sulfur - containing compounds have biological activity and thus have applications in the pharmaceutical and agrochemical industries . compounds with a thio group in the position alpha to a carbonyl group are referred to as -thio- or -sulfenylated carbonyl compounds and can be found in anti - infective , anti - tumor , anti - inflammatory , and nervous - system agents.[2 , 3 ] the carbonyl group of -sulfenylated carbonyl compounds can easily be transformed into other functional groups such as alcohol , imine , amine , and cyanohydrin . alternatively , the sulfur atom can be oxidized , producing the corresponding -carbonyl sulfoxides , which are important starting materials for biotransformation to produce chiral -hydroxy sulfoxides . various -amino thioether compounds , which could easily be synthesized by functional group interconversion of -sulfenylated carbonyl compounds , are reported to be apoptosis promoters ; their enantiomerically pure isomers are also widely employed as chiral ligands in asymmetric catalysis . moreover , in synthesis , -sulfenylated carbonyl compounds are used for the mono- and dialkylation of carbonyl compounds,[8d ] preparation of 1,2-dicarbonyl compounds by disulfenylation,[8f ] 1,2-carbonyl transposition,[8 g ] and for the synthesis of ,-unsaturated carbonyl compounds ( scheme 1).[8h ] these classes of compounds are employed as starting materials to synthesize butenolides as well as in silyl carbonyl chemistry for regio- and stereoselective synthesis of the corresponding enol silyl ethers and oxetanes . the sulfur substituent alpha to the carbonyl group can be reductively removed , making these compounds convenient precursors for acylations and alkylations.[8f ] substituted -sulfenylated carbonyl compounds also serve as starting materials for the synthesis of 2-halobenyl-3-arylbenzo[b]thiophene ethers , which act against breast cancer mcf7 cells , indicating antiproliferative activity against estrogen - dependent neoplasms . moreover , these types of compounds are used as starting materials for the preparation of therapeutically useful tumor - necrosis - factor--converting enzyme ( tace)-inhibitors , such as imidazolidinedione , and photochromic compounds , such as thieno-2h - chromene derivatives . -sulfenylated carbonyl compounds as important synthetic intermediates . [ 8f ] ) ; b ) traditional sulfur oxidation ; c ) mono- and dialkylation ( ref . [ 8d ] ) ; d ) biotransformation to chiral -hydroxy sulfoxides ( ref . ) ; e ) synthesis of ,-unsaturated carbonyl compounds ( ref . traditionally , -sulfenylated carbonyl compounds are prepared by sn2 displacement of the corresponding -halogenated carbonyl compounds by sulfide anions ( scheme 2 , route a ) . this is often associated with the generation of stoichiometric amounts of chemical waste both in the preparation of the -halogenated carbonyl compounds and in the subsequent substitution reaction to generate the -sulfenylated carbonyl products . moreover , the reactive -halo carbonyl intermediates are known warfare agents , for example , tear gas . alternatively , -sulfenylated carbonyl compounds are synthesized by the reaction of a carbonyl compound or a preformed enolate with sulfenylating agents such as disulfides , n-(phenylsulfanyl)succinimides , and sulfenyl chlorides ( scheme 2 , route b ) . this alternative route also suffers from severe limitations of multiple reaction steps , toxicity , difficulty in handling intermediates , and low atom efficiency . , stoichiometric versions of electrophilic asymmetric -sulfenylation , as well as catalytic asymmetric transformations employing organocatalysts and enantiopure titanium(iv ) or nickel(ii ) complexes , have been reported . these synthetic methods generally suffer from stoichiometric use of toxic and expensive catalysts , waste generation , long reaction times , and/or low product yields with limited substrate scope . therefore , an efficient , atom - economical , and sustainable method to synthesize -sulfenylated carbonyl compounds from readily available , simple starting materials is desirable . during a study on catalytic substitution of propargylic alcohol with thiophenol all screened catalysts except gold gave the expected thioether product by direct substitution of the hydroxyl group . surprisingly , a different reactivity was observed in the presence of au catalyst . instead of the expected thioether , the corresponding -sulfenylated carbonyl product was observed ( scheme 3 ) . the initial findings on this transformation