Prolinamides catalysis

L-Prolinamides (71) with a pendant alcohol act as recoverable bifunctional catalysts of direct nitro-Michael addition of ketones to -nitrostyrenes, giving syn-de s up to 94% and ees up to 80%.204 The pyrrolidine provides enamine catalysis, and the side-chain donors can hydrogen-bond the nitro oxygens. 

Several reports deal with aqueous media. Acid-base catalysis by pure water has been explored, using DFT, for the model aldol reaction of acetone and acetaldehyde.125 A Hammett correlation of nornicotine analogues (28) - a series of meta- and para-substituted 2-arylpyrrolidines - as catalysts of an aqueous aldol reaction shows p = 1.14.126 Also, direct aldol reactions have been carried out in water enantioselectively, using protonated chiral prolinamide organocatalysts.127... 

Kokotos and coworkers investigated the use of prolinamide-based thioureas as bifunctional organocatalysts for the direct aldol reaction. The amide and the thiourea functionalities, tethered by a chiral diamine motif, offered multiple hydrogen bonding sites for electrophile activation, while the pyrrolidine skeleton served to activate the nucleophile via enamine catalysis. Thiourea 61 proved to provide the best catalyst in the presence of 4-nitrobenzoic acid as cocatalyst at low temperature and delivered the anti-aXAoX products in moderate to high yields and in high to excellent... 

Enantioselective organocatalytic a-chlorination of aldehydes, via enamine catalysis, was independently reported by the groups of MacMillan and Jprgensen in 2004 (Scheme 13.20) [46, 47]. MacMillan utilized his imidazolidinone catalyst and a perchlorinated quinone as the chlorine source, to obtain the S-enantiomer of the a-chloroaldehyde products. Jprgensen employed NCS as the chlorine source, and either a prolinamide catalyst to access the / -enantiomer of the a-chloroaldehyde products, or a Ci-symmetric amine catalyst to access the 5-enantiomer. A recyclable fluorous pyrrolidine-thiourea bifunctional organocatalyst was later employed as an enamine catalyst in this transformation [48]. 

General reviews include the direct aldol/" aldoi and related processes,the Zimmerman-Traxler TS model used to explain the stereochemistry of the aldoi condensation,catalysis of direct asymmetric aldols by prolinamides versus prolinef/zioamides, " " the catalytic asymmetric aldoi reaction in aqueous media (considering both organometallic and organocatalytic approaches), " the use of BINAP oxide in enantioselective direct aldols,and the use of metal enolates as synthons. " ... 

Holbrook JJ, Stinson RA (1973) The use of ternary complexes to study ionizations and isomerizations during catalysis by lactate dehydrogenase. Biochem J 131 739-748 Hoshide F, Ohi S, Baba N, Oda J, Inouye Y (1982) Asymmetric reduction with bis(NADH) model compounds. Agric Biol Chem 46 2173-2175 Hoshide F, Baba N, Oda J, Inouye Y (1983) Asymmetric reduction by an NADH model compound with L-prolinamide in the N1 substituent. Agric Biol Chem 47 2141-2143... 

Scheme 30.14 Catalysis by aryl linked N,N -dioxides derived from L-prolinamide.

In addition to organometaUic dendrimers for asymmetric catalysis, a number of dendritic organocatalysts have been developed and successfully applied in different asymmetric reactions in the absence of any metal [63]. In 2009, Parquette and coworkers [64] reported a new kind of folded pyridine-2,6-dicarboxamide dendrons (36) for direct aldol reaction. These dendritic prolinamide catalysts were tested for the aldol reactions of various acycUc and cydic ketones with 4-nitrobenzaldehyde (Figure 4.33). Remarkable dendritic effects on both the enantioselectivity and... 

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