Enantioselectivity enantioselective sulfoxidation

Hoft reported about the kinetic resolution of THPO (16b) by acylation catalyzed by different lipases (equation 12) °. Using lipases from Pseudomonas fluorescens, only low ee values were obtained even at high conversions of the hydroperoxide (best result after 96 hours with lipase PS conversion of 83% and ee of 37%). Better results were achieved by the same authors using pancreatin as a catalyst. With this lipase an ee of 96% could be obtained but only at high conversions (85%), so that the enantiomerically enriched (5 )-16b was isolated in poor yields (<20%). Unfortunately, this procedure was limited to secondary hydroperoxides. With tertiary 1-methyl-1-phenylpropyl hydroperoxide (17a) or 1-cyclohexyl-1-phenylethyl hydroperoxide (17b) no reaction was observed. The kinetic resolution of racemic hydroperoxides can also be achieved by chloroperoxidase (CPO) or Coprinus peroxidase (CiP) catalyzed enantioselective sulfoxidation of prochiral sulfides 22 with a racemic mixmre of chiral hydroperoxides. In 1992, Wong and coworkers and later Hoft and coworkers in 1995 ° investigated the CPO-catalyzed sulfoxidation with several chiral racemic hydroperoxides while the CiP-catalyzed kinetic resolution of phenylethyl hydroperoxide 16a was reported by Adam and coworkers (equation 13). The results are summarized in Table 4. 

TABLE 27. Results of the titanium-catalyzed stoichiometric enantioselective sulfoxidation according to Kagan s and Modena s methods (yields are given and ee values are given in parentheses)... 

SCHEME 107. Catalytic enantioselective sulfoxidation using chiral ligand 186... 

SCHEME 108. Ti-catalyzed enantioselective sulfoxidation employing enantiopure diol (R,R)-187 as hgand... 

An overview of the results of the enantioselective sulfoxidation utilizing various chiral metal catalysts is given in Table 28. 

SCHEME 114. Titanium-catalyzed enantioselective sulfoxidation with secondary, optically pure hydroperoxides... 

Figure 10.21 Enantioselective sulfoxidation catalyzed by CPO in aqueous-ionic liquid mixtures.

Rather less attention has been paid to enzymatic oxidations in ionic liquids. Chloroperoxidase (CPO) catalyzed the chemo- and enantioselective sulfoxidation of thioanisole (Figure 10.21) in aqueous mixtures containing up to 50% [HOEtMe3N] [citrate] or [MMIm][Me2P04] [145]. 

Enantioselective sulfoxidations were performed with the peroxidase from Cop-rinus cinereus (CiPx) by employing glucose oxidase-catalyzed oxidation of glucose for the in situ generation of hydrogen peroxide in [BMIm][PF6]/buffer (90 10,... 

Colonna S, Gaggero N, Casella L, Carrea G, Pasta P (1992) Chloroperoxidase and Hydrogen Peroxide An Efficient System for Enzymatic Enantioselective Sulfoxidations. Tetrahedron Asym 3 95... 

F. van Rantwijk, and R. A. Sheldon, Enantioselective sulfoxidation mediated by vanadium-incorporated phytase a hydrolase acting as a peroxidase,... 

The enantioselective sulfoxidation of thioanisole for the (R)-isomer by H64D/V68A and H64D/V68S Mbs suggest the sulfoxidation intermediate shown in Scheme 9 could be stabler for (R)-sulfoxide formation over the (S)-isomer. The chiral discrimination for (R)- and ( -intermediates is caused by steric interaction between the transition state and the heme cavity. However, it is... 

Ozaki S -I, Ortiz de Montellano PR (1994) Molecular engineering of horseradish peroxidase. Highly enantioselective sulfoxidation of aryl alkyl sulfides by the Phe-41-Leu mutant. J Am Chem Soc 116 4487 1488... 

Wang W, Xu Y, Wang DIC et al (2009) Recyclable nanobiocatalyst for enantioselective sulfoxidation facile fabrication and high performance of chloroperoxidase-coated magnetic nanoparticles with iron oxide core and polymer shell. J Am Chem Soc 131 12892-12893... 

Another important class of enzymes able to catalyze sulfoxidation is the peroxidases. Of the peroxidases developed to date, the most versatile is a chloroperoxidase from Caldariomyces fumago (CPO), isolated in 1961 by Shaw and Hager 28 and used for the first time in enantioselective sulfoxidation by Kobayashi et al.,29 although in low... 

Various other heme-peroxidases were found to catalyze the enantioselective sulfoxidation of alkyl aryl sulfides. These included horseradish peroxidase (HRP),34,35 cytochrome c peroxidase (CcP),36 microsome peroxidase (MP),37 lac-toperoxidase (LPO),38 and dioxygenase.39 However, their turnover numbers (TON) and enantioselectivities were much lower than those observed with CPO (Table 4). 

Remarkably, there is a noticeable lack of general methods for the asymmetric preparation of chiral sulfoxides from sulfides. The most satisfactory method would be a generally applicable enantioselective sulfoxidation reaction which would allow the preparation of sulfoxides from any prochiral sulfide with high ee s and in which the sulfoxide would be amenable to enantioselective preparation in both senses. 

Maycock has recently reported the use of an optically pure 2-alkyl-2-acyl-l,3-dithiolane 1-oxide to synthesize optically active a-hydroxyketone derivatives.83 The acyl dithiolane 1-oxide was prepared by an enantioselective sulfoxidation procedure. Interestingly, Maycock has recently reported enhanced diastereo- and... 

Highly enantioselective sulfoxidation was observed using the di-/t-oxo Ti(salen)/UHP (salen = A. A -bisisalicylal-dehydolethylenediamine UHP = urea hydrogen peroxide) catalyst complex in methanol (Equation 43). In oxidations of 1,3-dithiolane derivatives, enantioselectivity increased with the size of the 2-substituent <2002TL3259>. 

Synthesis and utilization of chiral sulfoxides (enantioselective sulfoxidation of S-heterocycles and derivatives of other heterocycles) 03CRV3651. 

Scheme 10.13 GOx-peroxidase-mediated enantioselective sulfoxidation of thioanisole (Reproduced from Ref. [108], with kind permission of Elsevier)...

A platform had been created from which it was felt that the enantioselective sulfoxide synthesis could be developed into a process that would match logistical as well as quality requirements. However, it is important to stress that other variations of the titanium-catalyzed approach had been concomitantly identified but the decision was taken to focus solely on the present option. One of the most important and challenging aspects in this regard was to demonstrate how the oxidation step could be fitted into the existing manufacture of the prochiral sulfide (pyrmetazole) and, if not, what changes or modifications would be needed. This... 

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