Stereocontrolled homologation of 1,2 : 3,4-di-O-isopropylidene-alpha;-D-galacto-hexodialdo-1,5-pyranose to 7-deoxynonodialdose epimersviathiazole-aldehyde synthesis

摘要

J. CHEM. SOC. PERKIN TRANS. 1 1994 Stereocontrolled Homologation of 1,2 :3,4-Di-~-isopropyiidene-a-D-ga/acto-hexodialdo-I ,5-pyranose to 7-Deoxynonodialdose Epimers via Thiazole-Aldehyde Synthesist Alessandro Dondoni,*e8 Sandra lanellLb Ladislav Kniezo,8 Pedro Merino8 and Mario Nardelli $sb a Dipartimento di Chimica, Laboratorio di Chimica Organica, Universita degli Studi di Ferrara, Via L. Borsari 46, 1-44100 Ferrara, Italy lstituto di Chimica Generale, Universita degli Studi di Parma, Centro di Studio CNR per la Strutturistica Diffrattometrica, Viale delle Scienze 78, 1-43700 Parma, Italy The three-carbon chain elongation of the title dialdose has been carried out by two approaches employing thiazole-based reagents: (i) aldol condensation with the lithium enolate of 2-acetylthiazole; (ii) olefination with triphenyl(thiazol-2-ylcarbonylmethylene)phosphorane and 1,4-addition of benzyl oxide anion to the resultant vinyl ketone.The stereoselective reduction of the resultant (R) and (S) P-hydroxy ketones, followed by protection of the hydroxy groups as benzyl ethers, afforded four compounds consisting of the galactopyranosyl ring substituted at C-5 with stereoisomeric 1,3-bis( benzyloxy)propyl units bearing the thiazol-2-yl ring at the terminus of the chain. The unmasking of the formyl group from the thiazolyl ring to give 7-deoxynonodialdoses was carried out in two cases. The unequivocal assignment of the structures of two intermediates isolated in each route was established by X-ray room-temperature crystal-structure analyses.Recent reports from one of our laboratories have demonstrated application of the thiazole-aldehyde synthesis in carbohydrate chemistry. Based on this reaction, various methods have been developed for the chain elongation of sugar-derived aldehydes R-CHO (R = polyalkoxy chain) to give homologues bearing one, two, or three more carbon atoms. For example, 2-acetyl- thiazole (2-ATT, 1) and triphenyl(thiazo1-2-ylcarbonylmethyl-ene)phosphorane (ZTCMP, 2) have been used as three-carbon-atom units in synthetic routes to higher 3-deoxyaldos- 2-uloses and 2-ulosonic acids such as KD0,2 KDN,3and their epimers at C-4. The reagent 1acts via aldol condensation of its lithium enolate as a direct equivalent to pyruvaldehyde (route A), whereas phosphorane 2 affords, via Wittig olefination, an a,p-enone intermediate which then undergoes a Michael-type addition of an alkoxide anion (route B) (Scheme 1).These routes appeared to be complementary since they led to p-hydroxy and p-alkoxy ketones with opposite configurations at C-p. We now report application of routes A and B to 1,2: 3,4-di- 0-isopropylidene-a-D-galacto-hexodialdo-1,Spyranose 3 and show the stereoselective reduction of the resultant ketones 4 and 5 into four galactose derivates 6 bearing stereoisomeric 1,3-dialkoxy-3-(thiazol-2-yl)propylunits at C-5 (Scheme 2). The synthetic equivalence of compounds 6 to 7-deoxynono- dialdoses 7 is demonstrated by the aldehyde unmasking from the thiazole ring.The side-chain elongation of the dialdose 3 is of considerable importance4 since it provides an entry to biologically active higher sugars incorporating the 1,5-galacto- pyranosyl moiety.' Results and Discussion Homologation of the Dialdose 3.-Following route A, the generation of the lithium enolate of 2-ATT 1 in the presence of dialdose 3 at -50 "C in tetrahydrofuran (THF) using lithium t Thiazole-aldehyde synthesis: preparation of aldehydes from C-2-substituted thiazoles by thiazole-into-formyl conversion. 1Author to whom inquiries regarding the X-ray structure analysis should be addressed. 0 0 1 2 1piiz R*-nfThOHO R*-CHO + route 8 0 OR' 0 Scheme 1 3 4 R=H 6 R=Th 5 R=Bn 7 R=CHO Scheme2 (Th = thiazol-2-yl) tert-butoxide, afforded exclusively the aldol (R)-4(ds 2 95)6 which was isolated in 58 yield (Scheme 3).The R configura-tion at the newly formed stereocentre in this compound was established by X-ray crystallography of the 1,3-diol derived from it (see below). On the other hand, following route B, the dialdose 3 was initially treated with the phosphorane 2 in refluxing chloroform to give the vinyl ketone (E)-8 (85) together with a small amount of the isomer (Z)-8(not shown). The E configuration of the main olefin (E)-8 (coupling 1232 J. CHEM. soc. PERKIN TRANS. I 1994 Th4 1. 