康 · 学术 | Reaction of the Day No. 1708

Direct Stereospecific Deoxyamination of Alcohols Enabled by Li-Mediated SuFEx

Amaechi S. Odoh, Giovani Gutierrez, Austin G. Seilkop, Jorge Barroso, Andrew Storer, and Byoungmoo Kim

Clemson University, United States

Recommended by Bing Han_MC3

KEY WORDS: stereocontrolleddeoxyamination, deoxygenation (反应类型),C(sp3)?N (成键类型), alcohols, N-nucleophiles (原料), amines (产物), lithium triflate, PBSF, Sulfur(VI)-Fluoride Exchange (SuFEx) (其他)

ABSTRACT: Optically active nitrogen-bearing molecules are central to drug discovery, which has driven the development of efficient, stereocontrolled C(sp3)?N bond-forming methods. Herein we report a SuFEx-enabled platform that directly couples diverse alcohols and free N-nucleophiles via deoxygenative C(sp3)?N(sp3/sp2) bond formation with high stereospecificity without elimination. Using an inexpensive lithium triflate salt to suppress competitive deoxyfluorination, this method enables facile deoxyamination with broad substrate scope, N-heterocycle synthesis, late-stage functionalization, and stereodivergent synthesis of pharmaceuticals.

Reaction Design

Optimization of Reaction Conditions

Substrate Scope (selected examples)

DFT Computational Studies

Summary and Comments

Prof. Byoungmoo Kim and his co-workers reported a unified SuFEx-enabled deoxyamination for one-step, highly stereospecific C(sp3)? N(sp3/sp2) bond formation using diverse alcohols and free N-nucleophiles. The success of this method can primarily be attributed to the utilization of a simple lithium additive, facilitating deoxyamination while suppressing competitive deoxyfluorination. This work is versatility, robustness, and mildness, we anticipate that this work will be broadly applicable in drug development as well as user-friendly for non-experts.