Diastereoselective Friedel-Crafts alkylation of indoles with chiral alpha-phenyl benzylic cations. Asymmetric synthesis of anti-1,1,2-triarylalkanes.
The reactions of chiral benzyl carbocations bearing alpha-phenyl substituents with N-sulfonylated indoles afford 1,1,2-triarylalkanes with anti-selectivities. This outcome is a reversal of facial diastereoselectivity relative to Bach's alpha-alkyl-bearing benzyl cations. The reactions are promoted by either a Brønsted acid (TFA) or Lewis acid (BF3.OEt2), offering differential diastereoselectivities and reactivities. The electronic properties of both reacting partners strongly influence the reaction rates and the product diastereoselectivities and appear to operate under kinetic control. This chemistry provides an efficient access to sterically congested tetrasubstituted ethanes.
Chung
John Y L
JY
Process Research, Merck Research Laboratories, Rahway, New Jersey 07065, USA. john_chung@merck.com
Mancheno
Danny
D
Dormer
Peter G
PG
Variankaval
Narayan
N
Ball
Richard G
RG
Tsou
Nancy N
NN
D000473:Alkanes / Q000138:chemical synthesis* / Q000737:chemistry; D000478:Alkylation; D001555:Benzene Derivatives / Q000737:chemistry; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D007211:Indoles / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
D000473:Alkanes; D001555:Benzene Derivatives; D007211:Indoles