1 ii t Th S OBn Th R,OBn'r' Th S OBn Th RI.OBn GOB. T0-0E3n h0.0Bn (S,R )-6 Scheme 3 Reagents: i, 2-ATT (l),Bu'OLi; ii, DIBAL-H; iii, Me,amp; BH(OAc),; iv, 2-TCMP (2); v, BnONa constant of vinylic protons, J = 15.8 Hz) was expected on the basis of the stabilized nature of the phosphorus ylide 2 and the reaction conditions employed.' The Michael-type 1,4- addition of sodium benzyl oxide to (E)-8in THF at -50 "C was sufficiently diastereoselective to give rise to an 80:20 mixture of the epimers (29-5 and (R)-5which were individually isolated in 70 and 18 yield respectively.The X-ray structure determination of the major adduct (S)-5 demonstrated the S configuration at C-6 (see below). Hence the aldol condensation route A and the olefination-alkoxylation route B appeared quite efficient for the stereoselective installation of R p-hydroxy- and S p-benzyloxypropanoyl moieties at C-5 of the galactopyranosyl ring starting from the dialdose 3.A single transition-state model (Fig. 1) accounts for the above stereo- selective nucleophilic additions to both the aldehyde 3 and the olefin (19-8.Accordingly, attack of the nucleophile should take place on the face opposite to the plane of the pyranose ring of the aldehyde or alkene conformer as shown in Fig. 1. This model is reminiscent of the Cram open-chain model wherein the C=X double bond is flanked by the two least bulky groups attached to the adjacent centre.' Stereoselectivity according to a non-chelate model (in the Cram-Felkin sense) had been exhibited by the dialdose 3in reactions with other nucleophiles and in cycloaddition with dienes." On the other hand, the work on the internal asymmetric induction in Michael-type addition of heteronucleophiles to alkene sugars is much more scanty. 3~11 The p-hydroxy-directed diastereofacial reduction of the carbonyl group of (R)-4was then exploited to create a 1,3-diol unit with a new stereocentre in either configuration.The appropriate metal hydride reducing agent was easily chosen on the basis of previous work with this methodology.12 Thus, the reduction of aldol (R)-4 with diisobutylaluminium hydride DIBAL-H and tetramethylammonium triacetoxyborohydride Me,NBH(OAc), produced (ds 2 95 in both cases) syn-. Nu,' 3 X = 0: (euro;)a,X = CH-C(0)-Th Fig. 1 U A B Fig. 2 and anti-1,3-diol epimers, respectively, which were isolated as the 0-benzyl ethers (S,R)-6 (90) and (R,R)-6 (96).The structure of compound (R,R)-6 was established by X-ray crystallography (see below). The anti 1,3-diol unit in this compound was expected on the basis of a stereochemical model,I2 suggesting that the reduction of (R)-4 with the borohydride reducing agent l3 Me,NBH(OAc), should occur via intramolecular-hydride delivery in the chair-like chelate structure A involving an oxygen-boron bond (Fig. 2). On the other hand the syn-selectivity for the reduction of aldol (R)-4 with DIBAL-H is consistent with an external hydride attack on the half-chair chelate structure B involving an oxygen- J. CHEM. soc. PERKIN TRANS. 1 1994 aluminium bond. l4 It is worth mentioning that we have already exploited these hydroxy-directed stereocontrolled reductions of P-hydroxy ketones for the construction of I ,3-polyol chains.'' The P-benzyloxy group affected only rather weakly the asymmetric reduction of the carbonyl group of compound (S)-5. With either LiAlH, or DIBAL-H in the presence of lithium iodide (THF at -78 "C), the reaction was moderately selective (ds 7678 by 'H NMR spectroscopy) and gave rise to a mixture of syn and anti alcohols which were isolated as the 0-benzyl ethers (R,S)-6 (72) and (S,S)-6 (20). The assignment of the configuration to the major isomer (R,S)-6 was based on the assumption l6 that the reduction of (S)-5 occurred with syn selectivity via an external hydride delivery on the less hindered face of the carbonyl conformer shown in Scheme 2.The stabilization of this conformer by P-chelation of the carbonyl and ether oxygens with lithium cation can be assumed. On the other hand, the reduction of (R)-5under the above conditions was essentially unselective, giving rise to a mixture of alcohols in 55 :45 ratio. After benzylation, the NMR spectrum of the mixture superimposed on that of a mixture of bis ethers (S,R)-6and (R,R)-6.This correlation confirmed that the configuration of the newly formed stereocentre of the minor product obtained from the dialdose 3 uia the Wittig-Michael route B is identical with that of the major product formed uia the aldol condensation route A. Having prepared four galactose derivatives bearing stereo- isomeric thiazol-2-yl-l,3-dibenzyloxypropylunits at C-5, their equivalence to nonodialdoses was demonstrated by the formyl group unmasking of two of them.Thus, the application of the original one-pot thiazole-to-formyl deblocking protocol ' to compounds (R,R)-6 and (R,S)-6 afforded the corresponding protected nonodialdoses (R,R )-7 and (R,S)-7 in good isolated yields (Scheme 4). It is worth pointing out that further chain OHC R.,OBn OHC R OBnb Y-s OBnbsol;I-* (R R )-7 (R, 5)-7 Scheme 4 Reagents and conditions: i, MeI, MeCN, reflux; then NaBH,, MeOH, 0 "C; then HgCl,, aq. MeCN, room temp. elongation of these compounds is feasible by either process (A and B) or any other thiazole-based methodology.' Crystal Structure of Ketone (29-5and Bis ether (R,R)-6.Fig. 3 shows the ORTEP '* drawings of the two molecules studied by X-ray diffraction, and Table 1 compares the most relevant structural parameters of these compounds. As shown in Scheme 3, both C(6) and C(4) in the side-chain of bis ether (R,R)-6 have