LLB-type catalyst

Shibasaki reported the first catalytic asymmetric hydrophosphonylation of imines in 1995 (Scheme 5-45) using heterobimetallic LLB-type catalysts. 

LLB-type catalysts were also able to promote diastereoselective and enantioselective nitroaldol reactions starting from substituted nitroalkanes. In preliminary work, however, LLB itself gave unsatisfactory results in terms of both diastereoselectivity (syn/anti ratio 63 37 to 77 23) and enantioselectivity (<78% ee).32 To address the problem of modest enantio- and diastereoselectivities with... 

The LLB type catalysts were also successfully applied in the asymmetric nitroaldol reaction of the quite um-eactive a,a-difluoro aldehydes. In general, catalytic asymmetric syntheses of fluorine-containing compounds are rather difficult [32]. However, catalytic asymmetric nitroaldol reaction of a broad variety of a,a-difluoro aldehydes 20,22,24,26,28, and 30 proceeded satisfactorily when using the heterobimetallic asymmetric catalysts with modified, 6,6 -disubstitut-ed BINOL ligands [33] (Scheme 7). The best results were obtained with the sa-marium(III) complex (5mol%) generated from 6, 6 -bis (triethylsilyl)ethy-nyl BINOL with enantioselectivities up to 95% ee. 

A further application of the heterobimetallic lanthanoid catalysts of the LLB type to the field of catalytic asymmetric Diels-Alder reactions [47,48] was also achieved by Shibasaki et al. [49]. In general, LLB type complexes are multifunctional asymmetric catalysts, showing both Bronsted basicity and Lewis acidity. Nevertheless, in this study the use of LLB type catalysts acting as asymmetric Lewis acids alone was examined and led to the development of an LLB (type) catalyzed asymmetric Diels-Alder reaction [49]. Representative results for the catalytic asymmetric Diels-Alder reactions using 48 and cyclopentadiene in toluene as a solvent are shown in Scheme 16. 

Compared to the result with LLB, the use of a 6,6 -dibromosubstituted BINOL derived LLB type catalyst LLB led to significantly improved yield, endo exo ratio and enantioselectivity (86% ee). Interestingly, the addition of 12-crown-4 to the reaction medium resulted in the formation of the adduct 49 with much lower enantiomeric excess. This result appears to suggest that the lithium cation(s) play a key role in activation of the dienophile. 

Although the development of a range of catalytic asymmetric aldol-type reactions has proven to be a valuable contribution to asymmetric synthesis [35—37], in all of these reactions pre-conversion of the ketone moiety to a more reactive species such as an enol silyl ether, enol methyl ether, or ketene silyl acetal has been an unavoidable necessity. However, quite recently Shibasaki et al. reported that a direct catalytic asymmetric aldol reaction, which is known in enzyme chemistry, is also possible in the presence of heterobimetallic lanthanoid catalysts [38]. Using fR)-LLB (20 mol%), which shows both Lewis acidity and Bron-sted basicity similar to the corresponding aldolases, the desired optically active aldol adducts were obtained with up to 94% ee. A variety of aldehydes and unmodified ketones can be used as starting materials (Scheme 11). 

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