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. 2015 Jun 3;56(23):3489-3493.
doi: 10.1016/j.tetlet.2015.04.006. Epub 2015 Apr 9.

N-Substituted tertiary and O-substituted quaternary carbon stereogenic centers by site-, diastereo- and enantioselective vinylogous Mannich reactions

Daniel L Silverio  1 , Peng Fu  1 , Emma L Carswell  1 , Marc L Snapper  1 , Amir H Hoveyda  1
Affiliations

N-Substituted tertiary and O-substituted quaternary carbon stereogenic centers by site-, diastereo- and enantioselective vinylogous Mannich reactions

Daniel L Silverio et al. Tetrahedron Lett. .

Abstract

A readily accessible small-molecule phosphine, derived from commercially available starting materials such as an enantiomerically pure amino acid, serves as the precursor to a Ag-based chiral complex that can be prepared and used in situ to promote a variety of enantioselective vinylogous Mannich (EVM) reactions that involve siloxypyrroles as reaction partners. Transformations with unsubstituted nucleophilic components proceed efficiently and with exceptional site- (γ vs α-addition), diastereo- and enantioselectivity [up to 98% yield, generally >98:2 γ/α and diastereomeric ratio (dr) and up to 99:1 enantiomeric ratio (er)]. The first examples of efficient, diastereo- and enantioselective vinylogous Mannich additions with 5-methyl-substituted siloxyfuran, resulting in the formation of O-substituted quaternary carbon stereogenic centers are presented as well. Appreciable efficiency and diastereo- and enantioselectivity (up to >98:2 dr and >99:1 er) is accompanied by formation of α-addition products that can be oxidatively removed.

Keywords: Amines; Catalysis; Enantioselective synthesis; Quaternary carbons; Siloxyfurans; Silver complexes; Vinylogous Mannich reactions.

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Figures

Scheme 1
Scheme 1
Enantioselective Mannich Reactions Promoted by Ag-Based Catalysts
Scheme 2
Scheme 2
Additions of Siloxypyrrole 3 to Aryl-Substituted Aldiminesa aSee the Supporting Information for details. Boc, t-butoxycarbonyl
Scheme 3
Scheme 3
Additions of Siloxypyrrole 3 to Aryl-Substituted Aldiminesa aSee the Supporting Information for experimental and analytical details.
Scheme 4
Scheme 4
Multicomponent EVM Involving an Aryl-Substituted Aldiminesa aSee the Supporting Information for experimental and analytical details.
Scheme 5
Scheme 5
Additions of Siloxypyrrole 10 to Aryl-Substituted Aldiminesa aSee the Supporting Information for experimental and analytical details.
Scheme 6
Scheme 6
Additions of Siloxyfuran 10 to Alkynyl-Substituted Aldiminesa aSee the Supporting Information for experimental and analytical details.
See this image and copyright information in PMC

References

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