The asymmetric catalytic C À C bond formation by addition of an organozinc reagent to aldehydes for the synthesis of enantiomerically pure secondary alcohols as building blocks for bioactive compounds has been extensively studied, and numerous catalytic systems have been developed to yield excellent enantioselectivities.[1] Since tertiary alcohols appear in bioactive compounds, [2] the construction of chiral quaternary carbon centers is synthetically important owing to the inertness of ketones toward additions of carbon nucleophiles and less differentiation of the two groups attached to the carbonyl carbon atom. Despite efforts in recent years, only limited examples of catalytic asymmetric additions to ketones have been reported to give excellent stereoselectivities. Organozinc compounds have been used for asymmetric additions of alkyl compounds to ketones [3] or a-ketoesters [4] and for additions of vinyl, [5] alkynyl, [2c, 6] or aryl compounds [7] to ketones. For allyl addition reactions, the considerably toxic allyl tin compounds have been the commonly used reagents, [8] and in fewer cases, allyl silicon [2e, 9] or allyl boron compounds [10] have been used. In addition to these reagents, organoaluminum compounds are excellent nucleophiles for organic reactions [11] owing their high reactivities, a greater Lewis acidity of the aluminum center, and low toxicities. However, the use of organoaluminum compounds in asymmetric catalysis is rare. In the past few years, asymmetric catalytic alkylation, [12] allylation, [13] and alkynylation [14] reactions employing organoaluminum reagents have been established to achieve good to excellent enantioselectivities. Recently, we demonstrated that the novel [AlAr 3 (thf)] reagents are powerful aryl nucleophiles for additions to aldehydes catalyzed by the titanium catalyst of (R)-H 8 -binol (binol = 2,2'-dihydroxy-1,1'-binaphthyl) with the reactions complete in only 10 min. [15] In studies of asymmetric aryl additions to ketones, [7] only a few papers have been reported in just two catalytic systems. The first system is a zinc catalyst of (+)-daib (3-exo-(dimethylamino)isoborneol) with which direct additions of the ZnPh 2 reagent afford phenylation products.[7a] The second system is a series of titanium catalysts of disulfonamides [16] with which additions of ZnPh 2 or aryl zinc reagents furnish phenylation or arylation products. [7b-f] However, generation of aryl zinc reagents from excess ZnEt 2 and aryl boron compounds requires reaction conditions at elevated temperatures for 12-16 h. Furthermore, the arylation reactions have not reached a satisfactory level in yields and stereoselectivities.[7f] To extend applications of [AlAr 3 (thf)] reagents in catalysis, we report herein the first example of asymmetric aryl additions of organoaluminum reagents to ketones. The (S)-binol molecule was selected as the ligand since binol is a remarkable ligand applied to many varieties of asymmetric reactions [17] and since dititanium complexes of binol ligands with known structures [...
[reaction: see text] Immobilized dirhodium(II) catalysts having mixed chiral ligands enhance reactivity (AH = azetidinone) and influence stereoselectivity in cyclopropanation and carbon-hydrogen insertion reactions.
Chiral dirhodium(II) tetrakis[methyl 2-oxypyrrolidine-5(S)-carboxylate] has been immobilized on polystyrene-poly(ethylene glycol) and Merrifield resins.Intra-and intermolecular cyclopropanation reactions with these catalysts demonstrate their high selectivity, comparable to or better than their homogeneous counterpart, and recovery and reuse for up to nine sequential applications have been achieved without loss of selectivity. Catalyst stability is related to the percentage of available sites to which the ligand is affixed, but the percentage of ligand sites on the polymer that are bound to dirhodium(II) does not appear to influence stability or selectivity.
A series of dimeric complexes [TiL*X 2 ] 2 (H 2 L* ) (1R,2S)-2-(4-methylbenzenesulfonylamino)-1,3-diphenyl-1-propanol (5); X ) O-i-Pr (4), NMe 2 (6), or O-t-Bu (7)) were prepared, and the asymmetric Et 2 Zn additions to benzaldehyde catalyzed by the complex 4, 6, or 7 with the addition of excess Ti(O-i-Pr) 4 give excellent enantioselectivities up to 96.3% ee. The 1 H NMR study shows that the catalytic systems of these complexes involve a common active intermediate. The reaction of 4 with 2 molar equiv of Ti(O-i-Pr) 4 afforded another dimeric complex, 9, with the structure (i-PrO) 2 TiL*Ti(O-i-Pr) 4 . Complex 9 is demonstrated to provide a suitable environment, achieving an enantioselectivity of 95.6% ee. Complex 9 in solution is shown as a mixture of complexes 4, 9, and Ti(O-i-Pr) 4 , and the equilibrium among these three complexes is solvent and temperature dependent. The reaction of complex 4 or 9 with MeTi(O-i-Pr) 3 furnished the complex (i-PrO) 2 TiL*Ti(O-i-Pr) 3 Me (10), which reacted stoichiometrically with benzaldehyde to afford the complex (i-PrO) 2 TiL*Ti(O-i-Pr) 3 (OCHMePh) (11), which dissociates to give a mixture of the complexes 4, 11, and Ti(O-i-Pr) 4 . A complete scope of the mechanism is clearly deduced from stepwise reactions starting from complex 4 to 9, 10, 11 and then back to 4. This is an example of a mechanism with all intermediates confirmed structurally or spectroscopically except complex 12, which proceeds directly to complex 11. This mechanism is also suggested to apply for the reactions catalyzed by the titanium complexes of BINOLs and diols. One of the roles of excess Ti(O-i-Pr) 4 is to facilitate removal of the product from the metal center. However, more importantly, the two major roles of Ti(O-i-Pr) 4 are to exchange an alkyl group with the dialkylzinc reagent and to regenerate complex 9 from complex 11 for next cycles of reactions.
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