摘要:

~___~~ ~~ ~~ ~~~ Asymmetric induction using novel chiral auxiliaries derived from D-glucose n-4Vijay Nair * and Jaya Prabhakaran Organic Chemistry Division, Regional Research Laboratory (CSIR) Trivandrum 695 019, India Asymmetric synthesis of lactones 15a-l6b, using the novel auxiliaries 1 and 2 readily available from D-glUCOSe, is described. Asymmetric synthesis using chiral auxiliaries has continued to be an area of topical The auxiliaries that have attracted the most attention are those derived from natural amino acids and monoterpenes. Carbohydrates, although abundant and inexpensive, have found relatively less use as chiral auxiliaries6 and it was of interest to undertake some investigations in this area. The anhydrosugars 1 and 2, readily available from D-gl~cose,~appeared particularly attractive for chiral induction since the two cis fused five membered rings form a wedge and there are two hydroxy groups which can be differentiated in their reactivity. This difference in reactivity is due to the fact that the 5-OH group is pointing towards the wedge and is hydrogen bonded with the ring oxygen atom, whereas the 2-OH is projecting away from the wedge and is accessible for attaching prochiral groups.We have undertaken some investigations using 1 and 2 as auxiliaries for the reduction of 1 R=CH3 2 R = CH2W prochiral ketones (Scheme 1) and our preliminary results, which show a high level of enantioselectivity, are reported here. The keto esters 3-8 were synthesized by routine procedure and were reduced under different conditions to afford the hydroxy esters 9-14.These hydroxy esters were hydrolysed using LiOH (1 mol dm-,) and on acidification using aq. HCl(1 mol dm-3) afforded the lactones 15a-16b '-lo in optically active form. The structures of all the compounds were established by spectral and analytical data. Experimental conditions and the ee values obtained are given in Table 1. As shown in Table I high ee values are obtained when the reduction is carried out in the presence of ZnC1, especially when using the auxiliary 2. Both a chelating and steric effect can be attributed to the observed stereodifferentiati0n.t Presumably the observed configuration of the product resulting from hydride addition from the a-face of the prochiral ketone is predicated by the wedge shaped geometry of the ring system, cr-orientation of the OR group and the chelation of Zn2 + with the 5-OH and the keto group.In conclusion, we have achieved the highly enantioselective reduction of prochiral ketones using the auxiliaries 1 and 2. It is noteworthy that the ee values obtained for 15a compare favourably with those obtained in the alternative chemical and enzymatic procedures."." It is anticipated that the ready t Experiments with NaBH, afforded the lactones with very low ee values; this indirectly supports the probable chelating effect of Zn2+ 0 0 1 R=CH3 3 R = CH3, R' = C,&j, n = 1 2 R=CHZPh 4 R=CH3,R1=c&~,n=2 5 R = CHZPh, R' = c6H5, n = 1 6 R = CHZPh, R' = C&s, n = 2 7 R = CHZPh, R' = CH3, n = 1 8 R = CHZPh, R' = CH3, n = 2 I ii 0 15a n = 1, R' = Ph 9 R = CH3, R' = C&s, n = 1 16an =2,R'=Ph 10 R = CH3,R' = C&, n = 2 15b n = 1, R' = CH3 11 R = CHZPh, R' = C6H5.