Stereoselective synthesis of 2-deoxy-2-disubstituted ribonolactones through a TiCl4-mediated Evans-Aldol reaction

A convenient and novel route for the stereoselective synthesis of 3,5-Di-O-benzoyl-2-deoxy-2-chloro-2-C-methyl-D-ribono-c-lactone 5a and its analogues is developed by an Evans-Aldol reaction in the presence of TiCl4. Starting from 2-chloropropionyl chloride, 5a is efficiently and regioselectively produced on a kilogram scale in an overall yield of 32% with an HPLC purity of 98% by area. In addition, this approach allowed an efficient synthesis of 3,5-Di-O-benzoyl-2-deoxy-2-fluoro-2-C-methyl-D-ribono-c- lactone 5b in a total 20% yield. (c) 2022 Elsevier Ltd. All rights reserved.

Automated summary

In this study, a convenient and novel route for the synthesis of 3,5-Di-O-benzoyl-2-deoxy-2-chloro-2-C-methyl-D-ribono-c-lactone 5a and its analogues was developed using an Evans-Aldol reaction in the presence of TiCl4. The target compound 5a was efficiently produced on a kilogram scale with a high yield and purity, and 3,5-Di-O-benzoyl-2-deoxy-2-fluoro-2-C-methyl-D-ribono-c-lactone 5b was also successfully synthesized.