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Highly Enantioselective Synthesis of 11‐Substituted 10,11‐Dihydrodibenzo[ b,f ][1,4]thiazepines through a Proline‐Catalyzed Mannich Reaction of Seven‐Membered Cyclic Imines with Ketones
Author(s) -
Deng ZhuoFei,
Huang Bo,
Xu Huajing,
Shi Feng,
Wang YouQing
Publication year - 2017
Publication title -
asian journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.846
H-Index - 44
eISSN - 2193-5815
pISSN - 2193-5807
DOI - 10.1002/ajoc.201700283
Subject(s) - chemistry , stereocenter , enantioselective synthesis , mannich reaction , imine , medicinal chemistry , enantiomer , catalysis , alkyl , proline , organic chemistry , stereochemistry , amino acid , biochemistry
Highly enantioselective Mannich addition reactions of N,S‐heterocyclic dibenzo[ b,f ][1,4]thiazepines as seven‐membered cyclic imine substrates with ketones were developed by using proline as an organocatalyst. Substituted dibenzo[ b,f ][1,4]thiazepines and various unsymmetrical alkyl methyl ketones were used as substrates and optimized reaction conditions offered an efficient method to synthesize optically active 11‐substituted 10,11‐dihydrodibenzo[ b,f ][1,4]thiazepine derivatives that contained a carbonyl functional group in 91–99 % ee . Furthermore, we found that the reactions could also be performed on a gram scale, whilst maintaining high yields and enantioselectivities. The carbonyl group of the Mannich products also underwent diastereoselective reduction, thus yielding a new hydroxy‐substituted chiral stereogenic center with moderate‐to‐excellent diastereoselectivities, good yields, and without the loss of enantiomeric excess.