Xiao-Long Qiu

Synthesis of Boc-protected cis- and trans-4-trifluoromethyl-D-prolines

Both Boc-protected trans- and cis-4-trifluoromethyl prolines were synthesized starting from L-serine simultaneously. In our synthetic route, the key intermediate 4 was obtained through the reaction of Garners aldehyde 1 with ylide 2 followed by trifluoromethylation with FSO2CF2COOMe–CuI. After hydrogenation followed by reduction of 4, the alcohol 5 was obtained in low diastereoselectivity, however, the two diastereoisomers could be separated easily by flash chromatography in the following steps. The bromide 8b obtained from the alcohol 5 in a straightforward fashion could not afford the desired cyclization product because of the strong electron-withdrawing properties of the trifluoromethyl group and the low ability of bromide as a leaving group. Instead, mesylation of alcohols 12a and 12b followed by treatment with potassium bis(trimethylsilyl)amide (KHMDS) afforded the desired cyclization products 13a and 13b respectively, which were transformed into Boc-protected cis- and trans-4-trifluoromethyl-D-prolines in a straightforward fashion.

Synthesis of gem-difluoromethylenated analogues of boronolide

Summary The straightforward synthesis of four gem-difluoromethylenated analogues 4–7 of boronolide is described. The key steps of the synthesis include the concise preparation of the key intermediates 12a–b through the indium-mediated gem-difluoropropargylation of aldehyde 9 with the fluorine-containing building block 11 and the efficient construction of α,β-unsaturated-δ-lactones 15a–b via BAIB/TEMPO-procedure.

Synthesis of 2,3,4-Trideoxy-4,4-difluoro-D-ribo-hexopyranose Adenosines

A novel synthetic route to 2,3,4-trideoxy-4,4-difluoro-β-D-ribo-hexopyranose adenosine and 2,3,4-tnaeoxy-2,3-didehydro-4,4-difluoro-β-D-ribo-hexopyranose adenosine has been developed. The approach highlights the highly regio- and stereoselective palladium-catalyzed glycosylation of Boc-protected pyranose, which was prepared from the oxidation-cyclization of a difluorinated diol. The diol was provided through ozonization and Lindlar reduction of optically pure enynic alcohol.