Catalytic Asymmetric Synthesis of α‐Arylpyrrolidines and Benzo‐fused Nitrogen Heterocycles

Abstract

Herein, we report a practical two‐step synthetic route to α‐arylpyrrolidines through Suzuki–Miyaura cross‐coupling and enantioselective copper‐catalyzed intramolecular hydroamination reactions. The excellent stereoselectivity and broad scope for the transformation of substrates with pharmaceutically relevant heteroarenes render this method a practical and versatile approach for pyrrolidine synthesis. Additionally, this intramolecular hydroamination strategy facilitates the asymmetric synthesis of tetrahydroisoquinolines and medium‐ring dibenzo‐fused nitrogen heterocycles.

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

“…Without purification, the resultant aldehyde intermediate was then directly reduced using potassium borohydride to the corresponding primary alcohol 11a in 74% yield starting from 9a . Pd-catalyzed cross-coupling of 11a with pinacol vinylboronate afforded the o -hydroxyethyl-styrene 12a in 78% yield [ 22 – 23 ]. Next, Dess–Martin oxidation of the alcohol 12a was carried out, and the desired 2-(2-vinylphenyl)acetaldehyde ( 13a ) was successfully obtained in 85% yield.…”

Cascade Intramolecular Prins/Friedel–Crafts Cyclization for the Synthesis of 4-Aryl-tetralin-2-ols and 5-Aryl-tetrahydro-5H-benzo[7]annulen-7-ols

“…Pd-catalyzed cross-coupling of 3a with pinacol vinylboronate afforded the styrene 4a in 78% yield. 20,21 Next, Dess-Martin oxidation of alcohol 4a was carried out, and the desired 2-(2-vinylphenyl)acetaldehyde 5a was successfully obtained in 85% yield. Obviously, this modified method has the advantages of mild reaction condition, operation simplicity, and using cheap and non-toxic reagents.…”

Synthesis of Medium-Sized Heterocycles by Transition-Metal-Catalyzed Intramolecular Cyclization

“…Buchwald and co-workers dedicated efforts to developing many strategies for copper-catalyzed hydroamination of olefins. An asymmetric intramolecular variant was proposed and applied to the synthesis of medium-sized N,O-heterocycles [71]. In this process, the chiral alkylcuprate formed by hydrocupration of the double bond reacted with an electrophilic nitrogen.…”