Asymmetric titanium-catalyzed

Table 6.13 Asymmetric, titanium catalyzed hydrogenation of imines...

The asymmetric titanium-catalyzed sulfoxidation with BuOOH also works with chiral diols as ligands [66-68]. Various l,2-diaryl-l,2-ethanediols were employed as ligands, and the use of 15 mol% of Ti(0 Pr)4 with l,2-diphenyl-l,2-ethanediol gave... 

The chiral diol 17 derived from tartaric acid is exploited in the titanium-catalyzed asymmetric pinacol coupling in the presence of Zn and MesSiCl to give the corresponding diol in 11-71 ee % [44], The chiral salen ligands 18-20 are used in the titanium-catalyzed enantioselective coupling reaction, which achieves the higher selectivity [45-47]. The chromium complex with TBOxH (21) efficiently catalyzes the asymmetric coupling reaction of both aromatic and aliphatic aldehydes [48]. 

This approach provides a new method for carbohydrate synthesis. In the synthesis of tetritols, pentitols, and hexitols, for example, titanium-catalyzed asymmetric epoxidation and the subsequent ring opening of the thus formed 2,3-epoxy alcohols can play an essential role. 

SCHEME 59. Titanium-catalyzed asymmetric epoxidation of both enantiomers of aUyUc alcohol 39j... 

In 2003, Lattanzi and coworkers reported on the use of the tertiary camphor-derived hydroperoxide 61 in the titanium-catalyzed asymmetric epoxidation of allylic alcohols (equation 39f. Yields were moderate and ranged between 30 and 59%. Also, the enantio-selectivities obtained were only moderate (24-46%). After the reaction, the enantiomeri-cally pure camphor-derived alcohol can be recovered in good yields by chromatography without loss of optical purity and can be reconverted into the corresponding hydroperoxide. 

SCHEME 106. Titanium-catalyzed asymmetric oxidation of aryl alkyl sulfides using a chiral tetradentate trialkanolamine ligand... 

A new enantiopure, bidentate ligand (35, 45 )-2,2,5,5-tetramethyl-3,4-hexanediol [(35, 45)-186] was developed by Yamanoi and Imamoto and investigated as asymmetric inductor in the titanium-catalyzed sulfoxidation reaction with various hydroperoxides as oxygen donors (Scheme 107). The catalytically active species was then prepared in situ from Ti(OPr-/)4 and ligand (35,45)-186. The most efficient hydroperoxide in terms of enantio-selectivity turned out to be cumyl hydroperoxide (95% ee compared to 30% ee in the case of methyl p-tolyl hydroperoxide), and molecular sieves 4 A had a beneficial effect on the... 

In 2001, Scettri and coworkers could show that titanium-catalyzed asymmetric sulfoxidation with a tertiary furyl hydroperoxide 188a can be achieved under catalytic conditions by a modification of Uemura s approach employing (R)-BINOL as chiral ligand (equation 57). Under these conditions sulfoxides could be isolated in medium to good... 

A further catalytic method for asymmetric sulfoxidation of aryl alkyl sulfides was reported by Adam s group, who utilized secondary hydroperoxides 16a, 161 and 191b as oxidants and asymmetric inductors (Scheme 114) . This titanium-catalyzed oxidation reaction by (S)-l-phenylethyl hydroperoxide 16a at —20°C in CCI4 afforded good to high enantiomeric excesses for methyl phenyl and p-tolyl alkyl sulfides ee up to 80%). Detailed mechanistic studies showed that the enantioselectivity of the sulfide oxidation results from a combination of a rather low asymmetric induction in the sulfoxidation ee <20%) followed by a kinetic resolution of the sulfoxide by further oxidation to the sulfone... 

An overview of the obtained results of the titanium-catalyzed asymmetric sulfoxidation of various sulfides with different optically pure hydroperoxides as oxidant and asymmetric inductor is given in Table 29. 

TABLE 29. Results of the titanium-catalyzed asymmetric sulfoxidation with optically pure hydroperoxides (yields are given and ee values are given in brackets)... 

SCHEME 171. Titanium-catalyzed asymmetric Baeyer-VilUger oxidation of cyclobutanones... 

Asymmetric epoxidation. Sharpless et a .1 have reviewed the numerous applications of titanium-catalyzed asymmetric epoxidations developed in their own and other laboratories. All the reactions conform to the enantiomeric selectivity first observed and formulated as in Scheme (I). 

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. 

Three synthetic approaches were used to provide armodafinil during the process development by Cephalon/Novasep.34 Since the racemic modafinil is commercially available, the resolution via preferential crystallization of modafinic acid 6 was employed for phase I clinical trials and was subsequently replaced by large-scale chiral chromatography. Meanwhile, an economical enantioselective synthetic route was developed by using asymmetric oxidation catalyzed by a titanium (IV) isopropoxide and diethyl tartrate with cumene hydroperoxide (the Sharpless/Kagan system).363... 

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