Synthesis 2007(6): 950-956  
DOI: 10.1055/s-2007-965926
© Georg Thieme Verlag Stuttgart · New York

Copper(I)-Catalyzed Enantioselective 1,3-Dipolar Cycloaddition of Azomethine Ylides with Vinyl Sulfones

Tomás Llamas, Ramón Gómez Arrayás, Juan Carlos Carretero*
Departamento de Química Orgánica, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain
Fax: +34(914)973966; e-Mail:[email protected];
Further Information

Publication History

Received 16 November 2006
Publication Date:
08 February 2007 (online)


The combination of copper(I)-Taniaphos (5 mol%) is an efficient Lewis acid catalyst for the promotion of the asymmetric 1,3-dipolar cycloaddition of azomethine ylides to aryl vinyl sulfones, providing 3-sulfonylpyrrolidines in good yields and with nearly complete exo-selectivity and good enantiocontrol (typically 65-85% ee). The transformation of the cycloadducts into cis-2,5-disubstituted pyrrolidines of high enantiopurity (>99% ee) has been accomplished after simple recrystallization followed by N-methylation and subsequent reductive desulfonylation.


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The silver(I) acetate catalyzed reaction between 1a and 2a was also studied, providing generally poorer reactivities and enantioselectivities. Interestingly, Taniaphos proved to be also the best ligand in the silver-promoted reaction.


A number of well-established commercially available P,P-ligands such as Binap, Chiraphos, Norphos, and Phanephos led to low to moderate enantioselectivities (19-42% ee). Very poor results (<10% ee) were obtained with BOX, PyBOX and phosphoramidite ligands. Ferrocene-based ligands gave superior results in this reaction, the Fesulphos family and the Solvias’ ligands Walphos and Taniaphos providing enantioselectivities in the range of 50-83% ee (see ref. 13).


Sulfones 2b-d were readily available by reaction of the corresponding aryl disulfide with vinylmagnesium bromide and subsequent oxidation of the resulting sulfide to sulfone with Na2WO4·2 H2O/H2O2. On the other hand, 2e was prepared from 2-(dimethylamino)phenyl methyl sulfone and formaldehyde. See the Supporting Information in reference 13 for details.


Experimental details and analytical data regarding the preparation of imines 1a-j are found within the Supporting Information of reference 13.