~t= 1 16b n = 2, R' = CH3 12 R = CHZPh, R' = C6H5, n = 2 13 R = CHZPh, R' = CH3, n = 1 14 R = CH2Ph, R' = CH3. n = 2 Scheme 1 Reagents and conditions: i, pyridine, CHC13, RT; ii, for reduction conditions, see Table 1; iii, LiOH (1 mol drn-j); iv, HCI (1 moi dm-3) availability of 2 coupled with the experimental simplicity will make the present procedure useful in organic synthesis. Further work is in progress to evaluate the use of 2 and related auxiliaries in other asymmetric transformations.Experimental Typical experimental procedure for the keto esters 3-8 Benzyl 2-O-(4-oxo-4-phenylbutanoyl)-3,6dihydro-a-~-gluco-furanoside 5. A solution of 2(1.26 g, 5 mmol) in CHCl, (I 5 cm3) containing pyridine (0.81 cm3, 10 mmol) was treated with 4- 0x0-4-phenylbutanoyl chloride (1.17 g, 6 mmol) in dry CHCI, (10 cm3) at room temperature. After 3.5 h the reaction mixture was diluted with CHCl, (25 cm3) and successively washed with saturated aq. CuSO,, aq. NaHCO,, water and then brine. The organic layer was dried (Na2S04j and evaporated under reduced pressure. Chromatography of the product on silica gel, eluting with EtOAc-light petroleum (1 5 :85) afforded 5 (1.79 g, 87%) as a colourless solid; mp 105-106°C (EtOAc-light petroleum); v,,,(CH~C12)/cm 351 5, 2990, 1740, 1735 and 1428; 6,(270 MHz, CDCl,) 7.75 (2 H, m, Ar-H), 7.5 (8 H, m, Ar-H), 4.86 (1 H, d, J6.8 Hz), 3.65 (2 H, br s), 3.3-3.2 (6 H, m, OCH), 2.9 (4H, m, COCH) and 2.1 (1 H, br s, OH); 6,(22.4 J.Chern. Soc., Perkin Trans. 1, 1996 593 Table 1 Entry Ketoester Reduction conditions Lactone ee (%) Yield (%) 1 3 ZnCl,, NaBH,, -5 "C R- 15a 72 83 2 4 ZnCl,, NaBH,, -5 "C R-16a 31 79 3 3 ZnCl,, NaBH,, -78 "C R-15a 73 80 4 4 ZnCl,, NaBH,, -78 "C R-16a 30 76 5 5 ZnCl,, NaBH,, -5 "C R-15a 91 82 6 6 ZnCl,, NaBH,, -5 "C R-16a 56 76 7 5 ZnCI,, NaBH,, -78 "C R-15a 93 82 8 6 ZnCI,, NaBH,, -78 "C R-16a 53 76 9 7 ZnCl,, NaBH,, -5 "C S-15b 82 80 10 8 ZnCl,, NaBH,, -5 "C S-16b 48 75 MHz, CDC1,) 192.0, 135.1, 127.0, 88.2, 82.2, 75.9, 76.3, 71.9, 43.5 and 42.5 (Found: C, 66.9; H, 5.8.Calc. for C,,H,40,: C, 66.97; H, 5.87%). Typical experimental procedure for carbinol9-14 Renzyl 2-O-(4-hydroxy-4-phenylbutanoyl)-3,6-anhydro-a-~-glucofuranoside 11. To a stirred solution of compound 5 (1.65 g, 4 mmol) in THF (20 cm3), ZnCl, (0.33 g, 2.4 mmol) was added at -5 "C. After 15 min NaBH, (0.34 g, 6 mmol) was added and the mixture was stirred for 10 min. The excess of NaBH, was quenched with dilute HCl, the reaction mixture was diluted with water (15 cm3) and the product extracted into ethyl acetate (4 x 15 cm'). The combined organic extracts were dried (Na,SO,) and the product was purified by silica gel column chromatography. Elution with ethyl acetate-light petroleum (20:80) afforded 11 as a colourless solid (1.529 g, 92%); v,,,(KBr)/cm~' 3465, 