Allyl Phenyl Sulfoxide1

[19093-37-9]  · C9H10OS  · Allyl Phenyl Sulfoxide  · (MW 166.23)

(allylic sulfoxides undergo allylic rearrangement to form sulfenate esters, allowing the generation of allylic alcohols; metalated derivatives serve as ambident nucleophiles; precursors to Pummerer intermediates)

Physical Data: bp 103-104 °C/0.36 mmHg; d 1.1205 g cm-3.2

Solubility: insol water; sparingly sol hexane; sol most other organic solvents.

Preparative Methods: oxidation of Allyl Phenyl Sulfide in dichloromethane with m-Chloroperbenzoic Acid acid (1.2 equiv) added slowly as a solution in dichloromethane at -70 °C affords the sulfoxide in high yields with minimal over-oxidation to the sulfone. The m-chlorobenzoic acid formed may be removed simply by filtration. Other oxidizing agents such as Sodium Bromite3 and Trifluoroperacetic Acid4 afford the sulfoxide in yields greater than 80% and are also highly selective.

Purification: distillation in vacuo prior to use.

Handling, Storage, and Precautions: no special precautions are required. The sulfoxide may be handled normally at the bench for general weighing and transferring. However, for maximum shelf-life it is recommended that it be stored at 4 °C in a sealed vessel with exclusion of oxygen and moisture.

Sulfoxide-Sulfenate Rearrangement.

The important observation by Mislow and co-workers that allyl phenyl sulfoxide and other allylic sulfoxides may be prepared from allylic sulfenate esters, obtained from the corresponding allylic alcohol and an electrophilic sulfenylating agent,5 in an equilibrating [2,3]-sigmatropic rearrangement was the key to establishing the synthetic utility of these compounds. Conversely, the sulfoxide may be converted into the allylic alcohol by intercepting the intermediate sulfenate ester formed in the equilibrium with the sulfoxide by treatment with a thiophilic reagent typically Trimethyl Phosphite, tertiary phosphine, or secondary amine in methanol, which cleaves the sulfenate ester. Stereocontrol of the rearrangement is dependent on the types of groups attached to the allylic substituent. Selectivity for the (E) isomer occurs when R1 is larger than R2 (eq 1)1a,1c or when both R1 and R3 are alkyl groups and R2 is a proton.1c,6 In order to achieve (E) selectivity for 2,3,3-trisubstituted systems, a substituent at C-1 of the allylic sulfoxide must have b-branching (eq 2).7

Whilst optically active allyl tolyl sulfoxides may be prepared from allyl Grignard reagents and (-)-(1R,2S,5R)-Menthyl (S)-p-Toluenesulfinate,5a,8 the sulfoxide-sulfenate rearrangement causes facile epimerization at the sulfur atom. Racemization is generally less facile when the nonallylic substituent is alkyl rather than aryl.5a Thus, approaches to allylic sulfoxides derived from camphor9 and 10-mercaptoisoborneol10 have been developed wherein the configurational stability is promoted by a neighboring hydroxyl group. In another approach the rearrangement is not suppressed but rather is rendered highly stereoselective by the use of a bulky arylbiphenyl chiral auxiliary so that the other diastereomer is disfavored on thermodynamic grounds (eq 3).11


Treatment of allyl phenyl sulfoxide12 with Lithium Diisopropylamide in THF produces the lithiated sulfoxide. Alkyllithium reagents are not generally successful because of competing displacement at sulfur. The lithiated reagent is likely to be structurally akin to a lithium dienolate in that it possesses an O-Li contact, and a C-1-S bond which has double bond character.12 Reaction with alkyl halides proceeds preferentially at the a-carbon;1,13 however, regioselectivity is somewhat better than for allyl phenyl sulfide. Subsequent conversion of the a-substituted sulfoxide into the allylically transposed alcohol renders the starting sulfoxide operationally equivalent to a 3-hydroxyvinyl anion.1c,13 Reaction with cyclic enones is predominant conjugate (or 1,4) addition through the g-carbon, a regiochemical outcome which is not disrupted by external chelating agents.14,15 This regioselectivity has been exploited for lithiated allyl p-tolyl sulfoxide in a synthesis of pentalenolactone (E)-methyl ester16 and for lithiated 1-pentylallyl phenyl sulfoxide in syntheses of racemic prostaglandin I2 analogs14a and racemic 11-deoxyprostaglandin E1 (eq 4).14b Both the pronounced tendency of the lithiated reagent to undergo conjugate addition and the sigmatropic rearrangement of the neutral reagent to provide the allylic alcohol are well illustrated in the latter synthesis. The vinyl sulfoxide product (1) is converted via the intermediate allylic sulfoxide into the allylic alcohol (2) by means of Potassium t-Butoxide in t-butanol to give the 13SR isomer. The acetate is then converted into the allylically transposed allylic acetate (3) by means of PdCl2.2MeCN (see Palladium(II) Chloride) to form the 15SR diastereomer. For lithiated (E)- and (Z)-allylic sulfoxides bearing an alkyl group at C-3, highly stereoselective conjugate additions to cyclopentenone take place to give syn and anti vinylic sulfoxides such that the configuration at the two new stereogenic centers and at sulfur is rigidly defined by the double bond geometry of the allylic sulfoxide (eq 5).15b,15d

