Aryl alkyl sulfides, asymmetric oxidation

In combination with H2O2 (salen)Mn(III) complexes 173a, b, i-n have also been employed by Jacobsen and coworkers as catalysts for the asymmetric oxidation of sulfides to sulfoxides, without a need for additives. From the structurally and electronically different Mn-salen catalysts screened, 173i turned out to be the most active and selective one (equation 58) . While dialkyl sulfides underwenf uncafalyzed oxidation with H2O2, aryl alkyl sulfides were oxidized only slowly compared wifh fhe cafalyzed pathway. Using... 

A similar (salen)manganese(III) catalyst was used by Katsuki for asymmetric sulfide oxidations [35]. Chiral complex 20 bears additional asymmetric carbons in the salicylidene part of the salen. In this system, hydrogen peroxide, which was the preferred oxidant in the Jacobsen procedure, turned out to be inefficient. Instead, iodosylbenzene was chosen, and in the presence of only 1 mol % of catalyst several aryl alkyl sulfides were oxidized in acceptable yields having enantiomeric excesses in the range of 8% to 90%. As in the Jacobsen-KatsuJd-epoxida-tion, the presence of additives such as pyridine N-oxide has a beneficial effect on chemical and optical yields. In addition, such co-ligands suppress the overoxidation of sulfoxides to the corresponding sulfones so that a sulfoxide sulfone ratio of 47 1 can be achieved. Consequentely, as shown for the case of thioanisole. 

It is known that cydodextrins have a hydrophobic cavity (a binding site for aromatics) and a hydrophilic external surface. A template-directed asymmetric sulfoxidation has been attempted with various aryl alkyl sulfides. [91]. Oxidations were performed by using metachlo-roperbenzoic add in water in the presence of an excess of p-cyclodextrin. The best ee (33%) was attained for mem-(r-butyl)phenyl ethyl sulfoxide. The decrease in the amount of P-cyclodex-trin below 1 mol equiv. causes a sharp decrease in enantioselectivity because of competition with oxidation of free substrate by the oxidant. Similarly, Drabowicz and Mikolajczyk observed modest asymmetric induction (27% ee) in the oxidation of Ph-S-n-Bu with H2O2 in the presence of P-cyclodextrin [92]. 

According to this correlation model, in which the principles of steric control of asymmetric induction at carbon (40) are applied, the stereoselectivity of oxidation should depend on the balance between one transition state [Scheme 1(a)] and a more hindered transition state [Scheme 1(6)] in which the groups and R at sulfur face the moderately and least hindered regions of the peroxy acid, respectively. Based on this model and on the known absolute configuration of (+)-percamphoric acid and (+)-l-phenylperpropionic acid, the correct chirality at sulfur (+)-/ and (-)-5 was predicted for alkyl aryl sulfoxides, provided asymmetric oxidation is performed in chloroform or carbon tetrachloride solution. Although the correlation model for asymmetric oxidation of sulfides to sulfoxides is oversimplified and has been questioned by Mislow (41), it may be used in a tentative way for predicting the chirality at sulfur in simple sulfoxides. 

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

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... 

Recently, Feng and co-workers reported an asymmetric sulfide oxidation" catalyzed by titanium complexes bearing HydrOx ligands, for example, 576 (Scheme 8.199). ° Enantioselectivities approached a level of synthetic utility for oxidation of aryl alkyl sulfides 632 although the yields of the sulfoxide 633 were poor due to overoxidation to the sulfone 634. The overoxidation is especially significant for reactions with high enantioselectivity. 

Chiral (salen)Mn(III)Cl complexes are useful catalysts for the asymmetric epoxidation of isolated bonds. Jacobsen et al. used these catalysts for the asymmetric oxidation of aryl alkyl sulfides with unbuffered 30% hydrogen peroxide in acetonitrile [74]. The catalytic activity of these complexes was high (2-3 mol %), but the maximum enantioselectivity achieved was rather modest (68% ee for methyl o-bromophenyl sulfoxide). The chiral salen ligands used for the catalysts were based on 23 (Scheme 6C.9) bearing substituents at the ortho and meta positions of the phenol moiety. Because the structures of these ligands can easily be modified, substantia] improvements may well be made by changing the steric and electronic properties of the substituents. Katsuki et al. reported that cationic chiral (salen)Mn(III) complexes 24 and 25 were excellent catalysts (1 mol %) for the oxidation of sulfides with iodosylbenzene, which achieved excellent enantioselectivity [75,76]. The best result in this catalyst system was given by complex 24 in the formation of orthonitrophenyl methyl sulfoxide that was isolated in 94% yield and 94% ee [76]. 

