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

Abstract

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.

copper - azomethine ylides - 1,3-dipolar cycloaddition - ferrocene ligand - asymmetric catalysis - vinyl sulfones - pyrrolidines

References

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<A NAME="RZ23806SS-14">14</A>

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 NAME="RZ23806SS-15">15</A>

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).

<A NAME="RZ23806SS-16">16</A>

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.

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<A NAME="RZ23806SS-20">20</A> The acyclic γ,δ-unsaturated α-amino ester, methyl (R,E)-2-(methylamino)-5-phenylpent-4-enoate (10, see Scheme 3), was also isolated as a byproduct in 28% yield in the desulfonylation step as a result of a Julia-like reaction involving the cleavage of the C-N bond. For related Julia-like reactions, see: Iradier F. Gómez-Arrayás R. Carretero JC. Org. Lett.  2001,  3:  2957 ; and references cited therein

<A NAME="RZ23806SS-21">21</A>

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