Kobayashi 2 Aldol reactions

Chiral oxazolidinones were used also to determine the stereochemical outcome of aldol and aldol-type reactions (130L1898,13TL2171). In one case, a sy -selective Kobayashi aldol reaction was reported between silyldi-enol ethers and acetals (130L678). The chiral oxazolidine ligand 193 was... 

A j yn-selective Kobayashi aldol reaction of acetals has been used for polyketide synthesis, with des up to 98%. 0... 

It turned out that the dodecylsulfate surfactants Co(DS)i Ni(DS)2, Cu(DS)2 and Zn(DS)2 containing catalytically active counterions are extremely potent catalysts for the Diels-Alder reaction between 5.1 and 5.2 (see Scheme 5.1). The physical properties of these micelles have been described in the literature and a small number of catalytic studies have been reported. The influence of Cu(DS)2 micelles on the kinetics of quenching of a photoexcited species has been investigated. Interestingly, Kobayashi recently employed surfactants in scandium triflate catalysed aldol reactions". Robinson et al. have demonshuted that the interaction between metal ions and ligand at the surface of dodecylsulfate micelles can be extremely efficient. ... 

In 1991, Kobayashi el al. prepared novel chiral S/N ligands for the tin-mediated aldol reaction of silyl enol ethers with aldehydes. As an example, the reaction of benzaldehyde afforded the expected syn aldol product as the major product with a good yield and an enantioselectivity of up to 92% ee (Scheme 10.26). Moreover, other aldehydes such as substituted benzaldehydes or aliphatic unsaturated aldehydes were converted into their corresponding aldol products with enantioselectivities of more than 90% ee. It was checked that the corresponding diamine ligands provided less active complexes for the same reactions. 

Asymmetric Lewis-Acid Catalyzed. Another important advance in aqueous Mukaiyama aldol reaction is the recent success of asymmetric catalysis.283 In aqueous ethanol, Kobayashi and co-workers achieved asymmetric inductions by using Cu(OTf)2/chiral >A(oxazoline) ligand,284 Pb(OTf)2/chiral crown ether,285 and Ln(OTf)3/chiral Mv-pyridino-18-crown-6 (Eq. 8.105).286... 

This method has been applied in the enantioselective synthesis of d-erythro-sphingosine and phytosphingosine. Sphingosine became an important substance for studying signal transduction since the discovery of protein kinase C inhibition by this compound.48 Many efforts have been made to synthesize sphingosine and its derivatives.49 Kobayashi et al. reported another route to this type of compound in which a Lewis acid-catalyzed asymmetric aldol reaction was a key step. 

S. Kobayashi, L Hachiya, The Aldol Reaction of Silyl Enol Ethers with Aldehydes in Aqueous Media Tetrahedron Lett. 1992,1625-1628. 

S. Kobayashi, T. Wakabayashi, S. Nagayama, H. Oya-mada, Lewis Add Catalysis in MiceUar Systems. Sc(OTf)3-Catalyzed Aqueous Aldol Reactions of Silyl Enol Ethers with Aldehydes in the Presence of a Surfactant Tetrahedron Lett. 1997,38, 4559-4562... 

S. Kobayashi, Y. Mori, S. Nagayama, K Manabe, Catalytic Asymmdric Aldol Reactions in Water Using a... 

Although in the recent years the stereochemical control of aldol condensations has reached a level of efficiency which allows enantioselective syntheses of very complex compounds containing many asymmetric centres, the situation is still far from what one would consider "ideal". In the first place, the requirement of a substituent at the a-position of the enolate in order to achieve good stereoselection is a limitation which, however, can be overcome by using temporary bulky groups (such as alkylthio ethers, for instance). On the other hand, the ( )-enolates, which are necessary for the preparation of 2,3-anti aldols, are not so easily prepared as the (Z)-enolates and furthermore, they do not show selectivities as good as in the case of the (Z)-enolates. Finally, although elements other than boron -such as zirconium [30] and titanium [31]- have been also used succesfully much work remains to be done in the area of catalysis. In this context, the work of Mukaiyama and Kobayashi [32a,b,c] on asymmetric aldol reactions of silyl enol ethers with aldehydes promoted by tributyltin fluoride and a chiral diamine coordinated to tin(II) triflate... 

Saito, S. Kobayashi, S. Highly Anti-selective Catalytic Aldol Reactions of Amides with Aldehydes, f Am. Chem. Soc. 2006, 128, 8704-8705. 

Bismuth triflate has been reported by Dubac as an efficient catalyst for the Mukaiyama aldol reaction with silyl enol ethers [27] and was recently used with a chiral ligand, as reported by Kobayashi in an elegant hydroxymethylation reaction... 

Kobayashi S, Akiyama R, Moriwaki M, Three-component or four-component coupling reactions leading to 6-lactams, Facile synthesis of y-acyl-6-lactams from silyl enolates, a, /l-unsaturated thioesters, and imines or amines and aldehydes via tandem Michael-imino aldol reactions, Tetrahedron Lett., 38 4819—4822, 1997. 

