Asymmetric synthesis catalysts

For the performance of an enantioselective synthesis, it is of advantage when an asymmetric catalyst can be employed instead of a chiral reagent or auxiliary in stoichiometric amounts. The valuable enantiomerically pure substance is then required in small amounts only. For the Fleck reaction, catalytically active asymmetric substances have been developed. An illustrative example is the synthesis of the tricyclic compound 17, which represents a versatile synthetic intermediate for the synthesis of diterpenes. Instead of an aryl halide, a trifluoromethanesul-fonic acid arylester (ArOTf) 16 is used as the starting material. With the use of the / -enantiomer of 2,2 -Z7w-(diphenylphosphino)-l,F-binaphthyl ((R)-BINAP) as catalyst, the Heck reaction becomes regio- and face-selective. The reaction occurs preferentially at the trisubstituted double bond b, leading to the tricyclic product 17 with 95% ee. °... 

The methodologies described above lead to NHC precnrsors rather limited in terms of substitution at the four- and five-positions as their access is restricted to the accessibility of the appropriate diimine. As snch snbstitntions are of great interest in particular for the design of asymmetric catalysts, rontes to the synthesis of the NHC precursors have more recently been developed. Some of these approaches are described in Scheme 1.4. 

B. Potassium allyl- and crotyltrifluoroborates undergo addition to aldehydes in biphasic media as well as water to provide homoallylic alcohol in high yields (>94%) and excellent diastereoselectivity (dr >98 2). The presence of a phase-transfer catalyst (e.g., B114NI) significantly accelerates the rate of reaction, whereas adding fluoride ion retards the reaction (Eq. 8.70).165 The method was applied to the asymmetric total synthesis of the antiobesity agent tetrahydrolipstatin (orlistat).166... 

The development of catalytic asymmetric reactions is one of the major areas of research in the field of organic chemistry. So far, a number of chiral catalysts have been reported, and some of them have exhibited a much higher catalytic efficiency than enzymes, which are natural catalysts.111 Most of the synthetic asymmetric catalysts, however, show limited activity in terms of either enantioselectivity or chemical yields. The major difference between synthetic asymmetric catalysts and enzymes is that the former activate only one side of the substrate in an intermolecular reaction, whereas the latter can not only activate both sides of the substrate but can also control the orientation of the substrate. If this kind of synergistic cooperation can be realized in synthetic asymmetric catalysis, the concept will open up a new field in asymmetric synthesis, and a wide range of applications may well ensure. In this review we would like to discuss two types of asymmetric two-center catalysis promoted by complexes showing Lewis acidity and Bronsted basicity and/or Lewis acidity and Lewis basicity.121... 

The energy profiles for an enantioselective and a diasteroselective synthesis are compared in Figure 14.2. An interesting feature of the asymmetric catalytic synthesis is the nonlinear correlation between the optical purity of the chiral catalyst or auxiliary and that of the reaction product, reported... 

Scheme 4.62 Asymmetric allene synthesis via isomeration of alkyne 240 with the chiral phase-transfer catalyst 241.

The asymmetric synthesis of allenes by stereoselective manipulations of enantio-merically pure or enriched substrates relies on the availability of such optically active substrates. In contrast, a direct synthesis of allenes by the reaction of prochiral substrates in the presence of an external asymmetric catalyst is an almost ideal process [102]. Most of the catalytic asymmetric syntheses in organic chemistry involve the creation of chiral tetrahedral carbon centers [103], whereas the asymmetric synthesis of allenes requires the construction of an axis of chirality. 

Hatano, M. Ikeno, T Miyamoto, T Ishihara, K. Chiral lithium binaphtho-late aqua complex as a highly effective asymmetric catalyst for cyanohydrin synthesis. J. Am. Chem. Soc. 2005,127, 10116-10111. 

This chapter focuses on several recent topics of novel catalyst design with metal complexes on oxide surfaces for selective catalysis, such as stQbene epoxidation, asymmetric BINOL synthesis, shape-selective aUcene hydrogenation and selective benzene-to-phenol synthesis, which have been achieved by novel strategies for the creation of active structures at oxide surfaces such as surface isolation and creation of unsaturated Ru complexes, chiral self-dimerization of supported V complexes, molecular imprinting of supported Rh complexes, and in situ synthesis of Re clusters in zeolite pores (Figure 10.1). 

