Acetylene phenylthio

At room temperature, base-catalyzed addition of thiophenol to phenyl trifluo-romethyl acetylene gives exclusively (Z)-3-phenyl-3-phenylthio-l,1,1-tnfluoro-propene. At 150 °C, the predominant isomer is the E isomer (64%), with 23% of the Z isomer and 13% of the other two regioisomers [4] (equation 5). 

The third synthetic scheme is employed when the phenylthio substituent is in the a-position of the lactone function, which interferes with the cyclization (90JOC5894). Acetylenic ketone 194 (95% yield) is readily transformed to the acetal 195 (with potassium carbonate in methanol) however, under the above conditions neither its hydrolysis nor cyclization to the spiroketal occurs. The spirocyclic pyrone 197 is formed in quantitative yield on treatment of 195 with p-toluenesulfonic acid in a 4 1 THF-H2O mixture at reflux for 12 h. 

An efficient synthesis of the l-aUyl-6-(l, 2, 3 -triazolyl) analogue 170 of 1-[2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (KEPT), an anti-human immunodeficiency virus (HIV) reverse transcriptase inhibitor, was reported using an intermolecular 1,3-dipolar cycloaddition of the azide 169 with acetylenes (35) (Scheme 9.35). Azidouracil (169), when refluxed with an acetylene in equimolar proportions in toluene, gave the corresponding triazoles (170) in excellent yield. 

Radical cyclizations are often used in ring formations and are an effective methodology in the synthesis of piperidines. The intramolecular cyclization of an oxime ether, such as 63 onto an aldehyde or ketone gives a new entry into cyclic amino alcohols <99JOC2003, 99H(51)2711>. Similarly, reaction of a terminal acetylene with BujSnH generates a vinyl radical, which will cyclize with an imine moiety to give 3-methylenepiperidine <99TL1515>. The indolizidine alkaloid ipalbidine was prepared by a sulfur-controlled 6-exo-selective radical cyclization of an a/p/ia-phenylthio amide <99H(50)31>. 

If the pKa of the corresponding acid R1 - H from the stabilized carbanion is smaller than 35, the migration of R1 fails in (dichloromethyl)borate complexes. Failure to convert pinanediol [(phenylthio)methyl]boronate to an a-chloro boronic ester has been reported15. Reaction of (dichloromethyl)lithium with an acetylenic boronic ester resulted in loss of the acetylenic group to form the (dichloromethyl)boronate, and various attempts to react (dichloromethyl)boronic esters with lithium enolates have failed17. Dissociation of the carbanion is suspected as the cause, but in most cases the products have not been rigorously identified. 

The related lithium(phenylthio)cyclopropylcuprate, prepared from cyclopropyllithium and PhSCu, has been extensively used in the synthesis of /1-cyclopropyl enones by coupling with the corresponding fl-iodo enones (equation 10)34 36. Repetitive regioselective coupling of ethynylcyclopropane units by this method led to polyspirocyclopropyl acetylenes as precursors to [NJpericyclynes37. 

Unknown until recently, 2-(4-ethylthio)- and 2-(4-phenylthiophenyl)-pyrroles (8,9) are formed in a yield of up to 48% by the reaction of 4-ethylthio- and 4-phenylthio-acetophenone oximes with acetylene under atmospheric pressure at 96°C (Scheme 7) [90ZOR(ip)]. 

A new route to ( )-trachelanthamidine (6) and ( )-isoretronecanol (5) has been reported by Nossin and Speckamp.12 Cyclization of the ethoxy-lactam (28), which is formed on reduction of the imide (27), led to ring-closure with the acetylene to give, after hydrolysis, a 4 1 mixture of the epimers (29) and (30) (Scheme 7). The preferential formation of the five-membered ring is considered to be due to stabilization of an exocyclic vinyl cationic intermediate by the phenylthio group. Reduction of the separated diastereoisomers (29) and (30) yielded ( )-trachelanthamidine (6) and ( )-isoretronecanol (5), respectively. 

Sodium thiophenoxide and bis phenyliodonium acetylene triflate afforded cleanly l,2-bis(phenylthio)acetylene [6]. Alkynyl iodonium salts have alkynylated several arene sulphonates which were converted into alkynyl aryl sulphones. The process is probably the best among other methods, as far as yield, availability of starting materials, non-toxicity and ease of handling are concerned. 

Various functionalized alkynes can be submitted to carbocupration reactions, such as alkoxyalkynes,150 alkynyl carbamates,151 acetylenic orthoesters,152 and thioalkynes.153 The carbocupration of orthoesters, for example, 204, has been used to prepare a-substituted esters of the type 206 by acidic hydrolysis of the adduct 205 (Scheme 51).152 This allows the formation of regioisomers that are not accessible by copper-mediated addition to acetylenic esters. A stereoselective synthesis of trisubstituted alkenes has been described by Normant et al.lSd> starting from phenylthio-acetylene 207. Carbocupration with lithium di- -butylcuprate affords the intermediate 208 which, upon addition of /z-butyllithium, undergoes a 1,2-metalate rearrangement to the vinylcuprate 209. The latter can be trapped with various electrophiles, for example, ethyl propiolate, providing product 210 with complete regio- and stereocontrol. 

