diastereoisomer in the case of compound (29) in pure form.In the case of compound (30) the resulting oil contained a 3 :1 diastereoisomeric mixture of amp;-lactones and the major isomer was purified via m.p.1.c. using silica gel and cyclohexane-ethyl acetate (3:1). The following compounds were prepared in this way. 3,4,5,6-Tetrahydro-4-hydroxy-3,5-dimethyl-6-phenyl-2-pyrone (28).A 4: 1 diastereoisomeric mixture (270 mg, 61), m.p. 134- 137deg;C (hexane-ethyl acetate) (Found: C, 70.5; H, 7.3; M+, 220.1097. C13H1603 requires C, 70.89; H, 7.32; M, 220.1099); m/z (e.i.) 220 (M,273, 118 (16), 117 (12), and 107 (PhCHOH, 100); vmaX.(CHC1,) 3 600 (OH), 3 62amp;3 300 (OH), 3 110- 2 860 (CH), 1 735 (CO), 1 470 (CH), and 1 370 cm-' (CH); 6, J. CHEM. SOC. PERKIN TRANS.I 1988 (500 Mz, CDC1,) 0.92 and 0.97 (3 H, 2d, J7 Hz, 5-Me), 1.36 and 1.41(3 H, 2d, J7 and 7.2 Hz, 3-Me), 2.02 (1 H, d, J4.3 Hz, OH), 2.10-2.20 (1 H, m, 5-H), 2.76 (1 H, dq, J7.2 and 2.7 Hz, 3-H), 2.87 (1 H, dq, J 7 and 4.2 Hz, 3-H), 3.92 (1 H, ddd, J4.2,4.3 and 3.6 Hz, 4-H), 3.99 (1 H, br, 4-H), 4.74 and 5.27 (1 H, 2d, J 11 Hz, 6-H), and 7.36 (5 H, m, Ph). 6-Cyclohex~v1-3,4,5,6-tetrahydro-4-hydroxy-3,5-dimethyl-2-p-yrone (29). (182 mg, 40), m.p. 124-126 "C (hexane-ethyl acetate) (Found: C, 68.65; H, 9.75; M+ + 1, 227.1648. C13H2203 requires C, 68.99; H, 9.80; M + 1, 227.1647); m/z (c.1.) 227 (M + 1,23), 209 (M -OH, 13), 191 (12), 153 (M -C3H402, loo), 143 (M -c-Hex, 13), and 135 (20); v,,,.(CHCI,) 3 640-3 300 (OH), 3 020-2 860 (CH), 1 740 (CO), 1450 (CH), 1400-1 370 (CH), and 1260-1 180 cm-' (CO); 6,(500 Mz, CDCl,) 1.06 (3 H, d, J7 Hz, 5-Me), 1.27 (3 H, d, J 7 Hz, 3-Me), 1.10-1.90 (11 H, complex, c-Hex-H), 1.85 (1 H, d, J4.3 Hz, OH), 2.00 (1 H, ddq, J3.1, 10.1 and 7 Hz, 5-H), 2.68 (1 H, dq, J 3.8 and 7 Hz, 3-H), 3.70 (1 H, d with fine spl, J 10.1Hz, 6-H), and 3.76 (1 H, dd after exch.OH with CD,OD, J 3.1 and 3.8 Hz, 4-H). 3,4,5,6- Tetrahydro-4- hydroxy-6-isopropyl-3,5-dimethyl-2-pyrone (3q). (165 mg, 4473, m.p. 67-69deg;C (hexane-ethyl acetate) (Found: C, 64.35; H, 9.7; M+ + 1, 187.1330. CI0Hl8O3 requires C, 64.49; H, 9.74; M + 1, 187.1334); m/z (c.i.) 187 (M + 1, 24), 169 (M -OH, 12), 143 (M -Pr', 8), 126 (M -OH, -Pr', 15), 113 (M -Pr', -2 Me, loo), and 69 (15); 6H(500 Mz, CDC1,) 0.97, 1.06, and 1.09 (9 H, 3d, J 6.9 Hz, Pr' and 5-Me), 1.29 (3 H, d, J6.9 Hz, 3-Me), 1.88-1.98 (2 H, m, CHMe,, 5-H), 1.97 (1 H, d, J 4.8 Hz, OH), 2.69 (1 H, dq, J 6.9 and 3.9 Hz, 3-H), 3.74 (1 H, dd, J2.2 and 10.2 Hz, 6-H), and 3.77 (1 H, dd after exch.OH with CD,OD, J 3.8 and 3.9 Hz, 4-H). 3,4,5,6-Tetrahydro-4-hydroxy-3,3,5-trimethyl-6-phenyl-2-pyrone (31).