Asymmetric acryl amides

The first examples of the diastereoselective aminohydroxylation of chiral acryl amides, R3CH=C(R2)CONHCH (Me)R1, have been reported. The reaction is believed to proceed within the so-called second catalytic cycle with diastereoisomeric excesses (g) reaching >99 1. The reaction relies solely on the stereochemical information provided by the enantiomerically pure starting materials. A stereochemical model for the observed asymmetric induction has been proposed.128... 

Janus-type micelles were reported via electrostatic interaction between two double-hydrophilic block copolymers poly(acrylic acid)-fc-poly(acryl amide) (PAA-fc-PAAm), and poly(2-methylvinylpyridinium iodide)-fe-poly(ethylene oxide) (P2MVP- -PEO). The aggregate forms disc-shaped micelle with PAA/P2MVP complex coacervate core and microphase-separated asymmetric corona, with two distinct domains formed by PEO and PAAm. Eigure 14.20 shows a TEM image of Janus-type micelles... 

In recent years, the catalytic asymmetric hydrogenation of a-acylamino acrylic or cinnamic acid derivatives has been widely investigated as a method for preparing chiral a-amino acids, and considerable efforts have been devoted for developing new chiral ligands and complexes to this end. In this context, simple chiral phosphinous amides as well as chiral bis(aminophosphanes) have found notorious applications as ligands in Rh(I) complexes, which have been used in the asymmetric hydrogenation of a-acylamino acrylic acid derivatives (Scheme 43). 

The complete transformation of a racemic mixture into a single enantiomer is one of the challenging goals in asymmetric synthesis. We have developed metal-enzyme combinations for the dynamic kinetic resolution (DKR) of racemic primary amines. This procedure employs a heterogeneous palladium catalyst, Pd/A10(0H), as the racemization catalyst, Candida antarctica lipase B immobilized on acrylic resin (CAL-B) as the resolution catalyst and ethyl acetate or methoxymethylacetate as the acyl donor. Benzylic and aliphatic primary amines and one amino acid amide have been efficiently resolved with good yields (85—99 %) and high optical purities (97—99 %). The racemization catalyst was recyclable and could be reused for the DKR without activity loss at least 10 times. 

The Corey synthesis began with an asymmetric Diels-Alder reaction between butadiene and 2,2,2-trifluoroethyl acrylate in the presence of the 5-proline-derived catalyst ent-59 to form the adduct ent-69 in excellent yield (97%) and with >97% ee (Scheme 7.10). Ammonolysis of 60 produced amide 61 quantitatively, which underwent iodolacta-mization using the Knapp protocol to generate lactam 62. A-Acylation of 62 with... 

The asymmetric halolactonization reactions of unsaturated L-proline amides, developed by Terashima and coworkers,184 has been extended to a-alkyl acrylic acid derivatives (equation 75 and Table 21).185 This allows for the synthesis of either enantiomer of an a-methyl-a-hydroxy acid using L-proline as the auxiliary. Less successful approaches to asymmetric induction with a chiral auxiliary include iodolac-... 

Rhodium-BisP and -MiniPHOS catalysts are capable of high enantioselective reductions of dehydroamino acids in 96-99.9% ee.109 A variety of aryl enamides give optically active amides with 96-99% ee with the exception of ort/jo-substituted substrates.111 Despite the high enantio-selectivity, the rate of reaction in this transformation is slow. Rhodium-BisP and -MiniPHOS catalysts perform excellently in the asymmetric reduction of ( >P-(acylamino)acrylates to the corresponding protected-P-amino esters in 95-99% ee.112 Within the family of BisP and MiniPHOS, the ligands that contain t-Bu groups were found to be the most effective in a variety of asymmetric hydrogenations. 

Benovsky P, Stephenson GA, Stille JR (1998) Asymmetric formation of quaternary centers through aza-annulation of chiral P-enamino amides with acrylate derivatives. J Am Chem Soc 120 2493-2500... 

A chiral diaminodiphosphine ligand was attached onto poly(acrylic acid) through an amide linkage. The ruthenium(II) complex of the resultant polymeric ligand (169) was then applied to the asymmetric transfer hydrogenation of acetophenone in 2-propanol (Scheme 3.51) [101]. (S)-l-phenylethanol was obtained in 95% yield with 96% ee by using 158. 

Applications of chirally modified titanium Lewis acids have been reported most cases use various acetal diols derived from tartrate as the chiral auxiliary26 33,31 90. Various methods of catalyst preparation are known, as well as the use of different types of dienes (open-chained, cyclopentadiene) and dienophiles (acroleins, acrylates, crotonates, fumarates and amides derived from oxazolidinone), including intramolecular cycloaddition30. Addition of 4 A molecular sieves can improve asymmetric induction31,34 (as observed with the Sharpless epoxidation, loc. cit 31 in ref 6) and shows remarkable solvent effects on enantioselectivity. This method has been applied to the asymmetric Diels-Alder cycloaddition of cyclopentadiene and open-chain dienes to acrylamides28, 35. 

Amide and imide enolates. Scheme 5.31 illustrates several examples of asymmetric Michael additions of chiral amide and imide enolates. Yamaguchi [163] investigated the addition of amide lithium enolates to -ethyl crotonate, but found no consistent topicity trend for achiral amides. The three chiral amides tested are illustrated in Scheme 5.31a-c. The highest diastereoselectivity found was with the C2-symmetric amide shown in Scheme 5.3Ic. Evans s imides, as their titanium enolates, afforded the results shown in Scheme 5.31d and e [164,165]. The yields and selectivities for the reaction with acrylates and vinyl ketones are excellent, but the reaction is limited to P-unsubstituted Michael acceptors P-substituted esters and nitriles do not react, and 3-substituted enones add with no selectivity [165]. 

The use of amides and imides as chiral auxiliaries in [4 + 2]-cycloadditions has been the subject of numerous investigations. Oppolzer reported the use of camphorsultam 112 in asymmetric Diels-Alder reactions [26, 67. 68], The camphor sultam is readily available in both enantiomeric forms from cam-phorsulfonyl chloride. Acrylate 113 was found to react with cyclopentadiene in the presence of EtAlCl2 to give 115 with high selectivity (endo/exo = 99.5 0.5, dr = 97.5 2.5, Equation 10) [67]. Oppolzer also reported that triene 116 participated in an intramolecular Diels-Alder cycloaddition reaction to afford endo product 117 in 71 % yield and 96.5 3.5 dr (Scheme 17.19) [69]. This bicyclic product was subsequently converted into the pyridine alkaloid (-)-pulo upone (118). 

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