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Enantioselective Construction of Cyclic Indolyl α‐Amino Esters via a Friedel–Crafts Alkylation Reaction
Author(s) -
Wu Liang,
Liu RenRong,
Zhang Guoqi,
Wang DanJie,
Wu Hao,
Gao Jianrong,
Jia YiXia
Publication year - 2015
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201400987
Subject(s) - chemistry , enantioselective synthesis , stereocenter , alkylation , trifluoromethanesulfonate , indole test , isothiazole , sulfonyl , friedel–crafts reaction , pyrrole , organic chemistry , catalysis , medicinal chemistry , combinatorial chemistry , alkyl
An enantioselective Friedel–Crafts alkylation reaction of indoles with cyclic N ‐sulfonyl ketimino esters was developed. Under the optimized conditions using a chiral copper(II) triflate‐bisoxazoline complex as the catalyst, a range of N ‐sulfonyl ketimino ester derivatives and indoles reacted smoothly to afford indole‐containing chiral cyclic α‐amino esters bearing tetrasubstituted α‐stereogenic centers [3‐ethoxycarbonyl‐3‐(3‐indolyl)‐2,3‐dihydrobenzo[ d ]isothiazole 1,1‐dioxides] in excellent yields and with high enantioselectivities (up to 99% ee ). Pyrrole and N , N ‐dimethylaniline were also investigated as aromatic substrates to afford the corresponding products with good results. An asymmetric induction model was then proposed on the basis of the observed absolute configuration of the product 3‐ethoxycarbonyl‐3‐(5‐bromo‐3‐indolyl)‐2,3‐dihydrobenzo[ d ]isothiazole 1,1‐dioxide. Synthetic transformations to convert the products into cyclic chiral N ‐sulfonamido alcohols and the deprotection of the sulfonamides were performed. This study provides an efficient approach to chiral α‐tetrasubstituted indolic α‐amino acids as potential building blocks for peptides and biologically active molecules.