In recent years, synthetic method by the combination of isomerization and crystallization is studied intensively, especially in the practical optical resolution. In this paper, this isomerization-crystallization method is introduced from a point of view of practical organic synthesis. A number of examples of this isomerization-crystallization method in optical resolution, many of which were often reported as the example of second-order asymmetric transformation phenomena, are classified into following two groups, and reviewed. (1) Epimerization-crystallization method. (2) Racemization-preferential crystallization method. The potentialities and difficulities of each method are also discussed. The compounds resolved by this methods are α-amino acid derivatives, cyanohydrin derivatives, α-aromatic carboxylic acid esters, and so on.
Recent advances in catalytic asymmetric synthesis promoted by transition metal complexes are reviewed. This revew covers asymmetric hydrogenation, hydrocarbonylation, hydrosilylation, isomerization, epoxidation, oxidation, cyclopropanation, cross-coupling and allylic alkylation from 1982. Newer aspects of chiral catalysis are emphasized. Current trends and possible future development of potentially useful catalytic asymmetric reactions are disussed.
The baker's yeast mediated reduction of ketones with various kinds of functional groups provides a useful method for the synthesis of optically active secondary alcohols. Compared with the usual chemical methods using chiral metal hydride reagents, the advantages of the present method are the easier availability of the yeast, milder reaction conditions, i. e. at room temperature in water under air atmosphere, higher optical yield and chemoselectivity especially in the reduction of saturated ketones. Asymmetric reduction of carbon-carbon double bond and the carbon-carbon bond forming reaction of α, β-unsaturated carbonyl compounds are also accomplished by baker' s yeast. The products thus obtained are applied as chiral building blocks to the synthesis of various natural products.
Newly introduced trans-2, 5-bis (methoxymethyl) -and trans-2, 5-bis (methoxymethoxymethyl) -pyrrolidines were found to be highly effective chiral auxiliaries in asymmetric reactions of their N-acylated compounds. Alkylation of the lithium enolates derived from these amides proceeded with high diastereoface selectivity (> 95 % de) for various combinations of reactants. The enolates were also acylated diastreoselectively (> 96 % de) and the resulting 2-alkyl-3-oxo amides were reduced stereoselectively (> 96 % de) to syn-or anti-2-alkyl-3-hydroxy amides by Zn (BH4) 2 or by KBEt3H, respectively. The aldol condensation of the amide enolate with aldehydes proceeded with high diastereo and diastereoface selectivities, when the corresponding zirconium enolates were used. Zirconium enolates derived from (E) -alkenyloxyacetyl amides, exhibited high level of syn-diastereo and diastereoface selectivities in their [2, 3] Wittig rearrangement reaction. Zirconium mediated [2, 3] Wittig rearrangement of (E) -alkenyloxyacetic acid esters was also performed with syn-diastereoselectivity, high level of chirality transfer, and exclusive formation of (Z) -double bond. Thus, very effective and generally applicable asymmetric syntheses of α-alkyl, α-hydroxy, and α-amino acids, syn-and anti-2-alkyl-3-hydroxy acids, 4-unsaturated 3-alkyl-2-hydroxy acids, and acids bearing a quaternary α-carbon atom have been established. Some of these asymmetric reactions were applied to the synthesis of natural products.
Recent progress in the construction of chiral quaternary carbon centers by the method of asymmetric carbon-carbon bond forming reaction is described. The article covers, i) asymmetric sythesis by the use of chiral enamines, ii) asymmetric synthesis based on the strategy of fixing conformation of metalloenamines by chelate formation, iii) asymmetric synthesis based on the strategy of optionally controlling the diastereoface selection by an external ligand, iv) asymmetric alkylation by the use of conformationally rigid heterocycles. Asymmetric total syntheses of alkaloid mesembrine, sesquiterpene ivalin, and neolignan megaphone by the application of these methods are also described.
This article describes the attractive method for construction of acyclic systems using diastereoselective addition reactions of nucleophiles with chiral carbonyl compounds. The following topics are included : (a) the diastereofacial selective addition reaction of α-alkyl-β-trimethylsilyl-β, γ-unsaturated carbonyl compounds with nucleophiles and its application to the synthesis of some natural products including macrolides, (b) the addition reaction of Grignard reagents with α-alkoxy-β-trimethylsilyl-β, γ-unsaturated carbonyl compounds which affords the convenient method for construction of 1, 2-diol derivatives, and (c) the synthesis of the rarely obtained syn-adducts in the reaction of organocopper compounds with glyceraldehyde acetonide.
The progress in the asymmetric synthesis using chiral sulfoxides is reviewed based on the literature results since 1983. The asymmetric synthetic methods are classified into the type of the reactions ; reaction of α-sulfinylcarbanions, reduction of β-ketosulfoxides, 1, 4-addition reaction to α, β-unsaturated sulfoxides, asymmetric synthesis using Pummerer-type reactions, and asymmetric cycloadditions. Mechanistic aspects of asymmetric Diels-Alder reaction using chiral α, β-unsaturated sulfoxides and its application to organic synthesis are discussed on the basis of the results obtained quite recently in the author's laboratory.