Direct Carbon-Carbon Bond Formation via Soft Enolization of Thioesters: An Operationally Simple Mannich Addition Reaction

Abstract

Thioesters undergo soft enolization and direct Mannich addition to sulfonylimines on treatment with magnesium bromide ethyl etherate and N,N-diisopropylethylamine. The reactions proceed readily with a range of sulfonylimines and, in the case of 2,4,6-triisopropylphenyl thiopropionate, give moderate to good syn dia­stereoselectivity.

enolates - imines - Mannich addition reactions - magnesium - thioesters

References

<A NAME="RC04908SS-1A">1a</A> Benaglia M. Cinquini M. Cozzi F. Eur. J. Org. Chem.  2000,  563 

<A NAME="RC04908SS-1B">1b</A> Hart DJ. Ha D.-C. Chem. Rev.  1989,  89:  1447 

<A NAME="RC04908SS-2">2</A> For a recent example of an enolate addition to N-alkyl-imines, see: Tanaka S.-y. Tagashira N. Chiba K. Yasuda M. Baba A. Angew. Chem. Int. Ed.  2008,  47:  6620 

For pioneering applications of soft enolization in direct carbon-carbon bond formation, see:

<A NAME="RC04908SS-3A">3a</A> Rathke MW. Cowan PJ. J. Org. Chem.  1985,  50:  2622 

<A NAME="RC04908SS-3B">3b</A> Rathke MW. Nowak M. J. Org. Chem.  1985,  50:  2624 

<A NAME="RC04908SS-3C">3c</A> Tirpak RE. Olsen RS. Rathke MW. J. Org. Chem.  1985,  50:  4877 

<A NAME="RC04908SS-4">4</A> Lim D. Zhou G. Livanos AE. Fang F. Coltart DM. Synthesis  2008,  2148 

<A NAME="RC04908SS-5A">5a</A> Yost JM. Zhou G. Coltart DM. Org. Lett.  2006,  8:  1503 

<A NAME="RC04908SS-5B">5b</A> Zhou G. Yost JM. Coltart DM. Synthesis  2007,  478 

<A NAME="RC04908SS-5C">5c</A> Zhou G. Lim D. Coltart DM. Org. Lett.  2008,  10:  3809 

<A NAME="RC04908SS-6A">6a</A> Gizecki P. Youcef RA. Poulard C. Dhal R. Dujardin G. Tetrahedron Lett.  2004,  45:  9589 

<A NAME="RC04908SS-6B">6b</A> Wenzel AG. Jacobsen EN. J. Am. Chem. Soc.  2002,  124:  12964 

<A NAME="RC04908SS-7">7</A>

1 and 6 are commercially available (Aldrich).

<A NAME="RC04908SS-8">8</A> All sulfonylimines used here, with the exception of commercially available 1 (Aldrich), were prepared by condensation of the corresponding aldehyde and benzenesulfonamide according to: Jin T.-S. Yu M.-J. Liu L.-B. Zhao Y. Li T.-S. Synth. Commun.  2006,  36:  2339 

<A NAME="RC04908SS-9">9</A> Thioester 17 is commercially available (Aldrich). 16, 18 and 19 were prepared from the corresponding commercially available (Aldrich) thiols under typical conditions.^5a The thiol used in the synthesis of 20 was prepared according to: Garrattz DG. Beaulieu PL. Can. J. Chem.  1980,  58:  2737