Complexes asymmetric metallation

The use of asymmetric catalysts in chiral syntheses is taking on increasing importance. Asymmetric ligands or asymmetric metal complexes used in these transformations are quite expensive and need to be efficiently separated from reaction mixtures and recycled. Scheme 16 shows the preparation of a polymer-anchored dibenzophosphole-DIOP platinum-tin catalysts system. The asymmetric ligand places the Pt-SnClj system in a chiral environment. This catalyst has given the highest enantiometric excesses ever observed in catalytic hydroformylation. The initially achieved 70-83% e.e. values were improved to >95% by the use of triethylorthoformate (TEOF) as the solvent. ... 

Transition metal-catalyzed epoxidations, by peracids or peroxides, are complex and diverse in their reaction mechanisms (Section 5.05.4.2.2) (77MI50300). However, most advantageous conversions are possible using metal complexes. The use of t-butyl hydroperoxide with titanium tetraisopropoxide in the presence of tartrates gave asymmetric epoxides of 90-95% optical purity (80JA5974). 

Many chiral metal complexes with Lewis acid properties have been developed and applied to the asymmetric Diels-Alder reaction. High enantioselectivity is, of course, one of the goals in the development of these catalysts. Enantioselectivity is not, however, the only factor important in their design. Other important considerations are ... 

Catalytic, enantioselective cyclopropanation enjoys the unique distinction of being the first example of asymmetric catalysis with a transition metal complex. The landmark 1966 report by Nozaki et al. [1] of decomposition of ethyl diazoacetate 3 with a chiral copper (II) salicylamine complex 1 (Scheme 3.1) in the presence of styrene gave birth to a field of endeavor which still today represents one of the major enterprises in chemistry. In view of the enormous growth in the field of asymmetric catalysis over the past four decades, it is somewhat ironic that significant advances in cyclopropanation have only emerged in the past ten years. 

From a historical perspective it is interesting to note that the Nozaki experiment was, in fact, a mechanistic probe to establish the intermediacy of a copper carbe-noid complex rather than an attempt to make enantiopure compounds for synthetic purposes. To achieve synthetically useful selectivities would require an extensive exploration of metals, ligands and reaction conditions along with a deeper understanding of the reaction mechanism. Modern methods for asymmetric cyclopropanation now encompass the use of countless metal complexes [2], but for the most part, the importance of diazoacetates as the carbenoid precursors still dominates the design of new catalytic systems. Highly effective catalysts developed in... 

Monodentate dipolarophiles such as acrolein, methacrolein, and a-bromoacrolein could be successfully utilized in the l ,J -DBFOX/Ph-transition metal complex-catalyzed asymmetric nitrone cycloadditions [76]. The reactions of N-benzylideneani-line N-oxide with acrolein in the presence of the nickel(II) aqua complex R,R-DBF0X/Ph-Ni(C104)2 3H20 (10mol%) and MS 4 A produced a mixture of two regioisomers (5-formyl/4-formyl regioisomers ca 3 1). However, enantio-... 

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. 

An early success story in the field of catalytic asymmetric synthesis is the Monsanto Process for the commercial synthesis of l-DOPA (4) (see Scheme 1), a rare amino acid that is effective in the treatment of Parkinson s disease.57 The Monsanto Process, the first commercialized catalytic asymmetric synthesis employing a chiral transition metal complex, was introduced by W. S. Knowles and coworkers and has been in operation since 1974. This large-scale process for the synthesis of l-DOPA (4) is based on catalytic asymmetric hydrogenation, and its development can be... 

Ethane, (K)-l-cyclohexyl-L2-bis(diphenylphosphino)-rhodium complexes asymmetric hydrogenation, 6,253 Ethane, tetracyano-metal complexes, 2,263 Ethane, tetrakis(aminomethyl)-metal complexes, 2, 56 Ethane, tris[l, 1, l-(trisaminomethyl)]-complexes structure, 1,26... 

Phosphine, methyl-n-propylphenyl-rhodium complexes asymmetric hydrogenation, 6,250 Phosphine, neomenthyldiphenyl-rhodium complexes asymmetric hydrogenation, 6,250 Phosphine, phenyl-, 2,992 Phosphine, o-phenylenebis(dimethyl-, 2,993 Phosphine, p-phenylenebis(diphenyl-, 2,993 Phosphine, seleno-metal complexes, 2,664 bidentatc, 2, 664 Phosphine, triaryl-photographic stabilizer, 6,103 Phosphine, tributyl-, 2, 992 oxide... 

Significant advance in the field of asymmetric catalysis was also achieved with the preparation of l,2-bis(phospholano)benzene (DuPHOS 4) and its confor-mationally flexible derivative (l,2-bis(phospholano)ethane, known as BPE) by Burk et al. [59]. Two main distinctive features embodied by these Hgands, as compared to other known chiral diphosphine ligands, are the electron-rich character of the phosphorus atoms on the one hand and the pseudo-chirality at phosphorus atoms, on the other. These properties are responsible for both the high activity of the corresponding metal complex and an enantioselection indepen-... 

Ghosh et al. [70] reviewed a few years ago the utihty of C2-symmetric chiral bis(oxazoline)-metal complexes for catalytic asymmetric synthesis, and they reserved an important place for Diels-Alder and related transformations. Bis(oxazoline) copper(II)triflate derivatives have been indeed described by Evans et al. as effective catalysts for the asymmetric Diels-Alder reaction [71]. The bis(oxazoline) Ugand 54 allowed the Diels-Alder transformation of two-point binding N-acylimide dienophiles with good yields, good diastereos-electivities (in favor of the endo diastereoisomer) and excellent ee values (up to 99%) [72]. These substrates represent the standard test for new catalysts development. To widen the use of Lewis acidic chiral Cu(ll) complexes, Evans et al. prepared and tested bis(oxazoHnyl)pyridine (PyBOx, structure 55, Scheme 26) as ligand [73]. 

Zeijden [112] used chiral M-functionalized cyclopentadiene ligands to prepare a series of transition metal complexes. The zirconium derivative (82 in Scheme 46), as a moderate Lewis acid, catalyzed the Diels-Alder reaction between methacroleine and cyclopentadiene, with 72% de but no measurable enantiomeric excess. Nakagawa [113] reported l,T-(2,2 -bis-acylamino)binaphthalene (83 in Scheme 46) to be effective in the ytterbium-catalyzed asymmetric Diels-Alder reaction between cyclopentadiene and crotonyl-l,3-oxazolidin-2-one. The adduct was obtained with high yield and enantioselectivity (97% yield, endo/exo = 91/9, > 98% ee for the endo adduct). The addition of diisopropylethylamine was necessary to afford high enantioselectivities, since without this additive, the product was essentially... 

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