Asymmetric synthesis with chiral catalysts

Asymmetric hydrosilylation can be extended to 1,3-diynes for the synthesis of optically active allenes, which are of great importance in organic synthesis, and few synthetic methods are known for their asymmetric synthesis with chiral catalysts. Catalytic asymmetric hydrosilylation of butadiynes provides a possible way to optically allenes, though the selectivity and scope of this reaction are relatively low. A chiral rhodium complex coordinated with (2S,4S)-PPM turned out to be the best catalyst for the asymmetric hydrosilylation of butadiyne to give an allene of 22% ee (Scheme 3-20) [59]. 

Ishihara K., Yamamoto H. Asymmetric Synthesis With Chiral Lewis Acid Catalysts CATTECH1997 1 51-62... 

The first reported attempts of what was then called "absolute or total asymmetric synthesis" with chiral solid catalysts used nature (naturally ) both as a model and as a challenge. Hypotheses of the origin of chirality on earth and early ideas on the nature of enzymes strongly influenced this period [15]. Two directions were tried First, chiral solids such as quartz and natural fibres were used as supports for metallic catalysts and second, existing heterogeneous catalysts were modified by the addition of naturally occuring chiral molecules. Both approaches were successful and even if the optical yields were, with few exceptions, very low or not even determined quantitatively the basic feasibility of heterogeneous enantioselective catalysis was established. 

Asymmetric synthesis with chiral reagents and chiral catalysts... 

ASYMMETRIC SYNTHESIS WITH CHIRAL REAGENTS AND CHIRAL CATALYSTS... 

Transition metal salts or complexes are known to catalyze effectively the cyclopropanation of olefins with diazoalkanes. Asymmetric synthesis with chiral copper catalysts (Nozaki et ai, 1966, 1968 Noyori et al., 1969 Moser, 1969), as well as a detailed kinetic study (Salomon and Kochi, 1973), has suggested the intervention of copper-carbene complexes as reactive intermediates. Recently synthesis of crysanthemic acid (CCXXXIV) (R = H) with high optical yield (60-70 %) has been achieved by applying this asymmetric catalysis (Aratani et al., 1975). The camphorglyoxime-cobalt(I) complex is also effective for the enantioselective reaction (Tatsuno et al., 1974). 

Catalytic asymmetric synthesis with participation and formation of heterocycles (including asymmetric phase transfer reactions and asymmetric reactions with chiral Lewis catalysts) 93MI1. 

Stereoselective asymmetric synthesis with participation of diazocarbonyl intermediates in the presence of catalysts possessing chiral heterocyclic ligands 97CC983. 

Nucleophilic addition of metal alkyls to carbonyl compounds in the presence of a chiral catalyst has been one of the most extensively explored reactions in asymmetric synthesis. Various chiral amino alcohols as well as diamines with C2 symmetry have been developed as excellent chiral ligands in the enantiose-lective catalytic alkylation of aldehydes with organozincs. Although dialkylzinc compounds are inert to ordinary carbonyl substrates, certain additives can be used to enhance their reactivity. Particularly noteworthy is the finding by Oguni and Omi103 that a small amount of (S)-leucinol catalyzes the reaction of diethylzinc to form (R)-l-phenyl-1 -propanol in 49% ee. This is a case where the... 

In contrast to the success in the synthesis of optically active amino acids and related compounds, only limited success has been achieved in the asymmetric synthesis of chiral amines or related compounds. One breakthrough is the asymmetric hydrogenation of arylenamides with Rh catalysts containing... 

Scheme 3. Asymmetric Strecker synthesis with chiral Alm-Salen catalyst 5 (Sigman and Jacobsen). TFAA = trifluoroacetic anhydride.

Scheme 8. Asymmetric Strecker synthesis with chiral zirconium binuclear catalyst 22 (Kobayashi and co-workers).

The use of chiral ligands to facilitate asymmetric synthesis with these TMM synthons is difficult because the bond-formation process occurs away from the metal center. None the less, an enantioselective synthesis using a Tsuji TMM synthon has been achieved with a catalyst containing a chiral phosphine ligand (equation 133). While the enantiomeric excess is not very high in this case, the fact that one can achieve asymmetric induction at all is quite remarkable. 

The earliest report of a reaction mediated by a chiral three coordinate aluminum species describes an asymmetric Meerwein-Poimdorf-Verley reduction of ketones with chiral aluminum alkoxides which resulted in low induction in the alcohol products [1]. Subsequent developments in the area were sparse until over a decade later when chiral aluminum Lewis acids began to be explored in polymerization reactions, with the first report describing the polymerization of benzofuran with catalysts prepared from and ethylaluminum dichloride and a variety of chiral compounds including /5-phenylalanine [2]. Curiously, these reports did not precipitate further studies at the time because the next development in the field did not occur until nearly two decades later when Hashimoto, Komeshima and Koga reported that a catalyst derived from ethylaluminum dichloride and menthol catalyzed the asymmetric Diels-Alder reaction shown in Sch. 1 [3,4]. This is especially curious because the discovery that a Diels-Alder reaction could be accelerated by aluminum chloride was known at the time the polymerization work appeared [5], Perhaps it was because of this long delay, that the report of this asymmetric catalytic Diels-Alder reaction was to become the inspiration for the dramatic increase in activity in this field that we have witnessed in the twenty years since its appearance. It is the intent of this review to present the development of the field of asymmetric catalytic synthesis with chiral aluminum Lewis acids that includes those reports that have appeared in the literature up to the end of 1998. This review will not cover polymerization reactions or supported reactions. The latter will appear in a separate chapter in this handbook. 

Another noteworthy development is an asymmetric synthesis of chiral biaryls by a Pd-catalyzed enantioselective aryl-aryl coupling reaction of prochiral 2,6-bis(triflyloxy)biaryls [62], Using Cl2Pd[(53-Phephosl as a chiral catalyst, the first phenylation of l-[2,6-bis(triflyloxy)phenylJnaphthalene with PhMgBr proceeds in 85% ee. As might be expected, the minor enantiomer is the more reactive of the two in the second phenylation. This leads to a kinetic resolution, and the desired monophenylated enantiomer can be obtained in 93% ee. Similarly favorable enantioselective alkynylation results have also been reported [180]. 

The product is obtained in 95% yield and 94% ee. In the counterpart in solution, the ee was only 21-50%. Polymeric chiral catalysts have also been used in the addition of zinc alkyls to aldehydes. Use of a proline-based copolymer in a continuous asymmetrical synthesis with an ultra filtration membrane gave 80% ee (10.61).138 There was no deactivation in 7 days. A boron-containing polymer (10.62) gave only 28-51% ee compared with the 65-75% ee found with model compounds in solution.139... 

The creation of an asymmetric center by C-H bond formation is a very common process which can involve several types of reactions. Hydrogenation of prochiral olefins is often used with the rhodium catalysts of the Wilkinson type (5). These catalysts were shown to be inactive for ketone or imine reduction except in some cases (15), It was then interesting to develop an alternate method for asymmetric synthesis of chiral alcohols or amines. Since it was found that RhCl(PPh3)3 was able to catalyze silane additions to ketones (16,17) or imines (18), preparation of chiral alcohols or amines by asymmetric hydrosilylation could be envisaged (Figure 2). The 1,4-addition of silanes to conjugated... 

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