Kobayashi et al. also published experiments in which they applied polymer-bound rare earth metal triflates [9], The performance of Lewis acid-catalyzed imino-aldol reactions at the solid phase was realized by linking the silyl enolethers u5-(4 -chloromethylphenyl)pentylpolystyrene[10]. 

FIGURE 2. AMI-calculated reaction path for the aldol reaction of acetaldehyde with propionalde-hyde, using complex 150b as a model for the intermediate boron enolate complex 150a. Reproduced from Y. Makino, K. Iseki, K. Fujii, S. Oishi, T. Hirano and Y. Kobayashi, Tetrahedron Lett., 36, 6527. Copyright 1995, courtesy of Elsevier... 

Mukaiyama and Kobayashi et al. have developed the use of Sn(OTf)2 in diastereose-lective and enantioselective aldol-type reactions [26,27]. Initially, the stereoselective aldol reactions were performed with a stoichiometric amount of Sn(OTf)2 [28], The reaction between 3-acylthiazolidine-2-thione and 3-phenylpropionaldehyde is a representative example of a diastereoselective syn-aldol synthesis (Eq. 17). 

S. Kobayashi, T. Wakabayashi, S. Nagayama, H. Oyamada, Tetrahedron Lett. 1997,38,4559-4562. Judging from the amount of the surfactant used in the present case, the aldol reaction would not proceed only in micelles, (a) J. H. Fendler, E. J. Fendler, Catalysis in Micellar and Macromolecular Systems, Academic, London, 1975. (b) Mixed Surfactant Systems (Eds. P. M. Holland, D. N. Rubingh), ACS, Washington, DC, 19W. (c) Structure and Reactivity in Aqueous Solution (Eds. C. J. Cramer, D. G. Truhlar), ACS, Washington, DC, 1994. (d) Surfactant-Enhanced Subsurface Remediation (Eds. D. A. Sabatini, R. C. Knox, J. H. Harwell), ACS, Washington, DC, 1994. 

Kobayashi et al. studied the catalytic activity of many metal salts in Mukaiyama-aldol reactions in aqueous THE They came to the conclusion that the catalytic activity of a metal in aqueous media should be related both to the hydrolysis constant, /Ch, and water exchange rate constant (WERC) of the metal [8]. All metals with good catalytic activity had p/Ch values ranging between 4.3 and 10.08 and WERC > 3.2 X 10 s This was because when for a metal is < 4.3, the metal cation is readily hydrolyzed to generate oxonium ion, which then helps the decomposition of the silyl enol ethers. When pMh > 10.08 the Lewis acidity of the metal is too low to promote the reaction. When the WERC is < 3.2 x 10 m s, exchange of water molecules seldom occurred and aldehydes had a very little chance to coordinate to the metal to be activated. The metals which fulfill these criteria are Sc(III), Fe(II), Cu(II), Zn(ll), Y(IIl), Cd(Il), Ln(Ill) and Pb(ll). 

Kobayashi, S, Kawasuji, T, A new synthetic route to monosaccharides from simple achiral compounds by using a catalytic asymmetric aldol reaction as a key step, Synlett, 911-913, 1993. 

One of the most important goals in organic chemistry is the formation of C-C bonds. This field has advanced rapidly due to the introduction of transition metal catalysts. Engberts and co-workers [18] observed an extraordinary rate enhancement (up to 1.8 10 fold) in the Diels-Alder reaction between 3-(/7ara-substituted phenyl)-l-(2-pyridyl)-2-propen-l-ones and cyclopentadiene in presence of cop-per(II) or zinc(II) dodecylsulfate micelles. The lanthanide-catalyzed aldol reaction described by Kobayashi and Manabe [19] is also important as a typical method in... 

Makino, Y., Iseki, K., Fujii, K., Oishi, S., Hirano, T., Kobayashi, Y. Reversal of -face selectivity in the Evans aldol reaction with fluoral a computational study on the transition states using semiempirical calculations. Tetrahedron Lett. 1995, 36, 6527-6530. 

Kobayashi, S., Horibe, M., Saito, Y. Enantioselective synthesis of both diastereomers, including the a-alkoxy-p-hydroxy-p-methyl(phenyl) units, by chiral tin(ll) Lewis acid-mediated asymmetric aldol reactions. Tetrahedron 1994, 50, 9629-9642. 

Kobayashi et al. discovered that Yb(OTf)3 and other lanthanide triflates (l,ri(() lf)(, Ln=La, Pr, Nd, Sm, Eu, Gd, Dy, Ho, and Er) are excellent catalysts of hydroxymefhylation of propiophenone TMS enolate with aqueous formaldehyde solution at room temperature (Scheme 10.22) [70, 71]. The Yb(OTf) j-catalyzed hydroxymefhylation of a variety of SEE, including sterically hindered compounds, proceeds regiospecifically in high yield. In addition, almost 100% of Yb(OHf). is quite easily recovered from fhe aqueous layer and can be reused. Yb(OTf)3 also has high catalytic activity in fhe aqueous aldol reaction of other aldehydes. Interestingly, the catalytic activity is rather low in the absence of water. In aqueous media water would coordinate to ytterbium to form active ytterbium cations. 

