Abstract
A palladium(ii)-catalysed C(sp3)-H carbonylation of free(NH) secondary aliphatic amines to 2-pyrrolidinones is described. A correlation between the nature of the carboxylate ligand and the diastereoselectivity and yield of the process was observed. As such, under these optimal conditions a range of aliphatic amines were converted to the corresponding trans-4,5-disubstituted 2-pyrrolidines with good d.r. and yield.
Highlights
All publication charges for this article have been paid for by the Royal Society of Chemistry
As part of an ongoing research program in our laboratory towards establishing secondary alkylamines as viable feedstocks for catalytic C–H activation-based synthesis strategies,[7] we reasoned that a single step process capable of forging 2pyrrolidinones from carbon monoxide (CO) and unfunctionalized secondary alkylamines would represent a useful synthetic transformation.[8,9]
While important independent work by Carretero,[10] Wang[11] and Zhao[12] on Pd-catalyzed C–H carbonylation of auxiliary-derived alkylamines has enabled the synthesis of some 2-pyrrolidinonederived scaffolds (Fig. 1b), the use of more tractable unprotected secondary alkylamines is unknown and has presented
Summary
All publication charges for this article have been paid for by the Royal Society of Chemistry. A correlation between the nature of the carboxylate ligand and the diastereoselectivity and yield of the process was observed As such, under these optimal conditions a range of aliphatic amines were converted to the corresponding trans-4,5-disubstituted 2-pyrrolidines with good d.r. and yield. Five-membered ring saturated nitrogen-containing heterocycles are ubiquitous structural features in alkaloid natural products, small-molecule biological probes and pharmaceutical agents (Fig. 1a).[1] Among these scaffolds, 2-pyrrolidinones represent a synthetically versatile class of heterocycle due to the diverse reactivity imparted by the amide functional group. The majority of transformations that generate the 2-pyrrolidinone scaffold can be mainly divided into two reaction classi cations: cyclization of bifunctional substrates[2,3,4,5] and transformations of appropriately functionalized 5-membered ring core.[6] Of particular importance to the successful realization of these processes is the need for reactive functional groups resident within the framework of the precursors to the nitrogen heterocycle. While important independent work by Carretero,[10] Wang[11] and Zhao[12] on Pd-catalyzed C–H carbonylation of auxiliary-derived alkylamines has enabled the synthesis of some 2-pyrrolidinonederived scaffolds (Fig. 1b), the use of more tractable unprotected secondary alkylamines is unknown and has presented
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