were published in a recent communication . as an extension of this work , we herein report on the detailed scope and limitations of the regioselective sulfenylation of propargylic alcohols with gold catalysts . for optimization of the reaction conditions , 4-phenylbut-3-yn-2-ol ( 1 a ) and thiophenol ( 2 a ) were chosen as model substrates . different gold sources and additives were screened in the transformation of 1 a and 2 a into the -sulfenylated carbonyl product 3 a in different solvents at 65 c ( table 1 ) . optimization of reaction conditions [ a ] reaction conditions : 1 a ( 1 mmol ) , 2 a ( 1 mmol ) , and the catalyst were heated at 65 c in 2.5 ml of solvent for 24 h. [ b ] nmr yield with toluene as internal standard . schuster rearrangement followed by michael addition of thiophenol was observed . when a 1:1 mixture of 1 a and 2 a reacted in the presence of 5 mol % of gold(iii ) bromide , only 11 % product formation was observed after 24 h ( table 1 , entry 1 ) , whereas , gold(i ) iodide and gold(i ) thiophenolate gave 32 and 29 % product , respectively ( table 1 , entries 2 and 3 ) in 1,2-dichloroethane . attempts to increase the efficiency of the catalysis by adding different ligands to the reaction mixture were unsuccessful ( table 1 , entries 49 ) . no -sulfenylated product 3 a was formed on addition of agsbf6 to the ( pph3)aucl catalyst ( table 1 , entry 5 ) . instead , a different product resulted from meyer schuster rearrangement of 1 a followed by michael addition of 2 a. also , an n - heterocyclic carbene ligand and silver additives were tested , but gave poor results ( table 1 , entries 69 ) . using only silver(i ) trifluoromethanesulfonate as catalyst also led to meyer schuster rearrangement followed by michael addition ( table 1 , entry 10 ) . increased conversion to 3 a was observed when the reaction was performed with 2 mol % of gold(i ) chloride catalyst and 1.5 equivalents of 2 a with respect to 1 a ( table 1 , entry 15 ) . a further increase in the amount of 2 a to two equivalents did not increase the conversion to 3 a ( table 1 , entry 16 ) . substituting 1,2-dichloroethane ( dce ) by nitromethane ( meno2 ) increased the efficiency of the reaction to generate 97 % of 3 a ( table 1 , entry 17 ) . in contrast to the previous report , we chose nitromethane as solvent in the present study instead of 1,2-dichloroethane to obtain a better yield of the product , especially when aliphatic propargylic alcohols were employed as substrates at higher reaction temperature . chloroform and acetonitrile gave poor results ( table 1 , entries 1819 ) , and no reaction was observed in toluene ( table 1 , entry 20 ) . the optimized reaction conditions were applied to different substrates having an aromatic group in the r position ( table 2 ) . the reaction was general with respect to the aromatic propargylic alcohols . both primary and secondary propargylic alcohols were employed to produce the desired -sulfenylated ketones and aldehydes in high yields . secondary alcohols with different aliphatic groups at the r position reacted smoothly to produce the corresponding -sulfenylated products ( table 2 , entries 14 ) . the reactions also showed high generality for the aryl group at the r position of the alcohol . excellent yields of the products were observed for alcohols with a 1-naphthyl group at the r position ( table 2 , entries 7 and 10 ) . the effect of substituents of the phenyl ring at the r position of the alcohol was investigated . electron - withdrawing substituents such as 4-phenyl and 3,4-dichloro resulted in 89 and 95 % of 3 f and 3 h , respectively ( table 2 , entry 6 and 8) , whereas a 4-methyl substituent led to 3 e in 87 % yield ( table 2 , entry 5 ) . 1,3-diphenylprop-2-yn-1-ol with a phenyl ring in both r and r positions did not react with thiophenol to yield the desired product under the present reaction conditions . aryl thiols with different substituents in the para position of the aryl group were studied ( table 2 , entries 1225 ) . 4-chlorobenzenethiol ( 2 b ) and 4-bromobenzenethiol ( 2 c ) reacted smoothly with different primary and secondary propargylic alcohols to form the products in high yields ( table 2 , entries 1217 ) . carrying out the reaction at reflux for 48 h was required for reactions involving aryl thiols with electron - withdrawing substituents at the para position of the phenyl ring . thus , 4-fluorobenzenethiol ( 2 d ) gave 8086 % yield of product ( table 2 , entries 1820 , ) whereas n-(4-mercaptophenyl)acetamide ( 2 e ) generated 3 u in a 67 % yield ( table 2 , entry 21 ) . aryl thiols with electron - donating groups such as 4-methoxyl ( 2 f ) and 4-isopropyl ( 2 g ) gave the products 3 v3 y in lower yields ( table 2 , entries 2225 ) , whereby significant formation of disulfides as side products was observed . attempts to use aliphatic thiols were unsuccessful under the present reaction conditions , and no product formation was observed . -sulfenylated carbonyl compounds from aromatic propargyl alcohols 
