Binaphthoxide

Quite a number of asymmetric thiol conjugate addition reactions are known [84], but previous examples of enantioselective thiol conjugate additions were based on the activation of thiol nucleophiles by use of chiral base catalysts such as amino alcohols [85], the lithium thiolate complex of amino bisether [86], and a lanthanide tris(binaphthoxide) [87]. No examples have been reported for the enantioselective thiol conjugate additions through the activation of acceptors by the aid of chiral Lewis acid catalysts. We therefore focussed on the potential of J ,J -DBFOX/ Ph aqua complex catalysts as highly tolerant chiral Lewis acid catalyst in thiol conjugate addition reactions. 

Without question, the most significant advance in the use of sulfur-centered nucleophiles was made by Shibasaki, who discovered that 10 mol% of a novel gallium-lithium-bis(binaphthoxide) complex 5 could catalyze the addition of tert-butylthiol to various cyclic and acyclic meso-epoxides with excellent enantioselectiv-ities and in good yields (Scheme 7.11) [21], This work builds on Shibasaki s broader studies of heterobimetallic complexes, in which dual activation of both the electrophile and the nucleophile is invoked [22]. This method has been applied to an efficient asymmetric synthesis of the prostaglandin core through an oxidation/ elimination sequence (Scheme 7.12). 

By using LaNa3-tris(binaphthoxide) (LSB) 55, catalytic asymmetric Michael addition of thiols to cycloalkenones took place to provide the adduct 56 with high ees in good yields (Eq. 7.41) [48]. 

This finding is also in agreement with another three-component Michael/aldol addition reaction reported by Shibasaki and coworkers [14]. Here, as a catalyst the chiral AlLibis[(S)-binaphthoxide] complex (ALB) (2-37) was used. Such hetero-bimetallic compounds show both Bronsted basicity and Lewis acidity, and can catalyze aldol [15] and Michael/aldol [14, 16] processes. Reaction of cyclopentenone 2-29b, aldehyde 2-35, and dibenzyl methylmalonate (2-36) at r.t. in the presence of 5 mol% of 2-37 led to 3-hydroxy ketones 2-38 as a mixture of diastereomers in 84% yield. Transformation of 2-38 by a mesylation/elimination sequence afforded 2-39 with 92 % ee recrystallization gave enantiopure 2-39, which was used in the synthesis of ll-deoxy-PGFla (2-40) (Scheme 2.8). The transition states 2-41 and 2-42 illustrate the stereochemical result (Scheme 2.9). The coordination of the enone to the aluminum not only results in its activation, but also fixes its position for the Michael addition, as demonstrated in TS-2-41. It is of importance that the following aldol reaction of 2-42 is faster than a protonation of the enolate moiety. 

Heterobimetallic asymmetric complexes contain both Bronsted basic and Lewis acidic functionalities. These complexes have been developed by Shibasaki and coworkers and have proved to be highly efficient catalysts for many types of asymmetric reactions, including catalytic asymmetric nitro-aldol reaction (see Section 3.3) and Michael reaction. They have reported that the multifunctional catalyst (f )-LPB [LaK3tris(f )-binaphthoxide] controls the Michael addition of nitromethane to chalcones with >95% ee (Eq. 4.140).205... 

Anionic phosphorus has been used as well in a number of recent reports of additions to carbonyl compounds. Addition of dialkyl phosphite to aromatic aldehydes in the presence of catalytic amounts of La-BINOL and dilithium (R)-binaphthoxide occurs enantioselec-... 

Rath, N. P. and Spilling, C., The enantioselective addition of dialkylphosphites to aldehydes catalysis by a lanthanum binaphthoxide caomplex, Tetrahedron Lett., 35, 227, 1994. 

Figure 1. The structure of rare earth-alkali metal binaphthoxide complexes (LnMB).

Table 6. Catalytic asymmetric Michael reactions promoted by the AlMbis(R)-binaphthoxide) complex (AMB).

An efficient asymmetric Michael addition of thiols to cycloalkenones (103) (56-90% ee) and an effective asymmetric protonation in Michael additions of thiols to non-cyclic enones (104) (75-90% ee), catalysed by LaNas tris(binaphthoxide) (105) and SmNas-tris(binaphthoxide) (106) complexes, respectively, has been reported. ... 

