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...

Synthesis of enantioenriched sulfoxides

“…This trend has been observed in other investigations, 66,72,77,93 although to a lesser extent, indicating that the influence of the ligand is greater than that of the substituent on the aromatic ring of the sulfide. Interestingly, the report by Barbarini et al employing a polymer supported ligand showed the opposite trend.…”

“…93 An initial investigation using racemic sulfoxide 19 as substrate under the conditions in Scheme 88, yielded only limited amounts of sulfone, indicating that kinetic resolution was not a significant factor. Repeating the reaction at room temperature (20 o C) resulted in considerable kinetic resolution being observed.…”

Vanadium‐Catalyzed Asymmetric Oxidation of Sulfides Using Schiff Base Ligands Derived from β‐Amino Alcohols with Two Stereogenic Centers

“…Methanol and THF gave the product with very low ee values (5 and 6 % ee, respectively), and toluene afforded a moderate yield and enantioselectivity. Because chloroform was another good solvent for this reaction and there were some examples showing more efficient kinetic resolution in this solvent, [18] ligands 3a-i were also examined in chloroform at 0°C. The results showed that ligand 3i was still the best ligand under these reaction conditions (82 % yield and 84 % ee were obtained by using 1.1 equiv.…”

“…[17] Jackson et al successfully developed vanadium-catalyzed sulfur oxidation/kinetic resolution for the synthesis of chiral sulfoxides in chloroform. [18] Zeng et al combined enantioselective sulfoxidation with concomitant kinetic resolution to produce chiral sulfoxides with vanadium-Schiff base complexes derived from phenylalaninol or isoleucinol as the catalyst; moderate yields (40.6 %) and up to 99 % ee were obtained by using H 2 O 2 (2.0 equiv.) as the oxidant.…”

Catalytic enantioselective stereoablative reactions: an unexploited approach to enantioselective catalysis

“…It was found that a racemic mixture of sulfoxides was effectively resolved with a vanadium catalyst and diiodide ligand (R)-9 (Scheme 4). 12 The high selectivity in sulfoxide oxidative kinetic resolution led them to investigate a tandem enantioselective sulfide oxidation followed by sulfoxide resolution. Treatment of sulfide 11 with their oxidative conditions provided sulfoxide (R)-8 in 70% yield and >99.5% ee, along with achiral sulfone 10.…”