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

ABSTRACT: 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.

SUBMITTER: Mackey P

PROVIDER: S-EPMC8383304 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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

Mackey Pamela P Turlik Aneta A Ando Kaori K Light Mark E ME Houk K N KN McGlacken Gerard P GP

Organic letters 20210810 16

The stereoselective formation of 5 contiguous chiral centers in a single pot reaction is demonstrated using an aldol, aldol-Tishchenko reaction of <i>N</i>-<i>tert</i>-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 funn ...[more]

PMID: 34374288

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