Shibasaki’s catalysts

Reactions involving bimetallic catalysts, either homo-dinuclear or hetero-bimetallic complexes, and chemzymes were highlighted by Steinhagen and Helmchen96c in 1996. Some examples are discussed in Chapter 2. Among these examples, Shibasaki s reports have been of particular significance.97 Shibasaki s catalyst is illustrated as 130, which consists of one central metal M1 (La+3, Ba+2, or A1+3), three other metal ions (M2)+ [(M2)+ can be Li+, Na+, or K+], and three bidentated ligands, such as (R)- or (iS )-BINOL. The catalyst exhibits both Lewis acidic properties because of the existence of central metal and the Lewis basic properties because of the presence of the outer metal ions. 

Scheme 7 Shibasaki s catalyst in enantioselective cyanosilylation of ketones...

Scheme 5.115 Enantioselective conjugate addition of malonates 448 to cyclopentenone, mediated by Shibasaki s catalyst 449 and subsequent aldol addition. Conversion of adduct 452 into 11-deoxy-PGF, .

As shown in the next chapters, some of these reactions were also successfully employed to access the chiral skeletons of complex natural products or biologically active molecules. The following chapters will therefore highlight the successful use of the three most prominent chiral ammonium salt PTC classes Cinchona alkaloids, Maruoka s catalysts, and Shibasaki s catalysts) to facilitate demanding stereoselective key steps in complex natural product syntheses and in the synthesis of biologically active (either natural or synthetic) compounds. 

Table 5.10 Enantioselective epoxidation of a,p-unsaturated ketones 36 with heterogenized Shibasaki s catalysts 35. ...

An improved preparation of Shibasaki s LLB catalyst allowed higher asymmetric induction in the chemistry shown in Scheme 5-28. The new recipe involved mixing LaCl3 7H20 (1 equiv.), BINOL-dilithium salt (2.7 equiv.) and NaOt-Bu (0.3 equiv.) in THF at 50°C. This catalyst allowed asymmetric hydrophosphonylation of aldehydes in high yields and up to 95% ee (Scheme 5-33, Eq. 1), and gave better results for aliphatic aldehydes than a related aluminum catalyst (ALB, see Scheme 5-37 below). 

Catalytic Asymmetric Aldol Reaction Promoted by Bimetallic Catalysts Shibasaki s System... 

The effect of additives on Shibasaki s lanthanide-BINOL catalysts has been investigated by Inanaga and coworkers. From a variety of additives, triphenylphosphine oxide turned out to be the best one improving, for example, the obtained ee for the chalcone epoxide from 73% to 96% (Table 16) . The explanation for the positive effect of the additive was the disruption of the oligomeric structure of the catalyst by coordination of the phosphine oxide. As a consequence, epoxidation takes place in the coordination sphere of the ytterbium where the reaction site might become closer to the chiral binaphthyl ring due to the phosphine oxide ligand with suitable steric buUdness. In contrast to the Shibasaki... 

Trost et al. [11] reported another impressive example of bimetallic catalysts in which a Zn-Zn homobimetallic complex (17, Scheme 7) serves as an effective catalyst for direct aldol reactions [11-13]. The proposed structure of the catalyst was verified by mass spectrometry and the best ratio of Et2Zn and the ligand. The chemical yield was moderate in the reaction of methyl ketones (1) (Scheme 7, top) [11,12], but a highly atom-economic system was achieved when a-hydroxylated ketones (10) were used as a substrate (Scheme 7, bottom) [13]. Excellent diastereo- and enantioselectivity were obtained under mild conditions. In contrast to the case of Shibasaki s heteropolymetallic catalyst, syn-1,2-diols (syn-11) were obtained as the major diastereomers. 

Currently, the chiral phase-transfer catalyst category remains dominated by cinchona alkaloid-derived quaternary ammonium salts that provide impressive enantioselec-tivity for a range of asymmetric reactions (see Chapter 1 to 4). In addition, Maruoka s binaphthyl-derived spiro ammonium salt provides the best results for a variety of asymmetric reactions (see Chapters 5 and 6). Recently, some other quaternary ammonium salts, including Shibasaki s two-center catalyst, have demonstrated promising results in asymmetric syntheses (see Chapter 6), while chiral crown ethers and other organocatalysts, including TADDOL or NOBIN, have also found important places within the chiral phase-transfer catalyst list (see Chapter 8). 

