Heterobimetallic complexes, Mannich

K. Yamada, S. J. Harwood, H. Groger, M. Shibasaki, The First Catalytic Asymmetric Nitro-Mannich-Type Reaction Promoted by a New Heterobimetallic Complex, Angew. Chem, 1999, 38, 3504-3506. 

Shibasaki and coworkers have conducted extensive research on the use of hetero-bimetallic complexes as catalysts for asymmetric synthesis [11]. The reactions are catalyzed by heterobimetallic complexes that function as both a Lewis acid and a Bronsted base. Among these, LaLi3tris(binaphthoxide) catalyst 1 (LLB) was proven to be an effective catalyst in direct asymmetric aldol reactions (Fig. 1) [12]. On the basis of this research, Shibasaki et al. reported the first report of a direct catalytic asymmetric Mannich reaction [13],... 

For example, an effective procedure for the synthesis of LLB (where LL = lanthanum and lithium) is treatment of LaCls 7H2O with 2.7 mol equiv. BINOL dilithium salt, and NaO-t-Bu (0.3 mol equiv.) in THF at 50 °C for 50 h. Another efficient procedure for the preparation of LLB starts from La(0-/-Pr)3 [54], the exposure of which to 3 mol equiv. BINOL in THF is followed by addition of butyllithium (3 mol equiv.) at 0 C. It is worthy of note that heterobimetallic asymmetric complexes which include LLB are stable in organic solvents such as THF, CH2CI2 and toluene which contain small amounts of water, and are also insensitive to oxygen. These heterobimetallic complexes can, by choice of suitable rare earth and alkali metals, be used to promote a variety of efficient asymmetric reactions, for example nitroaldol, aldol, Michael, nitro-Mannich-type, hydrophosphonylation, hydrophosphination, protonation and Diels-Alder reactions. A catalytic asymmetric nitroaldol reaction, a direct catalytic asymmetric aldol reaction, and a catalytic asymmetric nitro-Mannich-type reaction are discussed in detail below. 

These rare earth-containing heterobimetallic complexes can be utilized for a variety of efficient catalytic asymmetric reactions, as shown in Sch. 13, and quite recently we have succeeded in realizing the first example of a catalytic asymmetric nitro-Mannich-type reaction using the newly developed heterobimetallic complex 71 (Table 17) [72]. 

The first catalytic enantioselective nitro-Mannich-type reaction was developed by Shibasaki by the use of chiral BINOL-derived heterobimetallic complex 90 (Scheme 2.51). The catalyst prepared from Yb(0/-Pr)3, KOt-Bu, and (/ )-BINOL in a ratio of 1 1 3 gave the best result (82-91% ee) in the reaction of aldimines with nitromethane, while the conventional ratio (Yb K BINOL = 1 3 3) was much less effective (52% ee) in the same reaction. Moreover, the complex with a ratio of Yb K BINOL=l l 2 did not promote the reaction. Therefore, the complex YbK((I )-BINOLate)2 itself or its aggregated complex [YbK((I )-BINOLate)2] was not likely to be tbe actual catalyst. The active catalyst might be 90, a complex of YbK((I )-BINOLate)2... 

The lanthanide-alkali metal heterobimetallic complexes have also been shown to promote other reactions, such as nitro-Mannich (aza-Henry) reaction [154],... 

Scheme 10 A catalytic asymmetric 5yn-selective nitro-Mannich reaction promoted by heterobimetallic Cu/Sm/dinucleating Schiff base complexes...

Direct catalytic asymmetric Maimich-type reactions of various aromatic and heteroaromatic hydroxyke-tones are catalyzed by a Y N(SiMe3)2 3/TMS-linked-BrNOL complex, whereas a heterobimetallic lanthanum arylox-ide/lithium aryloxide/pybox complex catalyzes direct catalytic asymmetric Mannich-type reactions of a-keto anilides as synthetic equivalents of homoenolates. A La(OTf)3/Me-PyBox/amine base/Bronsted acid combination was found to be effective for direct catalytic asymmetric Maiuiich-type reactions of y-butenolides. ... 

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