High‐Yielding Diastereoselective <i>syn</i>‐Dihydroxylation of Protected HBO: An Access to D‐(+)‐Ribono‐1,4‐lactone and 5‐<i>O</i>‐Protected Analogues

Abstract

A diastereoselective chemoenzymatic synthetic pathway to D‐(+)‐ribono‐1,4‐lactone, a versatile chiral sugar derivative widely used for the synthesis of various natural products, has been designed from cellulose‐based levoglucosenone ( LGO ). This route involves a sustainable Baeyer‐Villiger oxidation of LGO to produce enantiopure (S)‐γ‐hydroxymethyl‐α,β‐butenolide ( HBO ) that is further functionalized with various protecting groups to provide 5‐ O ‐protected γ‐hydroxymethyl‐α,β‐butenolides. The latter then undergo a diastereoselective and high‐yielding syn ‐dihydroxylation of the α,β‐unsaturated lactone moiety followed by a deprotection step to give D‐(+)‐ribono‐1,4‐lactone. Through this 4‐step synthetic route from LGO , D‐(+)‐ribono‐1,4‐lactone is obtained with d.r. varying from 82:18 to 97:3 and in overall yields between 32 and 41 % depending on the protecting group used. Moreover, valuable synthetic intermediates 5‐ O ‐ tert ‐butyldimethylsilyl‐, 5‐ O ‐ tert ‐butyldiphenylsilyl‐ as well as 5‐ O ‐benzyl‐ribono‐1,4‐lactones are obtained in 3 steps from LGO in 58, 61 and 40 %, respectively.