A Model for Double Asymmetric Induction in the Stereocontrolled Reduction of Glycosyl α-Ketoesters with Oxazaborolidines

Abstract

Experimental diastereoselectivities for the stereocontrolled reduction of glycosyl alpha-ketoesters into the corresponding alpha-hydroxyesters have recently been reported with unexpected results. The process is catalyzed by a chiral oxazaborolidine derivative (the so-called CBS catalyst) and represents the key step in the synthesis of glycosyl alpha-amino acids synthons, a class of compounds that allow preparation of natural glycopeptides analogues exhibiting potential therapeutic relevance. Good to very good diastereomeric excesses have been obtained for a series of reactions with different glucidic derivatives, but surprisingly, the major product obtained does not correspond to that predicted by using Corey's model. In the present work, we carry out a theoretical investigation of these reactions at the density functional level. Separated effects from the catalyst and from the glucidic derivative have been computed to rationalize the observed diastereoselectivities and the double asymmetric induction.

Diastereoselective Synthesis of Lincosamine Precursors

“…This surprising decrease in reactivity in the presence of this activating agent certainly results from difficult formation of the Lewis acid-base complex between the chiral ate complex catecholborane-oxazaborolidine and 8. [28,29] This hypothesis is confirmed by the stereochemical results where no influence of (R)-or (S)-oxazaborolidine can be observed compared with the reaction using catecholborane as a reducing agent. The absolute configurations of C-6 and C-7 in stereoisomers 10 were determined by chemical correlation as a result of their stereospecific reduction into the corresponding aminodiols 9 of known configuration (see above) with LiAlH 4 (2 equiv.…”

Efficient Synthesis of Direct Precursors of the Carbohydrate Moiety of New Antibacterials 6-Epi-VIC-105555 and 6-Epi-VIC-II

“…[16] In the case of epimer 14-L -glycero, 1 H NMR, 13 NMR, and X-ray analyses of the so-obtained olefin 12-L -glycero unambiguously demonstrated the configurational integrity of the chiral center at C-6. [17] When the reaction was performed using an epimeric mixture 14-L -glycero/14-D -glycero, the lower reactivity of 14-D -glycero compared with its C-6 epimer was observed, and that accounts for the lower yield of the reaction.…”

“…We have previously reported on several applications of dihalogenoacetate carbanions [11] and developed a general synthesis of α-ketoesters from carbonyl compounds using potassium alkyl dichloroacetates. [12] Applied to dialdosugar derivatives, the method proved to be very convenient for the chain extension with an α-ketoester unit [13] and to introduce a functionality at the C-6 position. [14] In this report we describe a successful application of this protocol for the stereoselective Downloaded by [Umeå University Library] at 12:53 17 November 2014 synthesis of the direct precursors of the carbohydrate moiety of new antibacterial agents, 6-epi-VIC-II 4 and 6-epi-VIC-105555 5.…”

“…-O-isopropylidene-7-methylene-L -glycero-α-D -galacto-1, 5-octopyranuronate (12-L -glycero) CH 3 , s, 3H), 1.24 (H10, d, 3H, J H10-H9 = 6.3 Hz), 1.22 (H10', d, 3H, J H10'-H9 = 5.6 Hz), 1.21 (CH 3 , s, 3H) 13. C NMR (CDCl 3 , 100 MHz): δ C 167.2 (C8, 1C), 140.5 (C Ph, 2C), 137.6 (C7, 1C), 129.1, 127.7, 126.3 (CH Ph, 10C), 126.9 (C11, 1C), 109.4, 108.7 (C13, C14, 2C), 96.9 (C1, 1C), 72.1 (C4, 1C), 71.3 (C3, 1C), 70.5 (C2, 1C), 68.0 (C9, 1C), 66.8 (C5, 1C), 58.9 (C6, 1C), 54.3 (C12, C12', 2C), 26.0, 26.0, 25.2, 25.1 (CH 3 * 4, 4C), 21.7 (C10, C10', 2C).…”

“…R f 0.58 (EtOAc/Hexane 1:4). 1 H NMR (CDCl 3 , 400 MHz): δ H 7.90-7.35 (H Ph, m, 10H), 5.72 (H1, d, 1H, J H1-H2 = 5.2 Hz), 4.63 (H3, dd, 1H, J H3-H4 = 7.9 Hz, J H3-H2 = 2.5 Hz), 4.38 (H2, dd, 1H, J H2-H1 = 5.2 Hz, J H2-H3 = 2.5 Hz), 4.26 (H5, dd, 1H, J H5-H6 = 10.3 Hz, J H5-H4 = 1.6 Hz),4.19 (H4, dd, 1H, J H4-H3 = 7.9 Hz, J H4-H5 = 1.7 Hz), 3.96 (H9, d, 2H, J = 13.3 Hz), 3.83 (H9', d, 2H, J = 12.6 Hz), 3.04 (H6, dd, 1H, J H6-H5 = 10.3 Hz, J H6-H7 = 3.1 Hz), 1.77-1.68 (H7, m, 1H), 1.60 (CH 3 , s, 3H), 1.52 (CH 3 , s, 3H), 1.40 (CH 3 , s, 3H), 1.32 (CH 3 , s, 3H), 0.89 (H8, d, 3H, J H8-H7 = 7.2 Hz), 0.64 (H8', d, 3H, J H8'-H7 = 6.7 Hz) 13. C NMR (CDCl 3 , 100 MHz): δ C 141.5 (C Ph, 2C), 129.8, 127.9, 126.5 (CH Ph, 10C), 109.2, 108.6 (C10, C11, 2C), 96.9 (C1, 1C), 72.3 (C4, 1C), 71.2 (C3, 1C), 70.4 (C2, 1C), 69.8 (C5, 1C), 58.3 (C6, 1C), 57.2 (C9, C9', 2C), 28.8 (C7, 1C), 26.3, 26.0, 25.1, 24.9 (CH 3 * 4, 4C), 21.6 (C8', 1C), 17.5 (C8, 1C).…”