Titanium asymmetric amplification

Mechanistic studies of asymmetric amplification using a chiral amino alcohol catalyst have continued to dale"1 151 155. In the case of the chiral titanium complex, the observed asymmetric amplification was influenced by the method of preparation of the catalyst153. Asymmetric amplification is also observed in the catalytic addition of diphenylzinc to ketones100. 

Reetz et al. [53] prepared analogues of (R)-binol as ligands for the titanium complex in the presence of water under the same conditions as Uemura s mentioned above. In this study, (R)-octahydrobinol and its dinitro derivative were synthesized. The reaction using (R)-dinitro-octahydrobinol ligand gave (. S j-methyl p-tolyl sulfoxide (86% ee) [53], which makes a sharp contrast to the reaction using (R)-binol wherein (A1 (-methyl p-tolyl sulfoxide was formed [50]. It is probable that kinetic resolution is involved, giving some asymmetric amplification. 

Mikami reported a highly enantioselective carbonyl-ene reaction where a chiral titanium complex 11 prepared from enantiomerically pure binaphthol (BINOL) and Ti(0-i-Pr)2Br2 catalyzed a glyoxylate-ene reaction with a-methylstyrene to give chiral homoallyl alcohol 12 with 94.6% ee [22]. In this reaction, a remarkable asymmetric amplification was observed and almost the same enantioselectivity (94.4% ee) was achieved by using chiral catalyst prepared... 

Keck reported an asymmetric allylation with a catalytic amount of chiral titanium catalyst [24]. The enantioselective addition of methallylstannane to aldehydes is promoted by a chiral catalyst 13 prepared from chiral BINOL and Ti(0-i-Pr)4 (Scheme 9.10). An example of asymmetric amplification was reported by using (R)-BINOL of 50% ee, and the degree of asymmetric amplification was dependent on the reaction temperature. Tagliavini also observed an asymmetric amplification in the enantioselective allylation with a BIN0L-Zr(0-i-Pr)2 catalyst [25]. 

Uemura reported a highly enantioselective oxidation of sulfides to sulfoxides using a chiral titanium complex prepared from chiral BINOL and Ti(0-i-Pr)4, and this reaction exhibits a remarkable asymmetric amplification (Scheme 9.15) [33]. 

The ene reaction between 1-methylstyrene and methyl glyoxylate, catalyzed by a BINOL-titanium complex, gives a considerable amplification, as reported by Nakai and Mikami (Scheme 9).33 Many reports of asymmetric amplifications have subsequently been published for a wide range of reactions (vide infra). 

Asymmetric amplification in the diethylzinc addition to aldehydes has been observed with many (3-amino alcohols as catalyst, presumably because of a reservoir effect similar to that discovered by Noyori et al. Asymmetric amplification has also been found for other classes of chiral catalysts—diamines, diols, titanium complexes, etc. The various examples are collected in Table 1. The... 

Sharpless asymmetric epoxidation of allylic alcohols, asymmetric epoxidation of conjugated ketones, asymmetric sulfoxidations catalyzed, or mediated, by chiral titanium complexes, and allylic oxidations are the main classes of oxidation where asymmetric amplification effects have been discovered. The various references are listed in Table 4 with the maximum amplification index observed. 

This was one of the first classes of catalyzed reactions that were shown to give rise to strong asymmetric amplifications (vide supra, Scheme 9).33 Many subsequent studies have been performed with variations in the structure of the chiral catalyst, generated from BINOL and titanium salts.50-52 Asymmetric amplification is frequently observed with these catalysts in the glyoxylate-ene reaction (Table 5). 

Oguni has reported asymmetric amplification [12] ((-i-)-NLE) in an asymmetric carbonyl addition reaction of dialkylzinc reagents catalyzed by chiral ami-noalcohols such as l-piperidino-3,3-dimethyl-2-butanol (PDB) (Eq. (7.1)) [13]. Noyori et al. have reported a highly efficient aminoalcohol catalyst, 2S)-3-exo-(dimethylamino)isobomeol (DAIB) [14] and a beautiful investigation of asymmetric amplification in view of the stability and lower catalytic activity of the het-ero-chiral dimer of the zinc aminoalcohol catalyst than the homo-chiral dimer (Fig. 7-5). We have reported a positive non-linear effect in a carbonyl-ene reaction [15] with glyoxylate catalyzed by binaphthol (binol)-derived chiral titanium complex (Eq. (7.2)) [10]. Bolm has also reported (-i-)-NLE in the 1,4-addition reaction of dialkylzinc by the catalysis of nickel complex with pyridyl alcohols [16]. 

The reaction of methallyltri-n-butylstannane 117 with achiral aldehydes is also effectively promoted by the binol-Ti complex [89 c]. In all but one case (cyclo-hexanecarboxaldehyde), the yields and enantioselectivities observed with the methallylstannane are identical or higher than those obtained in the reactions with allyltributylstannane with only 10 mol% of the binol-Ti complex (Scheme 10-50). Insight into the nature of the titanium catalyst is provided by the observation of asymmetric amplification [89 b] and chiral poisoning [89 g]. An intruiging hypothesis on the origin of enantioselection in allylation and related reactions [89 h]. 

Some carbonyl ene-reactions catalyzed by chiral titanium complexes were shown by Nakai and Mikami to generate a strong asymmetric amplification, as in curve B of Scheme 6 [18]. 

Various titanium or zirconium complexes have been shown to catalyze the addition of allyl(tri-M-butyl)tin [29,30,31] or allyltrimethylsilane [32,33] to aldehydes, giving good enantioselectivities and some asymmetric amplification. In all these examples the chiral auxiliary is derived from (R)- or (S)-BINOL. 

Chiral Lewis acids based on titanium [33, 36, 37] or scandium [38] have been used to catalyze the Diels-Alder reactions, and a high asymmetric amplification has been described by Narasaka et al. [36]. This occurs presumably because of... 

Faller, J. W., Sams, D. W. I., Liu, X. Catalytic Asymmetric Synthesis of Homoallylic Alcohols Chiral Amplification and Chiral Poisoning in a Titanium/BINOL Catalyst System. J. Am. Chem. Soc. 1996,118, 1217-1218. 

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