-ZnCl, (saturated solution in acetonitrile; 0.5 ml) was added to a stirred mixture of compounds (15) (475 mg, 2 mmol) and (1b) (465 mg, 4 mmol) in acetonitrile (2 ml), and the mixture was heated at 50 "C for 16 h. TEA (0.5 ml) was added and the temperature was allowed to come to room temperature. The mixture was treated as described for compounds (30)-(32).The crude product was crystallized using hexane-di-isopropyl ether-ethyl acetate to yield the title compound (31) (55 mg, 12"/,), m.p. 152-154 "C (hexane+thyl acetate) (Found: C, 71.85; H, 7.8; M+ + 1,235.1332. C14H1803 requires C, 71.77; H, 7.74; M + 1, 235.1334); m/z 235 (M + 1, 6), 217 (M -OH), 7), 171 (M -3Me, -H20, 16), 145 (13), 139 (M -Ph. -H20, 25), 119 (78), 118 (22), and 117 (100); v,,,.(CHCI,) 3 700 (OH), 3600 (OH), 3 580-3360 (OH), 3 140-2 860 (CH), 1 725 (CO), 1 530 (CH), 1430 (CH), and 1 280-1 160 cm-' (CO); GH(CDCl,) 0.93 (3 H, d, J6 Hz, 5-Me), 1.40and 1.46 (6 H, 2s, 3-Me), 1.83 (1 H, br d, J5 Hz, OH), 2.04- 2.38 (1 H, m, 5-H), 3.61 (1 H, dd, J 11 and 6 Hz, 4-H), 4.74 (1 H, d, J 11 Hz, 6-H), and 7.36 (5 H, br s, Ph).(S)-(+)-5,6-Dihydro-3,6-dimethyl-2-pyrone (37).-The pyrone (37)was synthesized from the 3-hydroxybutanoate (33) which was prepared by yeast reduction of the corresponding p-keto butanoate (32) as described by Seebach et al.,,* yield 61, b.p. 74-76 "Cjl5 mmHg, a;' +36.6" (c 4.1 in CHCl,) (lit.,28 b.p. 71--73 "C/12 mmHg, a;' +37.2" (c 1.3 in CHCl,). The alcohol (34) and the aldehyde (35) were syn- thesized as described for compounds (12) and (15). The products were distilled and identified on the basis of their 'H n.m.r. spectra: 3-(l-Ethoxyethoxy)butan-l-ol(34)(8673, b.p. 98-100 "C115 mmHg; G,(CDCI,) 1.09-1.37 9 H, m, 4-H, OCH(Me)OCH,- Me, 1.58-1.83 (2 H, m, 2-H), 2.29 and 2.96 (1 H, br t, J6 Hz, OH), 3.31-4.16 (5 H, m, 1-H, 3-H, OCH,Me), and 4.69 and 4.73 (1 H, 2q, J 5 Hz, OCHOEt).3-(l-Ethoxyethoxy)butan-l-a1(35)(82), b.p. 95-105 "C/14 mmHg; G,(CDCl,) 1.09-1.37 9 H, m, 4-H, OCH(Me)OCH,- Me, 2.49-2.69 (2 H,m, 2-H), 3.32-3.78 (2 H,m, OCH,Me), 4.24 (1 H, br septet, MeCHCH,), and 4.77 l H, br q,0CH(M e)O E t . The aldehyde (35) was allowed to react with the ketene acetal (la) as described for compound (15). The crude product was refluxed with di-isopropyl ether (50 ml) and toluene-p-sulphuric acid (100 mg) in a Dean-Stark apparatus for 16 h. After cooling to room temperature the di-isopropyl ether solution was washed with brine (3 x 20 ml), dried (Na,S04), and evap- orated to afford the crude product SO0 mg, prepared from 5 mmol of (35). This was purified by m.p.1.c.using silica gel and cyclohexane-ethyl acetate (3:l) to yield the pyrone (37) as a colourless oil (240 mg, 38), a;' + 160" (c 0.8 in CHCl,). A 'H n.m.r. spectrum in the presence of Eu(hfc), showed an e.e. of 80-85 (6-Me signal) indicating that the chirality was maintained during the reaction sequence. 'H N.m.r., mass, and i.r. spectra were identical with those of compound (25). References 1 G. Ohloff, in 'Progress in the Chemistry of Organic Natural Products,' ed. L. Zechmeister, Springer Verlag, Wien, 1978,vol. 35, p. 431. 