the R configuration, while the C(6) of (S)-5 has the S configuration. In both compounds the galactopyranosyl moiety shows the R configuration at C(7), C(11) and C(13) and Sat C(8) and C(10) according to the chirality of the common precursor D-galactose used in the syntheses.The absolute configuration of these stereocentres is in agreement with the Flack's index values (see Experimental section and Table 2). The C(3) C(7) carbon-atom chain is strictly planar in compound (R,R)-6,the maximum displacement from the least- squares plane being O.OlO(5) A for C(4).On the other hand, the same chain is deformed from planarity at the thiazole end in 1233 compound (S)-5 as it appears that C(3) is 0.568(3) A out of the least-squares plane through C(4), C(5), C(6) and C(7). This deformation is very likely to arise as a consequence of the n-conjugation between the heterocyclic ring and the carbonyl, as indicated by the small value 4.2(4)0 of the S-C(3)-C(4)-0(1) torsion angle. A value as large as 57.8(7)O is observed in compound (R,R )-6 where conformational freedom exists about the C(3)-C(4) bond. In both cases the orientation of the thiazole ring places the sulfur on the same side of the carbonyl oxygen. The contact distance between these atoms is shorter when the ring is conjugated with the carbonyl S oO(1) is 2.964(2) in (9-5 and 3.151(4) A in (R,R)-6.As expected, the thiazole ring is planar; n-conjugation with the carbonyl exerts some influence on the endocyclic bond distances not involving sulfur that become significantly longer, and on the exocyclic C(3)-C(4) bond that becomes shorter for compound (29-5. Unfortunately, the degree of accuracy in the analysis of (R,R)-6is much lower than that of (S)-5, so these differences cannot be discussed in more depth, although the observed trend is quite well defined. The conformation of the pyranose ring is a twist with two local pseudo-two-fold axes, one running along the mid-points of the C(7)-0(6) and C(lO)-C(ll) bonds and the other along the C(8) C(19) direction.The puckering parameters '' of the three rings of the sugar moiety, as set out in Table 3, are in acceptable good agreement for the two compounds. All the benzyloxy substituents in both compounds show extended conformations with the C(ar)-CH, bond antiperi- planar with respect to the 0-C (side-chain) bond. The conformation about the C(6)-C(7) bond is such as to have the 0(7)-C(6) bond of the 0(7)-benzyloxy substituent, antiperi- planar to 0(6)-C(7) in (R,R)-6 0(6)-C(7)-C(6)-0(7) = 174.1(4)', and synclinal 72.4(2)" in (29-5. Experimental M.p.s were taken using a Biichi 510 apparatus and are uncorrected. The 'H and 13C NMR spectra were recorded on a 300 MHz Gemini 300 Varian spectrometer unless otherwise stated. Chemical shifts are given in parts per million downfield from SiMe, as internal standard.J Values are given in Hz. IR spectra were recorded on a Perkin-Elmer Model 297 grating spectrometer. Elemental analyses were performed on a Model 1106 microanalyser (Carlo Erba). Optical rotations were measured at -20deg;C using a Perkin-Elmer Model 214 polarimeter, and are given in units of lo-' deg cm2 g-' .TLC was carried on glass slides precoated with silica gel (Merck Kieselgel 60 F254), and preparative chromatography on columns of silica gel (Merck 70-230 mesh). All experiments were carried out with freshly distilled and dried solvents. 6,7-Dideoxy- 1,2 :3,4-di-O-isopropylidene-8-(thiazol-2-yl)-a-~-galacto-oct-6-enodialdo-1,5-pyranose (@-8.-To a well stirred solution of 1,2:3,4-di-0-isopropylidene-a-D-galacto-hexodi-aldo-l,5-pyranose 2o 3 (2.48 g, 9.6 mmol) in CHCl, (100 cm3) was added triphenyl(thiazol-2-ylcarbonylmethylene)phosphor-ane 2 (4 g, 10.3 mmol) and the reaction mixture was stirred for 24 h at 50deg;C and then for an additional 60 h at room temperature.The solvent was evaporated off under reduced pressure and the residue was chromatographed (hexane-diethyl ether 4 :1) to give the alkenes (3-8 and (9-8. 2-8: (0.2 g, 673, oil (Found: C, 55.5; H, 5.7; N, 3.6. Cl,H21N06S requires C, 55.6; H, 5.8; N, 3.8); alD -129.7 (c 1.18, CHCl,); 6,(300 MHz; CDCl,) 1.32 (3 H, s), 1.34 (3 H, s), 1.49 (3 H, s) 1.57 (3 H, s), 4.37 (1 H, dd, J2.4 and 5.1), 4.63 (1 H, dd, J 1.9 and 7.9), 4.70 (1 H, dd, J2.4 and 7.9), 5.53 (1 H, ddd, J, 1.6, 1.9 and 7.1), 5.58 (1 H, d, J5.1), 6.53 (1 H, dd, J7.1and11.9),7.49(1H,dd,J1.6and11.9),7.68(1H,d,J3.0) 1234 J.CHEM. SOC. PERKIN TRANS. 1 1994 S C Fig. 3 ORTEP drawings of the molecules of compounds (a)(R,R)-6and (b)(S)-5, showing the atom labelling assumed for the crystal structure analysis. Ellipsoids at 50 probability level. and 8.02 (1 H, d, J 3.0); 6,(75.5 MHz; CDCl,) 24.10, 24.78, 25.76, 25.82, 66.46, 70.24, 71.15, 73.17, 96.56, 109.11, 109.57, 122.32, 126.84, 145.27, 149.40, 168.82 and 182.96. E-8:(3.0 g, 85), m.p. 140-141 "C (Found: C, 55.5; H, 5.9; N, 4.0); aD -119.0 (C 0.63, CHClJ; 6,(300 MHz; CDCl,) 1.01 (3H,s), 1.09(3H,s), 1.32(3H,s), 1.36(3H,s),3.81(1H,dd7J 2.2and7.8),4.13(1 H,dd,J2.4and4.9),4.40(1 H,dd,J2.4and 7.8), 4.54 (1 H, ddd, J2.1,2.2 and 3.9), 5.53 (1 H, d, J4.9), 6.56 (1 H, d, J3.0), 7.46 (1 H, d, J3.0), 7.52 (1 H, dd, J 15.8 and 3.9) and 8.04 (1 H, dd, J 15.8 and 2.1); 6,(75.5 MHz; CDCl,) 23.91, 24.17, 25.55, 25.61, 68.13, 70.68, 71.15, 72.78, 96.71, 108.37, 109.58, 125.30, 125.94, 144.71, 145.11, 168.83 and 181.70.6-0-Benzyl-7-deoxy- 1,2 :3,4-di-O-isopropylidene-8-(thiazol-2-yl)-~-~-glycero-~-galacto-octodialdo-175-pyranose(S)-5 and a-D-glycero-epimer (R)-5.