  [ a ] reaction conditions : 1 ( 1 mmol ) , 2 ( 1.5 mmol ) , and aucl ( 2 mol % ) were heated at 65 c in 2.5 ml of nitromethane for 24 h. [ b ] yield of isolated product . [ c ] reactions at 100 c for 48 h. propargylic alcohols with different aliphatic groups at the r positions were also studied ( table 3 , entries 16 ) . aliphatic alcohols generally showed lower reactivity than aromatic alcohols , and an increased catalyst loading to 5 mol % was required . the reactions were also performed for 72 h with an excess ( 3 equiv ) of thiophenol with respect to the alcohol at 100 c oil bath temperature . propargylic alcohols with cyclopentyl ( 1 l ) and cyclohexyl ( 1 m ) groups at the r position generated the products in 71 and 70 % yields , respectively ( table 3 , entries 1 and 2 ) . due to the low boiling point of alcohol 1 n with an ethyl group at the r position , three equivalents were used to yield the product 4 c in 63 % ( table 3 , entry 3 ) , whereas 71 % yield of product was observed for alcohol 1 o with a 2-phenylethyl substituent ( table 3 , entry 4 ) . importantly , alcohols with functional groups such as an olefinic double bond ( 1 p ) or ester ( 1 q ) at the r position gave the products 4 e and 4 f in 67 and 47 % yield , respectively ( table 3 , entries 5 and 6 ) . -sulfenylated carbonyl compounds from aliphatic propargyl alcohols 
  [ a ] reaction conditions : 1 ( 1 mmol ) , 2 ( 3 mmol ) , and aucl ( 5 mol % ) were heated at 100 c in 2.5 ml of nitromethane for 72 h. [ b ] yield of isolated product . [ c ] three equivalents of 1 n were used with respect to 2 a. experimental studies : during the course of the reaction between primary propargyl alcohol 1 i and thiophenol 2 a , we observed the appearance of new h nmr signals in the crude reaction mixture which did not correspond to the starting materials or the product . in a control experiment , after structural elucidation , we concluded that the new compound was an e / z mixture ( 2/7 ) of sulfenylated allylic alcohol 5 ( scheme 4 ) , which was found to be the true intermediate of this reaction ( see below ) . such intermediates were observed during the course of all reactions of propargylic alcohols and aryl thiols . intermediate 5 formed in the aucl - catalyzed reaction of 1 i and 2 a. the hydrothiolation reaction to generate 5 from 1 i and 2 a without a catalyst has recently been reported . the effect of a gold catalyst on the formation of allylic alcohol 5 was therefore investigated . three separate reactions between 1 i and 2 a to generate 5 were carried out with and without the aucl ( 2 mol % ) catalyst at room temperature in nitromethane . the gold - catalyzed reaction produced 60 % of 5 , whereas only a trace amount of 5 ( < 10 % ) was observed in the uncatalyzed reaction after 2 h ( table 4 ) . we also tested whether addition of a proton sponge affects the formation of compound 5 in the presence of aucl , but there was no difference to the reaction in the absence of the proton sponge ( table 4 , entry 3 vs. entry 1 ) . effect of aucl on the formation of 5 from 1 i and 2 a 
  [ a ] reaction conditions : 1 i ( 1 mmol ) , 2 a ( 1.5 mmol ) , aucl , and additive were stirred at room temperature in nitromethane ( 2.5 ml ) for 2 h. since the experimental data showed that sulfenylated allylic alcohol 5 is an intermediate in the overall reaction , we studied the conversion of 5 to the final product 3 i separately . compound 5 was stable in nitromethane at 65 c , and no conversion was observed ( table 5 , entry 1 ) . also , addition of thiophenol 2 a did not result in any conversion to 3 i , and compound 5 remained intact under these reaction conditions ( table 5 , entry 2 ) . on the other hand , quantitative formation of aldehyde 3 i was observed in 8 h in the presence of 2 mol % of aucl ( table 5 , entry 3 ) . however , no conversion of 5 to 3 i was observed when 30 mol % of proton sponge or molecular sieves was used together with aucl ( table 5 , entries 4 and 5 , respectively ) . the