Prolines acrylic derivatives

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-... 

A series of diastereoselective Diels-Alder reactions of 3-proline derivatives have been reported (94JOC3246, 95JOC16, 96TL2133). In a typical example, the derivative 207 reacts with methyl acrylate to give predominantly the isomer 208 (Eq. (35)). 

Analogous additions were later reported by Ito and co-workers (Scheme 9) (20). The enamines for these additions were prepared from the corresponding aminals using a mild base in the presence of trimethylsilyl chloride. In turn, the aminals used are available from (— )-ephedrine and (S)-prolinol. The byproduct amine hydrochloride was removed either by distillation or by precipitation from a benzene solution. Enamines prepared by this method were found to be unreactive toward unsaturated carbonyl compounds in a variety of solvents. Importantly, it was found that use of a mild Lewis acid such as anhydrous MgCl2 or ZnCl2 in THF promoted the reactions. Thus, the addition of enamines 9.1 and 9.2 to methyl acrylate is achieved. Of the two enamines, the proline-derived 9.1 is the more effective auxiliary. The... 

A stereoselective Diels-Alder reaction can be an efficient route to make oseltamivir because it can construct the densely functionalized cyclohexene ring with a reduced number of reaction steps. Corey et al. have developed an enantioselective Diels-Alder reaction for the synthesis of (—)-oseltamivir (Scheme 16.1)." A Diels-Alder reaction of butadiene 1 with trifluoroethyl acrylate 2 in the presence of (5)-proline-derived catalyst 3 produced adduct 5 in an excellent yield (97%) and with a high enantioselectivity (>97% ee). The high enantioselectivity was explained by a transition state model 4, in which the diene 1 approached the activated... 

In 1969 Yamada and coworkers reported the first in a series of investigations on the alkylation of chiral enamines, derived from L-proline esters, with methyl acrylate and acrylonitrile170. The enamines were prepared under the usual azeotropic conditions but were not distilled since this resulted in cyclization, by nucleophilic attack of the enamine on the ester function, or partial racemization171. Optical yields were found to be... 

P, N] Some of the earliest examples of asymmetric Michael additions were reported by Yamada and co-workers, who used enamines derived from cyclohexanone and proline esters (19). The results of this study are summarized in Scheme 8 and Table 1. Although yields were generally poor, enantiomeric excesses as high as 59% were found using the tert-butyl ester of proline at low temperature (entry 5). Asymmetric induction was also observed with acrylonitrile, but no enantiomeric purities were reported. The enantiomeric purities of the methyl acrylate products were determined by measurement of optical rotations. 

In the past Lewis acid-catalyzed [4+2] cycloaddition reactions of chiral alkyl acrylates have been systematically studied. Chiral auxiliaries derived from camphor, menthol and amino acids or from carbohydrates have been developed. Stereochemical and theoretical aspects of these chiral inductors have been intensively reviewed (see. Chapter 6). Asymmetric Diels-Alder reactions of chiral acrylamides derived from Ca-symmetrical secondary amines lead selectively to the cycloadducts in the presence of Lewis acids such as AICI3. In reactions of chiral auxiliaries derived from (iS)-proline and (iS)-prolinol excellent endo/exo selectivities and diastereoselectivities were obtained in the presence of catalytic amounts of Et2AlCl or TiCL. Cycloadducts of chiral crotonoyl derivatives derived from oxazolidinones 62, sultam 63 or for example (S)-lactate IS were obtained with high selectivities in the presence of Lewis acids such as Et2AICl. 

To improve the enantioselectivities, we then reinvestigated Hatakeyama s cinchona-derived catalyst, p-ICD, promoted MBH reaction of aldehydes with methyl vinyl ketone or (ot)-naphthyl acrylate in the presence of co-catalyst. The enantioselectivities increased in some cases, and the absolute configuration of the MBH adducts can be inverted by the use of proline or lithium... 

The polymers were acrylate esters, the amino-alcoholic portionheing a derivative of ephedrine (XXXVI), proline (XXXVII) or quinine (XXXVIII). Their structures are shown below. The molecular weight of the polymer ranged between 5000 and 14 000 it was used... 

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