Copper catalysts Mukaiyama aldol reaction, enantioselectivity

Chiral //A(oxazolinc) ligands disubstituted at the carbon atom linking the two oxazolines by Frechet-type polyether dendrimers coordinated with copper(II) triflate were found to provide good yields and moderate enantioselectivities for Mukaiyama aldol reactions in water that are comparable with those resulting from the corresponding smaller catalysts.291 AgPF6-BINAP is very active in this reaction and the addition of a small amount of water enhanced the reactivity.292... 

Chiral Catalysts Containing Group 11 Metals (Cu, Ag, and Au). The most recent publications on the chiral copper catalysts are mainly dealing with those containing bis(oxazoline)-type ligands (Fig. 22). Cationic [Cu( Bu-BOX)] + complexes with OTf , [SbFe] , counterions catalyze Michael reactions, and various types of cycloadditions (292). Copper(II)-PYBOX complexes have been shown to catalyze enantioselective Mukaiyama aldol reactions (293). Similarly, bisoxa-zoline derivatives serve as ligands in the catalytic system prepared in situ from Cud) salts and are used for asymmetric peroxidation and enantioselective Meer-wein arylation of activated olefins (294). The copper-BOX-triflate complexes have found wide applications in cyclopropanation of alkenes (60), furans (295), and aziridination of alkenes (296). 

The use of chiral copper Lewis acids in enantioselective aldol processes has seen rapid development over the past 10 years. In particular, copper-catalyzed variants of the Mukaiyama aldol reaction received considerable attention in the years leading up to the new millennium. Evans and coworkers first demonstrated Cu(II)/pybox complex (59) as an efficient catalyst for highly enantioselective addition of a variety of silylketene acetals to aldehydes capable ofbidentate coordination (Scheme 17.12) [17]. In reactions utilizing silylketene acetals (61) and (63) with an additional stereoelement, diastereoselectivities and enantioselectivities were also high. A square pyramidal model (65), which has been further supported by a crystal structure of the complex, with the a-alkoxy aldehyde bound in a bidentate fashion accounts for the observed selectivity. 

Given the utility of chiral Cu(II)/bisoxazoline complexes in enantioselective Mukaiyama aldol reactions, a number of reports detailing the development of polymer-bound or dendritic bisoxazoline copper (I I) complexes have been developed. Development of such catalyst systems provides the potential for easy recovery and reuse of the relatively expensive catalyst. To this end, Salvadori and CO workers reported Mukaiyama aldol addition of ketene thioacetal (57) to methyl pyruvate catalyzed by a Cu(OTf)2 complex of polystyrene-supported bisoxazoline (89) (Scheme 17.18) [23]. The enantioselectivity of the addition remained high over eight cycles of the catalyst, however, reactivity was gradually reduced over time. 

The major developments of catalytic enantioselective cycloaddition reactions of carbonyl compounds with conjugated dienes have been presented. A variety of chiral catalysts is available for the different types of carbonyl compound. For unactivated aldehydes chiral catalysts such as BINOL-aluminum(III), BINOL-tita-nium(IV), acyloxylborane(III), and tridentate Schiff base chromium(III) complexes can catalyze highly diastereo- and enantioselective cycloaddition reactions. The mechanism of these reactions can be a stepwise pathway via a Mukaiyama aldol intermediate or a concerted mechanism. For a-dicarbonyl compounds, which can coordinate to the chiral catalyst in a bidentate fashion, the chiral BOX-copper(II)... 

Mukaiyama-aldol [45] (8.3) and Diels-Alder [46] (8.4) reactions. Lectka and coworkers [47] reported an efficient catalytic enantioselective imino-ene reaction using a copper catalyst in BTF (8.5), which gave better results in BTF compared to traditional solvents like THF or dichloromethane. They suggested that the aromatic character of BTF has a favorable influence for the enantiosel-ectivity. Trimethylaluminum and dimethylaluminum-perfluorophenolate were successfully used for the cleavage of acetals derived from C2-symmetric diols... 

Finally, stereochemical aspects of the mechanism have been extensively studied by Evans and coworkers during their construction of a model to map the diastereoselective induction observed in the course of the aldol reaction. Similarly, mechanistic studies were performed by the Evans group with regards to their bis(oxazolinyl)-pyridine (pybox)-copper(II) complex, a catalyst for the enantioselective Mukaiyama reaction. ... 

Scheme 5.67 Evans Mukaiyama aldol and vinylogous aldol reactions mediated by the copper PYBOX catalyst 217 enantioselective synthesis of callipeltoside A building block 225.

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