Recently, chiral phase-transfer-catalyzed asymmetric Michael addition has received much attention, and excellent enantioselectivity (up to 99% ee) has been reported using cinchona alkaloid-derived chiral phase-transfer catalysts [40]. Among noncinchona alkaloid-derived chiral phase-transfer catalysts Shibasaki s tartrate derived C2-symmetrical two-center catalyst provided a Michael adduct with up to 82% ee [41]. 

Initial investigations showed that the treatment of trimethylsilyl nitronate 23a (R1 = Me) with benzaldehyde (R2 = Ph) in the presence of (S,S)-6b (X = HF2, 2 mol %) in TH F at —98 °C for 1 h and at —78 °C for 1 h and subsequent hydrolysis with 1M HC1 at 0 °C, resulted in clean formation of the corresponding nitroalkanol 24 (R1 = Me, R2 = Ph) in 83% yield (anti/syn = 74 26) with 33% ee (anti isomer) (entry 1 in Table 9.5). Notably, the poor diastereo- and enantioselectivities were dramatically improved by switching the catalyst to (S,S)-6c (X = HF2) possessing a radially extended 3,3-aromatic substituent (Ar), and 24 (R1 = Me, R2 = Ph) was obtained in 92% yield (anti/syn = 92 8 with 95% ee (anti isomer) (Table 9.5, entry 2). This asymmetric nitroaldol protocol tolerates various aromatic aldehydes to afford anti-nitroaldols selectively, being complementary to Shibasaki s method... 

Next, the mechanism of the Type II reactions is discussed. To discriminate one of the enantiofaces of the acceptor it is desirable to place and to activate the electrophiles in a chiral environment. At the same time, effective activation of the Michael donor is required. In Shibasaki s ALB-catalyzed reaction (Scheme 3), it was proposed that the aluminum cation functioned as a Lewis acid to activate enones at the center of the catalyst, and that the Li-naphthoxide moiety deproton-ated the a-hydrogen of malonate to form the Li enolate (Scheme 9). Such simultaneous activation of both reactants at precisely defined positions became feasible by using multifunctional heterobimetallic complexes the mechanism is reminiscent of that which is operative in the active sites of enzymes. The observed absolute stereochemistry can be understood in terms of the proposed transition state model 19. Importantly, addition of a catalytic amount of KOt-Bu (0.9equiv. to ALB) was effective in acceleration of the reaction rate with no deterioration of the... 

Mikami and co-workers reported a hetero Diels-Alder reaetion of butyl glyoxylate using a chiral lanthanide eatalyst reported by Shibasaki s group in 1994 (Sch. 4) [37]. They found that addition of water (11 mol equiv. to catalyst) resulted in the formation of the product in higher yield and ee. Such tolerance of water is never encountered in conventional Lewis acid catalysis. The catalyst (10 mol %) promoted the reaction of Danishefsky s diene with butyl glyoxylate in the presence of water to afford the corresponding product in up to 88% yield and 66% ee. 

Some of the metal-based catalysts used in the asymmetric hydrophosphonylation of aldehydes (see Section 6.4) can also be applied to the phosphonylation of imines. For instance, Shibasaki s heterobimetallic BINOL complexes work well for the catalytic asymmetric hydrophosphonylation of imines. In this case lanthanum-potassium-BINOL complexes (6.138) have been found to provide the highest enantioselectivities for the hydrophosphonylation of acyclic imines (6.139). The hydrophosphonylation of cyclic imines using heterobimetallic lanthanoid complexes has been reported. Ytterbium and samarium complexes in combination with cyclic phosphites have shown the best results in the cases investigated so far. For example, 3-thiazoline (6.140) is converted into the phosphonate (6.141) with 99% ee using ytterbium complex (6.142) and dimethyl phosphite (6.108). The aluminium(salalen) complex (6.110) developed by Katsuki and coworkers also functions as an effective catalyst for the hydrophosphonylation of both aromatic and aliphatic aldimines providing the resulting a-aminophosphonate with 81-91% ee. ... 

