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.

Using chiral phosphoric acids as organocatalysts, a formal asymmetric (4+2) cycloaddition of 3‐methylene isoindolinone and in situ‐generated ortho‐quinone methide substrates is disclosed. This reaction exhibited a broad substrate scope with various substituted cyclic enamides and ortho‐hydroxybenzyl alcohol derivatives to construct a series of spiro chroman‐isoindolinones containing spiro‐N,O‐heterocycles with 56 to 93% ee. This strategy demonstrates significant potential towards establishing a chiral spiro‐N,O‐aminal systems bearing two chiral carbon centers, including a tetrasubstituted carbon stereocenter.