Asymmetric induction with supported catalysts

Chiral pyridine addition to cobalt catalysts derived from dicobalt octacarbonyl has a positive influence on cherno- and regioselectivity, but not on stereoselectivity. Thus, no asymmetric induction is observed with Co ( + )-(.S )-3-.vtx-butylpyridine in the hydroformylation of styrene23. Again no induction is observed with chiral cobalt clustersl08. Cobalt is also used in catalytic systems of the type Co(An)n(alkene)m(CO)pLq [An = coordinating or noncoordinat-ing anions, e.g., BPhJ with various chiral ligands [L = ZR4R5R6 (Z = As, N, P, Sb)]166. Low catalytic activities and inductions are observed with supported catalysts of cobalt on silica gel or alumina [in situ preparation from salt, modified with phosphanes, e.g., (+)- or (—)-Diop]89. 

Electroreduction [5b] (with chiral quat as the supporting electrolyte) has been compared with chemical reduction (NaBH4) in the presence of chiral quats for ketone (up to 28% op) and imine (up to 22% op) reductions [57,58], The reduction (NaBH4) of a chiral a,p-enone prostaglandin intermediate in the presence of ephedra-derived catalysts led to the formation of the enol with 70% de [59]. Other reductions with lower asymmetric inductions are noted for ketone [lli,24h,24i,47e,60], imine [5b,57], and hydrodehalogenation of a cyclic a,a-dichlo-roamide [61],... 

In all the examples of exodendrally functionalized enantioselective den-drimer catalysts, the active sites in the periphery of the support were well-defined immobilized molecular catalysts. An alternative is provided by the possibility of attaching chiral multi-functional molecules to the end groups of dendrimers which, due to their high local concentrations, may interact more or less strongly with an achiral reagent and thus induce enantioselectivity in a transformation of a prochiral substrate. Asymmetric induction thus occurs by way of a chiral functionalized microenvironment for a given reaction. 

The first chiral aluminum catalyst for effecting asymmetric Michael addition reactions was reported by Shibasaki and coworkers in 1986 [82], The catalyst was prepared by addition of two equivalents of (i )-BINOL to lithium aluminum hydride which gave the heterobimetallic complex 394. The structure of 394 was supported by X-ray structure analysis of its complex with cyclohexenone in which it was found that the carbonyl oxygen of the enone is coordinated to the lithium. This catalyst was found to result in excellent induction in the Michael addition of malonic esters to cyclic enones, as indicated in Sch. 51. It had previously been reported that a heterobimetallic catalyst prepared from (i )-BINOL and sodium and lanthanum was also effective in similar Michael additions [83-85]. Although the LaNaBINOL catalyst was faster, the LiAlBINOL catalyst 394 (ALB) led to higher asymmetric induction. 

Polymer-supported TADDOL-Ti catalyst 79 prepared by chemical modification was poorly active in the Diels-Alder reaction of 3-crotonoyloxazolidinone with cyclo-pentadiene (Eq. 24) whereas polymeric TADDOL-Ti 81 prepared by copolymerization of TADDOL monomer 80 with styrene and divinylbenzene had high activity similar to that of the soluble catalyst. In the presence of 0.2 equiv. 81 (R = H, Aryl = 2-naphthyl) the Diels-Alder adduct was obtained in 92 % yield with an endolexo ratio of 87 13. The enantioseleetivity of the endo product was 56 % ee. The stability and recyclability of the catalyst were tested in a batch system. The degree of conversion, the endolexo selectivity, and the enantioseleetivity hardly changed even after nine runs. Similar polymer-supported Ti-TADDOLate 82 was prepared by the chemical modification method [99]. Although this polymer efficiently catalyzed the same reaction to give the (2R,2S) adduct as a main product, asymmetric induction was less than that obtained by use of a with similar homogeneous species. 

Optically active a, -epoxy stdfones. - The Darzens reaction of ethyl methyl ketone with chloromethyl / -tolyl sulfone in a two-phase system in the presence of chiral ammonium salts such as N-ethylephedrinium bromide results in a,/3-epoxy sulfones with 0-2.57o optical yields. However, if the supported catalyst (1) is used, optical yields of up to 23% can be obtained as in the example formulated in equation (I). On the other hand, the reaction is slower when the catalyst is supported. The presence of a hydroxy group jS to the nitrogen atom of the catalyst is essential for asymmetric induction. 

Gilbertson and co-workers have reported a peptide-based high-throughput approach in which a library of 136 polymer-supported diphosphines, linked predominantly through a / -turn peptide motif, were screened in the presence of [(77 -allyl)PdCl]2, for their ability to catalyze the enantioselective addition of dimethylmalonate to cyclopentenyl acetate.The screening results revealed the importance of the /3-tum motif for asymmetric induction. Optimization experiments generated catalysts with ee values up to 95%, comparable to the best catalysts known for this reaction. 

An important factor which could influence asymmetric induction would be that cycloaddition is faster than catalyst decomplexation from the ylide. Although the precise mechanism remains unclear, the high levels of enantios-election in intermolecular cycloadditions with dipolarophiles provide definite support for the intermediacy of a chiral rhodium(II)-associated carbonyl ylide involved in the cycloaddition step. These examples indicate that metal-catalyzed dipole formation followed by cycloaddition has the potential to be a powerful method for asymmetric synthesis. 

The scope of this chemistry has recently been extended to terminal alkene substrates [68]. For example, 1-hexene was transformed to 88 in 68% yield under solvent-free conditions using Pd(PPh3)4 as catalyst (Eq. (1.39)). Asymmetric induction has also been achieved in these reactions, and ees of up to 94% have been obtained with a catalyst supported by a chiral phosphoramidite ligand [68c]. The mechanism of the terminal alkene diamination reactions has not yet been fiiDy elucidated, but it appears likely that allyUc C H activation/amination is involved. 

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