-To a well stirred suspension of NaH (0.38 g of a 60 dispersion in mineral oil, 9.5 mmol) in THF (15 cm3) at room temperature was added anhydrous benzyl alcohol (1.08 g, 10 mmol). The mixture was refluxed for 30 min, then was cooled to -50 "C and a solution of enone (E)-8 (0.95 g, 2.59 mmol) in THF (40 cm3) was added at such a rate that the temperature inside the flask remained constant at -50 "C. After being stirred for 8 h at -50 "C, the reaction mixture was partitioned between saturated aq.NH,Cl and diethyl ether. The organic layer was dried, and evaporated J. CHEM. soc. PERKIN TRANS. 1 1994 Table 1 Comparison of selected bond distances (A),bond angles (") and torsion angles ("). Esds in parentheses 1.692( 12) 1.696(4) 1.386(6) 1.21 l(3) 1.430(6) 1.423(3) 1.424(7) 1.4233) 1.419(5) 1.424(3) 1.423(8) 1.438(3) 1.428(5) 1.442(3) 1.432(5) 1.429(3) 1.343( 13) 1.380(4) 1.289(11) 1.340(6) 1.482(10) 1.509(4) 1.510(9) 1.515(3) 1.542(9) 1.534(3) 1.517(9) 1.514(4) 1.522(9) 1.529(3) 1.533(8) 1.51 l(4) 90.7(4) 89.4(2) 10934) 108.6( 2) 106.9(3) 107.2(2) 113.3(3) 114.7(2) 1 11.2(6) 110.1(3) 117.6(10) 1 1 5.1(3) 126.7(6) 124.3(2) 1 1 1.0(4) 119.6(2) 105.9(4) 122.6(2) 110.2(4) 105.1(2) 106.1(4) 110.2(2) 114.4(5) 114.2(2) 109.3(4) 1 09.0(2) 104.2(4) 104.3(2) 109.3(4) 110.7(2) 107.2(5) 109.1(2) 114.3(7) 113.1(2) 114.2(4) 115.1(2) 106.7(3) 1 07.5( 2) 104.3(4) 103.3( 2) 109.0(4) 108.9(2) 110.5(4) 1 08.5( 2) 1 1 1.8(4) 113.2(2) 1 04.8(4) 104.0(2) 106.2(4) 108.8(2) 12 1.6(6) 119.1(3) 67.2(7) 75.1(5) 79.5( 2) -165.2(4) -168.1(2) -147.2(5) 147.0(2) -62.2(7) -177.2(2) -179.1(5) 153.1 (2) under reduced pressure. Chromatography (silica gel; hexane- diethyl ether 4: 1) afforded the p-hydroxy ketones (R)-5 and (S)-5.(R)-5:(0.086 g, 18), oil (Found: C, 60.7; H, 6.3; N, 3.1. C24H29N0,S requires C, 60.6; H, 6.15; N, 2.95); alD-27.9 (C 0.38, CHCl,); 6,(300 MHz; C@6) 1.28 (3 H, s), 1.35 (3 H, s), 1.45 (3 H, s) 1.52 (3 H, s), 3.47 (1 H, dd, J7.8 and 17.0), 3.64(1 H,dd, J3.7and17.0),3.82(1 H,dd, J1.7and9.0),4.26 (1 H, dd, J2.4and 5.0), 4.41 (1 H, ddd, J3.7, 7.8 and9.0), 4.45 (1 H, dd, J 1.7 and 8.0), 4.59 (1 H, dd, J2.4 and 8.0), 4.66 (1 H, d, J 10.9), 4.67 (1 H, d, J 10.9), 5.48 (1 H, d, J 5.0), 7.18-7.28 (5 H, m), 7.63 (1 H, d, J 3.2) and 7.98 (1 H, d, J 3.2); 6,(75.5 MHz; C6D6) 24.18, 24.70, 25.79, 25.85, 41.42, 69.13, 70.48, 70.84,70.95,73.55, 74.30,96.56, 108.82, 109.28, 126.22, 127.84, 128.36, 128.54, 138.91, 145.07, 168.19 and 193.07 (S)-5: (0.86 g, 70), m.p.120-121 "C (Found: C, 60.4; H, 6.4; N, 2.9); a,, -87.5 (C 0.72, CHCl3); 6amp;00 MHz; C6D6) 1.32 (3 H, s), 1.36 (3 H, s), 1.48 (3 H, s), 1.54 (3 H, s), 3.47 (1 H, dd, J3.4 and 16.8), 3.70 (1 H, dd, J9.3 and 16.8), 4.06 (1 H, dd, J 1.8 and 7.4), 4.34 (1 H, dd, J2.4 and 5.1), 4.38 (1 H, dd, J 1.8 1.701(5) 1.707(3) 1.457( 1 1) 1.426(9) 1.425(3) 1.423(5) 1.417(3) 1.426(6) 1.428(3) 1.404(5) 1.410(3) 1.403(7) 1.399(3) 1.428(6) 1.406(3) 1.301(9) 1.294(4) 1.467( 10) 1.463(4) 1.519(8) 1.516(3) 1.50l(9) 1.526(3) 1.484( 10) 1.492(4) 1.510(6) 1.504(3) 1.50l(7) 1.5oq4) 1.528(7) 1.49 l(4) 112.4(4) 108.2(3) 106.5(2) 110.0(3) 110.8(2) 114.6(4) 1 15.2(2) 108.8(7) 110.4(3) 1 1 1.6(4) 114.9(2) 121.7(5) 120.7(2) 114.6(6) 1 17.8(2) 1 15.2(5) 112.2(2) 113.3(5) 1 12.4(2) 107.4(4) 106.9(2) 109.3(4) 1 09.0( 2) 113.9(5) 112.9(2) 103.1(5) 104.8(2) 112.0(5) 110.2(2) 110.2(5) 108.7(2) 103.1(4) 104.5(2) 108.5(3) 109.3(2) 115.8(4) 114.2(2) 104.9(5) 104.2(2) 110.9(4) 110.3(2) 109.6(4) 11 1.3(2) 114.4(5) 114.6(2) 110.5(3) 11 1.3(2) 120.3(7) 121.9(3) -179.4(5) 177.4(2) 174.5(4) -49.8(2) -44.9(6) -4332) 1 65.7(4) 169.9(2) -80.0(5) -72.9(2) and 8.0), 4.44 (1 H, ddd, J 3.4, 7.4 and 9.3), 4.63 (1 H, dd, J 2.4 and 8.0), 4.69 (1 H, d, J 11), 4.89 (1 H, d, J ll), 5.62 (1 H, d, J5.1), 7.18-7.43 (5 H, m), 7.66 (1 H, d, J3.2) and 7.99 (1 H, d, J 3.2); 6, (75.5 MHz; C6D,) 24.12, 24.76, 25.74, 25.81, 40.23, 69.24, 70.57, 70.93, 71.15, 73.97, 75.67, 96.58, 108.86, 109.63, 126.22, 127.56, 128.30, 128.36, 139.37, 145.01, 168.10 and 192.38.(6S,8S)-6,8-Di-O-benzyl-7-deoxy-1,2 :3,4-di-O-isopropylid-ene-8-(thiuzol-2-yl)-D-threo-a-D-galacto-octopyranose(S,S)-6 and Epimer (R,S)-6.