Molybdenum-catalyzed asymmetric anti-dihydroxylation of allylic alcohols

Pei Fan,Chuan Wang

doi:10.1038/s42004-019-0208-2

Pei Fan, Chuan Wang

Open Access

https://doi.org/10.1038/s42004-019-0208-2

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Abstract

Asymmetric dihydroxylation of alkenes is one of the fundamental reactions in organic synthesis, but the anti-dihydroxylation is much less developed than its syn-variant. Here we report a highly enantio- and diastereoselective anti-dihydroxylation of allylic alcohols by using a chiral molybdenum-bishydroxamic acid complex as catalyst and environmentally benign hydrogen peroxide as oxidant. This reaction enables the construction of the 1,2,3-triol structural unit in high enantio- and diastereocontrol starting from simple allylic alcohol precursors. Our reaction complements the Sharpless dihydroxylation not only in its diastereoselectivity, but also in regiocontrol. The mechanistic studies indicate that this dihydroxylation reaction consists of an initial enantioselective epoxidation and the following in situ regioselective ring opening, both of which are promoted by the molybdenum-catalyst.

Highlights

Asymmetric dihydroxylation of alkenes is one of the fundamental reactions in organic synthesis, but the anti-dihydroxylation is much less developed than its syn-variant
Asymmetric dihydroxylation of alkenes is one of the cornerstone reactions in organic synthesis, as it provides a direct entry to optically active vicinal diols, which are a subunit in a large number of naturally occurring compounds and important building blocks in many syntheses[1,2]
A series of chiral bishydroxamic acids (BHA) L1-6 bearing trans-cyclohexane diamine scaffold were investigated as ligands in the reaction using MoO2(acac)[2] as catalyst in EtOAc at 40 °C (Table 1, entries 1–6)

Summary

Introduction

Asymmetric dihydroxylation of alkenes is one of the fundamental reactions in organic synthesis, but the anti-dihydroxylation is much less developed than its syn-variant. We report a highly enantio- and diastereoselective anti-dihydroxylation of allylic alcohols by using a chiral molybdenum-bishydroxamic acid complex as catalyst and environmentally benign hydrogen peroxide as oxidant. This reaction enables the construction of the 1,2,3-triol structural unit in high enantio- and diastereocontrol starting from simple allylic alcohol precursors. In the past two decades, a number of Os-free asymmetric syn-dihydroxylations have been developed[11], including the examples using chiral Mn- 12,13 or Fe- 14,15 complexes, bimetallic nanoclusters[16] and organic phase transfers as catalysts[17,18].

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