Asymmetric imidations of aryl alkyl sulfides with [(tosylimino)iodo]ben-zene, catalyzed by various chiral (salen)manganese(III) complexes, have been investigated in some detail [31,32]. The influence of catalyst structure, solvent, temperature, 3°-amine AT-oxides, and the presence of molecular sieves on product yields and the enantioselectivity of imidation with 17 was evaluated. Enan-tioselectivities as high as 90 % ee and 97 % ee with methyl 2-nitrophenyl sulfide and methyl 2,4-dinitrophenyl sulfide, respectively, were achieved. 

Table 6C. 1 lists representative results for the asymmetric oxidation of thio ethers with r-butyl hydroperoxide under the standard conditions (in dichloromethane at -20°C). Enantioselectivi-ties are especially good (80-95% ee) for the oxidation of aryl methyl sufoxides (Table 6C.1). A substantial decrease in enantioselectivity is observed for oxidation of aryl-S-alkyl-type sulfides in which an alkyl group is larger than methyl such as n-propyl an n-butyl.

Kinetic resolution of secondary alcohols is performed by asymmetric oxidation using an optically active (nitroso)(salen)ruthenium(II) chloride 12 (Eq. 3.14) [48]. The ruthenium catalyst 12 is also effective for asymmetric imidation of alkyl aryl sulfide [48c]. 

Optically active sulfoxides can also be prepared by asymmetric oxidation of sulfides. However, numerous papers have reported very low enantioselectivity." Only one report, " using a modified Sharpless reagent, H20/Ti(0Pr )4/diethyl tartrate/BuKX)H, described asymmetric oxidation of alkyl aryl sulfoxides with good enantiomeric excesses 75 to 95%. 

Asymmetric oxidation of ArSR with H202 The chiral (salen)MnCI complexes derived from this diamine can effect asymmetric oxidation of alkyl aryl sulfides. The highest enantioselectivity is obtained with (R,R)-3. 

The absolute configurations of the sulfoxides resulting from the asymmetric oxidation of sulfides are safely predicted by the method shown in Scheme 1.7. In aryl methyl sulfides, one takes aryl as the large (L) group. For methyl alkyl sulfides, it is the methyl group which is the smaller. 7t-Systems play a special role, as often encountered in asymmetric synthesis thus in the oxidation of Me— C=C—Bu", the triple bond has to be taken as the (L) group [54,55]. 

Table 1.5 Asymmetric oxidation of alkyl aryl sulfide using manganese catalyst...

A chiral Ti complex formed in situ by reacting Ti(0 Pr)4, (J ,P)-diphenylethane-1,2-diol, and water was reported to be effective for asymmetric oxidation of aryl alkyl and aryl benzyl sulfides using TBHP as the oxidant to obtain optically active sulfoxides in good yields and high enantiomeric excesses [274] (Scheme 14.115). 

Steric and electronic effects have been investigated for the Cu(acac)2-catalysed asymmetric oxidation of aryl benzyl, aryl alkyl and alkyl benzyl sulfides with H2O2 in presence of hexane/MeOH and the ligand 4-chloro-2-[( )-[( 17 )-l-(hydroxymethyl)-2,2-dimethyl-propyl]iminomethyl]phenol. High enantioselectivity is dependent on the attachment of an aryl group to the sulfur and was highest, with up to 97% ee, for 2-naphthyl benzyl sulfoxide. Cu-mediated oxidation of substituted aryl benzyl sulfides shows modest steric and electronic effects. ... 

The complex (70) is the most efficient catalyst in the titaniumsalan-catalysed asymmetric oxidations of bulky aryl benzyl sulfides and small alkyl phenyl sulfides by H2O2 in CH2CI2 to corresponding sulfoxides with 77% ee. The kinetics suggest that a direct attack of the sulfide on the electrophilic active oxygen species occurs... 

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