Scope and Limitations of the T-reaction: the Tert.-amino-effect in the Synthesis of Chiral Heterocycles

The quinoline motif is an integral part of a wide variety of bioactive classes of compounds. An increasingly popular entry into tetrahydroquinolines is represented by the T-reaction, i. e. a subtype of the transformations relying on the isomerization-cyclization sequence known as the tert.-amino-effect. The latter was shown to proceed via a most remarkable helical dipolar intermediate generated upon a hydrideshift from an alpha-amino-C-H in tert.-anilines to an unsaturated ortho-substituent, accomplishing C-C-bond formation from a nonactivated NCH-moiety. The tert.-amino-effect was first brought to the attention of the synthetic community in the seminal contribution of O. Meth-Cohn and H. Suschitzky from 1972. Since then, the protocol has progressively evolved into a convergent, economical and yield-efficient preparation of structurally diverse, highly functionalized and pharmacologically valuable heterocycles, bearing stereoselectively introduced centers of chirality.