Homologation chemistry with nucleophilic α-substituted organometallic reagents: chemocontrol, new concepts and (solved) challenges.

Laura Castoldi,Serena Monticelli,Vittorio Pace,Laura Ielo,Raffaele Senatore

doi:10.1039/c8cc02499e

Laura Castoldi, Serena Monticelli + Show 3 more

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https://doi.org/10.1039/c8cc02499e

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Abstract

The transfer of a reactive nucleophilic CH2X unit into a preformed bond enables the introduction of a fragment featuring the exact and desired degree of functionalization through a single synthetic operation. The instability of metallated α-organometallic species often poses serious questions regarding the practicability of using this conceptually intuitive and simple approach for forming C-C or C-heteroatom bonds. A deep understanding of processes regulating the formation of these nucleophiles is a precious source of inspiration not only for successfully applying theoretically feasible transformations (i.e. determining how to employ a given reagent), but also for designing new reactions which ultimately lead to the introduction of molecular complexity via short experimental sequences.

Highlights

The introduction of C1 units into organic frameworks – usually referred to as homologation – represents a versatile tool with widespread applications in organic synthesis.[1]
The transfer of a reactive nucleophilic CH2X unit into a preformed bond enables the introduction of a fragment featuring the exact and desired degree of functionalization through a single synthetic operation
Given the nucleophilicity of nitrile-type carbanions[27] and the unique acylating properties of Weinreb amides, we have developed a simple, efficient, protocol for the synthesis of variously functionalized a-cyanoketones (Scheme 7).[28]

Summary

Introduction

The introduction of C1 units into organic frameworks – usually referred to as homologation – represents a versatile tool with widespread applications in organic synthesis.[1].

Results

Conclusion