Shibasaki s heterobimetallic complexes, active in the asymmetric aldol reaction (see Section 7.1) provide the opportunity to activate both the nucleophile and Michael acceptor. Whilst the aluminium lithium bis-BlNOL complex (ALB) (11.28) does not catalyse conjugate addition of a-phosphonate ester (11.29) with cyclopentenone (11.30) by itself, addition of sodium terf-butoxide allows a highly enantioselective reaction to take place. A postulated model for enantioinduction in this process involves simultaneous binding of the metallated nucleophile and acceptor to the catalyst by interaction with a BINAP oxygen and the aluminium centre respectively. Heterobimetallic complexes have also been used to catalyse the addition of a-nitroesters and malonatesto Michael acceptors. 

Scheme 6 Shibasaki s heterobimetallic catalyst in asymmetric Michael additions...

As depicted in Scheme 90, Shibasaki s two-center tartaric acid-derived catalysts 402 and 403 worked well for the installation of the stereogenic centers... 

In 1996, Shibasaki s group developed highly efficient bimetallic Al-M- / )-BINOL (M = Li, Na, K, or Ba) catalysts for asymmetric Michael reactions of malonic esters to enones, and excellent results were obtained (84-99% enantiomeric excess) (Table 19.1). Mechanistic studies on Al-Li-(/ )-BINOL ent-18 complex revealed that it worked as a multifunctional heterobimetallic asymmetric catalyst. 

On the basis of this finding, Shibasaki s group developed a series of asymmetric reactions using soft copper(I) Brpnsted base catalysts and a wide variety of pre-nucleophiles (thioamides [34 3], isocyanide [44, 45], unsaturated butyrolactones [46, 47], nitroalkanes [48], allyl cyanide [49, 50], and a-trifluoromethylacetamide [51]) via proton transfer strategy (Fig. 5). 

At the time these relatively modest results represented the state-of-the-art in direct catalytic asymmetric aldolizations with a-unbranched aldehyde acceptors. Neither Shibasaki s nor Trost s bimetallic catalysts, the only alternative catalysts available, gave superior results. Moreover, even non-asymmetric amine-catalyzed cross aldolizations with a-unbranched acceptors are still unknown. That the practicality of the process can compensate for the modest yield and enantioselectivity was illustrated by a straightforward synthesis of the natural pheromone (S)-ipsenol (139) from aldol 136d, featuring a high-yielding Stille coupling (Scheme 4.27). 

Scheme 5.81 Shibasaki s direct aldol reaction mediated by the lanthanum-lithium complex 285 assumed structures of loaded intermediate catalysts 288 and 289.

It is almost always the case that the overall increase in reaction rate is greater than that for either catalyst alone when researchers use more than one catalyst to speed up a chemical reaction [5]. As a consequence, much effort has been made in creating designer catalyst systems in the past decade, such as Yamamoto s designer acids [6], Shibasaki s bimetallic systems [7], Trosfs dizinc complexes... 

In 1995, Shibasaki s group disclosed the first example of multifunctional heterobimetallic complex-catalyzed Michael reaction of malonate to enone. The chiral catalyst, lanthanum-sodium-BINOL complex (/ )-LSB, was prepared from La(Of-Pr)3, (/ )-BINOL, and NaOt-Bu. Two different metals indeed play their unique roles to enhance the reactivity of both substrate partners by locating them in designated positions. The Lewis acidic metal (lanthanides or group 13 elements) has been found capable to activate the acceptor, whereas the second metal center (alkali metals bound to a Brpnsted base) assists the coordination of enolate. The proposed catalytic cycle is shown in Scheme 9.5. 

In addition, Lygo s biphenyl-based spirocyclic catalysts 8 [21], Shibasaki s tartaric acid-derived bidentate PTCs 9 [22], our group s TADDOL-derived N-spiro catalysts 10 [23], or Denmark s tricyclic ammonium salts 11 [24] have been carefully investigated in the past (Fig. 3). 

Activation of both the aldehyde and the cyanide is a recurring theme for a number of catalysts that furnish optically active cyanohydrins. Shibasaki developed the efficient BlNOL-derived catalyst 273, which is believed to provide dual activation as the complex incorporates both Lewis acidic and Lewis basic sites (Scheme 2.34) [175], Catalyst 273 displays broad substrate scope including aromatic, unsaturated, and aliphatic aldehydes, all of which are converted into optically active cyanohydrins. The utility of chiral cyanohydrins has been showcased in Shibasaki s elegant synthesis of the antitumor agents epothilone A and B (275 and 276, respectively), proceeding via the optically active cyanohydrin 274 (99% ee) [176]. 

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