above results suggest that the reaction may be catalyzed by a protic acid . to verify this , compound 5 was treated with acetic acid , but no conversion to 3 i was observed ( table 5 , entry 6 ) . interestingly , the reaction took place in the presence of the proton sponge ( 30 mol % ) if a combination of 2 mol % of aucl with 1.5 equiv of thiophenol 2 a was used ( table 5 , entry 7 ) . moreover , application of au thiophenolate led only to a low conversion ( table 5 , entry 8) . these experiments support that the presence of both aucl and a proton source ( e.g. , hcl or thiophenol ) is necessary for the reaction to proceed efficiently . formation of product 3 i from intermediate 5 
  [ a ] reaction conditions : 5 ( 1 mmol ) and aucl ( 2 mol % ) were heated at 65 c in 2.5 ml of nitromethane for 8 h. [ b ] nmr yield . the above experiments also confirmed that the overall reaction is indeed a two - step process and identified sulfenylated allylic alcohol 5 as the true intermediate . the first step is a regioselective aucl - catalyzed addition of thiophenol 2 a to the triple bond of alcohol 1 i , and the second step is a rearrangement of the resulting intermediate 5 into the final product 3 i ( scheme 5 ) . efficient transformation of 5 into 3 i requires both aucl and a proton source . the overall reaction between 1 i and 2 a to form product 3 i via intermediate allylic alcohol 5 . formation of the -sulfenylated carbonyl compound is atom - efficient , since all atoms of the reacting alcohol and thiol end up in the -sulfenylated carbonyl product . the -hydrogen atom at the 1-position of the alcohol and the protons of the alcohol and thiol are transferred to the triple bond of the alcohol during the course of the reaction . to determine the positions to which the individual hydrogen atoms are transferred , reactions were carried out with deuterium - labeled 1 i - od ( d in the protic position ) , 1 i - cd ( d in the hydridic position ) , and 2 a - sd ( d in the protic position ) . first , the oh proton of alcohol 1 i and sh proton of thiophenol 2a were exchanged for deuterium atoms . the reaction between 1 i - od and 2 a - sd ( 80 % deuterium purity ) was carried out for 24 h in cdcl3 at reflux with 5 mol % of gold(i ) chloride , and the product was isolated in a 80 % yield ( scheme 6 ) . h and h nmr spectroscopic studies on the purified product revealed that the total deuterium content was 75 % , of which deuterium incorporation at the benzylic 3-position ( 3 this labeling experiment shows that the protons from both the oh group of 1 i and the sh group of 2 a are transferred to the benzylic 3-position of 3 i. deuterium incorporation with labeled 1 i - od and 2 a - sd . alcohol 1 i - cd ( 90 % deuterium purity ) labeled with a deuterium atom in the hydridic 1-position was prepared and used as substrate in the -sulfenylation reaction . the reaction was run for 24 h and the product was isolated in a 73 % yield ( scheme 7 ) . h nmr and h nmr spectroscopic studies on the purified product showed that the total deuterium content of the product was 90 % , of which deuterium retention at the aldehyde 1-position ( 3 i - d2 ) was 79 % and the remaining 11 % deuterium was incorporated at the 2-position of the product ( 3 i - d3 ) . this labeling study shows that the hydride or deuteride of 1 i - cd is transferred to the 2-position of the product . deuterium incorporation with labeled 1 i - cd . to investigate the intramolecularity of the hydride migration , a crossover experiment was carried out with 1 i - cd , 1 j , and 2 a ( scheme 8) . h and h nmr spectral studies on the purified products showed no deuterium incorporation in 3 j , whereas deuterium incorporation in 3 i was obtained in similar ratios to scheme 7 . crossover experiment to investigate the intramolecularity of the hydride shift . to study the scope of chirality transfer of the present reaction , optically pure ( s)-1 a was used as substrate in the gold(i)-catalyzed -sulfenylation reaction ( scheme 9 ) . no chirality transfer was observed when ( s)-1 a reacted with thiophenol 2 a under the optimized reaction conditions , and rac-3 a was generated . investigation of chirality transfer for the conversion of ( s)-1 a into 3 a. theoretical studies : to gain further insight into the reaction mechanism , a theoretical study was performed with the dft functional m06 ( see experimental section ) . first , formation of the experimentally observed sulfenylated allylic alcohol intermediate 5 by gold - catalyzed