BINOL Michael reactions

Moreover, these rare earth heterobimetallic complexes can be utilized for a variety of efficient catalytic asymmetric reactions as shown in Scheme 7 Next we began with the development of an amphoteric asymmetric catalyst assembled from aluminum and an alkali metal.1171 The new asymmetric catalyst could be prepared efficiently from LiAlH4 and 2 mol equiv of (R)-BINOL, and the structure was unequivocally determined by X-ray crystallographic analysis (Scheme 8). This aluminum-lithium-BINOL complex (ALB) was highly effective in the Michael reaction of cyclohexenone 75 with dibenzyl malonate 77, giving 82 with 99% ee and 88 % yield at room temperature. Although LLB and... 

Soon thereafter, the Yamamoto group reported an extension of this work to the highly diastereo- and enantioselective synthesis of nitroso Diels-Alder-type bicycloketones using dienamines in the presence of the BINOL derivative 44 (Scheme 5.61) [115]. This reaction was thought to proceed through a sequential N-NA/ hetero-Michael reaction mechanism. Support for this mechanism was provided from an experiment employing bulkyl 4,4-diphenyl dienamine where the N-NA... 

Another highly useful heterobimetallic catalyst is the aluminum-lithium-BINOL complex (ALB) prepared from LiAlH4 and 2 equiv. of (/ )-BINOL. The ALB catalyst (10 mol %) is also effective in the Michael reaction of enones with various malonates, giving Michael products generally with excellent enantioselectivity (91-99% ee) and in excellent yields [23]. These results ate summarized in Table 8D.3. Although LLB and LSB complement each other in their ability to catalyze asymmetric nitroaldol and Michael reactions, respectively, the Al-M-(/ )-BINOL complexes (M = Li, Na, K, and Ba) are commonly useful for the catalytic asymmetric Michael reaction. 

Third heterobimetallic asymmetric catalyst reported by Shibasaki et al., gallium-sodium-BINOL complex (GaSB) 26 and indium-potassium-BINOL complex (InPB), are also rather effective catalysts for asymmetric Michael reactions, and GaSB was better than InPB in terms of enantioselectivity. The GaSB catalyst was prepared from GaCl3, NaO Bu (4 mol equiv. to... 

Arai et al. also reported another BINOL-derived two-center phase-transfer catalyst 31 for an asymmetric Michael reaction (Scheme 6.11) [8b]. Based on the fact that BINOL and its derivatives are versatile chiral catalysts, and that bis-ammonium salts are expected to accelerate the reaction due to the two reaction sites - thus preventing an undesired reaction pathway - catalyst 31 was designed and synthesized from the di-MOM ether of (S)-BINOL in six steps. After optimization of the reaction conditions, the use of 1 mol% of catalyst 31a promoted the asymmetric Michael reaction of glycine Schiff base 8 to various Michael acceptors, with up to 75% ee. When catalyst 31b or 31c was used as a catalyst, a lower chemical yield and selectivity were obtained, indicating the importance of the interaction between tt-electrons of the aromatic rings in the catalyst and substrate. In addition, the amine moiety in catalyst 31 had an important role in enantioselectivity (34d and 34e lower yield and selectivity), while catalyst 31a gave the best results. 

In contrast, asymmetric Michael reactions are promoted by alkali metal free La-BINOL ester enolate complexes (Scheme 28) [251]. The catalyst is best prepared by successive addition of the Michael donor and (S)-BINOL to La(0 Pr)3. 

A multinuclear Zn-binaphthoxide complex prepared from Et2Zn and the linked-BINOL 28 has recently been developed as an effective catalyst for the Michael reaction (Scheme 13) [15], The a-hydroxy acetophenone derivative 29 was a suitable substrate, reacting with the Zn complex to afford the configurationally stable Zn enolate. Reaction with a variety of enones proceeded smoothly and... 

For Type II reactions also a variety of useful compounds can be synthesized by changing the combination of the starting materials. In the Michael reaction with cyclic enones, availability of the La-linked-BINOL complex broadened the scope of the Michael acceptor (Scheme 14). It should be noted that less reactive medium-ring-size cyclic enones (7-9membered ring size) underwent conjugate addition highly enantioselectively (up to > 99 % ee) [17]. 

Scheme14. Use of the La-linked-BINOL complex in the Michael reaction with cyclic enones.

C. Catalytic, asymmetric Michael reaction promoted by the La-BINOL complex... 

The first part of this chapter describes recent advances in the use of novel, chiral, alkali metal free-lanthanoid-BINOL derivative complexes for a variety of efficient, catalytic, asymmetric reactions. For example, using a catalytic amount of chiral Ln-BINOL derivative complexes, asymmetric Michael reactions and asymmetric epoxidations of enones proceed in a highly enantioselective manner. 

