Remote enantioselective Friedel-Crafts alkylations of furans through HOMO activation.
Catalytic asymmetric Friedel-Crafts alkylation is a powerful protocol for constructing a chiral C(sp(2))-C(sp(3)) bond. Most previous examples rely on LUMO activation of the electrophiles using chiral catalysts with subsequent attack by electron-rich arenes. Presented herein is an alternative strategy in which the HOMO of the aromatic π system of 2-furfuryl ketones is raised through the formation of a formal trienamine species using a chiral primary amine. Exclusive regioselective alkylation at the 5-position occurred with alkylidenemalononitriles, and high reactivity and excellent enantioselectivity (up to 95% ee) was obtained by this remote activation.
Key Laboratory of Drug-Targeting and Drug Delivery System of the Ministry of Education, West China School of Pharmacy, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041 (China).
Jun-Long
JL
Li
Cai-Zhen
CZ
Yue
Peng-Qiao
PQ
Chen
You-Cai
YC
Xiao
Ying-Chun
YC
Chen
D000478:Alkylation; D000588:Amines / Q000737:chemistry; D002384:Catalysis; D005663:Furans / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry; D009570:Nitriles / Q000737:chemistry; D011789:Quantum Theory; D013237:Stereoisomerism; D013890:Thiourea / Q000737:chemistry
D000588:Amines; D005663:Furans; D007659:Ketones; D009570:Nitriles; C000945:dicyanmethane; D013890:Thiourea
alkylation; heterocycles; organocatalysis; regioselectivity; synthetic methods