Synthesis 2012; 44(12): 1863-1873
DOI: 10.1055/s-0031-1290964
special topic
© Georg Thieme Verlag Stuttgart · New York

A New Tandem Cross Metathesis–Intramolecular Aza-Michael Reaction for the Synthesis of α,α-Difluorinated Lactams

Santos Fustero*
Departamento de Química Orgánica, Universidad de Valencia, 46100 Burjassot, Spain, Fax: +34(96)3544939   Email: santos.fustero@uv.es   Email: carlos.pozo@uv.es
,
Claribel Báez
Departamento de Química Orgánica, Universidad de Valencia, 46100 Burjassot, Spain, Fax: +34(96)3544939   Email: santos.fustero@uv.es   Email: carlos.pozo@uv.es
,
María Sánchez-Roselló
Departamento de Química Orgánica, Universidad de Valencia, 46100 Burjassot, Spain, Fax: +34(96)3544939   Email: santos.fustero@uv.es   Email: carlos.pozo@uv.es
,
Amparo Asensio
Departamento de Química Orgánica, Universidad de Valencia, 46100 Burjassot, Spain, Fax: +34(96)3544939   Email: santos.fustero@uv.es   Email: carlos.pozo@uv.es
,
Javier Miro
Departamento de Química Orgánica, Universidad de Valencia, 46100 Burjassot, Spain, Fax: +34(96)3544939   Email: santos.fustero@uv.es   Email: carlos.pozo@uv.es
,
Carlos del Pozo*
Departamento de Química Orgánica, Universidad de Valencia, 46100 Burjassot, Spain, Fax: +34(96)3544939   Email: santos.fustero@uv.es   Email: carlos.pozo@uv.es
› Author Affiliations
Further Information

Publication History

Received: 07 March 2012

Accepted: 13 March 2012

Publication Date:
27 April 2012 (eFirst)

Abstract

A new tandem cross metathesis–intramolecular aza-Michael­ reaction in which an α,α-difluorinated amide serves as a source of nucleophilic nitrogen is described. This process gives rise to a new family of fluorinated γ- and δ-lactams. The tandem protocol is catalyzed by the Hoveyda–Grubbs second-generation ruthenium catalyst with titanium(IV) tetraisopropoxide as a co-catalyst and it is highly efficient when conjugated ketones are used as the Michael acceptors. With conjugated esters, however, it is necessary to perform a step-by-step procedure in which the cyclization event is activated by the addition of a base. An asymmetric version of the process is also evaluated.

 
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