-A well stirred solution of compound (S)-5 (0.2 g, 0.42 mmol) and LiI (0.064 g, 0.46 mmol) in anhydrous diethyl ether (1 5 cm3) was cooled to -78 "C and DIBAL-H (1 cm3 of a 1.5 mol dmP3 solution in toluene, 1.5 mmol) was added. After the mixture had been stirred for 1 h at -78 "C,ethyl acetate (2 cm3) was added and the reaction mixture was partitioned between saturated aq. sodium hy- drogen carbonate and diethyl ether. The organic layer was dried over sodium sulfate and the solvent was evaporated under reduced pressure.The residue (0.2 g) was shown by 'H 1236 J. CHEM. soc. PERKIN TRANS. I 1994 Table 2 Experimental data for the X-ray analyses C31H37N07S C24H29N07SM 566.7 475.6 Space group P3J1 p212121./A 10.31O( 5) 22.453(3)blA 10.3 1 O(5) 12.151( 1) 52.101(10) 9.220(1) $$3 4796(3) 25 15.5(5) z 6 4 DJMg m-3 1.177 1.256 Reflections for lattice parameters: number 27 30 8 range/rdquo; 13/27 20138 F(ow 1806 1008 TIK 292(2) 292(2)Crystal sizelmm 0.13 x 0.37 x 0.77 0.34 x 0.39 x 0.44 p/mm-rsquo; 1.223 1.502 Scan speedldeg min-rsquo; 3-12 3-12 Scan width/rdquo; 1.2 + 0.35 tan 8 1.2 + 0.35 tan 6 8-range for intensity collection/rdquo; 4.9170.1 3.9170.2 h-range 10112 -27/27k-range -12/0 0114 I-range -63/10 -7111 Standard reflection -3 23 3 235 Intensity variation none none No.of measured reflections 9745 5307 No. of unique reflections 6102 4783 R(int) 0.0573 0.0141 No. of reflections used in the refinementrsquo; (N) 6074 4778 No. of reflections omitted (A/c 5) 28 5 No. of reflections with I 241) 2074 3040 No. of refined parameters (P) 329 307 Extinction parameter (SHELXL),bg O.O065( 8) 0.0066(2)Max. LS shift to esd ratio -0.044 -0.001 Min/max height in final Ap map e -0.1710.26 -0.13/0.14 wR2 = ~W(AF~)~/CW(F,~)~rsquo;~~ 0.1424 0.0790 wR2 for all data 0.2336 0.0892 S2 = Fw(AF2)rsquo;/(N -P)rsquo;rdquo; 1.104 0.977 R1 = Z~AFl/Z~F,~for I 20(I) 0.0621 0.0364 R1 for all data 0.1779 0.0671 Flack x parameter O.Oo(5) -0.02(2) g (w = 1/a2(F:) + (gP)rsquo; where P = (F,rsquo; 0.0871 0.0363 a Refinement on F2 for all reflections except those flagged for possible systematic errors.The observed threshold I 2a(I) is used only for calculating R(obs),etc. given here for comparison with refinements on F. lsquo;Fc* = kF, 1 + 0.001 Fc2A3/sin(2s)-rsquo;/4. Table 3 Puckering parameters for the sugar moieties Ring OW, C(7), C@),C(lO), C(1I), C(3) 92 0.607(4) A 0.625(2) A 93 -0.132(4) 8, 0.101(2) A QT 0.622(4) 8, 0.633(2) A cp -149.0(4)0 -145.8(2)rdquo; 0 102.3(4)rdquo; 99.2(2)rdquo; conformation half chair half chair Ring C(9), W), C(8), C(W, O(3) 9 0.306(5) A 0.305(2) 8( cp 16 1.8(9)rdquo; -163.2(4)rdquo; conformation half chair half chair Ring C(12), 0(4), C(l l), C(13), O(5) 4 0.282(4) A 0.300(2) A cp 29.4(8)rdquo; 9.q4)O conformation envelope-half chair half chair-envelope NMR spectroscopy to be a mixture of two diastereoisomers in a another 12 h.The reaction mixture was poured into water 78 :22 ratio. This material was dissolved in dimethylformamide (30 an3) and extracted with diethyl ether. The organic layer (6 an3),cooled to 0 ldquo;C and NaH (50 mg of a 60 dispersion in was dried over sodium sulfate, and evaporated under reduced mineral oil, 1.25 mmol) was added. After 20 min at 0 ldquo;C the pressure. Chromatography (silica gel; hexaneaiethyl ether 7 :3) (stirred) reaction mixture was treated with benzyl bromide afforded compounds (S,S)-6and (R,S)-6. (0.09 g, 0.53 mmol) and was stirred at room temperature for (S,S)-6:(0.048 g, 2073, oil (Found: C, 65.2; H, 6.6; N, 2.6.J. CHEM. soc. PERKIN TRANS. 1 1994 C,,H,,NO,S requires C, 65.5; H, 6.7; N, 2.6); alD -36.4 (C 0.45, CHCl3); dH(300 MHz; C$6) 1.28 (3 H, s), 1.31 (3 H, s), 1.45 (3 H, s), 1.50 (3 H, s), 2.05 (1 H, ddd, J2.8, 10.9 and 14.1), 2.28 (1 H, ddd, J2.7,10.3 and 14. l), 3.87 (1 H, dd, J 1.8 and 7.6), 4.08 (1 H, ddd, J2.7,7.6 and 10.9), 4.21 (1 H, dd, J 1.8 and 7.9), 4.28(1H,dd,J2.4and5.0),4.29(1H,d,J11.4),4.39(1H,d,J 11. l), 4.53 (1 H, dd, J2.4 and 7.9), 4.55 (1 H, d, J 1 1.4), 4.91 (1 H, d,J11.1),5.08(1H,dd,J2.8and10.3),5.59(1H,d,J5.0),7.19-7.37 (1 H, m) and 7.73 (I H, d, J 3.2); dc(75.5 MHz; C6D6) 24.16,24.76,25.76,25.81,38.53,70.60,70.89,71.14,71.49,72.07, 73.38,75.06,75.71,96.62,108.80,109.57,119.32,127.56,127.95, 128.19,128.31,128.47,128.61,138.36,139.64,142.88and174.66. (R,S)-6: (0.172 g, 72), oil (Found: C, 65.6; H, 6.6; N, 2.5); ff~ -38.8 (C 0.85, CHCl,); dH(300 MHz; C6D6) 1.30 (3 H, s), 1.34 (3 H, s), 1.37 (3 H, s), 1.50 (3 H, s), 2.35 (2 H, m), 3.69 (1 H, m), 4.00 (1 H, dd, J 1.9 and 7.6), 4.30 (1 H, dd, J2.4 and5.0),4.34(1H,d,Jl1.0),4.38(1H,dd,J1.9and8.0),4.53 (2 H, s), 4.57 (1 H, dd, J 2.4 and KO), 4.58 (1 H, d, J 1 1 .O), 5.19 (1 H, dd, J6.9 and 7.2), 5.59 (1 H, d, J5.0), 7.23-7.48 (11 H, m) and 7.80 (1 H, d, J 3.2); dc(75.5 MHz; Camp;) 24.17, 24.72, 25.66,25.80,38.50,65.76,70.50,70.88,71.17,71.60,71.96,73.44, 76.12, 96.50, 108.71, 109.31, 119.59, 127.53, 127.94, 128.21, 128.32, 128.42, 128.63, 138.13, 139.62, 142.68 and 174.00.