chirality in the synthesis of 10 (50% yield) and a CH3NO2-assisted or a Yb(OTf)3-catalyzed regioselective coupling with indole.4
OHOHOOHONH(+)-Kurasoin A (1)(+)-Kurasoin B (2)
Figure 1
In recent years, the asymmetric synthesis of carbinols by nucleophilic addition to enantiomerically pure •-keto sulfoxides has been widely used.5 Alkylation6 and hydrocyanation7 reactions of these compounds with aluminum reagents have been described to prepare tertiary alcohols and cyanohydrins, respectively. However, the stereoselective reduction of •-keto sulfoxides has been the most extensively investigated and used reaction.5,8 The stereochemical outcome in the reduction of the •-keto sulfoxides can be controlled by the configuration of the sulfoxide, the reducing agent, and the absence or presence of a Lewis acid. The hydroxy sulfoxides resulting from these reactions can be transformed into epoxides,9 which can be subsequently opened with nucleophiles.10 As •-keto sulfoxides are easily obtained by reaction of esters with enantiomerically pure methyl p-tolyl sulfoxide,11 we envisioned the synthesis of chiral epoxy ketone 10 making use of the above-mentioned reactions on (S)-phenyllactic acid 3. Herein, we report the application of this process to the synthesis of 10, a key intermediate in the synthesis of kurasoin B (2).
Results and Discussion
The overall synthetic sequence is depicted in Scheme 1. Methyl (S)-2-hydroxy-3- phenylpropanoate 4 was easily prepared in 97% yield by esterification of (S)-phenyllactic acid (3) with diazomethane. Then, the hydroxyl group of 4 was protected by using tert- butyldimethylsilyl chloride to give methyl ester 5 in 96% yield. The synthesis of •-keto sulfoxide 6 was performed, in 82% yield, by reaction of 5 with 2 equiv of the anion generated from enantiomerically pure (R)-(+)-methyl p-tolyl sulfoxide and LDA at -78 °C, according to the procedure reported by Solladié.11 The reduction of •-keto sulfoxide 6 with DIBAH in the presence of ZnBr2 afforded, in a completely diastereoselective way, the hydroxy sulfoxide 7 (85% yield) having the R absolute configuration at the newly created C-2 stereogenic center. This result demonstrated that the well-established protocol to reduce •-keto sulfoxides, first