Similar reactions have been carried out on acetylene.In an interesting variation, thiocarbonates add to aUcynes in the presence of a palladium catalyst to give a p-phenylthio a,p-unsaturated ester.Aldehydes add to alkynes in the presence of a rhodium catalyst to give conjugated ketones.In a cyclic version of the addition of aldehydes, 4-pentenal was converted to cyclopentanone with a rhodium-complex catalyst. An intramolecular acyl addition to an alkyne was reported using silyl ketones, acetic aid and a rhodium catalyst. In the presence of a palladium catalyst, a tosylamide group added to an alkene unit to generate A-tosylpyrrolidine derivatives. 

Solid state excitation of electron donor-acceptor complexes of various diaryl-acetylenes and dichlorobenzoquinone in either the acceptor or the 1 2 complex absorption bands induces [2+2] cycloaddition and produces identical mixtures of the quinone methides. Evidence is presented for the participation of an ion-radical pair as the reactive intermediate in both cases. Irradiation of an appropriately substituted o-hydroxybenzyl alcohol precursor generates the corresponding o-quinone methide which is reported to undergo an efficient [4+2] cycloaddition to form the hexahydrocannabinol system. Time-resolved studies confirm the intermediacy of the o-quinone methide and show its lifetime to be > 2 ms. Laser photolysis of 1,2-bis(phenoxymethyl)benzene, l,2-bis[(phenylthio)-methyl]benzene, and l,2-bis[(phenylseleno)methyl]benzene occurs by a two-photon process to produce o-quinodimethane which will cycloadd to various dienophiles including maleic anhydride, dimethyl maleate, dimethyl fumarate, fumaronitrile and dimethyl acetylenedicarboxylate. ... 

The reaction of diphenyl disulfide with a variety of substituted acetylenes, promoted by thermal decomposition of di-rert-butyl peroxide, provides l,2-bis(phenylthio)ethylene adducts together with the corresponding benzothiophenes in reasonable yield ". The mechanism conceived for these transformations is depicted in Scheme 3, where the key step is the intramolecular cyclization of vinyl radicals. 

Aryl methyl ketones can be converted to a-keto dithioates, as shown in Scheme 11 [43]. Therefore, on treatment with iodine and pyridine, the ketone 44 yields pyridinium salt 45, and 45 can then be treated first with elemental sulfur in the presence of triethylamine in DMSO and DMF and then with methyl iodide to give S-methyl a-keto dithioate 46. The reaction of l-(diethylamino)-2-(phenylthio)acetylene (47) with elemental sulfur in refluxing chlorobenzene gives compound 48 in which the dithioester and thioamide groups directly connected to each other (Eq. 17) [44]. 

Lithium n butyl (phenylthio) cuprate has been used in nucleophilic substitution reactions of arenesulfonyl fluorides, al-lylic acetates, 9 BBN, propargyllc carbamates, and bromo-alkenes, as well as in nucleophilic additions to acetoxy-epoxides. It Is a good choice for 1,4-addItIon of an n-Bu group, having been used in 1,4 addition-elimination reactions of a-oxoketene dithloacetals and 3-halo-2-cycloalkenones, and in tandem vicinal dialkylation reactions of 5-methyleneoxa-zolones and alkynes. A typical example Is the use of the reagentin the stereospecific synthesis of (, -2-heptenoicacidfrom acetylene (eq 1). ... 

Thus, the reaction of mixed (phenylthio)alkylcuprates with 9-BBN overcomes the problem associated with (1) the thermal instability of phenoxy- and tert-bu-toxyalkylcuprates, (2) the low reactivity of mixed acetylenic cuprates, and (3) the wasting of one R group of the homocuprates. 

Piers and Morton have reported that lithium (phenylthio)(trimethyl-stannyOcuprate smoothly transfers one trimethylstannyl group to a,/3-acetylenic esters in a conjugate sense to give /3-trimethylstannyl-a,/3-olefinic esters. Importantly, products of almost exclusive E- or Z-geometry are formed under conditions of kinetic or thermodynamic control. Partial reduction followed by Wittig... 

Bj-fEj-Methoxyallyldiisopinocampheylborane 16 was synthesized via the reduction of methoxy-3-(phenylthio)propene 145 with potassium naphthalenide under Hoffmann et al. conditions, followed by the treatment of the resulting anion with Ipc2BOMe. Ganesh and Nicholas demonstrated the use of this reagent for the synthesis of anti-P-alkoxyhomoallylic alcohols anti-1% via the alkoxyallylbo-ration of cobalt-complexed acetylenic aldehydes 77 (Scheme 25.16). 

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