Palladium/N-heterocyclic carbene catalysed regio and diastereoselective reaction of ketones with allyl reagents via inner-sphere mechanism.

Da-Chang Bai,Wan-Ying Wang,Fei-Le Yu,Qing-Rong Liu,Xue-Long Hou,Bo Chen,Chang-Hua Ding,Di Chen,Hao Li

doi:10.1038/ncomms11806

Abstract

The palladium-catalysed allylic substitution reaction is one of the most important reactions in transition-metal catalysis and has been well-studied in the past decades. Most of the reactions proceed through an outer-sphere mechanism, affording linear products when monosubstituted allyl reagents are used. Here, we report an efficient Palladium-catalysed protocol for reactions of β-substituted ketones with monosubstituted allyl substrates, simply by using N-heterocyclic carbene as ligand, leading to branched products with up to three contiguous stereocentres in a (syn, anti)-mode with excellent regio and diastereoselectivities. The scope of the protocol in organic synthesis has been examined preliminarily. Mechanistic studies by both experiments and density functional theory (DFT) calculations reveal that the reaction proceeds via an inner-sphere mechanism—nucleophilic attack of enolate oxygen on Palladium followed by C–C bond-forming [3,3']-reductive elimination.

Highlights

The palladium-catalysed allylic substitution reaction is one of the most important reactions in transition-metal catalysis and has been well-studied in the past decades
This work: N-heterocyclic carbene (NHC) as ligand with Oxygen nucleophile branched products with three contiguous stereocentres d contiguous stereocentres can be obtained with excellent regio and diastereoselectivities (Fig. 1d)
The linear product was obtained as the major component in both cases, with branched to linear ratios (B/L) of 6/94 and 15/85, respectively, despite high yields (95% and 98%)

Summary

Introduction

The palladium-catalysed allylic substitution reaction is one of the most important reactions in transition-metal catalysis and has been well-studied in the past decades. The reaction proceeds through an outer-sphere mechanism, in which the nucleophile attacks the allyl carbon of p-allyl-Pd complex, and affords linear products when monosubstituted allyl reagents are used[1,2,3,4,5,6,7,8,9,10,11,12]. Several studies on Pd-catalysed allylic substitution/ coupling reactions via inner-sphere mechanism have been reported[21,22,23,24,25,26,27,28,29,30,31,32,33].

Results

Conclusion