Chemo- and diastereoselective tandem dual oxidation of B(pin)-substituted allylic alcohols: synthesis of B(pin)-substituted epoxy alcohols, 2-keto-anti-1,3-diols and dihydroxy-tetrahydrofuran-3-ones

Abstract

A novel retrosynthetic disconnection for the stereoselective preparation of α,α′-dioxygenated carbonyl compounds is disclosed. Herein we report a method to divert the oxidation of vinyl boronate esters from the B–C bond to the CC bond, resulting in a new stereoselective class of oxidation products from vinyl boronate esters. Treatment of 2-B(pin)-substituted allylic alcohols with catalytic OV(acac)₂ and TBHP resulted in a highly chemo- and diastereoselective directed epoxidation to provide B(pin)-substituted epoxy alcohols (55–96% yield, dr > 20 : 1). In the case of B(pin)-substituted bis-allylic alcohols, highly substituted bis-epoxy alcohols with five contiguous stereocenters were obtained (dr > 20 : 1). Furthermore, the difference in reactivity between allylic alcohols and 2-B(pin)-substituted allylic alcohols towards epoxidation enabled the selective oxidation of the allylic alcohol in the presence of TBHP and VO(acac)₂. The reactivity difference between the two allylic alcohols suggests CCB(pin) to be more electron deficient than CC(alkyl). The B(pin)-substituted epoxy alcohols are also useful synthetic intermediates. Tandem vanadium catalyzed epoxidation of the 2-B(pin)-substituted allylic and bis-allylic alcohols with excess TBHP generated the intermediate epoxides and bis-epoxides, respectively. Subsequent addition of NaOH resulted in the oxidation of the B–C bond of the B(pin)-substituted epoxides to afford 2-keto-anti-1,3-diols (60–83% yield) and epoxide-substituted 2-keto-anti-1,3-diols (60–78% yield, dr > 20 : 1). The latter underwent a novel facile acid-mediated cyclization to furnish fully substituted dihydroxy-tetrahydrofuran-3-ones (65–91% yield, dr > 20 : 1). Such compounds are difficult to efficiently access via conventional synthetic methods.