Prolinamides carbonyl compounds

In direct nitroso aldol reactions of a-branched aldehydes, an L-prolinamide (50) catalyses to give a-hydroxyamino carbonyl compounds which are otherwise dis- favoured ees up to 64% were found.149 Another prolinamide derivative gives similar results in a nitrosobenzene reaction.150 For proline-catalysed cases involving highly substituted cyclohexanones, DFT calculations have highlighted the roles of electro- static and dipole-dipole interactions in the level of de achieved.151 (g)... 

The most widely accepted hypothesis to explain the regio- and stereo outcome of the prolinamide-catalysed aldol reactions supposes the formation of the most stable enamine (generally E-anti) by reaction of the donor carbonyl compound with the pyrrolidine nucleus, and simultaneous activation of the acceptor by hydrogen-bond formation with the carboxamide substituent. Then, the major product is formed by preferential attack of the enamine re-face to the re-face of the carbonyl, as summarised in the ternary complex A (Scheme 6.1). 

Organocatalysed asymmetric Michael addition has been extensively studied because of the interest in the adducts as valuable intermediates in organic synthesis. The use of a carbonyl compound as donor and prolinamides as catalysts supposes the formation of the corresponding enamine which adds to the a,p-unsaturated compound activated by formation of hydrogen bonds with the carboxamide substituent. In general, the major diastereoisomer has syn configuration because the enamine attacks from its re-face to the re-face of the double bond (Scheme 6.2). 

A Toluensulfonyl-L-prolinamide 15b was used as catalyst in the enan-tioselective Michael addition of carbonyl compounds to (B)-nitrostyrene in ionic liquids under different reaction conditions. The best yields (up to 98%) and enantioselectivity (70% ee) were obtained in a basic ionic liquid [bmim]BF4 at room temperature. 

Scheme 6.4 a-Functionalisation of carbonyl compounds promoted by prolinamides. 

Heterofunctionalisation of carbonyl compounds in the a-position has become an important facet of oiganocatalytic enamine-mediated reactions. In 2005, the Jorgensen group described asymmetric a-sulfenylation of aliphatic aldehydes using TMS-protected prolinol catalysts. The best sulfenylating agent was M-benzylsulfanyl-1,2,4-triazole. Other catalysts, such as proline, prolinol, prolinamide or other secondary amide were less effective. The catalyst with bulkier aromatic groups (C2a) afforded the most enantioselective reaction (Scheme 8.39). 

---