A-Phenylthiomethylation

Esters of A -(phenylthiomethyl)AAs undergo a base (NaH)-promoted addition to unsaturated esters to give a mixture of diastereroisomeric regioi-somers (Scheme 9) (84TL1579). 

Similarly, the conjugated addition of thiolate derivatives to a,p-unsaturated ester 63a in the presence of chiral N-sulfinimines 64 afforded a-phenylthiomethyl-p-... 

From a dialkyl acetal Bu3SnSPh, Bp3 Et20, toluene, —78° -> 0°, 64-100% yield. These conditions also convert MOM and MEM groups to the corresponding phenylthiomethyl groups in 64-77 % yield. 

From a dialkyl acetal MgBr2, Et20, it, PhSH, 91% yield. MOM groups are converted to phenylthiomethyl groups, 75% yield. 

In a prostaglandin synthesis a carbonyl group was protected as an oxime in which the hydroxyl group was protected against Collins oxidation by the phenylthiome-thyl-group. The phenylthiomethyl group is readily removed to give an oxime that is then cleaved to the carbonyl compound. ... 

In the reaction of 88 with /(-phenethyl bromide, l-phenethyl-3-phenylpropyl methyl sulfoxide and bis-3-phenylpropyl sulfoxide, besides 3-phenylpropyl methyl sulfoxide are obtained118. Sulfoxides, bearing a /1-hydrogen to the sulfmyl function, give olefins upon thermolysis. Utilizing this reaction, Trost and Bridges120 alkylated benzyl phenyl sulfoxide, 3,4-methylenedioxybenzyl phenyl sulfoxide, phenylthiomethyl phenyl sulfoxide, phenylsulfinylmethyl phenyl sulfoxide and cyanomethyl phenyl sulfoxide with alkyl, allyl and benzyl halides and subjected these sulfoxides to thermolysis, obtaining olefins in one-pot processes. 

Scheme 9.1 describes reactions with several lithiated compounds, including dichloromethane, dichloromethyl methyl ether, phenylthiomethyl methyl ether, and phenylthioacetals. Compare the structure of these reagents and the final products for these reactions. Develop a mechanistic outline that encompasses these reactions. Discuss the features that these reagents have in common with one another and with carbon monoxide. 

Rearrangement of an intermediary S-ylide is the key step of a synthesis of 142 from the 6-phenylthiomethyl-2-pyrone 140 and ethyl diazoacetate in the presence of a catalytic amount of Cu(acac)2 158>. The primary rearrangement product 141 is smoothly isomerized to 142 by treatment with silica gel. 

Q -Phenylthiomethyl-jS-hydroxy esters (50) can be prepared, predominantly as the iyn-isomer, by a stereoselective one-pot Michael-aldol tandem reaction. The seleno analogue can similarly be prepared (again, mainly syn), using PhSeLi in diethyl ether, but phenoxide ion is not sufficiently reactive for this sequence. 

Polymetalated systems of this type without phenyl substitution at the lithiated carbon centre are only accessible when solutions of LiCioHg (144a) or LiDBB (145) in THF instead of a suspension of metallic lithium in THF are reacted with bis(phenylthiomethyl)silanes of type 155. In our group, variously substituted bis(lithiomethyl)silanes 117a, 156b-e and 101 were synthesized by reductive cleavage of the carbon-sulphur bond with LiCioHg... 

As a particular example, reactions of diphenylbis(phenylthiomethyl)silane (155f) are shown. While the reaction of 155f with four equivalents of LiCioHg at —40 °C yields the dimetalated bis(lithiomethyl)diphenylsilane (101), a selective monolithiation (compound 158) can be achieved by using only two equivalents of the electron transfer reagent at —60°C. A side reaction of the monolithiated silane 158 is observed, when the reaction temperature rises above —30°C, giving [lithio(phenylthio)methyl]methyldiphenylsilane (159) (Scheme 57). This problem, also observed for other (phenylthiomethyl)element systems, can mostly be avoided by an exact control of the reaction temperature . 

By prior substitution at the a-carbon centre (deprotonation, followed by sUylation), also asymmetrically functionalized bis(lithiomethyl)silanes like compound 161 are accessible from their substituted parent compounds (e.g. compound 160). This selective reaction sequence is based on the possibility of deprotonating bis(phenylthiomethyl)silane 155f with w-butyllithium without attacking the thioether groups (Scheme 58). ... 

By the same Mannich-type reaction, Af,Af -bis(phenylthiomethyl)piperazine (182) can be synthesized from piperazine (181), which is converted into A, A -bis(lithiomethyl)pipe-razine (183) by the use of LiCioHg (144a) in THF (Scheme 61). ... 

Phenyl trimethylsilylmethyl sulphide [(phenylthiomethyl)trimethylsilane] [17873-08-4] M 196.4, b 48°/0.04mm, 113-115°/12mm, 158.5°/52mm, d4° 0.9671, n3D° 1.5380. If the sample is suspect then add H2O, wash with 10% aqueous NaOH, H2O again, dry (anhydrous CaCl2) and fractionally distil through a 2ft column packed with glass helices. [JACS 76 3713 7954]. 

Alkyl phenyl ketonesAlkylation of the anion of 1 followed by oxidation and rearrangement gives a mixed acetal, which is hydrolyzed by acid to a ketone (cf. Phenylthiomethyl(trimethyl)silane, this volume). 

We have just seen in a preceding scheme (see Section 4.2.1.5) an example of alkylation of a silylated enolate with phenylthiomethyl chloride. The Lewis acid-promoted phenylthioalkylation of O-silylated enolates of ketones, aldehydes, esters and lactones has been used by Paterson and Fleming as a convenient synthetic route to a-alkylated or alkylidenated carbonyl compounds [323-325] according to the accompanying scheme. 

The cyclization of the 3-(phenylthiomethyl)derivative of 160 (R = 3-CH2SPh) was carried out by heating in polyphosphoric acid at 110°C for 1 hour to afford 3-(tetrazol-5-yl)-4//-pyrido[l,2-a]pyrimidin-4-one 159 (R = 9-CH2SPh) in 8% yield (89EUP329126). 

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