(40 an3),stirred for 10 min, and then allowed to warm to room temperature. Water (20 an3)was added, and the two liquid layers were separated. The aqueous layer was extracted with diethyl ether (4 x 25 an3).The combined organic layers were dried over sodium sulfate, and the solvent was evaporated under reduced pressure. Chromatography (silica gel; hexane-diethyl ether 1: 1) yielded the aldol adduct (R)-4 (2.23 g, 58, ds 95) as an oil (Found: C, 52.9; H, 6.2; N, 3.9. C17H23- N07S requires C, 53.0; H, 6.0; N, 3.6); ffD -60.5 (c 0.39, CHCl,); dH(300 MHz; CDCl,) 1.27 (3 H, s), 1.35 (3 H, s), 1.44 (3 H, s), 1.49 (3 H, s), 3.35 (1 H, dd, J8.7 and 17.4), 3.55 (1 H, d, J 5.6), 3.62 (1 H, dd, J2.7 and 17.4), 3.73 (1 H, dd, J 1.9 and 8.7), 4.30(1 H,dd, J2.4and5.1),4.40(1 H,dddd, J2.7,5.2,8.7and 8.7), 4.51 (1 H, dd, J 1.9 and KO), 4.63 (1 H, dd, J2.4 and 8.0), 5.51 (1 H, d, J5.1), 7.69 (1 H, d, J 3.2) and 8.01 (1 H, d, J3.2); 6,(75.5 MHz; CDCl,) 24.17, 24.66, 25.70, 25.76, 42.63, 66.68, 69.39,70.56,70.74,73.62,96.58,108.83, 109.56, 126.61,145.18, 167.54 and 194.34.(6R,SS)-6,8-Di-O-benzyl-7-deoxy-1,2:3,4-di-O-isopropyl-idene-8-( thiazol-2-yl )-a-D-erythro-D-galact o-octopyranose (S,R)-6.-The method described above for the reduction of compound (S)-5, but without LiI, was applied to compound (R)-4 (100 mg, 0.26 mmol) to give, after column chromato- 6,s-Di-0-benzyl- 1,2 :3,4-di-O-isopropylidene-P-~-erythro-~-graphy (silica gel; hexane-diethyl ether 7 :3) pure title compound galacto-nonodialdo- 1,5-pyranose (R,S)-7.-A solution of the thiazole derivative (R,S)-6 (0.15 g, 0.26 mmol) in freshly distilled acetonitrile (5 an3)was treated with methyl iodide (2.2 g, 15.5 mmol) and the reaction mixture was refluxed under nitrogen for 24 h.The solvent was evaporated under reduced pressure, and the residue was dissolved in methanol (10 cm3) and treated with NaBH, (50 mg, 1.3 mmol). After the mixture had been stirred for 15 min at room temperature it was evaporated under reduced pressure and the residue was par- titioned between CH,Cl, and saturated aq. sodium hydrogen carbonate. The organic layer was separated, dried over sodium sulfate, and the solvent was distilled under reduced pressure.The residue was dissolved in acetonitrile (2 an3)and then treated with a solution of HgCl, (90 mg, 0.33 mmol) in a 4: 1 mixture of acetonitrile-water (3 cm3). After being stirred for 15 min at room temperature the mixture was distilled to dryness under reduced pressure, the residue was treated with aq. potassium iodide (10 cm3), and the mixture was extracted with chloroform (3 x 10 cm3). The organic layers were combined, dried over sodium sulfate, and evaporated under reduced pressure. Chromatography (silica gel; hexane-diethyl ether 3 :2) yielded the aldehyde (R,S)-7(0.1 1 g, 82) as an oil (Found: C, 67.9; H, 7.2. C29H3608 requires C, 68.2; H, 7.1); alD -51.6 (c 0.79, CHCl,); dH(3O0 MHz; CDC1,) 1.24 (3 H, s), 1.26 (3 H, s), 1.37(3 H, s), 1.42 (3 H, s), 1.942.05 (1 H, m), 2.18-2.29 (1 H, m), 3.81-3.95(3H,m),4.194.26(2H,m),4.45(1H,d,J10.8),4.51 (1 H,m),4.57(2H,m),4.79(1 H,d, J10.8), 5.51 (1 H,d, J5.1), 7.14-7.35 (10 H, m) and 9.45 (1 H, d, J 0.9); dc(75.5 MHz; CDCl,) 24.23, 24.71, 25.76, 25.84, 32.04, 70.47, 70.87, 71.30, 71.84, 72.12, 73.40, 74.82, 80.32, 96.48, 108.82, 109.50, 127.66, 127.90,128.19,128.46,128.69,128.76,138.68,139.19and203.05. 7-Deoxy-1,2:3,4-di-O-isopropylidene-8-(thiazol-2-yl)-a-~-glycero-D-galacto-octodialdo-1,5-pyranose (R)-4.-To a well stirred solution of tert-butyl alcohol (0.74 g, 10 mmol) in anhydrous THF (15 cm3)was added, drop by drop, butyl- lithium (10.24 mmol, 6.4 cm3 of a 1.6 mol dm-, solution in hexane) at room temperature.The mixture was stirred for 30 min, before being cooled to -50 "C, and a solution of 1,2 :3,4-di-O-isopropylidene-a-~-gal~c~o-hexodialdo-1,5-pyranose2o 3 (2.58 g, 10 mmol) and 2-acetylthiazole 1(1.3 g, 10.24 mmol) in anhydrous THF (40 an3)was added drop by drop. After 2 h at -50 "C,the mixture was treated with saturated aq. NH,Cl (S,R)-6 (0.132 g, 90, ds 95) as an oil (Found: C, 65.3; H, 6.4; N, 2.3. C31H37N07S requires C, 65.5; H, 6.7; N, 2.6); aD -63.6 (C 0.81, CHCl,); dH(300 MHz; CDCl3) 1.28 (3 H, s), 1.32 (3 H, s), 1.40 (3 H, s), 1.47 (3 H, s), 2.28 (1 H, dt, J6.7 and 14.4), 2.40 (1 H, ddd, J4.4, 7.2 and 14.4), 3.70-3.83 (2 H, m), 4.24 (1 H, dd, J2.3 and 5.0), 4.41 (1 H, dd, J 1.8 and 8.0), 4.50-4.70 (5 H, m), 5.09 (1 H, t, J7.0), 5.47 (1 H, d, J5.0),7.2Cb7.38 (11 H, m) and 7.74 (1 H, d, J3.0); dc(75.5 MHz; CDCl,) 24.12, 24.62, 25.69, 25.72, 40.28, 66.80, 70.02, 70.52, 70.81, 71.56, 72.79, 74.15, 76.75, 96.54, 108.66, 109.02, 119.48, 127.71, 127.87, 128.32, 128.46, 128.64, 128.83, 138.32, 139.07, 142.63 and 174.43.(6R,SR)-6,8-Di-O-benzyl-7-deoxy-1,2:3,4-di-O-isopropyl-idene-8-(thiazol-2-yl)-~-~-threo-~-galacto-octopyranose(R,R)-6.