Organocatalysts derived from amino acids

While primary amine organocatalysts derived from amino acids have shown very low enantioselectivities and activities in the typical aldol reactions of acetone with aldehydes. Da et al. demonstrated that the introduction of the optimal co-catalyst DNP (2,4-dinitrophenol) dramatically elevated both the activities and the enantioselectivities of these catalysts. As shown in Scheme 2.39, the combination of a primary amino acid with DNP allowed the aldol products to be obtained in moderate to high yields and excellent enantioselectivities of up to 99% ee. In addition, the scope of this methodology could... 

An enantioselective variant of Petasis reaction catalyzed by the chiral biphenol 10 was applied to the synthesis of optically active amines 11 (eq 7) (32). Enantioselective addition ofalkyne catalyzed by the chiral copper-phosphine ligand in MCR offers a practical pathway to obtain homochiral propargylamines like 12 (eq 8) (33). The last decade has also wimessed the emergence of organocatalysts, derived from natural products like amino acids (with more emphasis... 

The use of L-proline, amides derived from it, and related amino acids and small peptides as asymmetric organocatalysts for aldols - and indeed many other reactions mentioned elsewhere in this chapter - expanded hugely in 2006. A review deals with the direct aldol case.96... 

The P-chirogenic organocatalysts 294 and 295 were found to promote the enantioselective aza-Morita-Bayhs-Hillman reaction of ketimines derived from acyclic a-keto esters. In the P-chirogenic organocatalyzed aza-Morita-Baylis-Hillman reactions, a,a-disubstituted a-amino acid derivatives 296 were obtained in high yields and with high enantioselectivities (up to 97% cc) (Scheme 98) [195]. 

Jurczak and co-workers reported hybrid diamines derived from l,r-binaphthyl-2,2 -diamine and a-amino acids as organocatalysts for 1,3-dipolar cycloaddition of aromatic nitrones 187 to ( )-crotonaldehyde 28b, Scheme 3.62 [79]. The L-phenylalanine-based l,r-binaphthyl-2,2 -diamine (BINAM) catalyst 194, with trifluoromethanesulfonic acid as an additive, afforded the optimal results with good endo-diastereoselectivity and enantioselectivity up to 95% ee. 

Asymmetric addition of diorganozincs to aldehydes and ketones has been reviewed, focusing on bifunctional catalysts such as those prepared from salens or BINOLs. Regioisomeric chiral amine-sulfonamide organocatalysts give >99% yield and up to 98% ee in addition of diethylzinc to aldehydes. Switching between regioisomers effectively switches the direction of selectivity. Amino-acid-derived (15,l 5)-4,4 -biquinazoline primary amines catalyse ethylation of aryl aldehydes in up to 95%... 

The chiral nickel(II)/Al,A -dioxide complex-catalysed asymmetric 3 + 2-cycloaddition of nitrones to alkylidene malonates produced isoxazolidine derivatives in good yields and excellent diastereo- and enantio-selectivities. (94 6 dr and 99% ee). Asymmetric organocatalysts obtained from (X)-BINAM and L-Q -amino 0 acids catalysed the 3 + 2-cycloaddition of alkyl glyoxylate-derived nitrones with (g)... 

In 2008, Barbas et al. reported the first primary amine-containing amino acid-catalysed indirect a n -Mannich reactions of dihydroxyacetone and acyclic protected dihydroxyacetone derivatives with a variety of imines derived from both aliphatic and aromatic aldehydes.In spite of moderate diastereoselec-tivities, good to high yields and enantioselectivities were obtained by using an L-threonine derivative as the organocatalyst in A -methylpyrrolidinone as the solvent and 5-methyl-l-7/-tetrazole as an additive, as shown in Scheme 3.14. 

Huge success of benzodiazepenes as pharmaceutical scaffolds has prompted preparation and evaluation of het-erocyde-annulated benzodiazepine derivatives. A tandem Michael addition-condensation sequence xmder MW irradiation was also proved to be useful for the synthesis of amino-substituted pyrimidine-fused diazepine derivatives of the type 96 from 4,5,6-triaminopyrimidine and chalcones [57]. Similarly, the pyridine-fused derivatives (97) were prepared xmder MW-assisted solvent and catalyst-free condition [58], Condensation of thiadiazole-annulated phen-ylene diamines with appropriate carbonyl compounds using sulfamic acid as organocatalyst led to the formation of corresponding diazepine derivatives 98 in excellent yields [59] (Figure 4). 

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