Diastereocontrol in the reaction of amide-homoenolates with aromatic aldehydes

摘要

J. CHEM. SOC. PERKIN TRANS. I 1995 Diastereocontrol in the Reaction of Amide-homoenolates with Aromatic Aldehydes Satoshi Sakami, Takashi Houkawa, Morio Asaoka and Hisashi Takei Department of Life Chemistry, Tokyo Institute of Technology, Midoriku, Yokohama 227, Japan The reaction of chiral Ti'" amide- homoenolates with aromatic dominantly, whereas the corresponding Zn" gave the anti-adducts preferentially. Stereocontrolled reactions with chiral organometallic reagents are of indisputable importance in asymmetric synthesis. Though there are many reports on stereocontrol with chiral enolates, allyl-metal reagents and related species, only few examples with simple chiral organometallic reagents have appeared.' In this paper, we describe our preliminary results on diastereocontrol in the homo-Reformatsky and related reactions with sec-homoenolates under various conditions.Amide-homoenolates 2 were chosen since the high chelating ability of amides was expected to result in a high stereoselectivity. The amide-homoenolates were generated by Knochel's method and reacted with aldehydes uia titanium reagents by applying Ochiai's method5 (Method A). A high degree of syn-selectivity was observed (Table 1, entries 1-5). Inversion of diastereoselectivity by a change in reaction mode was then envisioned. Initially, the reaction of the zinc amide-homoenolates 2 (Metal = ZnI), generated in THF by Knochel's method, with benzaldehyde by using BF,-OEtz or chlorotrimethylsilane as an activator was examined, however, the reaction did not work.6 In examining the reaction conditions, we found that the zinc amide-homoenolate can be easily prepared with activated zinc' in CH2Cl, in the presence of 0.05-0.I equiv. of chlorotrimethylsilane at room temperature for 0.5 -1 h. The corresponding ester-homoenolate could not be prepared by the same method. The generated zinc amide- homoenolates were found to react with aromatic aldehydes in the presence of chlorotrimethylsilane. For example, the homoenolates reacted with benzaldehyde at room temperature exothermically in the presence of 2 equiv. of chlorotrimethyl- silane to give anti-3 preferentially (entries 6 and 7h8 Other aromatic aldehydes also gave anri-adducts preferentially (entries 8-10), In the silyl reagents examined, iodotrimethyl- silane and trimethylsilyl trifluoromethanesulfonate were also effective, however, chlorotriethylsilane was less effective and tert-butylchlorodimethylsilanewas ineffective.In the range of 0-40 "C, the reaction temperature did not affect the anti:syn ratios. The reaction of acetophenone with the zinc amide- Table 1 Diastereoselective reactions of the homoenolate 2 with several aromatic aldehydes Entry 1 R3 Method" aldehydes gave syn-adducts pre- reagents in the presence of chlorotrimethylsilane R' @N /OLtCR' la R1R2=-CH-lb R', R2=Pt 2 R' @N OH anti-3 Scheme 1 homoenolates under the above reaction conditions resulted in failure. Transformation of adducts into lactones was also examined. Though the treatment of the diastereoisomerically pure anti-3b (R3= Ph) with a catalytic amount of p-TsOH gave a diastereoisomeric mixture of lactones, treatment with 6 equiv.of CF,CO,H in THF at reflux for 18.5 h gave the diastereoisomerically pure anti-lactone in quantitative yield. In summary, we have demonstrated for the first time that preferential formation of each diastereoisomer is possible in the reactions of chiral amide-homoenolates and aromatic aldehydes. Experimental Typical Procedure (Method B).-To a mixture of the iodide 1 (3 mmol) and activated Zn '(3.6 mmol) in CH,CIZ (4 cm3) was added chlorotrimethylsilane (0.3 mmol). The mixture was stirred at room temperature for 1 h, whilst the consumption of the iodide 1was monitored by TLC hexane-EtOAc (1 : 1): lb, R, 0.561.The relevant aldehyde (2.1 mmol) and further chloromethylsilane (6 mmol) were then added to the mixture, which was stirred for 0.5-3 h at room temperature and then diluted with CH,Cl, and washed with water. Purification by silica gel column chromatography or preparative TLC with ethyl acetate-hexane as eluent gave the pure syn-3 and anti-3 Time (h) Yield 3 () Ratio syn : anri I la Ph 97:3A 3 80 2 lb Ph 94:6A 3 79 3 lb o-MeOC,H, 85:15A 3 87 4 5 6 lb Ib la 2-Fury1 I-Naphtyl Ph 96:4 91 :9 19:81 A A B 0.5 61 14 59 2.5 72 7 lb Ph 13:87B 2.5 82 8 lb o-MeOC,H, 25: 75B 0.6 95 9 10 lb lb 2-Fury1 1-Naphtyl 38 :62 21:79 B B 0.6 60 2.5 84 Method A: Metal = Ti(OPr'),, THF, 0 "C--room temp.; Method B: Metal = ZnI, 2 equiv.Me,SiCI, CH,Cl,, room temp adducts hexane-EtOAc (1 : 1): syn3b (R3= Ph), Rf 0.37; anti-3b (R3= Ph), Rf 0.331 or a mixture of the two. Yields were based on the aldehydes and the diastereoisomeric ratios were determined by 'H NMR (270 MHz) analysis of the crude product. References 1 J. D. Morrison, Asymmetric Synthesis, Academic Press, New York, 1983-1985, VO~S. 1-5. 2 G. J. McGarvey and M. Kimura, J. Urg. Chem., 1982, 47, 5420; P. G. McDougal, B. D. Condon, M. D. Laffosse, Jr., A. M. Lauro and D. VanDerveer, Tetrahedron Left.,1988,21,2547; W. H. Miles, S. L. Rovera and J. D. Rosario, Tetrahedron Lett., 1992, 33, 305; R. Duddu, M. Eckhardt, M. Furlong, H.P. Knoess, S. Berger and P. Knochel, Tetrahedron, 1994, 50, 2415; P. Beak, S. T. Kerrick, S. Wu and J. Chu, J. Am. Chem. Soc., 1994,116, 3231 and references cited therein. 3 I. Kuwajima and E. Nakamura, in Comprehensive Organic Synthesis, ed. B. M. Trost and I. Fleming, Pergamon Press, Oxford, 199 I, vol. 2, pp. 441454. J. CHEM. SOC. PERKIN TRANS. 1 1995 4 M. C. P. Yeh and P.Knochel, Tetrahedron Lett., 1988, 29, 2395; P. Knochel and R. D. Singer, Chem. Rev., 1993,93,2117. 5 Two examples of the reaction of a chiral ester-homoenolate with aldehydes are reported: H. Ochiai, T. Nishihara, Y. Tamaru and Z. Yoshida, J. Org. Chem., 1988,53, 1343. 6 Recently, a BF,.Et,O mediated reaction of an organozinc iodide with an aldehyde in CH,Cl, was reported: U. Koert, H. Wagner and U. Pidum, Chem. Ber., 1994, 127, 1447. 7 S. Yamamura, M. Toda and Y. Hirata, Org. Synth., Coll. Vol. VI, 1988,289. 8 Skeletal rearrangement is reported in the chlorotrimethylsilane mediated reaction of a chiral zinc ester-homoenolate with benzaldehyde: Y. Tamaru, T. Nakamura, M. Sakaguchi, H. Ochiai and Z. Yoshida, J. Chem. Soc., Chem. Commun., 1988,610. Paper 41076 13C Received 13th December 1994 Accepted 14th December 1994