The conjugate addition proceeds under kinetic control15a and is explained by invoking a trans-decalyl-like transition state model.15b,15d By using optically pure allylic sulfoxides, single enantiomeric products are obtained. The use of camphor as the nonallylic substituent enables single enantiomeric allyl sulfoxides to be prepared9 and these undergo conjugate addition to cyclopentenones with complete face selectivity (eq 6),9b albeit in moderate yields (50-60%). The use of an arylbiphenyl chiral auxiliary attached to sulfur affords in some cases higher yields of the adducts with good to excellent diastereoselectivity.11b

Similarly, lithiated reagents from optically pure p-tolyl allylic sulfoxides5a undergo conjugate addition to a variety of cyclic enones, and the adducts have been converted into (+)-pentalenene,17 (+)-hirsutene,18 and (+)- and (-)-13-epoxytrichothec-9-ene.19 In other cases, configurational integrity of the products is maintained during conversion into bicyclo[2.2.1]heptanones14d,20,21 and bicyclo[3.3.0.]octanones.21,22 The regio- and stereoselectivity of reactions of lithiated allyl phenyl sulfoxide with carbonyl compounds is not as pronounced as that with cyclopentenones.23 Nevertheless, the introduction of additives to modify the reactivity of the reagent has made carbonyl addition a synthetically useful transformation.24 Whereas reaction with a-methyl aldehydes gives a mixture of a- and g-adducts, addition of Hexamethylphosphoric Triamide enhances a-addition while transmetalation with cadmium(II) encourages g-addition (eq 7).24a This outcome is contrary to that observed with the carbonyl addition of metalated allyl sulfides (see Allyl Phenyl Sulfide). For alkoxyaldehydes, use of lithiated 2-pyridyl allyl sulfoxide gives higher a-selectivity and superior yields,24b a reactivity paralleling that of the corresponding sulfide.

The a-adducts obtained from the reaction of lithiated allyl p-tolyl sulfoxide with aldehydes in the presence of HMPA,24 and of lithiated prenyl phenyl sulfoxide with 1,2-epoxy-2-methyl-3-butene,25 are converted via the sulfoxide-sulfenate rearrangement into functionalized diols (eq 8).

Vinylthionium Ions.

Polarity reversal may be achieved by converting allyl phenyl sulfoxide into the corresponding vinylthionium ion or equivalent via a Pummerer reaction. Such an electrophilic species also has ambident reactivity and may react with nucleophiles through the a- or the g-carbon (eq 9).26

Thus allyl phenyl sulfoxide reacts with silyl enol ethers in the presence of Trimethylsilyl Trifluoromethanesulfonate and Diisopropylethylamine with high g-selectivity. The reaction proceeds in good yields, although the scope is limited to the parent allyl system and to 2-alkylallyl aryl sulfoxides (eq 10).26a

In the absence of the silyl enol ether the vinylthionium ion is converted by the tertiary amine in high yield into a quaternary ammonium salt which can be alkylated with dimethyl sodiomalonate in the presence of Tetrakis(triphenylphosphine)palladium(0) in 60% yield.26b The use of N,N-diethyl(trimethylsilyl)amine as the tertiary amine to generate the quaternary salt followed by silyl group removal with Trimethylsilyl Trifluoromethanesulfonate affords the neutral amine adduct, a masked Mannich derivative, in 90% yield (eq 11).26b (a-Trimethylsilyloxy)allyl phenyl sulfide is generated in 53% yield from allyl phenyl sulfoxide and trimethylsilyl ketene acetals in the presence of Zinc Iodide in acetonitrile via the silyl-Pummerer reaction.27 Transfer of the silyl group from the ketene acetal to the sulfoxide oxygen leads to a sulfonium intermediate which then traps the liberated silyloxide (eq 12).

Nucleophilic Substitution of the Sulfinyl Group.

Allylic substitution of the sulfinyl and the sulfonyl (see Allyl Phenyl Sulfone) group in 1-alkyl-2-methylallylic sulfoxides and sulfones by lithium dialkylcuprates proceeds with high regio- and stereoselectivity to give trisubstituted alkenes.28

Related Reagents.

Allyldiphenylphosphine Oxide; Allyl Phenyl Selenide; Allyl Phenyl Sulfide.

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Richard K. Haynes

Hong Kong University of Science and Technology, Hong Kong

Simone C. Vonwiller

The University of Sydney, NSW, Australia

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