Cation Radical-Mediated Semi-Pinacol and n+2 Ring Expansions via Organic Photoredox Catalysis

Abstract

In this report, we disclose a photoredox-catalyzed cation radical-mediated semi-pinacol (CRM-SP) rearrangement along with a similar, but mechanistically distinct, n+2 ring expansion with protocols for obtaining either dearomatized or rearomatized products. We present a substrate scope of >30 entries largely focused on the ring expansion of easily appended cyclobutanols and targeting medicinally relevant scaffolds, highlighting the utilization of the methodology for diversi-fication. Gram scale reactions in batch and continuous flow were investigated. Additionally, the mechanism is probed both experimentally and computationally with results suggesting a substrate-dependent set of pathways featuring either A) a concerted 1,2-shift or B) a sequence of proton-coupled electron transfer (PCET), β-scission, Giese addition, and terminal hydrogen atom transfer (HAT).