Variable Strategy toward Carbasugars and Relatives. 2.¹ Diversity-Based Synthesis of β-d-Xylo, β-d-Ribo, β-l-Arabino, and β-l-Lyxo 4a-Carbafuranoses and (4a-Carbafuranosyl)thiols

Abstract

The silyloxy diene-based construction of carbasugars, previously exploited for the synthesis of four carbocyclic furanose and pyranose analogues, has been investigated further. By introducing a novel silylative cycloaldolization protocol and by adjusting a couple of minor transformations, the efficiency of this synthetic sequence was greatly improved. Through a series of lactone/thiolactone aldehyde cyclization precursors, four carbafuranoses (4a-carba-beta-D-xylofuranose, 4a-carba-beta-D-ribofuranose, 4a-carba-beta-L-arabinofuranose, and 4a-carba-beta-L-lyxofuranose) and four (carbafuranosyl)thiols [(4a-carba-beta-D-xylofuranosyl)thiol, (4a-carba-beta-D-ribofuranosyl)thiol, (4a-carba-beta-L-arabinofuranosyl)thiol, and (4a-carba-beta-L-lyxofuranosyl)thiol] were assembled. From this study, it was shown that these constructions tolerate a variety of precursors, and in many instances, they are suitable for scaling-up.

Synthesis of a Small Repertoire of Non-Racemic 5a-Carbahexopyranoses and 1-Thio-5a-carbahexopyranoses

“…Targeting the title carbapyranoses 1 and 2 entailed the use of the advanced lactone intermediate 8, whose preparation from 2-[(tert-butyldimethyl)silyloxy]furan (6) and 2,3-O-isopropylidene--glyceraldehyde (7) has been previously reported (four steps, 65% yield, Scheme 2). [1] Scheme 2.…”

“…Our group has presented [1,7] a synthetic strategy with a high variability potential capable of targeting carbafuranose and carbapyranose structures, as well as carbafuranosyl-and carbapyranosylamines and 1-thio derivatives in diverse stereochemical variants. Basically, the chemistry we employ is founded upon the use of readily available starting materials, namely, the heterocyclic silylketene acetals of type I [8] and glyceraldehyde II (Figure 1), and features two key carbonϪcarbon bond-forming reactions, an intermolecular Mukaiyama-type aldol manoeuvre in its vinylogous version (arrow a), [9] followed by an intramolecular silylative aldol junction (arrows b or c).…”

Asymmetric syntheses of (−)-methyl shikimate and (−)-5a-carba-β-d-gulopyranose from d-arabinose via Mukaiyama-type intramolecular aldolization

“…The reaction was complicated, and none of the desired product was isolated, although Rassu and his colleagues obtained moderate yields in a similar intramolecular aldolization. 15 Fortunately, when we employed a Mukaiyama-type aldolization protocol, the desired cyclization via an intramolecular aldolization occurred. 16 The aldehyde 7 was treated with 3.0 equiv of tert-butyldimethylsilyl trifluoromethanesulfonate (TBSOTf) and with 3.0 equiv of diisopropylethylamine (DIPEA) in dichloromethane at 0°C to room temperature to produce a bicyclic lactone 8 in 81% yield.…”

“…15 Fortunately, when we employed a Mukaiyama-type aldolization protocol, the desired cyclization via an intramolecular aldolization occurred. 16 The aldehyde 7 was treated with 3.0 equiv of tert-butyldimethylsilyl trifluoromethanesulfonate (TBSOTf) and with 3.0 equiv of diisopropylethylamine (DIPEA) in dichloromethane at 0°C to room temperature to produce a bicyclic lactone 8 in 81% yield. The structure and stereochemistry of compound 8 were unequivocally identified by 1 H NMR, 13 C NMR, 1 H-1 H COSY, and 1 H-1 H NOESY spectra.…”

“…The mixture was stirred at room temperature for 12 h, and then was heated at reflux. After stirring was continued at reflux for 16 h, methanol was removed under a reduced pressure to produce a glassy solid that was dried in vacuum for 5 h to afford the title compound 11 (41.4 mg, 0.232 mmol) in 98% yield, 15,20 …”