-To a solution of tetramethylammonium triacetoxyborohy- dride (1.7 g, 6.4 mmol) in acetonitrile (4 cm3) was added anhydrous acetic acid (4 cm3). The mixture was stirred at room temperature for 30 min, then cooled to -40 "C and a solution of compound (R)-4 (0.35 g, 0.91 mmol) was added.The reaction mixture was stirred at -40 "C for 24 h, then aq. 1 mol dm-, sodium potassium tartrate (5 an3)was added. The reaction mixture was allowed to warm to room temperature and partitioned between ethyl acetate and saturated aq. sodium hydrogen carbonate. The organic layer was dried over sodium sulfate and evaporated under reduced pressure to give the crude diol(0.33 g, 94) which, according to 'H NMR spectroscopy, was at least 95 diastereomerically pure. Benzylation as described above afforded, after column chromatography (silica gel; hexanediethyl ether 7 :3) pure bis ether (R,R)-6(0.41 g, 96, ds 9579, m.p. 118-120 "C (Found: C, 65.3; H, 6.6; N, 2.3) ffD +0.58 (C 1.55, CHCl,); ffD +6.35 (C 1.15, MeOH); dH(300 MHz; CDCl,) 1.24 (3 H, s), 1.32 (3 H, s), 1.41 (3 H, s), 1.45 (3 H, s), 1.90 (1 H, ddd, J2.9, 10.1 and 14.6), 2.44 (1 H, ddd, J2.5, 10.6and 14.6),3.58(1 H,dd, JlSand9.1),4.0(1 H, ddd, J2.5,9.1 and 10.1),4.22(1 H,dd, Jl.Sand4.5),4.26-4.35 (2 H, m), 4.38 (1 H, dd, J 1.5 and 7.2), 4.514.65 (3 H, m), 5.06 (1 H, dd, J2.9 and 10.6), 5.49 (1 H, d, J5.1), 7.18-7.36 (11 H, m) and 7.69 (1 H, d, J 3.2); d,(75.5 MHz; CDCl,) 24.14, 24.61, 25.77, 25.81, 42.15, 68.88, 69.90, 70.53, 70.85, 71.20, 73.57, 73.86, 75.95, 96.62, 108.57, 109.16, 119.54, 127.78, 127.98, 128.11, 128.38, 128.60, 128.79, 138.19, 139.18, 142.61 and 174.89.6,8-Di-O-benzyl-7-deoxy-1,2:3,4-di-O-isopropylidene-P-~-threo-D-galact o-nonodialdo- 1,5-pyranose (R,R)-7.-The method described above for the conversion of compound (R,-29-6 into the nonodialdose (R, S)-7 was applied to compound (R,R)-6 (170 mg, 0.3 mmol) to give, after column chromato- graphy (silica gel; hexaneaiethyl ether 2 :3), the aldehyde (R,R)-7 (110 mg, 72) as an oil (Found: C, 68.3; H, 6.9.C29H3608 requires C, 68.2; H, 7.1); aID -0.4 (c 1.02, CHCl3); amp;(300 MHz; CDCl,) 1.28 (3 H, s), 1.33 (3 H, s), 1.45 (3 H, s), 1.47 (3 H, s), 1.81 (1 H, ddd, J4.0,9.3 and 14.7), 2.22 (1 H, ddd, J2.2, 9.4 and 14.7), 3.66 (1 H, dd, J 1.6 and 8.8), 3.88 (1 H, dt, J 2.9 and 8.8), 4.01 (1 H, ddd, J 2.2, 4.0 and 93, 4.26 (1 H, dd, J2.2 and LO), 4.40 (1 H, m), 4.35 (1 H, d, J 11.6), 4.41 (1 H, d, J 11.8), 4.59 (1 H, m), 4.61 (1 H, d, J 11.8), 4.64 (1 H, d, J 11.6), 5.50 (1 H, d, J 5.0), 7.20-7.40 (10 H, m) and 9.61 (1 H, d, J2.2);6,(75.5 MHz; CDCl,) 24.06,24.56,25.73,25.80, 33.01, 69.57, 70.48, 70.79, 71.10, 72.14, 73.22, 73.75, 80.73, 96.56, 108.60, 109.19, 127.88, 127.93, 128.27, 128.38, 128.63, 128.70, 137.84, 138.77 and 203.54.Reduction of Compound (R)-5.-The reduction of compound (R)-5 (0.12 g) as described above for diastereoisomer (S)-5 afforded a 55:45 mixture (lsquo;H NMR) of diastereoisomeric alcohols (0.12 g). Benzylation as described above gave a 56 :44 mixture of dibenzyl derivatives whose lsquo;H NMR spectrum was superposable on those bis ethers (S,R)-6and (R,R)-6. X-Ray Crystallography .-The relevant data for the crystal- structure analyses are summarized in Table 2.The lattice parameters were determined using Cu-Kal radiation (A = 1.540 562 0 A) and refined by a least-squares procedure 21 using the Nelson and Riley 22 extrapolation function. The integrated intensities were measured on a Siemens-AED diffractometer with Cu-Ka mean radiation, using the 8-28 scan mode and a modified version 23 of the Lehmann and Larsen 24 peak-profile analysis procedure. All reflections were corrected for Lorentz and polarization effects; no correction for absorption was considered. The structure of compound (S)-5 was solved by the direct methods of SHELXS-86,25 while attempts to solve the structure of compound (R,R)-6by means of the commonly used direct- method programs failed. This structure was solved by using the new version of program SIR (SIR92)26 which succeeded in giving a partially refined structure (R = 0.11) excepting the C(26) C(31) phenyl ring which, afterwards, turned out to be highly disordered.Both structures were refined by full-matrix least-squares on F using SHELX-76,27 and on F2 using SHELXL-92 28 programs. The two types of refinement gave final results not significantly differentso all the data of Table 2 and the structural parameters of Table 1 as well as those discussed in the text are from the F2 refinements. The hydrogen atoms were located in calculated positions riding on the attached carbon atoms, and the dis- ordered phenyl of compound (R,R)-6 was treated as a rigid body with calculated geometry and high isotropic displacement parameters.This disorder, giving intensity data of poor quality, is responsible for the difficulties encountered in solving the structure of compound (R, R)-6 and the relatively low accuracy of the results obtained from its refinement. No attempt was made to define the disorder, this probably being a rotational one about the C(25)--C(26) bond. The absolute configurations were assigned on the basis of Flackrsquo;s2rsquo; index and on the known chirality of the galactose ring. All calculations were carried out on the ENCORE-91 and POWERNODE-6040 computers of the lsquo;Centro di Studio per la Strutturistica Diffrattometrica del C.N.R. (Parma)rsquo;. In addition to the above programs, PARST3rsquo; was used for the J. CHEM. SOC. PERKIN TRANS. 1 1994 calculations concerning the geometrical aspects of the crystal structures.Atomic scattering factors and anomalous-scattering coeffi- cients were taken from the International Tables for X-Ray Crystallography. The final atomic coordinates, fractional coordinates for all atoms, bond lengths, bond angles, and torsional angles have been deposited at the Cambridge Crystallographic Data Centre.