Asymmetric condensation

Aldolases cataly2e the asymmetric condensation of intermediates common in sugar metaboHsm, such as phosphoenolpymvic acid, with suitable aldehyde acceptors. Numerous aldolases derived from plants or animals (Class I aldolases) or from bacteria (Class II) have been examined for appHcations (81). Efforts to extend the appHcations of these en2ymes to the synthesis of unusual sugars have been described (2,81). 

An extension of the asymmetric condensation of organometallics onto aldehydes is the enantioselective silver-promoted allylation reaction of aldehydes with allyltributyltin, which has recently been performed by Shi et al. in the presence of chiral diphenylthiophosphoramide ligands and more efficiently, with binaphthylthiophosphoramide ligands. According to the nature of the ligand substituents, the corresponding allylation products were obtained in enantioselectivities of up to 98% ee, as depicted in Scheme 3.70. 

A new and general approach to chiral aliphatic or aromatic sulfinates has been recently described by Mikofajczyk and Drabowicz (107). It consists of the asymmetric condensation of racemic sulfinyl chlorides at low temperature with achiral alcohols in the presence of chiral tertiary amines as asymmetric reagents. The optical purity (up to 45%) of the sulfinates formed is strongly dependent on the structure of all the reaction components. 

Chiral butyrolactones of type 27 and 28 have substantial value in asymmetric synthesis because they contain readily differentiable difunctional group relationships e.g. 1,5-di-carboxylic acid, 1,4-hydroxy carboxylic acid, 1,6-hydroxy-carboxylic acid, 1,6-diol etc.) that would be difficult to assemble by existing asymmetric condensation and pericyclic processes. Applications of these chiral derivatives of glutaric acid to syntheses of indole, indoline and quinolinone alkaloids are illustrated in Schemes 16-18. 

Scheme 9.3 Asymmetric condensation of aromatic aldehydes, as proposed by Enders and colleagues.

Aza Diels-Alder reactions. The p-tol-BINAP ligand is used to promote asymmetric condensation between the IV-tosyl derivative of ethyl glyoxylate and Danishefsky s diene at -78°. 

ALA dehydratase (ALAD) Cytosolic enzyme that catalyzes the asymmetric condensation of two molecules of ALA to form PBG. 

Chiral boronales are generated m situ by reaction of binaphthols 3.7 (R = H, Ph) [231] with BH3 in the presence of acetic acid [778], with H BBr [781] or with B(OPh)3 [782, 783], Chiral borates are formed by reactions of substituted (S)-prolinol derivative 2.13 (R =- CPl OH) and BBr3 [784], These boronates and borates are valuable catalysts in asymmetric Diels-Alder reactions [73, 231, 601, 780], Tartaric acid derivatives, such as borate 3.8 and acyloxyboranes 3.9 recommended by Yamamoto and coworkers [73,601,778,780,785-791], are very efficient catalysts in asymmetric Diels-Alder reactions and in condensations of aldehydes with allylsilanes, enoxysilanes or ketene acetals. These catalysts are generated in situ from substituted monobenzoates of (RJl)- or (S -tartaric acid and BH3 (R = H) or an arylboric acid (R = Ar). The best asymmetric inductions are observed with catalysts 3.9, R = /-Pr. 1,3,2-OxazaboroMnes 3.10, prepared from a-aminoacids [44, 601, 780, 792, 793], are efficient catalysts in asymmetric Diels-Alder reactions. The catalyst generated from A -tosyltrytophan 3.11 is more efficient than borolidines 3.10 (R = Et, /-Pr). The catalysts 3.10 prepared from 3.11, 3.12 and 3.13 are also useful in asymmetric condensations of aldehydes with ketene acetals [794-797]. 

Lewis add complexes formed by the reactions of various aminoalcohols with Et2AlG [778, 824] or by the reaction of Et2Zn with a chiral sulfamide [806] have displayed a low efficiency in the asymmetric condensations of ketene and thioketene silyiacetals derived from acetic acid with aldehydes. Disappointing se-lectivities have also been observed with some binaphtol-titanium complexes [778]. However, Mikami and Matsukawa [1296] recently performed the enantioselective condensation of various aldehydes with acetic acid derivatives in the presence of a chiral binaphtol-titanium complex. Good selectivities were observed when the reaction was performed at 0°C in toluene (Figure 6.95). Quaternary ammonium fluorides derived from cinchona alkaloids have been proposed as catalysts to perform additions of enoxysilanes derived from ketones to PhCHO, but the observed selectivities are modest [1303],... 

A number of asymmetric syntheses have been developed. Aldol-type asymmetric condensations have also been effected in the naphthol series. To 1-naphthol in dichloromethane at -60°C, titanium tetrachloride was added, followed after 15 mins, stirring by menthyl pyruvate introduced over 15 mins. Quenching gave menthyl (-)2-hydroxy-2-(1-hydroxy-2-naphthyl)propionate in 81% yield (diastereoisomeric excess 92%) (ref.79). 

Chiral bisoxazolines, a chiral diaminoether and an aminodiether have been used to catalyse the asymmetric condensation of lithium enolates with imines to provide enantioselectivity in the formation of 3,3-dimethyl-4-substituted-2-azetidinones . 

Osinovskii A.G. and Erofeev B.V. (1982) On opportunity of asymmetric condensation of formaldehyde into sacharides, in "Coordinating Meeting on asymmetric catalysis", 1982, Sci. Council Acad. Sci. on Catal. Inst. Org. Chem. Acad. Sci. USSR and Dept Chem. Chem. Technol. Acad. Sci. Georgian SSR, Tbilisi State Univ., Abstracts, Boqomi.Georgia, p. 43-44. 

In 1921 Carl Neuberg discovered that actively growing yeast cells would convert added benzaldehyde into (R)-l-phenyl-l-hydroxy-propan-2-one. The other substrate in this asymmetric condensation reaction is acetaldehyde, which the yeast derives from its degradation of carbohydrate (see section 6.2.1.2). In 1930 this reaction was developed by Hildebrandt and Kalavehn as a key stage in the synthesis of D-ephedrine, (IR, 2S)-l-phenyl-l-hydroxy-2-methylaminopropane (Figure 6.25). ... 

More recently, Patil et al. reported a cascade reaction of 2-aminobenzaldehydes and 2-amino benzamides by combining chiral Brpnsted acid and achiral gold catalysis [76]. The attractive optically pure 1,2-dihydroisoquinolines were prepared by chiral phosphoric acid-catalyzed asymmetric condensation of alkyne-tethered aldehydes with 2-aminobenzamides to give rise to the chiral aminal 136, which was followed... 

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