Vanadium‐Catalyzed Sulfur Oxidation/Kinetic Resolution in the Synthesis of Enantiomerically Pure Alkyl Aryl Sulfoxides

Abstract

Chiral sulfoxides are an important class of compounds that find increasing use as chiral auxiliaries in asymmetric synthesis. [1,2] Current interest also reflects the existence of products with biological properties containing a sulfinyl group with a defined configuration. [3] Several methods for the asymmetric oxidation of prochiral sulfides have been reported, including the use of chiral oxidants, such as chiral oxaziridines, [4] chiral hydroperoxides, [5] and enzymes. [6,7] The majority of investigations have concentrated on the use of chiral metal complexes [1,3,[8][9][10][11] following the initial reports by Kagan and co-workers [12,13] and Modena and co-workers [14] on the use of variously modified Sharpless reagents for this reaction.One of the most widely studied metal-based systems has been that discovered by Bolm and Bienewald, [15,16] who employed a combination of Schiff bases 1 derived from chiral amino alcohols and [VO(acac) 2 ] (1.0 mol %; acac = acetylacetanoate), with aqueous hydrogen peroxide as the oxidant, in a two-phase system using dichloromethane as the solvent at 20 8C (Scheme 1). The advantages of the system developed by Bolm et al. include high activity, the very simple reaction conditions, and the use of hydrogen peroxide as the oxidant. The only drawback associated with the initial ligands tested was that the levels of enantiomeric excess were good, rather than excellent. Other research groups sought to optimize the system, by variation of the aromatic aldehyde, [17][18][19] the amino alcohol, [20] and the manner of addition of hydrogen peroxide, [21] and in many cases it is striking that the best outcome was usually obtained when the reaction was conducted in dichloromethane at 0 8C. A very nice application of the system developed by Bolm et al. was the asymmetric oxidation of ditert-butyl disulfide, reported by Ellman and co-workers, [22] who have since reported the results of spectroscopic studies with a view to understanding the nature of the active catalytic species better.[23] The nature of the active species is still not completely established, but while spectroscopic studies indicate the presence of a vanadium(v)oxomonoperoxo species, [24] recent calculations suggest that the active species may be a vanadium(v)oxohydroperoxide. [25] Recently, the use of analogous salan ligands has been reported to give high levels of enantioselectivity (95 % ee) in the oxidation of methyl phenyl sulfide, but lower levels of enantioselectivity were observed with other substrates. [26] Anson and co-workers screened a variety of chiral Schiff base ligands, and found that the 3,5-diiodo ligand (S)-2, in combination with [VO(acac) 2 ] gave excellent results in the catalytic asymmetric sulfoxidation of alkyl aryl sulfides with hydrogen peroxide, again in dichloromethane at 0 8C.[27] For example, methyl phenyl sulfide was oxidized to (S)-methyl phenyl sulfoxide (81 %, 90 % ee). Recently, Bolm and coworkers reported that a combination of this ligand with iron is also very effective for the asymmetric ox...

Investigation of Functionalized α‐Chloroalkyllithiums for a Stereospecific Reagent‐Controlled Homologation Approach to the Analgesic Alkaloid (−)‐Epibatidine

“…www.chemeurj.org using the resonant scattering technique; [29] the result was in accord with Jacksons precedent [28] for the stereochemical outcome of this highly efficient process. Further conversion to scalemic chlorosulfoxides syn-H-24 was achieved by the nonracemizing chlorination protocol popularized by Yamakawa.…”

“…[26] Two of these compounds (syn-H-24 a,d) were next prepared in scalemic form in both S S and R S configurations from thioethers by Ellman-Bolm enantioselective oxidation [27] using the appropriate enantiomer of Jacksons tert-leucinol derived ligand 25 (Scheme 6). [28] Excellent enantiomeric excess was obtained from this process by extending the reaction time to allow for a degree of over-oxidation to the sulfone; under this scenario, enantiopurity of the desired product is improved (albeit at the expense of yield) by a ligand-controlled kinetic resolution, which selectively consumes the minor sulfoxide enantiomer by its advancement to the sulfone. The absolute configuration of sulfoxide (R S )-23 d prepared using ligand (R)-25 was determined by X-ray diffraction (XRD) analysis Scheme 5.…”

“…2-[(S S )-2-(4-Methyl-phenyl)sulfinylethyl]-1,3-dioxolane [(S S )-23 d]: This was prepared by the method of Jackson et al [28] A 100 mL RB flask equipped with a magnetic stirrer bar was charged with (S)-tert-leucinol derived ligand (S)-25 (158 mg, 0.334 mmol) and vanadyl acetoacetonate (59 mg, 0.223 mmol) followed by CHCl 3 (20 mL). The resulting mixture was stirred at RT for 2 h during which time the initially emerald-green solution became a caramel-brown color.…”

Enantioselective Synthesis of Benzyl tert‐Butyl Sulfoxides

“…The preparation of this class of sulfoxides through the asymmetricoxidation of sulfides has been studied, and very good results have been obtained using chiral reagents,14 but catalytic asymmetric oxidation resulted in modest enantioselectivity 15. We briefly investigated asymmetric oxidation using vanadium16 and titanium17 catalysis, but the results were not promising and therefore were not pursued.…”

Sulfoxide‐Based Enantioselective Nazarov Cyclization: Divergent Syntheses of (+)‐Isopaucifloral F, (+)‐Quadrangularin A, and (+)‐Pallidol

“…2) Enantiomerically pure methyl para-tolyl sulfoxides [14] are readily available, extensively used, and undoubtedly one of the most efficient auxiliaries in asymmetric synthesis, and are therefore employed for the stereoselective control of the new stereogenic center at C3 in the Nazarov cyclization process.…”