When ethyl cyanoformate was used as the cyanide source and a heterobimetallic YLi3(binaphthoxide) complex (YLB) (Figure 5.15) was used as catalyst, asymmetric cyanoethoxycarbonylations of aldehydes were achieved in high yields and enantioselectivities in the presence of three achiral additives water, tris(2,6-... 

Stoichiometric amount of methyl aluminum p-binaphthoxide as the Lewis acid. This reaction has recently been extended to a catalytic enantioselective version using an enantiopure methylaluminum p-binaphthoxide (Scheme 11.59) (210,211). Although the actual reacting species were not assigned, 5-alkoxyoxazoles behave as nitrile ylide 1,3-dipole equivalents in Lewis acid catalyzed reactions with aldehydes. 

A direct catalytic asymmetric Mannich reaction using unmodified ketones was reported using cooperative catalysis of a AlLibis((i )-binaphthoxide) complex ((.R)-ALB) and La(0Tf)3-nH20 [27,28]. It was also reported that enantiose-lective and diastereoselective catalytic nitro-Mannich reactions of N-phosphi-noylimines proceeded smoothly using the complex of ALB and ferf-BuOK [29, 30] [(Eq. (5)]. 

Complex LSB 9 is readily prepared either by the reaction of La(0 Pr)3 with 3 equiv. of B1NOL followed by the addition of NaO Bu (3 equiv.) or by the reaction of LaCl nfLO with sodium binaphthoxide. The complex 9 is stable to oxygen and moisture and has been proven to be effective in the catalytic Michael reaction of various enones with either malonates or p-keto esters. The Michael adducts with up to 92% ee were obtained in almost quantitative yield. Typical results with malonates are summarized in Table 8D.1 (Ln = lanthanide) [18], In general, the use of THF as solvent gave the best results except for the case of the LSB-catalyzed reaction of rmns-chalcone with dimethyl malonate, wherein the use of toluene was essential to give the adduct with good enantiomeric excess. The effects of the central metal (La, Pr, and Gd) on asymmetric induction were also examined in the same reaction, and LSB was found to be the best catalyst. 

LLB = LaLi3tris(binaphthoxide. LPB = LaK3tris(bmaphthoxide). PrSB = PrNa3tris(binaphthoxide). GdSB = GdNa3tris(binaphthoxide). 

Other nucleophiles such as nitromethane can also be used for this reaction. Thus, by the catalysis of (fl)-LPB (LaK3tris((/ )-binaphthoxide) (20 mol %), in which La works as a Lewis acid and K-naphthoxide works as a Brpnsted base, nitromethane reacted with chalcone to give the Michael adduct in 85% yield and 93% ee (Scheme 8D.8) [22], Addition of BuOH (120 mol %) gave a beneficial effect on the reactivity as well as the enantioselectivity of this reaction. 

The structure of AlLibis((/ )-binaphthoxide) complex (ALB) was determined unequivocally by X-ray crystallographic analysis shown in Figure 8D.2 [23]. The complex has a tetrahedral geometry around aluminum with an average Al-O distance of 1.75 A), The long Li-0 distance of 2.00 A] is indicative of the ionic character between Li+ and A1-2BINOL-. 

Shibasaki et al. described the first direct three-component catalytic enantioselec-tive Mannich reaction [3], wherein propiophenone 1, paraformaldehyde 2 and pyrrolidine 3 were reacted using (R)-LaLi tris(binaphthoxide) [(R)-LLB, 4] as catalyst to form Mannich product 5 with 64% ee and in 16% yield (Scheme 9.2). 

Scheme 9.2. (R)-LaLi3tris(binaphthoxide)-catalyzed enantioselective three-component Mannich reaction.

Shibasaki and co-workers reported an elegant asymmetric total synthesis of 11-deoxy-PGFic 19 using the Al-Li bis(binaphthoxide) complex (ALB) 21 [15], a member of a novel class of heterobimetallic chiral catalysts showing dual behavior as both a Bronsted base and a Lewis acid (Scheme 12.5) [16]. 

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... 

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],... 

Figure . LaLi3tris(binaphthoxide) catalyst 1 and AlLibis(binaphthoxide) (ALB) 2.

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