Bidentate ferrocene ligands containing a chiral oxazoline substituent possess both planar chiral and center chiral elements and have attracted much interest as asymmetric catalysts.However, until recently, preparation of such compounds had been limited to resolution. In 1995, four groups simultaneously communicated their results on the asymmetric synthesis of these structures using an oxazoline-directed diastereoselective lithiation (Scheme 8.141). " When a chiral oxazolinylferrocene 439 was metalated with butyllithium and the resulting aryllithium species trapped with an electrophile, diastereomer 442 was favored over 443. The structure of the major diastereomer 442 was confirmed, either by conversion to a compound of known stereochemistry or by X-ray crystallography of the product itself or of the corresponding palladium complex. ... 

Chemists in Japan have studied an asymmetric cyanohydrin synthesis addition of hydrogen cyanide to benzaldehyde using synthetic peptides as catalysts 75). 

Chirality plays a central role in the chemical, biological, pharmaceutical and material sciences. Owing to the recent advances in asymmetric catalysis, catalytic enantioselective synthesis has become one of the most efficient methods for the preparation of enantiomer-ically enriched compounds. An increased amount of enantiomerically enriched product can be obtained from an asymmetric reaction using a small amount of an asymmetric catalyst. Studies on the enantioselective addition of dialkylzincs to aldehydes have attracted increasing interest. After the chiral amino alcohols were developed, highly enantioselective and reproducible —C bond forming reactions have become possible. 

Asymmetric autocatalysis is defined as an enantioselective synthesis in which the chiral product acts as an asymmetric catalyst for its own production (equation 39). Asymmetric autocatalysis is an efficient method for the catalytic enantioselective automultiplication of a chiral molecule without the need for any other chiral auxiliary158. 

Inoue,S., Tsukuma.I., Kawaguchi,M., Tsuruta,T. Synthesis of optically active polymers by asymmetric catalysts. VI. Behavior of organozinc catalyst systems in the stereoselective polymerization of propylene oxide. Makromol. Chem. 103,151 (1967). 

Asymmetric diols synthesis from olefins over the hybrid catalyst of TI-MCM4I and Co(lll) Salen complexes. 

With Tartrate-Derived Chiral 1,4-Diol/Ti Complexes A catalytic asymmetric Diels-Alder reaction is promoted by the use of a chiral titanium catalyst prepared in situ from (Pr O TiC and a tartrate-derived (2.R,3.R)-l,l>4,4-tetraphenyl-2,3-0-(l-phenylethylidene)-l,2,3,4-butanetetrol. This chiral titanium catalyst, developed by Narasaka, has been successfully executed with oxazolidinone derivatives of 3-borylpropenoic acids as P-hydroxy acrylic acid equivalents [40] (Eq. 8A.21). The resulting chiral adduct can be utilized for the first asymmetric total synthesis of a highly oxygenated sesquiterpene, (-i-)-Paniculide. 

A similar chiral bis(oxazoline)/Cu(II) catalyst is useful for the asymmetric hetero Diels-Alder reaction of Danishefsky s diene and glyoxylates [63] (Eq. 8A.39). Other bis(oxa-zoline)/M(OTf)2 (M = Sn, Mg) complexes are not effective. This method provides new routes to asymmetric aldol synthesis upon hydrolysis of the resulting adducts. 

The aldol reaction constitutes one of the most fundamental bond-construction processes in organic synthesis [56]. Therefore, much attention has been focused on the development of asymmetric catalysts for the Mukaiyama aldol reaction in recent years. 

Significant improvement in the catalytic activity of ALB was realized without any loss of enantioselectivity by using the second-generation ALB [27] generated by the self-assembled complex formation of ALB with alkali metal-malonate or alkoxide. This protocol allowed the catalyst loading to be reduced to 0.3 mol %, for example, the Michael addition of methyl malonate to cyclohexenone catalyzed by the self-assembled complex of (ff)-ALB (0.3 mol %) and KO Bu (0.27 mol %) in the presence of MS 4A gave the adduct in 94% yield and 99% ee [28]. This reaction has been successfully carried out on a 100-g scale wherein the product was purified by recrystallization. The kinetic studies of the reactions catalyzed by ALB and ALB/Na-malonate have revealed that the reactions are second-order to these catalysts (the rate constant ALB = 0.273 M 1h 1 ALB/Na-maionate = 1-66 M 1h 1) [27]. This reaction was used as the first key step for the catalytic asymmetric total synthesis of tubifolidine (Scheme 8D. 11) [28]. 

Shibasaki and co-workers reported an elegant asymmetric total synthesis of 11-deoxy-PGFic 19 using the Al-Li bis(binaphthoxide) complex (ALB) 21 [15], a member of a novel class of heterobimetallic chiral catalysts showing dual behavior as both a Bronsted base and a Lewis acid (Scheme 12.5) [16]. 

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