Stereoselective Installation of Five Contiguous Stereogenic Centers in a Double Aldol–Tishchenko Cascade and Evaluation of the Key Transition State through DFT Calculation

[Image: see text] The stereoselective formation of 5 contiguous chiral centers in a single pot reaction is demonstrated using an aldol, aldol–Tishchenko reaction of N-tert-butyl sulfinimines. One diastereoisomer (from 32 possibilities) predominates, and a series of cyclic and acyclic 3-amino-1,5-diol derivatives are synthesized in good yields (up to 80%) and excellent diastereoselectivities (up to >98:2 dr). Investigations support two reversible aldol steps, and multiple intermediates which are funnelled through a remarkably selective, irreversible, Tishchenko reduction, in a Curtin–Hammett phenomenon. DFT calculations using a disolvated (THF) model reveal the factors controlling stereoselectivity in the final irreversible Tishchenko step.