摘要:
J. CHEM. SOC. PERKIN TRANS. 1 1993 Stereoselective C-3Substitution of 1,5-Anhydro-2-deoxy-2-formyl-3,4,6-tri-O-methylhex-I -enitols: Entry to rib0 and xy/o Series Cannan Booma and Kalpattu Kuppuswamy Balasubramanian * Department of Chemistry, Indian Institute of Technology, Madras 600 036, Jndia Reaction of l,5-anhydro-2-deoxy-2-formyl-3,4,6-tri-O-methyl-~-/yxo-hex-I -enitol 1 and its arabino epimer 3 with various nucleophiles under Lewis acid catalysis led to stereoselective C-3substitution. The chemistry of glycals in general has received wide attention. ' However, there are only a few reports on glycals with electron- withdrawing groups at C-2 despite their synthetic potential and added conformational intere~t.~ The existence of scanty literature on this class of glycals may be due to the paucity of convenient methods for their preparation.Recently we reported a simple and expedient method for the synthesis of 1&anhydro-2-deoxy-2-formyl-3,4,6-tri-O-methyl-~-lyxo-hex-I -enitol 1 and its arabino epimer 34and observed some unusual reactivity with these compo~nds.~ Extension of this direct formylation for the preparation of 2-formyl-rib0 4 and xyfo 2 derivatives required the respective glycals which are not easily accessible.6 In fact, reduction of hex- 1-en-3-uloses has been reported to yield equatorial a1coho1s.' Normally, in glycals, inversion at 3-OH under Mitsunobu conditions 6'*8 and nucleophilic displacement at C-3 6f lead only to the 2,3-unsaturated derivatives (by allylic rearrange- ment) and not to the desired axial product, excepting for the report of Vasella et af.' and the more recent one by Fraser-Reid et af." In this communication we report a general route for a concise synthesis of 2-formyl-rib0 and xyfo derivatives involving the nucleophilic displacement of 3-OMe in 13-anhydro-2-deoxy-2-formyl-3,4,6-tri-0-meth yl-D-urabino-hex- 1-enitol3 and the lyxo epimer 1under Lewis acid catalysis.Thus, the glycal 1 in benzene was treated with various nucleophiles under identical conditions with BF3*Et,0 (see Experimental section) to afford the corresponding xyfo derivatives 2 (Scheme 1, Table 1). I-CHO Nu CHO 1 2a Nu =OM 2b Nu=OEt 2~ Nu=OBA 2d Nu=SPh 20 Nu=OH Scheme 1 Reagents and conditions: i, BF,*Et,O (1.2 equiv.), NuH, room temp.Application of this methodology to the arabino epimer 3 yielded both rib0 4 and urubino 5 derivatives, the former being major in all the cases. The stereoselectivity decreases in the order PhSH > PhCH,OH > MeOH. When benzyl alcohol and thiophenol (entries 2 and 3, Table 2) were used as nucleophiles the epimers could be separated and purified by preparative HPLC.7 However, with methanol (entry 1, Table 2) the product was obtained as an inseparable mixture (Scheme 2, Table 2). The conformational aspects were studied and the t Acetonitrile-water (40-60,v/v) and methanol-water (80-20, v/v) were used for the separation of epimers 4b-5b and 4c-5c respectively. Table 1 Reaction of 1with various nucleophiles Reaction Entry Product Nu" time/h Yield (%) 1 2a OMe 24 72 2 2b OEt 24 75 3 2c OBzl 12 78 4 M SPh 8 80 5 2e OH 24 f30 [a];' (CHCI,) 148.2 (c, 0.5) 156.1 (c, 0.43) 196.5 (c, 1.1) 136.9(c, 1) 134.8 (c, 0.93) 1.2 Equiv.of each nucleophile was required; excess resulted in acetal formation except in the case of 2e. Me(e($&MeO&$ Me00+ CHO Nu CHO CHO 3 4 5 4a,5a Nu=OMe 4b, 5b NU= OBZI 4~,5cNu=SPh Scheme 2 Reagents and conditions: i, BF,*Et,O (1.2 equiv.), NuH, room temp, structures assigned using 'H and "C NMR spectroscopy. In the I3CNMR spectrum of 2d (entry 4, Table I), the signal at 6 37 (C-3) confirms the regiochemistry. The axial stereochemistry of 3-SPh and the 4H, conformation of 2d are confirmed by 'H NMR coupling constants.$ In the same way, the stereo- chemistry at the substitution site and the conformation are fixed for the rest of the compounds in this series.In the "C NMR spectra of 4c and 5c (entry 3, Table 2), C-3 appears at 6 41 and 29 respectively proving the substitution site to be C-3. The configuration at C-3 is assigned by comparing the 'H NMR spectra of the products with that of the starting material. In 5c the splitting pattern of the ring protons is exactly similar to that of the starting material 3, indicating it to be an arabino derivative. The similarity in the J values of 5c§ and the parent arabino 3 showed that both exist in the 'inverted' 'H4 (D) conformation3 (Fig.1) because of A's2 train.