Highly Enantioselective Oxidation of Sulfides Mediated by a Chiral Titanium Complex

Brunel, Jean‐Michel; Diter, Patrick; Duetsch, Michael; Kagan, Henri B.

doi:10.1021/jo00129a060

Cited by 157 publications

(60 citation statements)

References 3 publications

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“…The enantiomeric excess was determined by chiral HPLC analysis by using a Chiralcel OD column. The elution order of the (R)-and (S)-methylphenyl sulfoxides formed [t r (R) ϭ 11.7 min; t r (S) ϭ 14.2 min] was adapted from Brunel et al (6).…”

Section: Methodsmentioning

confidence: 99%

Substrate Specificity and Enantioselectivity of 4-Hydroxyacetophenone Monooxygenase

Kamerbeek

Olsthoorn

Fraaije

et al. 2003

Appl Environ Microbiol

108

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The 4-hydroxyacetophenone monooxygenase (HAPMO) from Pseudomonas fluorescens ACB catalyzes NADPH-and oxygen-dependent Baeyer-Villiger oxidation of 4-hydroxyacetophenone to the corresponding acetate ester. Using the purified enzyme from recombinant Escherichia coli, we found that a broad range of carbonylic compounds that are structurally more or less similar to 4-hydroxyacetophenone are also substrates for this flavin-containing monooxygenase. On the other hand, several carbonyl compounds that are substrates for other Baeyer-Villiger monooxygenases (BVMOs) are not converted by HAPMO. In addition to performing Baeyer-Villiger reactions with aromatic ketones and aldehydes, the enzyme was also able to catalyze sulfoxidation reactions by using aromatic sulfides. Furthermore, several heterocyclic and aliphatic carbonyl compounds were also readily converted by this BVMO. To probe the enantioselectivity of HAPMO, the conversion of bicyclohept-2-en-6-one and two aryl alkyl sulfides was studied. The monooxygenase preferably converted (1R,5S)-bicyclohept-2-en-6-one, with an enantiomeric ratio (E) of 20, thus enabling kinetic resolution to obtain the (1S,5R) enantiomer. Complete conversion of both enantiomers resulted in the accumulation of two regioisomeric lactones with moderate enantiomeric excess (ee) for the two lactones obtained [77% ee for (1S,5R)-2 and 34% ee for (1R,5S)-3]. Using methyl 4-tolyl sulfide and methylphenyl sulfide, we found that HAPMO is efficient and highly selective in the asymmetric formation of the corresponding (S)-sulfoxides (ee > 99%). The biocatalytic properties of HAPMO described here show the potential of this enzyme for biotechnological applications.In nature, many oxygenation reactions are carried out by flavin-dependent monooxygenases (24). The diversity of conversions that can be catalyzed is large; the reactions include Baeyer-Villiger reactions, aromatic hydroxylations, sulfoxidations, amine oxidations, and epoxidations. Many of these conversions occur with high enantio-and/or regioselectivity. The variety of reactivity is also reflected in the diverse physiological processes in which these enzymes play a prominent role, including xenobiotic compound metabolism in humans (49), biosynthesis of toxins (21), and pollutant degradation by bacteria (46).Enantio-and regioselective oxygenations are often difficult to achieve by chemical means, while these types of reactions can lead to valuable optically active compounds. Due to their exquisite regio-and/or enantioselectivity and catalytic efficiency, flavin-dependent monooxygenases are useful biocatalysts for the synthesis of a variety of fine chemicals (12,35,41,47). However, so far, only a limited number of flavin-dependent monooxygenase genes have been cloned and overexpressed, which has limited the application of these biocatalysts for synthetic processes.The Baeyer-Villiger reaction, i.e., the oxidation of ketones or aldehydes by peroxides resulting in oxygen insertion adjacent to the carbonyl group (2), has many applications in organic ...