* Acknowledgements We thank the Progetto Finalizzato Chimica Fine e Secondaria, n. 2 (CNR, Rome) for financial support, the Ministerio de Educacion y Ciencia (Spain) for a postodoctoral fellowship to P. M., and the EEC (Bruxelles) for a Tempus grant to L. K. We are also indebted to Professor C. Giacovazzo (University of Bari) who solved the structure of compound (R,R)-6 and to Professor G.M. Sheldrick (University of Gottingen) who made available his SHELXL-92 program at the beta-test stage. *See lsquo;Instructions for Authorsrsquo;, J. Chem. SOC., Perkins Trans. 1, 1994, issue 1. References A. Dondoni, Carbohydrate Synthesis via Thiazoles, in Modern Synthetic Methoh, ed. R. Scheffold, Verlag Helvetica Chimica Acta, Basel, 1992, p. 377; Bull. SOC. Chim. Belg., 1992, 101,433. A. Dondoni and P. Merino, J. Org. Chem., 1991, 56, 5294; A. Dondoni, P. Merino and J. Orduna, Tetrahedron Lett., 1991, 32, 3247. A. Dondoni, A. Marra and P. Merino, J. Am. Chem. SOC., 1994,116, in the press. A. M. Sepulchre, A. Gateau-Olesker, G. Lukacs, G. Vass, S. D. Gero and W. Voelter, Tetrahedron Lett., 1972,3945;P. Coutrot, C.Grison, M. Tabyaoui, S. Czernecki and J.-M. Valery, J. Chem. SOC., Chem. Commun., 1988, 1515; S. Czernecki and J.-M. ValCry, J. Carbohydr. Chem., 1988, 7, 151; A. Dondoni, G. Fantin, M. Fogagnolo and P. Merino, J. Carbohydr. Chem., 1990,9,735; Ph. Maillard, C. Hue1 and M. Momenteau, Tetrahedron Lett., 1992,33,8081. S. J. Danishefsky and M. P. DeNinno, Angew. Chem., Znt. Ed. Engl., 1987, 26, 15; J. S. Brimacombe, in Studies in Natural Product Chemistry, ed. A.-ur Rahman, Elsevier, Amsterdam, 1989, vol. 4, part C, p. 157. For the convenient use of diastereoselectivity (ds) instead of diastereoisomeric excess (de), see: S. Thaisrivongs and D. Seebach, J. Am. Chem. SOC., 1983,105,7407. B. E. Maryanoff and A. B. Reitz, Chem. Rev., 1989,89,863.For reviews on the so-called Cramrsquo;s Rule see: E. L. Eliel, in Asymmetric Synthesis, ed. J. D. Morrison, Academic Press, New York, 1983, vol. 2, part A, p. 125; J. Mulzer, H.-J. Altenbach, M. Braun, K. Krohn and H.-U. Reissig. Organic Synthesis Highlights, VCH Verlagsgesellschaft, Weinheim, 199 1, p. 3. S. J. Danishefsky, W. H. Pearson, D. F. Harvey, C. J. Maring and J. P. Springer, J.Am. Chem. SOC., 1985,107,1256; S. J. Danishefsky, M. P. DeNinno, G. B. Phillips, R. E. Zelle and P. A. Lartey, Tetrahedron, 1986,42,2809; A. Dondoni, G. Fantin, M. Fogagnolo and A. Medici, Tetrahedron, 1987,43,3533; A. Dondoni, G. Fantin, M. Fogagnolo, A. Medici and P. Pedrini, J. Org. Chem., 1989, 54,693. 10 S. J. Danishefsky, C. J. Maring, M.R. Barbachyn and B. E. Segmuller, J. Org. Chem., 1984,49,4564. 11 A. Dondoni, A. Boscarato and A. Marra, Synlett, 1993,256. 12 For recent articles with leading references on the reduction of p-hydroxy ketones to either syn or anti 1,3-diols see: D. A. Evans, K. T. Chapman and E. M. Carreira, J. Am. Chem. SOC.,1988,110, 3560; D. A. Evans and A. H. Hoveyda, J. Org. Chem., 1990, 55, 5190; D. A. Evans, J. A. Gauchet-Prunet, E. M. Carreira and A. B. Charette, J. Org. Chem., 1991,56,741. 13 For a review of the uses of acyloxyborohydrides in synthesis see: G. W. Gribble and C. F. Nutaitis, Org. Prep. Proced. Znt., 1985, 17, 317. 14 S. Kiyooka, H. Kuroda and Y. Shimasaki, Tetrahedron Lett., 1986, 27,3009. J. CHEM. SOC. PERKJN TRANS.1 1994 15 A. Dondoni and P. Merino, Synthesis, 1993,903. 16 Y. Mori, M. Kuhara, A. Takeuchi and M. Suzuki, Tetrahedron Lett., 1988,29,5419. 17 For an improved procedure see: A. Dondoni, A. Marra and D. Perrone, J. Org. Chem., 1993,58,275. 18 C. K. Johnson, ORTEP, Report ORNL-3794, Oak Ridge National Laboratory, Tennessee, 1965. 19 D. Cremer and J. A. Pople, J. Am. Chem. Soc., 1975,97, 1354. 20 R. F. Butterworth and S. Hanessian, Synthesis, 1971,70. 21 M. Nardelli and A. Mangia, Ann. Chim. (Rome), 1984,74, 163. 22 J. B. Nelson and D. P. Riley, Proc. Phys. SOC.London, 1945, 57, 160,477. 23 D. Belletti, F. Ugozzoli, A. Cantoni and G. Pasquinelli, Internal Report, March 1, 1979, Centro di Studio per la Strutturistica Diffrattometrica del C.N.R., Parma, Italy, 1979. 24 M. S. Lehmann and F. K. Larsen, Acta Crystallogr., Sect. A, 1974, 30, 580. 25 G. M. Sheldrick, SHELXS-86, Program for Crystal Structure Solution, University of Gottingen, Germany, 1986. 26 G. Giacovazzo, private communication. 27 G. M. Sheldrick SHELXL-76, Program for Crystal Structure Determination, University of Gottingen, Germany, 1976. 28 G. M. Sheldrick, SHELXS-92, Program for Crystal Structure Refinement, University of Cambridge, England, 1992. 29 H. D. Flack, Acta Crystallogr., Sect. A, 1983,39, 876. 30 M. Nardelli, Comput. Chem., 1983,7,95. 31 International Tables for X-ray Crystallography, Kynoch Press (Present Distributor Kluver Academic Publishers, Dordrecht), 1974, vol. 4, pp. 99 and 149. Paper 3/06 1545 Received 14th October 1993 Accepted 23rd December 1993