Hypervalent Iodine(III)-Catalysed Enantioselective α-Acetoxylation of Ketones.

Tobias Hokamp,Thomas Wirth

doi:10.1002/chem.202000927

Abstract

An enantioselective catalytic synthesis of α‐acetoxylated ketones through I(I)/I(III) catalysis using a resorcinol/lactamide‐based chiral iodoarene is reported. Catalyst turnover by in situ generation of the active iodine(III) derivative is achieved by oxidation with mCPBA in the presence of acetic acid. The prior transformation of ketones to easily accessible acetyl enol ethers is beneficial and yields up to 97 % with enantioselectivities up to 88 % ee are obtained using only low catalyst loadings of only 5 mol % under mild reaction conditions.

Highlights

An enantioselective catalytic synthesis of a-acetoxylated ketones through I(I)/I(III) catalysis using a resorcinol/lactamide-based chiral iodoarene is reported
The synthesis of enantioenriched a-oxygenated carbonyl compounds represents a highly relevant transformation mediated by hypervalent iodine chemistry as the resulting molecules are versatile building blocks for natural products and pharmaceuticals.[7]
While enantioselective a-oxytosylations of carbonyl compounds are extensively described, enantioselective a-oxygenations including other nucleophiles remain scarce in the literature.[7b]. Surprisingly, the a-acetoxylation of ketones is one of the least described a-oxygenation reactions it is the oldest of all hypervalent iodine(III)-mediated a-oxygenation reactions.[14,15]

Summary

Introduction

An enantioselective catalytic synthesis of a-acetoxylated ketones through I(I)/I(III) catalysis using a resorcinol/lactamide-based chiral iodoarene is reported. Propiophenone 2, silyl enol ether 3 and acetyl enol ether 4 a were oxidised in presence of lactate/ resorcinol-based chiral hypervalent iodine(III) reagent 6 a and BF3·OEt2 to product (R)-5 a (Table 1, entries 1–3) under optimised reaction conditions (see Supporting Information).

Results

Conclusion