Alkyl Aryl and Diaryl Sulfoxides

Andersen (75,76), as well as Mislow (221), discovered that the ORD curves of alkyl aryl sulfoxides show a strong Cotton effect in the region below 250 nm. An extensive study by Mislow and his coworkers (47) led to the following empirical rules, correlating the sign of the Cotton effect with the absolute configurations of chiral dialkyl, alkyl aryl, and diaryl sulfoxides, as well as menthyl esters of aromatic sulfinic acids ... 

Various diaUsyl, alkyl aryl and diaryl sulfoxides were readily oxidized to the corresponding sulfone in excellent yields under mild conditions at —30°C by 51. Interestingly,... 

Finally, the sulfinates were transformed to o.p. sulfoxides by treatment with either Grignard or organolithium reagents. The presence of a free hydroxyl group in the sulfmate esters involves the use of two molar equivalents of the organometallic in THF at room temperature. Various dialkyl, alkyl aryl, and diaryl sulfoxides have been obtained in quantitative yield and in 100% ee (Table 12). 

Both enantiomers of Whitesell s chiral auxiliary (8) are available by enzymatic resolution of commercially available racemic rrarw-2-phenylcyclohexanol [20,21], allowing ready and equal access to dialkyl, alkyl aryl and diaryl sulfoxides of high optical purity and with either absolute configuration. 

Oxidation of Sulfoxides. Dialkyl, alkyl aryl, and diaryl sulfoxides are readily oxidized to sulfones in excellent yields under mild conditions (—30 °C) in MeCN by the peroxy intermediate (1). Oxidation of the unsaturated sulfoxide (11) was chemose-lective it furnished the sulfone (12) in 70% yield when reacted with (1) for 5 h. The double bond was not epoxidized. Similar chemoselective epoxidation has been carried out with only one other reagent (potassium hydrogen persulfate). ... 

In order to account for the unusually facile thermal racemization of optically active allyl p-tolyl sulfoxide (15 R = p-Tol) whose rate of racemization is orders of magnitude faster than that of alkyl aryl or diaryl sulfoxides as a result of a comparably drastically reduced AH (22kcalmol- ), Mislow and coworkers44 suggested a cyclic (intramolecular) mechanism in which the chiral sulfoxide is in mobile equilibrium with the corresponding achiral sulfenate (equation 10). 

Various alkyl aryl and diaryl sulfides were oxidized selectively to the corresponding sulfoxides in high yields as the major products using sulfonylperoxy intermediate 51 (equation 86) ". ... 

Dialkyl sulfides, alkyl aryl sulfides, diaryl sulfides, and cyclic sulfides are oxidized to the corresponding sulfoxides or sulfones. Often, both products can be obtained on oxidation with the same oxidant, depending on... 

This section is broken up into three parts 1.) benzylic and ally lie systems, 2.) aryl alkyl and diaryl sulfoxides, and 3.) extrusions. It turns out that the isolated materials from these reactions are only infrequently the primary photochemical products. Thus we shall also see photochemistry of a few other functional groups, notably the sulfenic ester/sultene and the sulfine (R2C=S=0). While secondary photochemistry can be a disadvantage in synthetic respects, the variety of rearrangements observed in sulfoxide photochemistry is all the richer for it. 

In related work, the groups of Ujaque and Asensio showed that the products formed in the intramolecular variant of this reaction using asymmetric aryl-heteroaryl and diaryl sulfoxides are inconsistent with the punitive gold-carbene intermediate (Eqs. (5.11) and (5.12)) [43]. in these cases, alkylation occurred exclusively at the position adjacent to the thioaryl substituent. 

Cheng, C. and Stock, L. M., Photochemical anion-promoted carbon—sulfur cleavage reactions of diaryl sulfides, aryl alkyl sulfides and related sulfoxides and sulfones,/. Org. Chem., 56,2436,1991. 

Miscellaneous Reactions. Bromodimethylborane can also be used to convert dialkyl, aryl alkyl, and diaryl sulfoxides to the corresponding sulfides (eq 15). Typically, the sulfoxides are treated with 2.5 equiv of Me2BBr in dichloromethane at —23 °C for 30 min and at 0°C for 10 min. Bromine is produced in the reaction and must be removed in order to avoid possible side reactions. This is accomplished by saturating the solution with propene prior to introducing the reagent or by adding cyclohexene. Phosphine oxides and sulfones failed to react under the conditions used to deoxygenate sulfoxides. 