1735 and 1425; 6,(90 MHz, CDCl,) 7.4 (10 H, br s, Ar-H), 4.8 (1 H, d, J 6.7 Hz), 3.8-3.6 (9 H, m, OCH), 2.8 (2 H, m, COCH), 2.0 (2 H, br s, OH) and 1.85-1.70 (4 H, m); 6,(22.4 MHz, CDC1,) 179.5, 135.6, 129.2, 127.0, 126.5, 87.5, 86.0, 82.4, 75.6, 44.6, 44.0, 25.7 and 25.0; [cr]k6 +81 (c 1, CHCI,); Diastereoisomeric ratio J 96 :4.Typical experimental procedure for lactones 15a-16b 5-Phenyltetrahydrofuran-2-one 15a. Compound 11 (0.83 g, 2 mmol) in THF (25 cm3) was saponified using LiOH (1 mol dm ,;10 cm3). The reaction mixture was acidified with HCl (1 mol dm-3) and the products were extracted into ethyl acetate (4 x 15 cm3).The combined extracts were dried (Na,SO,) and the product was purified by column chromatography on silica gel. Elution with ethyl acetate-light petroleum (10 :90) afforded 15a as a viscous liquid (0.26 g, 79%); Calk6 + 31 (c 1 .O, CHCI,), [lit.9b + 32.5 (c 4.3, CHCl,)]. 1Determined by HPLC analysis: 254 nm, ODS column Acknowledgements The authors thank Professor S. Chandrasekaran, IISc, Bangalore for spectral data and Dr J. M. Rao, RRL, Trivandrum for optical rotation measurements. J. P. thanks CSIR, New Delhi for the award of a Senior Research Fellowship, References 1 J. D. Morrison, Asymmelric Synthesis, Academic Press, New York, 1983, vols. 1-5 and references cited therein.2 A. Fischli, Chimia, 1976, 30,4. 3 W. Oppolzer, Comprehensive Organic Synthesis: Selectivity, StrategAv and Efjciency in Modern Orgunic Chemistry, B. M. Trost and I. Fleming, Pergamon Press, Oxford, 1991, p. 315. 4 Amino acid based chiral dienophiles: (a) D. A. Evans, K. T. Chapman and J. Bisaha, TetrahedronLett., 1984,25,4071; (b) D. A. Evans, K. T. Chapman and J. Bisaha,J. Am. Chem. Soc., 1988, 110, 1238. 5 Terpene derived auxiliaries: (a) H. M. Walborsky, L. Barash and T. C. Davis, J. Org. Chem., 1961, 26, 477; Tetrahedron, 1963, 19, 2333; (b) E. J. Corey and H. E. Ensley, J. Am. Chem. Soc., 1975,97, 6908; (c) J. K. Whitesell and D. Allen, J. Org. Chem., 1985,50, 3026; (d)C. Palomo, F. Berree, A. Linden and J. M. Villalgordo, J. Chem. Soc., Chem. Commun., 1994, 1861. 6 Carbohydrate derived chiral auxiliaries: (a)H. Kunz, B. Muller and D. Schanzenbach, Angew. Chem., Int. Ed. Engl., 1987, 26, 267; (b) H. Kunz and K. Ruck, Angew. Chem., Int. Ed. Engl., 1993,32,336. 7 W. N. Haworth, L. N. Owen and F. Smith, .I.Chem. Sue., 1941,88. 8 D. Enders, R. Grobner and J. Runsink, Synrhesis, 1995, 949 and references cited therein. 9 ((I) A. I. Gutman, K. Zuobi and T. Bravdo, J. Org. Chem., 1990,55, 3546; (b) H. C. Brown, S. V. Kulkarni and U. S. Racherla, J. Org. Chem., 1994, 59, 365; (c)T. Izumi, F. Tamura and M. J. Akutsu, J. Heterocyclic Chem., 1994, 31,441. 10 D. W. Armstrong, A. M. Stalcup, M. L. Hilton, J. D. Duncan, J. R. Faulkner Jr. and S-C. Chang, Anal. Chern., 1990,62, 1610. Puper 5/07 1 82H Received 31st October 1995 Accepted 25th January 1996 594 J. Chem. SOC.,Perkin Trans. 1,1996

ISSN:1472-7781    

DOI:10.1039/P19960000593

出版商:RSC    

年代:1996

数据来源: RSC