Stereoselective metal complexes

Chira.lHydrogena.tion, Biological reactions are stereoselective, and numerous dmgs must be pure optical isomers. Metal complex catalysts have been found that give very high yields of chiral products, and some have industrial appHcation (17,18). The hydrogenation of the methyl ester of acetamidocinnamic acid has been carried out to give a precusor of L-dopa, ie, 3,4-dihydroxyphenylalanine, a dmg used in the treatment of Parkinson s disease. 

In a catalytic asymmetric reaction, a small amount of an enantio-merically pure catalyst, either an enzyme or a synthetic, soluble transition metal complex, is used to produce large quantities of an optically active compound from a precursor that may be chiral or achiral. In recent years, synthetic chemists have developed numerous catalytic asymmetric reaction processes that transform prochiral substrates into chiral products with impressive margins of enantio-selectivity, feats that were once the exclusive domain of enzymes.56 These developments have had an enormous impact on academic and industrial organic synthesis. In the pharmaceutical industry, where there is a great emphasis on the production of enantiomeri-cally pure compounds, effective catalytic asymmetric reactions are particularly valuable because one molecule of an enantiomerically pure catalyst can, in principle, direct the stereoselective formation of millions of chiral product molecules. Such reactions are thus highly productive and economical, and, when applicable, they make the wasteful practice of racemate resolution obsolete. 

Recent studies on isolated BVMOs using Rh-complexes as NADPH substitutes for facile cofactor recycling suggested a pivotal role of the native cofactor to generate the proper environment within chiral induction in sulfoxidation reactions. While biooxidation was still observed in the presence of the metal complex, stereoselectivity of the enzyme was lost almost completely [202]. 

Thus, this first example of stereoselective radical reaction, initiated with the system based on Fe(CO)5, shows opportunities and prospects of using the metal complex initiators for obtaining the stereomerically pure adducts of bromine-containing compounds to vinyl monomers with chiral substituents. 

The use of chiral transition-metal complexes as catalysts for stereoselective C-C bond forming reactions has developed into a topic of fimdamental importance. The allyhc alkylation is one of the best known of this type of reaction. It allows the Pd-catalyzed substitution of a suitable leaving group in the allylic position by a soft nucleophile. 

To date, direct asymmetric synthesis of optically active chiral-at-metal complexes, which by definition leads to a mixture of enantiomers in unequal amounts thanks to an external chiral auxiUary, has never been achieved. The most studied strategy is currently indirect asymmetric synthesis, which involves (i) the stereoselective formation of the chiral-at-metal complex thanks to a chiral inductor located either on the ligand or on the counterion and then (ii) removal of this internal chiral auxiliary (Fig. 4). Indeed, when the isomerization of the stereogenic metal center is possible in solution, in-... 

After the initial two reports of Rh- and Co-catalyzed reductive aldol couplings, further studies did not appear in the literature until the late 1990s. Beyond 1998, several stereoselective and enantioselective reductive aldol reactions were developed, which are catalyzed by a remarkably diverse range of metal complexes, including those based upon Pd, Cu, Ir, and In. In this chapter, transition metal-catalyzed aldol, Michael, and Mannich reactions that proceed via transition metal hydride-promoted conjugate reduction are reviewed. 

Metal complexes of tetra-4-ferf-butylphthalocyanine [PcM, M = Mn(III)OAc, Cu(II), Co(II), Ni(II), Fe(II) (C5H5N)2, Rh(III)Cl] have also been tested for their stereoselective potential in the cyclopropanation of styrene with ethyl diazoacetate 101K The Co(II) and Rh(I) complexes, already highly active at room temperature, produced the 2-phenylcyclopropanecarboxylic esters in a E Z isomer ratio of 1.0-1.2 which compares well with the value obtained with the rhodium(III) porphyrin 47 a (1.2). In the other cases, E.Z ratios of 2.0-2.2 were observed, except for M = Fe(II) (C5HsN)2 where it was (3.0) the E.Z ratio of the purely thermal reaction was 2.0. 

The catalytic cyclo-oligomerization of 1,3-butadiene mediated by transition-metal complexes is one of the key reactions in homogeneous catalysis.1 Several transition metal complexes and Ziegler-Natta catalyst systems have been established that actively catalyze the stereoselective cyclooligomerization of 1,3-dienes.2 Nickel complexes, in particular, have been demonstrated to be the most versatile catalysts.3... 

The ability of transition-metal complexes to activate substrates such as alkenes and dihydrogen with respect to low-barrier bond rearrangements underlies a large number of important catalytic transformations, such as hydrogenation and hydroformy-lation of alkenes. However, activation alone is insufficient if it is indiscriminate. In this section we examine a particularly important class of alkene-polymerization catalysts that exhibit exquisite control of reaction stereoselectivity and regioselec-tivity as well as extraordinary catalytic power, the foundation for modern industries based on inexpensive tailored polymers. 

Some synthetically useful isomerization reactions of alkenes, other than nitrogen- or oxygen-substituted allylic compounds, were reported by the use of a catalytic amount of transition metal complexes. The palladium complex, /ra r-Pd(C6HsCN)2Gl2, effectively catalyzed the stereoselective isomerization of /3,7-unsaturated esters to a,/3-unsaturated esters (Equation (26)). 

Pyridines can be functionalized by a range of metal complexes, notably ruthenium analogs. Ruthenium vinylidene complexes promote the reaction of pyridines with silylalkynes in both a regio- and stereoselective manner, affording 2-styrylpyridines (Equation (78)). 

The Alder-ene reaction has traditionally been performed under thermal conditions—generally at temperatures in excess of 200 °C. Transition metal catalysis not only maintains the attractive atom-economical feature of the Alder-ene reaction, but also allows for regiocontrol and, in many cases, stereoselectivity. A multitude of transition metal complexes has shown the ability to catalyze the intramolecular Alder-ene reaction. Each possesses a unique reactivity that is reflected in the diversity of carbocyclic and heterocyclic products accessible via the transition metal-catalyzed intramolecular Alder-ene reaction. Presumably for these reasons, investigation of the thermal Alder-ene reaction seems to have stopped almost completely. For example, more than 40 papers pertaining to the transition metal-catalyzed intramolecular Alder-ene reaction have been published over the last decade. In the process of writing this review, we encountered only three recent examples of the thermal intramolecular Alder-ene reaction, two of which were applications to the synthesis of biologically relevant compounds (see Section 10.12.6). 

The [5 + 2]-cycloadditions of air-stable 7]3-pyranyl and 7]3-pyridinyl molybdenum 7T-complexes (4758 and 48,59 respectively) with alkenes reported by Liebeskind and co-workers provide a novel method for the construction of oxabicyclo[3.2.1]octenes and highly functionalized tropanes (Scheme 20). This process involves the formation of a TpMo(CO)2 complex which in the presence of EtAlCl2 reacts with an alkene in a stereoselective [5 + 21-cycloaddition to give metal-complexed cycloadducts 50 and 51 (Tp = hydridotrispyrazolylborato). Metal decomplexation via protiodemetalation or oxidation affords the products in good to excellent yields (Scheme 21). 

A large number of homogeneous transition-metal complexes have been reported as catalysts for the stereoselective hydrogenation of alkynes, although the... 

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