The second part of the chapter deals with several kinds of asymmetric reactions catalyzed by unique heterobimetallic complexes. These reagents are lanthanoid-alkali metal hybrids which form BINOL derivative complexes (LnMB, where Ln = lanthanoid, M = alkali metal, and B = BINOL derivative). These complexes efficiently promote asymmetric aldol-type reactions as well as asymmetric hydrophosphonylations of aldehydes (catalyzed by LnLB, where L = lithium), asymmetric Michael reactions (catalyzed by LnSB, where S = sodium), and asymmetric hydrophosphonylations of imines (catalyzed by LnPB, where P = potassium) to give the corresponding desired products in up to 98% ee. Spectroscopic analysis and computer simulations of these asymmetric reactions have revealed the synergistic cooperation of the two different metals in the complexes. These complexes are believed to function as both Brpnsted bases and as Lewis acids may prove to be applicable to a variety of new asymmetric catalytic reactions.1,2... 

C. Catalytic, Asymmetric Michael Reaction Promoted by the La-BINOL... 

Figure 4. Proposed mechanism for the La-BINOL (La-17)-catalyzed asymmetric Michael reaction.

The Ln-BINOL derivative complexes are efficient asymmetric catalysts for Michael reactions and the epoxidations of enones. However, as was mentioned above, almost racemic products are obtained in the case of the asymmetric nitroaldol reaction of 2 with 12. For this transformation, a new class of catalysts, heterobimetallic species, have been developed. 

In both catalytic, asymmetric Michael reactions and nitroaldol reactions, enones and/or aldehydes appear to coordinate to the lanthanoid metal. Why, then, is LSB more effective for catalytic, asymmetric Michael reactions, whereas LLB is more effective for catalytic, asymmetric nitroaldol reactions This disparity might arise from slight differences in bond lengths in the chelated intermediate, as well as slight differences in bite angle for the BINOL moiety caused by varying the alkali metal. 

In both types of catalytic asymmetric Michael reactions, the use of 6,6 -substituted BINOL-derived LSB-type catalysts did not result in significantly improved results. 

In 2002, Sasai et al. reported the synthesis of dendritic heterobimetal-lic multi-functional chiral catalysts, containing up to 12 l,l/-bi-2-naphthol (BINOL) units at their terminal positions (Fig. 9) [30]. On treating these functionalized dendrimers with AlMe3 and n-Buli, insoluble metallated Al-Ii-bis(binaphthoxide) generation x (GX-ALB) catalysts were obtained, which showed moderate catalytic activity in the asymmetric Michael reaction of 2-cyclohexenone with dibenzyl malonate (Scheme 4). 

Figure 6.21 The proposed mechanism of Michael reaction of enones with malonates catalyzed by (R, i )-Ln-M-linked BINOL complex, a bifunctional asymmetric catalyst developed by Shibasaki.

The Lewis acid-catalyzed conjugate addition of silyl enol ethers to a,y3-unsaturated carbonyl derivatives, the Mukaiyaraa Michael reaction, is known to be a mild, versatile method for carbon-cabon bond formation. Although the development of catalytic asymmetric variants of this process provides access to optically active 1,5-dicarbonyl synthons, few such applications have yet been reported [108], Mukiyama demonstrated asymmetric catalysis with BINOL-Ti oxide prepared from (/-Pr0)2Ti=0 and BINOL and obtained a 1,4-adduct in high % ee (Sch. 43) [109]. The enantioselectiv-ity was highly dependent on the ester substituent of the silyl enol ether employed. Thus the reaction of cyclopentenone with the sterically hindered silyl enol ether derived from 5-diphenylmethyl ethanethioate proceeds highly enantioselectively. Sco-lastico also reported that reactions promoted by TADDOL-derived titanium complexes gave the syn product exclusively, although with only moderate enantioselectiv-ity (Sch. 44) [110]. 

It was proposed that a Lewis acid lanthanum center controls the direction of the carbonyl function and activates the enone while the sodium alkoxide forms enolate intermediates and regenerates the catalyst by hydrogen abstraction (Scheme 6). Other Ln/alkali metal combinations, including La/Li, show negligible asymmetric induction, yet give almost racemic products in excellent yield. In contrast, alkali-metal free BINOL ester enolate complexes catalyze Michael reactions with high enantioselectivities, albeit at lower temperatures. 

La-linked-BINOL complex 23 was introduced as a stable, storable, and reuse-able asymmetric catalyst for the Michael reaction [120]. Optimization of the reaction between dibenzyl malonate and 2-cyclohexene-1-one in DME afforded the Michael adduct in 94% yield and >99% ee. The extraordinary versatility of LnLB catalyts is also documented in the highly efficient Michael addition of thiols to a,y9-unsaturated carbonyl compounds [121] and tandem Michael-aldol reactions [122]. 

In 1988, Mukaiyama et al. reported the Sn(OTf)2-50d-catalyzed asymmetric Michael reaction of a trimethylsilyl enethiolate, CH2=C(SMe)SSiMej (up to 70% ee) [243]. It was proposed that the catalytic reaction proceeded via an Sn(II) enethiolate. They also demonstrated that a BINOL-derived oxotitaniurn catalyzes the Michael addition of ketene silyl thioacetals to a-enone with high enantioselectivity (up to 90% ee) [244]. After this pioneering work other research groups developed new reaction systems for enantioselective Mukaiyama-Michael reactions. 

Direct catalytic asymmetric michael reaction of c<-hydroxyketone promoted by Et2Zn/LINKED-BINOL COMPLEX... 

Table 11.3 Direct catalytic asymmetric Michael reaction with the first generation Et2Zn/ linked-BINOL = 2/1 system (1).

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