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Section: Methodsmentioning

confidence: 99%

Substrate Specificity and Enantioselectivity of 4-Hydroxyacetophenone Monooxygenase

Kamerbeek

Olsthoorn

Fraaije

et al. 2003

Appl Environ Microbiol

108

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“…[23] Thus, several methods have been developed for the asymmetric oxidation of prochiral sulfides with chiral metal complex catalysts, such as titanium-, [2,[24][25][26][27][28][29][30][31][32][33][34][35][36] manganese-, [37][38][39] vanadium-, [40][41][42][43][44][45][46] iron-, [47][48][49] and aluminium-based [50] systems. Despite the above-mentioned practical importance of the asymmetric sulfoxidation reactions, the basic mechanistic features of the titanium tartrate-based process used for the synthesis of esomeprazole ( Figure 1) remained mainly unexplored.…”

Section: Full Papersmentioning

confidence: 99%

Mechanism of the Asymmetric Sulfoxidation in the Esomeprazole Process: Effects of the Imidazole Backbone for the Enantioselection

2009

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Abstract:The asymmetric sulfoxidation reaction of imidazole-based prochiral sulfides was studied to explore the mechanistic details of the highly efficient esomeprazole process, which is one of the few industrial scale catalytic asymmetric procedures. The synthetic studies revealed that the smallest subunit governing the selectivity in the esomeprazole process is an imidazole ring. Thus, by using the esomeprazole procedure methyl imidazole sulfide could be oxidized as efficiently as its several functionalized derivatives, including pyrmetazol. However, alkylation of the imidazole nitrogen led to a major drop of the enantioselectivity. Our atmospheric pressure chemical ionization-mass spectrometry (APCI/MS) studies indicate that addition of small amounts of water to the reaction mixture facilitates the formation of mononuclear titanium species, which are the active catalytic intermediates of the selective oxidation reaction. One of the most important features of the esomeprazole procedure is that amine additives increase the enantioselectivity of the oxidation process. The NMR studies of the presumed reaction intermediates show that under catalytic conditions the amines are able to coordinate to titanium and dissociate the coordinated imidazole substrate. The density functional theory (DFT) modelling studies provided new insights in the mechanism of the asymmetric induction. It was found that the oxidation requires a lower activation energy if the imidazole sulfide precursor does not coordinate to titanium. Two possible reaction paths were explored for this out of sphere oxidation mechanism. The most important interaction governing the enantioselection is hydrogen bonding between the N À H of the imidazole ring and the chiral tartrate ligand on titanium. Furthermore, the oxidation reaction imposes an important structural constraint to the TS structure involving a linear arrangement of the peroxide oxygens and the sulfur atom. This constraint and the N coordination of imidazole leads to a very strained structure for the inner sphere mechanism of the oxidation, which leads to a much higher activation barrier than the corresponding out of sphere process, and therefore it is unlikely.

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“…In a 1995 paper, Kagan 28 explored the possibilities of increasing the selectivity of the oxidation by varying parameters such as temperature, time, rate of addition and aging of the catalyst complex. Up to this point, the optimum conditions as reported in an Organic Synthesis paper 26 had been employed.…”

Section: Asymmetric Sulfur Oxidation Of the -Chloroacrylamidesmentioning

confidence: 99%

Investigation of the chemoselective and enantioselective oxidation of α-thio-β-chloroacrylamides

Kissane

Lynch

Chopra

et al. 2008

Tetrahedron: Asymmetry

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Highly Enantioselective Oxidation of Sulfides Mediated by a Chiral Titanium Complex

Cited by 157 publications

References 3 publications

Substrate Specificity and Enantioselectivity of 4-Hydroxyacetophenone Monooxygenase

Substrate Specificity and Enantioselectivity of 4-Hydroxyacetophenone Monooxygenase

Mechanism of the Asymmetric Sulfoxidation in the Esomeprazole Process: Effects of the Imidazole Backbone for the Enantioselection

Investigation of the chemoselective and enantioselective oxidation of α-thio-β-chloroacrylamides

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