Abstract
Nature routinely engages alcohols as leaving groups, as DNA biosynthesis relies on the removal of water from ribonucleoside diphosphates by a radical-mediated "spin-center shift" (SCS) mechanism. Alcohols, however, remain underused as alkylating agents in synthetic chemistry due to their low reactivity in two-electron pathways. We report herein an enantioselective α-benzylation of aldehydes using alcohols as alkylating agents based on the mechanistic principle of spin-center shift. This strategy harnesses the dual activation modes of photoredox and organocatalysis, engaging the alcohol by SCS and capturing the resulting benzylic radical with a catalytically generated enamine. Mechanistic studies provide evidence for SCS as a key elementary step, identify the origins of competing reactions, and enable improvements in chemoselectivity by rational photocatalyst design.
Original language | English (US) |
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Pages (from-to) | 3322-3330 |
Number of pages | 9 |
Journal | Journal of the American Chemical Society |
Volume | 140 |
Issue number | 9 |
DOIs | |
State | Published - Mar 7 2018 |
All Science Journal Classification (ASJC) codes
- Catalysis
- Chemistry(all)
- Biochemistry
- Colloid and Surface Chemistry