Organocatalysis Henry reaction

Recent advances in the catalytic asymmetric nitroaldol (Henry) reaction including application of heterocyclic organocatalysis and hgands 07EJO2561. 

The derivatives 3 and 6 without any additional modification at the C9 position are infrequently used for organocatalysis. Recent examples include the synthesis of enantioenriched 1,3,4-trisubstituted thiochromanes by a tandem conjugate addition-Henry reaction between 2-thio-substituted benzaldehydes and nitrosty-renes (Scheme 6.10) [26] and the Henry reaction between isatin and simple nitro-alkanes to form 3-substituted 3-hydro-oxindoles (Scheme 6.11) [27]. 

The asymmehic reaction of nihomethane with aldehydes as well as activated ketones (e.g., hifluoroacetophenone and a-ketoesters) is possible with various chiral metallic complexes or organocatalysis under atmospheric pressure with good yield and enanhoselectivity. However, the Henry reaction of aryl alkyl ketones shll remains problematic and challenging. Matsumoto s group also tested the very difficult reaction of acetophenone and nitromethane with quinidine. No product was observed under Ibar and only traces at 7 kbar, but application of 10 kbar resulted in a significant improvement in yield (31%) - unfortunately, no enantioselectivity was detected (Scheme 21.3). 

Finally, a remarkable four-component tandem Michael-aza-Henry-hemi-aminalisation-dehydration tandem reaction was recently developed by Lin and co-workers on the basis of a dual organocatalysis involving a chiral diaryl prolinol trimethylsilyl ether and a chiral cinchona alkaloid." As shown in Scheme 2.37, the reaction began with the Michael addition of an aldehyde to a nitroalkene catalysed by the L-proline-derived catalyst, giving the corresponding intermediate aldehyde. The latter intermediate... 

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