Catalytic Asymmetric Inverse‐Electron‐Demand Oxa‐Diels–Alder Reaction of In Situ Generated ortho‐Quinone Methides with 3‐Methyl‐2‐Vinylindoles

Abstract

The first catalytic asymmetric inverse‐electron‐demand (IED) oxa‐Diels–Alder reaction of ortho‐quinone methides, generated in situ from ortho‐hydroxybenzyl alcohols, has been established. By selecting 3‐methyl‐2‐vinylindoles as a class of competent dienophiles, this approach provides an efficient strategy to construct an enantioenriched chroman framework with three adjacent stereogenic centers in high yields and excellent stereoselectivities (up to 99 % yield, >95:5 d.r., 99.5:0.5 e.r.). The utilization of ortho‐hydroxybenzyl alcohols as precursors of dienes and 3‐methyl‐2‐vinylindoles as dienophiles, as well as the hydrogen‐bonding activation mode of the substrates met the challenges of a catalytic asymmetric IED oxa‐Diels–Alder reaction.

Catalytic Asymmetric Inverse‐Electron‐Demand Hetero‐Diels−Alder Reactions

“…With o ‐hydroxybenzyl alcohols 102 as the precursors of o ‐quinone methides, the catalytic asymmetric IEDHDA reactions of 3‐methyl‐2‐vinylindoles 103 with in situ generated o ‐quinone methides were developed by Shi's group in 2015 (Scheme ) . Catalyzed by chiral phosphoric acid 105 , a range of chromans 104 with three adjacent stereogenic centers were obtained in up to 99 % yield, >95:5 d.r., and 99 % ee.…”