Oae and coworkers oxidized several diaryl, dialkyl and alkyl aryl sulfides to their corresponding sulfoxides using purified cytochrome P-450 obtained from rabbit liver microsomes138. In agreement with expectations, this enzyme did not exhibit much stereospecificity. Some examples including the observed e.e. values are shown by 121-125. A model was proposed to account for the absolute configurations of the sulfoxides produced (126). The sulfur atom is preferentially oxidized from the direction indicated. 

In the case of diaryl sulfoxides the formation of both the aryl radical and the hydroxycyclohexadienyl radical was observed optically. Veltwisch and coworkers45 studied also the reaction of OH radicals from radiolysis of aqueous solutions of mixed (alkyl phenyl) sulfoxides (PhSOR). They found the formation of both alkylsulfinic and phenylsulfinic acids. 

When thionyl chloride is used, diaryl sulfoxides are usually the main products. Unsymmetrical diaryl sulfides can be obtained by treatment of an aromatic compound with an aryl sulfenyl chloride (ArSCl) in the presence of a trace amount of iron powder.Aromatic amines and phenols can be alkylthiolated (giving mostly ortho product) by treatment with an alkyl disulfide and a Lewis acid catalyst. With certain substrates (primary amines with a chloro group, or a group not replaceable by chloro, in the para position), treatment with S2CI2 and NaOH gives thiophenolate salts ... 

The second approach to chiral aminosulfonium salts consists of the conversion of chiral sulfoxides into aminosulfonium salts by means of MA -diethylaminosulfinyl tetrafluoroborate (165). The reaction occurs with predominant retention of configuration at sulfur with dialkyl and alkyl aryl sulfoxides. However, its stereospecificity is strongly dependent on the nature of substituents in the starting sulfoxide. In the case of diaryl sulfoxides this method failed to give chiral aminodiarylsulfonium salts. 

All diaryl sulfoxides, some alkyl aryl sulfoxides (e.g., methyl p-tolyl sulfoxide, 41), and some dialkyl sulfoxides (e.g., methyl 1-adamantyl sulfoxide), were found to undergo racemization according to the pyramidal inversion mechanism. Mislow and co-workers (248) have found that for most of the compounds investigated, irrespective of the nature of the substituents attached to sulfur, the first-order rate constant for racemization in p-xylene at 210 C is about 3 X 10" sec", corresponding to a half-life of about 6 hr. Moreover, the activation parameters do not show significant differences and their values were contained in a narrow range 35 to 42 kcal/mol and... 

Racemization of diaryl and alkyl aryl sulfoxides accompanied by oxygen exchange was also observed in a-halogenoacetic acids (270, 271) and phosphoric acid (272). 

The activation parameters of the pyramidal inversion have been determined for various dialkyl, diaryl, and alkyl aryl sulfoxides. They vary between 35 and 42 keal/mol for AH, and -8 and +4 cal/(mol-K) for AS. These values indicate that, in most cases, the thermal stereomutation of sulfoxides occurs at a significant rate only at about 200 °C. There are a few exceptions, such as benzyl and allyl sulfoxides, whose racemization is raised at 130-150 and 50-70 °C, respectively. 

The use of THF as solvent with organolithium nucleophiles, as described by Wudl and Lee, resulted in significant reduction in the levels of diastereoselectivity. Entries 7-9 of Table 2.9 highlight the limitations of this procedure for the synthesis of diaryl sulfoxides and therefore dictate that alkyl aryl sulfoxides are synthesized... 

The procedure described is an example of a more general synthetic method for the direct conversion of ketones into cyanides. " The reaction has been carried out successfully with acyclic and cyclic aliphatic ketones, including numerous steroidal ketones and aryl-alkyl ketones. The conversion of diaryl or highly hindered ketones such as camphor and )3,j8-dimethyl-a-tetralone requires the use of a more polar solvent. The dimethoxyethane used in the present procedure should be replaced by dimethyl sulfoxide. ... 

Since the classical paper of Meyerson and coworkers in 1964 on the electron impact(EI) mass spectra of diaryl sulfones, only some more than one hundred original reports dealing with the mass spectra of sulfoxides and sulfones have been published. These data have been reviewed quite extensively, most recently by Khmel nitskii and Efremov in a review on The rearrangements in sulfoxides and sulfones induced by electron impact and by Porter. Several less comprehensive surveys have also been presented " . Since Reference 2 and to a lesser extent Reference 4 cover the El mass spectra of alkyl and aryl sulfoxides and sulfones up to 1974 fairly completely, and Reference 3 together with Reference 2 the mass spectra of heterocyclic sulfoxides and sulfones and their nitrogen-containing counterparts up to 1980, the present chapter will mainly concentrate on the most recent developments and some complementary material not described in the above-mentioned reviews. 

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