Synthesis Of Chiral Dihydrodibenzo[B,F][1,4]Thiazepines By Asymmetric Organocatalysis Of Seven-membered Cyclic Imines

Dibenzo[b,f][1,4]thiazepine derivatives are a class of nitrogen-containing heterocyclic compounds containing a special sulfur-nitrogen double heteroatom backbone.The compounds can show significant biological and pharmacological activity in many biomolecules.Asymmetric organocatalysis is the most effective method for the construction of chiral dibenzo[b,f][1,4]thiazepine derivatives.In this paper,highly enantioselective Mannich reaction of seven-membered cyclic imines dibenzo[b,f][1,4]thiazepines with ketones via organocatalysis using(S)-Proline were studied.In addition,chiral NHC(N-heterocyclic carbine)catalyzed [3+2] annulation of α,β-unsaturated aldehydes with the cyclic imines were also be investigated.The different chiral dihydrodibenzo[b,f][1,4]thiazepine derivatives could be synthesized.1.(S)-Proline catalyzed high enantioselective Mannich reaction of dibenzo[b,f][1,4]thiazepines with methyl alkyl ketonesHighly enantioselective Mannich reaction of seven-membered cyclic imines dibenzo[b,f][1,4]thiazepines with ketones were studied via organocatalysis using(S)-Proline.Substituted dibenzo[b,f][1,4]thiazepines and various methyl alkyl ketones were used as substrates,and under optimized catalyst,solvent,temperature etc.,the Mannich reaction offered an efficient method to synthesize optically active 11-substituted 10,11-dihydrodibenzo[b,f][1,4]thiazepine derivatives with 91-99% ee.The carbonyl group of the Mannich products was also found to undergo a diastereoselective reduction,yielding a new hydroxyl substituted chiral stereogenic center with moderate to excellent diastereoselectivities,good yields and without the loss of enantiomeric excess.2.Chiral NHC catalyzed [3+2] annulation of α,β-unsaturated aldehydes with dibenzo[b,f][1,4]thiazepinesChiral NHC catalyzed [3+2] annulations of α,β-unsaturated aldehydes with seven-membered cyclic imines dibenzo[b,f][1,4]thiazepines were described.With the screening of catalyst,solvent,temperature etc.,both different substituted seven-membered cyclic imines and aliphatic or aromatic α,β-unsaturated aldehydes worked well,affording chiral dihydrodibenzo[b,f][1,4]thiazepine derivatives with high diastereoselectivities and excellent enantioselectivity(up to 92% ee).