2 J. M. Brand, J. Young, and R. M. Silverstein, in 'Progress in the Chemistry of Organic Natural Products,' ed. L. Zechmeister, Springer Verlag, Wien, 1980, vol. 37, p. 1. 3 W. H. Pirkle and P.E. Adams, J. Org. Chem., 1979, 44, 2169. 4 R. Bacardit and M. Moreno-Mafias, J. Chem. Ecol., 1983, 9, 703. 5 K. Mori and S. Senda, Tetrahedron, 1985,41, 541. 6 M. Pohmakotr and P. Jarupan, Tetrahedron Lett., 1985, 26, 2253. 7 R. W. Dugger and C. H. Heathcock, J. Org. Chem., 1980,45, 1181. 8 R. M. Carlson, A. R. Oyler, and J. R. Peterson, J. Org. Chem., 1975, 40, 1610. 9 N. C. Barua and R. R. Schmidt, Synthesis, 1986, 1067. 10 D. B. Gerth and B. Giese, J. Org. Chem., 1986, 51, 3726. 11 H. A. Khan and I. Paterson, Tetrahedron Lett., 1982, 23, 5083. 12 R. W. M. Aben, R. G. Hofstraat, and J. W. Scheeren, Recl. Trav. Chim. Pays-Bas, 1981, 100, 355. 13 J. W. Scheeren, R. W. M. Aben, P. H. J. Ooms, and R. J. F. Nivard, J. Org. Chem., 1977,42, 3128.14 R. Tsumara, M. Kanemura, and N. Ishii, Jap. Pat. Kokai 75 05.315, (Cl. 16B602, 21 Jan. 1975) (Chem. Abstr., 1975,83, P2753q). 15 Y. Yamamoto, K. Maruyama, and K. Matsumoto, J. Am. Chem. SOC.,1983, 105, 6963. 16 (a) G. Wittig, H. D. Frommeld, and P. Suchanek, Angew. Chem., 1963,75,978; (b)W. G. Dauben, G. H. Beasley, M. D. Broadhurst, B. Muller, D. J. Peppard, P. Pesnelle, and C. Suter, J. Am. Chem. SOC., 1975, 97,4793. 17 A. I. Meyers, J. L. Durandetta, and R. Munavu, J. Org. Chem., 1975, 40, 2025. 18 E. J. Corey and G. Schmidt, Tetrahedron Lett., 1979, 19, 2317. 19 (a)S. Masamune, H. Murase, N. Matsue, and A. Murai, Bull. Chem. SOC.Jpn., 1979,52, 135; (b) R.-T. Grobel and D. Seebach, Synthesis, 1977, 357. 20 C. H. Heathcock in 'Asymmetric Synthesis,' ed. J. D. Morrison, Academic Press, New York, 1984, vol. 3B, p. 111; A. I. Meyers, ibid., p. 213. 21 R. G. Hofstraat, H. W. Scheeren, and R. J. F. Nivard, J. Chem. SOC., Perkin 1, 1985, 561. 22 R. W. M. Aben and J. W. Scheeren, Synthesis, 1978, 401. 23 J. J. Tufariello and E. J. Trybulski, J. Org. Chem., 1974, 39, 3378. 24 (a) G. E. Keck, D. F. Kachensky, and E. J. Enholm, J. Org. Chem., 1985,50,4317; (b) R. W. Hoffmann and U. Weidmann, Chem. Ber., 1985, 118, 3966; (c) L. Banfi, A. Bernardi, L. Colombo, C. Gennari, and C. Scolastico, J. Org. Chem., 1984, 49, 3784. 25 R. Ratcliff and R. Rodehorst, J. Org. Chem., 1970, 35, 4000. 26 A. J. Mancuso and D. Swern, Synthesis, 1981, 165. 2322 J. CHEM. SOC. PERKIN TRANS. I 1988 27 (a) E. L. Eliel and D. Nasipuri, J. Org. Chem., 1965, 30,3812; (b) 29 H. 0.House, L. J. Czuba, M. Gall, H. D. Olmsteadt, J. Org. Chem., R. W. Aben and H. W. Scheeren, Synthesis, 1982,779; (c) P. Barbier 1969, 34, 2324. and C. Benezra, J. Org. Chem., 1983,48, 2705. 30 R. W. M. Aben and J. W. Scheeren, J. Org. Chem., 1987,52, 365. 28 D. Seebach, M. A. Sutter, R. H. Weber, and M. F. Zuger, Org. Synth., 1985, 63, 1. Received 3 1st March 1987; Paper 71596