Sc(() l f) ( is an effective catalyst of the Mukaiyama aldol reaction in both aqueous and non-aqueous media (vide supra). Kobayashi et al. have reported that aqueous aldehydes as well as conventional aliphatic and aromatic aldehydes are directly and efficiently converted into aldols by the scandium catalyst [69]. In the presence of a surfactant, for example sodium dodecylsulfate (SDS) or Triton X-100, the Sc(OTf)3-catalyzed aldol reactions of SEE, KSA, and ketene silyl thioacetals can be performed successfully in water wifhout using any organic solvent (Sclieme 10.23) [72]. They also designed and prepared a new type of Lewis acid catalyst, scandium trisdodecylsulfate (STDS), for use instead of bofh Sc(OTf) and SDS [73]. The Lewis acid-surfactant combined catalyst (LASC) forms stable dispersion systems wifh organic substrates in water and accelerates fhe aldol reactions much more effectively in water fhan in organic solvents. Addition of a Bronsted acid such as HCl to fhe STDS-catalyzed system dramatically increases the reaction rate [74]. 

Kobayashi et al. have demonstrated fhat some metal salts (e.g. Fe(II), Cu(II), Zn(II), Cd(II), and Pb(II) perchlorates) other fhan rare earth metal salts are also water-stable Lewis acids and work as catalysts of fhe aqueous aldol reaction of SEE [75]. Metal salts wifh good catalytic activity have pKh values (/hydrolysis constant) from 4.3 to 10.08 and WERC (water exchange rate constant) greater than 3.2 X10 m s . If p/metal cations are readily hydrolyzed to give oxo-nium ions, which promote hydrolysis of SEE. Metal cations with pKh> 10.08 do not have sufficient Lewis acidity to promote the aldol reaction. When fhe WERC... 

Loh et al. reported that InClj worked as an effective catalyst of aldol reactions of SEE in water [77]. Later, Kobayashi et al. reported different results [78] - hydrolysis of SEE is faster than the desired reaction in the InCls-catalyzed aqueous system the InCls-catalyzed reaction proceeds to some extent under solvent-free conditions InCls is an effective catalyst in micellar systems. 

Kobayashi et al. recently developed the Pb(OTf)2-crown ether 56 complex as an efficient chiral catalyst of asymmetric aldol reactions in aqueous media (Scheme 10.51) [146]. This catalyst system achieves good to high yields and high levels of diastereo- (syn-selective) and enantioselectivity in the aldol reaction of a variety of aldehydes with propiophenone TMS enolate. The hole size of 56 is essential because 57 and 58 show no chiral induction. The unique structure of the Pb(OTf)2-56 complex as a chiral catalyst has been revealed by X-ray diffraction. 

Three-component coupling reaction of a-enones, silyl enolates, and aldehydes by successive Mukaiyama-Michael and aldol reactions is a powerful method for stereoselective construction of highly functionahzed molecules valuable as synthetic intermediates of natural compounds [231c]. Kobayashi et al. recently reported the synthesis of y-acyl-d-lactams from ketene silyl thioacetals, a,/l-urisalu-rated thioesters, and imines via successive SbCl5-Sn(OTf)2-catalyzed Mukaiyama-Michael and Sc(OTf)3-catalyzed Mannich-type reactions (Scheme 10.87) [241]. 

Sinou and co-workers [73] studied the influence of different surfactants on the palladium-catalyzed asymmetric alkylation of l,3-diphenyl-2-propenyl acetate with dimethyl malonate in presence of potassium carbonate as base and non-water-soluble chiral ligands. Best results in activity and enatioselectivity (> 90% ee) were observed with 2,2 -bis(diphenylphosphino)-l,l -binaphthyl (BINAP) as ligand and cetyltrimethylammonium hydrogen sulfate as surfactant in aqueous medium. Water-stable Lewis acids as catalysts for aldol reactions were developed by Kobayashi and co-workers [74]. An acceleration of the reaction was indicated in presence of SDS as anionic surfactants. An additional promotion could be observed by combination of Lewis acid and surfactant (LASCs = Lewis acid-surfactant-combined catalysts) as shown in Eq. (3). Surfactant the anion of dodecanesulfonic acid. 

Figure 5.6. Chiral catalysts for the Mukaiyama aldol reaction (a) Kiyooka catalyst [112,113] (b) Masamune catalyst [114] (c) Corey catalyst [115] (d) Yamamoto catalyst [116,117] (e-f) Kobayashi-Mukaiyama catalysts [118-120].

Kobayashi s group37 developed a new enantioselective synthesis of Cis phytosphingosine using catalytic asymmetric aldol reactions as a key step (Scheme 23). The key catalytic aldol reaction of acrolein with the ketene silyl acetal 148 derived from phenyl a-benzyloxyacetate was carried out by using tin(II) triflate, chiral diamine 149, and tin(II) oxide. The desired aldol product... 

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