Substituted prolinamides

The AgOTf-catalyzed, PhSeBr-induced ring closure of the prolinamide-derived cinnamoylamide 92 proceeded via A-addition to the olefin, which afforded the fra r-substituted pyrrolo[l,2- ][l,4]diazepin-l,5(277)-dione 93 in 73%... 

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)... 

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... 

Shi et al7 reported a highly enantioselective allylic substitution of Morita-Baylis-Hillman (MBH) acetate with TMSOF that could be achieved by chiral prolinamide phosphane organocatalysts 43 in good yield and high ee. 

In the last year, an impressive number of highly efficient enantioselective aldolisations have been catalysed by variously substituted prolinamides. As an example, Chimni et ctl. have demonstrated that very simple protonated (5)-prolinamide derivatives efficiently catalysed aldol reactions of ketones with aromatic aldehydes in water. The best results concerning a range of cyclohexanones are collected in Scheme 2.11. When applied to aliphatic ketones, the protocol provided the aldol adducts in good yields, albeit with lower diastereo-and enantioselectivities (<63% de and <48% ee, respectively). 

In 2009, Fu et al. developed highly 4-phenoxy-substituted prolinamide phenols, which could promote the asymmetric aldolisation of cyclohexanone with a range of aldehydes with a high degree of diastereo- and enantioselectivity in a large amount of water (Scheme 2.12). The best enantioselectivities of up to 97% ee were obtained with the most steric hindered catalyst that bore a tert-butyl group on the phenol moiety. The scope of the reaction could be extended to aliphatic ketones with enantioselectivities of up to 94% ee, albeit with low to moderate diastereoselectivities of up to 50% de. 

In this context, prolinamide 2 [5-8] and its aryl-substituted homologs such as 3-5 have been developed [9-14]. Analogous to these examples, binaphthyldiamine-derived compounds such as 6 and 7 have been introduced for use in aqueous systems and as recoverable catalysts [15-18]. For example, Benaglia and coworkers reported that the prolinamide catalyst 7 with a UpophiUc side chain showed efficient catalytic activity in water [16b]. Chiral spiro diamine-derived catalysts have also been designed, albeit in moderate enantioselectivity [19]. Owing to the increased acidity of an NH group of thioamide relative to a normal amide, proline-thioamide catalysts such as 8 have been shown to be more effective [20-23]. 

With regard to aldol chemistry, Mannich or domino-Mannich-Michael reactions can also be promoted by N-arylsulfonyl-substituted prolinamide catalysts such as 17 with high levels of enantioselectivity [82, 83). 

Analogously to these examples, proline-derived peptide catalysts can also efficiently promote Michael addition reactions [97-99]. Prolinamide or prolyl sulfonamide catalysts are also effective for intramolecular Michael addition reactions [100-102]. Recently, Yang and Carter reported a short-cut strategy to construct an all-carbon substituted quaternary carbon stereogenic center on a cyclohexe-none framework via Robinson-type annulation using the 17-type catalyst (Scheme 1.4) [103]. 

Proposed transition states for 4-substituted proline and prolinamide-catalyzed... 

Several substituted prolinamides, derived from chiral enantiopure aziridines, of general formula 42 (Figure 24.13), were used in aldol reactions. Optimization of the reaction conditions with cyclic ketones showed that no product was formed when the reaction was carried out in organic solvents such as CHCI3 and DMF. 

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