Stereoselective synthesis asymmetric phase-transfer

This compilation embraces a wide variety of subjects, such as solid-phase and microwave stereoselective synthesis asymmetric phase-transfer asymmetric catalysis and application of chiral auxiliaries and microreactor technology stereoselective reduction and oxidation methods stereoselective additions cyclizations metatheses and different types of rearrangements asymmetric transition-metal-catalyzed, organocatalyzed, and biocatalytic reactions methods for the formation of carbon-heteroatom and heteroatom-heteroatom bonds like asymmetric hydroamina-tion and reductive amination, carboamination and alkylative cyclization, cycloadditions with carbon-heteroatom bond formation, and stereoselective halogenations and methods for the formation of carbon-sulfur and carbon-phosphorus bonds, asymmetric sulfoxidation, and so on. 

Asymmetric phase-transfer catalysis with (S,S)-lg can be successfully extended to the stereoselective N-terminal alkylation of Gly-Ala-Phe derivative 61 (i.e., the asymmetric synthesis of tripeptides), where (S,S)-lg turned out to be a matched catalyst in the benzylation of DL-61, leading to the almost exclusive formation of DDL-62. This tendency for stereochemical communication was consistent in the phase-transfer alkylation of DDL-63, and the corresponding protected tetrapeptide DDDL-64 was obtained in 90% yield with excellent stereochemical control (94% de) (Scheme 5.30) [31]. 

The paramount importance of Michael additions as versatile C-C bond forming transformations was discussed in some detail earlier in this volume. Thus, it is not surprising that, besides the use of chiral PTCs in asymmetric a-alkylation reactions, their use for stereoselective Michael additions is one of the most carefully investigated reactions in asymmetric phase-transfer catalysis (328, 329). Accordingly, the additional use of this methodology in asymmetric total synthesis has been reported on several occasions. 

Asymmetric phase-transfer catalysis is a method that has for almost three decades proven its high utility. Although its typical application is for (non-natural) amino acid synthesis, over the years other types of applications have been reported. The unique capability of quaternary ammonium salts to form chiral ion pairs with anionic intermediates gives access to stereoselective transformations that are otherwise very difficult to conduct using metal catalysts or other organocatalysts. Thus, this catalytic principle has created its own very powerful niche within the field of asymmetric catalysis. As can be seen in Table 5 below, the privileged catalyst structures are mostly Cinchona alkaloid-based, whereas the highly potent Maruoka-type catalysts have so far not been applied routinely to complex natural product total synthesis. 

Enantioselective oxidation is one of the most important and yet useful transformations in organic synthesis, and the asymmetric phase-transfer catalysis has made notable contributions to this field. The stereoselective epoxidation of electron-deficient olefins with peroxides is a representative example, and Taylor demonstrated the synthetic utility of this system by accomplishing the total syntheses of three natural products of manumycin family, (-l-)-MT 35214 131, (-l-)-manumycin A 132, " and (—)-alisamycin 133 (Scheme 4.31). The syntheses were undertaken by the... 

Considerable efforts made for the synthesis of biologically relevant molecules by means of asymmetric phase-transfer catalysis are summarized in this chapter. Because the phase-transfer reaction is usually insensitive to the contamination of air, moisture, and even acidic or inorganic-salt impurities, and it is set up with simple and user-friendly protocols. It is recognized as one of the easiest methods for large-scale, stereoselective production of functional molecules as exemplified by the studies reported from pharmaceutical companies. In addition, ready accessibility of chiral onium salts as a catalyst facilitates an initial trial in... 

SCHEME 35.30. An asymmetric phase-transfer-catalyzed epoxidation in the stereoselective synthesis of loxistatin. 

Asymmetric phase-transfer catalysis is a unique method that has for almost three decades proven its high utility. Although its typical application is for (nonnatural) amino acid synthesis, over the years, other types of applications have been reported. The unique capability of quaternary ammonium salts to form chiral ion pairs with anionic intermediates gives access to stereoselective... 

Since the aldimine Schiff base 21 can be readily prepared from glycine, direct stereoselective introduction of two different side chains to 21 by appropriate chiral phase-transfer catalysis would provide an attractive, yet powerful, strategy for the asymmetric synthesis of structurally diverse a,a-dialkyl-a-amino acids. This possibility of a one-pot asymmetric double alkylation has been realized by using N-spiro chiral quaternary ammonium bromide le (Scheme 5.21). 

Dialkylamino-aryloxosulfonium alkylides may be employed for enantioselective epoxidation if the ylide with its chiral sulfur center is resolved into its enantiomeric form, " An enantioselective oxirane is obtained by means of a chiral phase-transfer catalyzed procedure with dimethylsulfonium methylide. The utilization of arsonium ylides was reported some time ago. ° A highly stereoselective synthesis of trans-epoxides with triphenylarsonium ethylide has recently been described.Optically active arsonium ylide has been used in the asymmetric synthesis of diaryloxiranes. ... 

A variety of methods exists for the synthesis of optically active amino acids, including asymmetric synthesis [85-93] and classic and enzymatic resolutions [94-97], However, most of these methods are not applicable to the preparation of a,a-disubstituted amino acids due to poor stereoselectivity and lower activity at the a-carbon. Attempts to resolve the racemic 2-amino-2-ethylhexanoic acid and its ester through classic resolution failed. Several approaches for the asymmetric synthesis of the amino acid were evaluated, including alkylation of 2-aminobutyric acid using a camphor-based chiral auxiliary and chiral phase-transfer catalyst. A process based on Schollkopf s asymmetric synthesis was developed (Scheme 12) [98]. Formation of piperazinone 24 through dimerization of methyl (5 )-(+)-2-aminobutyrate (25) was followed by enolization and methylation to give (35.6S)-2,5-dimethoxy-3,6-diethyl-3.6-dihydropyrazine (26) (Scheme 12). This dihydropyrazine intermediate is unstable in air and can be oxidized by oxygen to pyrazine 27, which has been isolated as a major impurity. 

The stereoselective conjugate addition of /3-keto-ester anions to substituted cyclopentenones has been reported. Similar anions also add in conjugate fashion to a,/3-unsaturated aldehydes in the presence of a phase-transfer catalyst. Asymmetric induction in the conjugate addition of cyclic /3-keto-esters to enones is achieved by the use of cinchona alkaloids as bases. A further 1,5-dicarbonyl synthesis is achieved by a seven-stage sequence involving two conjugate additions the yields reported in each step are excellent (Scheme 80). ... 

The use of the chiral aminoborane (24) for the asymmetric synthesis of alcohols from ketones shows promise optical yields are in the range 14—23% for the three ketones tested. Stereoselective reduction of acetophenone and isobutyl methyl ketone has been observed on addition of the chiral phase-transfer catalyst (25) (derived from L-ephedrine) to sodium borohydride and the ketone in aqueous dichloromethane. ... 

The phase-transfer-catalyzed alkylation strategy was successfully appHed to the asymmetric cyanomethylation of oxindole 92 by the use of catalyst Hi [123]. This reaction allowed a simple and stereoselective synthesis of (—)-esermethole, a precursor to the clinically useful anticholinesterase agent (—)-physostigmine... 

---