Conjugate addition reactions chiral catalysts

Quite a number of asymmetric thiol conjugate addition reactions are known [84], but previous examples of enantioselective thiol conjugate additions were based on the activation of thiol nucleophiles by use of chiral base catalysts such as amino alcohols [85], the lithium thiolate complex of amino bisether [86], and a lanthanide tris(binaphthoxide) [87]. No examples have been reported for the enantioselective thiol conjugate additions through the activation of acceptors by the aid of chiral Lewis acid catalysts. We therefore focussed on the potential of J ,J -DBFOX/ Ph aqua complex catalysts as highly tolerant chiral Lewis acid catalyst in thiol conjugate addition reactions. 

The l ,J -DBFOX/Ph-transition metal aqua complex catalysts should be suitable for the further applications to conjugate addition reactions of carbon nucleophiles [90-92]. What we challenged is the double activation method as a new methodology of catalyzed asymmetric reactions. Therein donor and acceptor molecules are both activated by achiral Lewis amines and chiral Lewis acids, respectively the chiral Lewis acid catalysts used in this reaction are J ,J -DBFOX/Ph-transition metal aqua complexes. 

As is the case for aldol addition, chiral auxiliaries and catalysts can be used to control stereoselectivity in conjugate addition reactions. Oxazolidinone chiral auxiliaries have been used in both the nucleophilic and electrophilic components under Lewis acid-catalyzed conditions. (V-Acyloxazolidinones can be converted to nucleophilic titanium enolates with TiCl3(0-/-Pr).320... 

The first application of NMR diffusion measurements to determine the aggregation state of a transition metal catalyst concerned the chiral, tetranuclear Cu(i) catalysts 130-132, used in the conjugate addition reactions of anions to a,p-unsatu-rated cyclic ketones. Compounds 130-132 react wdth isonitriles to form 133-135, and do not degrade to lower molecular weight species (see Eq. (20)) [109]. 

Aluminum salen complexes have been identified as effective catalysts for asymmetric conjugate addition reactions of indoles [113-115]. The chiral Al(salen)Cl complex 128, which is commercially available, in the presence of additives such as aniline, pyridine and 2,6-lutidine, effectively catalyzed the enantioselective Michael-type addition of indoles to ( )-arylcrolyl ketones [115]. Interestingly, this catalyst system was used for the stereoselective Michael addition of indoles to aromatic nitroolefins in moderate enantiose-lectivity (Scheme 36). The Michael addition product 130 was easily reduced to the optically active tryptamine 131 with lithium aluminum hydride and without racemization during the process. This process provides a valuable protocol for the production of potential biologically active, enantiomerically enriched tryptamine precursors [116]. 

The copper-catalyzed conjugate addition reaction of organozinc reagents has reached a prominent level of success by the development of sophisticated chiral phosphorus ligands. Nickel catalysts have also been surveyed by several groups. 

Sibi et al. [66] reported the first examples of highly enantioselective conjugate amine additions [67] by use of catalytic amounts of a chiral Lewis acid complex. Addition of 0-benzylhydroxyamine 87 (1.1 equiv.) to the pyrazole-derived crotonamide 86 proceeded smoothly in the presence of stoichiometric amounts of the chiral catalyst prepared from the bis(oxazoline) 50 and MgBr2 OEt2 with high enantiomeric excess (96 % ee) (Sch. 37). This conjugate addition reaction was equally effective with catalytic amounts of the chiral Lewis acid (92 % ee with 30 mol % 88 % ee with 10 mol %). A re face amine addition to the s-cis substrate bound to the chiral complex with tetrahedral- or ds-octahedral arrangements XXXII and XXXni accounts for the product stereochemistry observed (Fig. 7). 

Enantioselective conjugate addition reactions of strongly coordinating nucleophiles with the use of chiral 4,6-dibenzofurandiyl-2,2 -6A(4-phenyloxazoline)-based aqua complexes as catalysts 03YGK1073. 

Carbons and Carbon Supported Catalysts in Hydroprocessing 2 Chiral Sulfur Ligands Asymmetric Catalysis 3 Recent Developments in Asymmetric Organocatalysis 4 Catalysis in the Refining of Fischer-Tropsch Syncrude 5 Organocatalytic Enantioselective Conjugate Addition Reactions A Powerful Tool for the Stereocontrolled Synthesis of Complex Molecules... 

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