Enantioselective Copper(I)‐Catalyzed Alkynylation of Oxocarbenium Ions to Set Diaryl Tetrasubstituted Stereocenters

Abstract

An enantioselective,copper(I)-catalyzed addition of terminal alkynes to isochroman ketals to set diaryl, tetrasubstituted stereocenters has been developed. The success of this reaction relies on identification of aCu/PyBoxcatalyst capable of distinguishing the faces of the diaryl-substituted oxocarbenium ion. This challenging transformation enables efficient conversion of readily available,racemic ketals into high-value enantioenriched isochroman products with fully substituted stereogenic centers.High yields and enantiomeric excesses are observed for various isochroman ketals and an arrayo f alkynes.Scheme 1. Enantioselective additions to oxocarbeniumions.

Enantioselective Alkynylation of Unstabilized Cyclic Iminium Ions

“…The additional steric bulk of o-tolylacetylene is accommodated with high yield and ee observed (10). Functional groups, such as p-bromo, mchloro, and p-Bpin, can be incorporated effectively (11,12,14), enabling downstream cross-couplings of the alkynylated products. High enantioselectivities were observed for other aryl acetylenes with electron-withdrawing substituents such as ether (13), nitrile (15), trifluoromethyl (16), and ester (17).…”

Stereospecific and stereoconvergent nucleophilic substitution reactions at tertiary carbon centers

“…Watson reported a copper-catalyzed enantioconvergent substitution of racemic acetals 90 with alkynes as nucleophiles (Scheme 18). 45 Boron trifluoride diethyl etherate was used as Lewis acid to initiate the ionization of C-O bond. The tertiary carbocation intermediate 93 was stabilized by the formation of oxygen-atom-stabilized oxocarbenium ion 94.…”