Stereoselective VO(acac)2 catalyzed epoxidation of acyclic homoallylic diols. Complementary preparation of C2-syn-3,4-epoxy alcohols

Abstract

A substrate-controlled stereoselective epoxidation of free and monoprotected homoallylic diols was developed. This second-generation approach is based on the incorporation of a primary hydroxy directing group at the C2 methyl carbon, which changes the nature of the vanadium ester intermediate providing a new diastereoselectivity manifold for the preparation of 3,4-epoxy alcohols. This modification favored the formation of the challenging C2-syn epoxy alcohol product not previously available using the standard homoallylic alcohol substrates. These new epoxy alcohol diastereomers expand the scope and generality for the utilization of 3,4-epoxy alcohols as precursors for stereoselective polypropionate synthesis.

Reiterative epoxide-based strategies for the synthesis of stereo-n-ads and application to polypropionate synthesis. A personal account

“…The use of functionalized alkynes allowed access to allylic alcohols that, after some protecting group manipulation, enabled the synthesis of syn,anti,trans epoxide 17 , which could not be obtained with our first generation methodology (Scheme 5a) [28]. A variation of our second generation approach was also developed to reach the remaining epoxy alcohols, where a C2-hydroxymethyl was incorporated to enable syn selective epoxidations using the microwave-assisted VO(acac) 2 conditions [37]. Free and monoprotected 1,3-diols were stereoselectively epoxidized, and the directing effect was prompted by the C2-hydroxymethyl group, providing access to C2- syn epoxide 20 (Scheme 5b).…”

Regiocontrolled Ring Opening of Monoprotected 2,3-Epoxy-1,4-diols by Using Alkynyl Aluminum Reagents: Synthesis of Differentially Monoprotected Alkynyl Triol Derivatives

“…3 In this instance, and contrary to the first-generation epoxides 1 -cis and 1 -trans , the regioselective cleavage of epoxides 4 at the C2 or the C3 position produces monoprotected the alkynyl triols 5 or 6 , respectively. These derivatives are equally useful for the synthesis of propionates as they are differentially protected stereoisomeric triols.…”

“…In this regards, we recently prepared several challenging C2 syn epoxy alcohols not previously available with the first-generation method. 3 …”

Concise epoxide-based synthesis of the C14–C25 bafilomycin A1 polypropionate chain

“…The ease of access and the predictability of their cleavage reaction is what has interested us in developing a methodology for the synthesis of polypropionates based on the regioselective cleavage of disubstituted epoxides. 27–35 Our methodology consists in three reiterative steps: the cleavage of a disubstituted epoxide with an alkynyl alane reagent, reduction of the alkyne, and stereoselective epoxidation of the newly formed alkenol (Scheme 1). This provides a new epoxide to which the three-step process is repeated, allowing the preparation of a number of stereochemical possibilities.…”

“…Because of this, several polypropionate permutations can be constructed without the need for any aldolic steps. For this approach to be successful, we have studied the stereoselective epoxidation of homoallylic alcohols 27,30,35 , and the regioselective cleavage of these epoxides. 31–33 This methodology has led to the successful linear synthesis of the all anti fragment of streptovaricin U and other polypropionate modules.…”