^ The conformation for 5a and 5b is also assigned in the same way. Analysis of the spectrum of 4cy showed it to be the ribo derivative which exists in the 'normal' 4H,conformation (Fig. I). The conformation for 4a and 4b is assigned similarly. It is also interesting to note that in none of the cases studied, there seems to be any evidence for the formation of products $ 2d:S 3.5 (myJ4,32.6, J4,51.3 Hz, 4-H) and 4.2 (d, J3,42.6 Hz, 3-H). 1:S 4.4 (dd, J3,43.7, J3,5 1.1 Hz, 3-H); the conformation could not be precisely fixed from the J values. 0 5c: 6 4.1 (t, J3.42.6, J3,52.6 Hz, 3-H) and 3.67 (t, J4.,2.6, J4.52.6 Hz, 4-H).7 4c: 6 4.56 (d, J3,44 Hz, 3-H) and 3.64 (dd, J4.,4 Hz, J4,51 I Hz, 4-H). 394 J.CHEM. soc. PERKIN TRANS. 1 1993 Table 2 Reaction of 3 with various nucleophiles Entry Products Nu" Reaction time/h Yield (4:5)b(%) 4 5 1 4aand5a OMe 24 70 (55:45) 141.9' (c, 0.42) 2 4band5b OBzl 12 75 (60 :40) 280.3 (c, 0.8) 125.9 (c, 0.42)3 4cand5c SPh 8 80 (80 :20) 336.9 (c, 0.29) 114.8 (c, 0.77) " 1.2Equiv. of each nucleophile was required; excess resulted in acetal formation. Ratio based on 'HNMR and HPLC analyses. 'Rotation reported for the mixture. bme 4 5 4H5Conformation 5H4Conformation Fig. 1 arising out of Ferrier rearrangement or Michael reaction. From the present study, it is clear that the introduction of a formyl group at C-2 has a marked effect on the reactivity and conformational behaviour of glycals.This substitution reaction allows a convenient entry to 2-formyl-ribo and -xylo derivatives which can be useful as synthetic intermediates.2c*d*6f The selective introduction of diverse substituents at C-3 such as an axial hydroxy (entry 5, Table I), formally 'deprotection with inversion' and an axial phenylthio group (entry 4, Table 1 and entry 3, Table 2), provides scope for further functionalisation at this centre. Experimental To a solution of hexenitol 1 (2 mmol) and nucleophile (2.4 mmol) in benzene (10 cm3), BF3-Et,0 (2:4 mmol) was added and the mixture stirred at room temp. for the appropriate period (Table 1). Work-up with aqueous NaHCO, yielded the corresponding xylo derivatives 2 which were purified by preparative HPLC (Shimadzu LC 8A) and analysed thoroughly by spectral and HRMS data.A similar procedure was followed in the corresponding arabino series 3 also. Acknowledgements One of us (C. B.) is grateful to TIT, Madras for a fellowship. The authors thank the Department of Science and Technology, for financial assistance. RSIC, IIT Madras is acknowledged for spectral data. Thanks are due to Dr. K. Vijayakumaran for helpful discussions. References 1 (a)R. J. Ferrier, Adu. Carbohydr. Chem. Biochem., 1969,24, 199; (b) B. Fraser-Reid, Acc. Chem. Res., 1985, 18,347. 2 (a) R. U. Lemieux, T.L. Nagabhushan and I. K. ONeil, Can. J. Chem., 1968,46,413;(6)A. Jordaan, 0.G. de Villiers, A. J. Brink, K. BischofbergerandR. H. Hal1,J. Chem. Soc., Perkin Trans. I, 1979, 781; (c) J.C. Lopez, E. Lameignere and G. Lukacs, J. Chem. Soc., Chem. Commun., 1988,514;(d)C. Burnouf, J. C. Lopez, F. G. Calvo-Flores, M. A. Laborde, A. Olesker and G. Lukacs, J. Chem. SOC., Chem. Commun., 1990, 823; (e)Y. Ishido, K. Hirasawa, H. Iizuka, A. Yamamoto, I. Takai and T. Sakakibara, Tetrahedron Lett., 1990, 31,3749. 3 A. A. Chalmers and R. H. Hall, J. Chem.Soc., Perkin Trans. 2, 1974, 728. 4 N. G. Ramesh and K. K. Balasubramanian, Tetrahedron Lett., 1991, 32,3875. 5 C. Booma and K. K. Balasubramanian, Tetrahedron Lett., 1992,33, 3049. 6 For some previous preparations of rib0 and xylo derivatives, see (a)A. R.Feast, W. G. Overend and W. A. Williams, J. Chem. Soc., 1965,7378;(b)M. Sharma and R. K. Brown, Can.J. Chem., 1966,44, 2825;(c)R. U. Lemieux, E. Fraga and K. A. Watnabe, Can. J. Chem., 1968, 46, 61; (d) R. D. Dawe and B. Fraser-Reid, J. Carbohydr. Chem., 1982, 1, 21; (e) S. Brandange, 0.Dahlman, B. Lindquist, A. Mahlen and L. Morch, Acta Chem. Scand. (Ser. B), 1984,38,837; (f)L. Halcomb, M.D. Wittman and S. J. Danishefsky, J. Org. Chem., 1990,55, 1979. 7 M. P. DeNinno and S. J. Danishefsky, Angew. Chem., Int. Ed. Engl., 1987,26, 15. 8 N. G. Ramesh and K. K. Balasubramanian, unpublished results. 9 F. Braumberger, R. Schauer and A. Vasella, Helu. Chim. Acta., 1988, 71,429. 10 J. C. Lopez and B. Fraser-Reid, J. Chem.SOC.,Chem. Commun., 1992, 94. Paper 3/00037K Receiued 4th January 1993 Accepted 5th January 1993
ISSN:1472-7781
DOI:10.1039/P19930000393
出版商:RSC
年代:1993
数据来源: RSC