A primary challenge in C-H functionalization is achieving control over the chemo-, site-, and stereoselectivity of the reaction when the precursor contains multiple, competing reactive functional groups. Our group has designed a suite of silver(I) complexes for C=C and C-H functionalizations via metal-catalyzed nitrene transfer (NT) that: 1) enable us to tune the selectivity of the C-N bond-forming event in a broad array of substrates, 2) alter the mechanism of intermolecular NT to influence chemoselectivity, 3) achieve asymmetric aziridination and C-H bond amidations, and 4) accomplish the late-stage amination of complex natural products and drug targets. Application of silver-catalyzed NT to a variety of alkenes, dienes, and allenes, followed by carbene transfer, generates unusual aziridinium ylide intermediates. Judicious choice of substrate, catalyst, carbene precursor, and reaction conditions allow us to divert the ylide intermediate along diverse pathways, providing a unified strategy to furnish stereochemically complex, densely functionalized azetidines, pyrrolidines, piperidines, and other N-heterocycles occurring in many natural products and pharmaceuticals. Synthetic and mechanistic aspects of these versatile tandem nitrene/carbene transfer reactions will be discussed.

Taming nitrene reactivity with silver: Construction (and destruction!) of N-heterocycles

2019 Spring National Meeting

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