regioselective addition of thiophenol 2 a to the triple bond of propargylic alcohol 1 i was studied . second , gold - catalyzed rearrangement of compound 5 to the final product 3 i was investigated . while the gold - catalyzed additions of various nucleophiles to triple and double bonds have been the subject of both experimental and theoretical mechanistic studies , the corresponding reaction with aryl thiol nucleophiles has been less studied . the present calculations on the gold - catalyzed hydrothiolation reaction complement our experimental results and increase the mechanistic understanding of this class of reactions . the experimental results presented above point to aucl being the true catalyst of the reaction ( tables 1 and 4 ) . therefore , we considered several different complexes of aucl with thiophenol 2 a and propargylic alcohol 1 i as the starting point for the catalytic cycle of the hydrothiolation reaction . the lowest - energy complex is formed between aucl and thiophenol 2 a ( int0 , figure 1 ) with a binding energy of 22.1 kcal mol . therefore , int0 serves as the zero point in the free - energy plots below . the catalytically relevant aucl complex with propargylic alcohol 1 i ( int1 , figure 1 ) is , however , only 1.4 kcal mol less stable ( see figure 1 for the calculated free - energy profile ) . free - energy profile for the regioselective gold - catalyzed addition of thiophenol 2 a to the triple bond of propargylic alcohol 1 i. the first step in the mechanism is nucleophilic attack of thiophenol on the triple bond of the propargylic alcohol bound to aucl . furthermore , both the syn addition of thiophenol and aucl ( which can be termed inner - sphere ) and anti addition ( outer - sphere ) pathways are possible . the barriers for the two outer - sphere attacks via ts1a and ts1b ( see figure 2 for optimized structures ) were both calculated to be 23.8 kcal mol relative to int0 . in both ts1a and ts1b , and also in the resulting intermediates int2a and int2b , a hydrogen bond is present between the thiol proton and the oxygen atom of the hydroxyl group . the calculations show that the transition states for the alternative inner - sphere additions ( ts1c and ts1d ) have significantly higher energies than those of the outer - sphere additions ( 6 - 11 kcal mol , see figure 1 for energy diagram and figure 2 for optimized structures ) . this result is in line with previous findings on gold - catalyzed additions to double and triple bonds , which were shown to take place preferentially by an outer - sphere mechanism . therefore , the subsequent steps of the inner - sphere addition pathways were not further evaluated in the present study . the outer - sphere course of thiophenol addition implies that the reaction will afford only the z isomer of allylic alcohol 5 . however , since a mixture of e and z isomers of 5 was observed experimentally , some other process must be responsible for the formation of the e isomer . optimized transition - state structures for the key steps of the gold - catalyzed hydrothiolation of propargylic alcohol 1 i. the phenyl hydrogen atoms have been omitted for clarity . the next step in the gold - catalyzed addition of thiophenol to propargylic alcohol is a protodeauration . this reaction can not take place directly from int2a or int2b , because that would require transferring the proton from the sulfur atom to a distant carbon atom . instead , this step is facilitated by the adjacent hydroxyl group , which can transfer the proton intramolecularly in a stepwise fashion . hence , an initial proton transfer from sulfur to oxygen takes place ( ts2a and ts2b , figure 2 ) , followed by protodeauration ( ts3a and ts3b ) . transition states ts3a and ts3b are the highest points in the free - energy profiles of the respective pathways , and their relative energies therefore determine the overall regioselectivity of the addition . protodeauration via ts3a is calculated to be favored by 6.0 kcal mol compared to ts3 b ( 25.9 versus 31.9 kcal mol relative to int0 , respectively ) . this difference in energy corresponds well to the experimental finding that only -sulfenylated carbonyl compounds were observed . the difference in barriers can be explained by the fact that the ts3b contains a strained , four - membered cyclic structure , while ts3a has a more relaxed , five - membered cyclic structure . thus , according to the calculations , the hydroxyl group of the reactant plays an important role in controlling the regioselectivity of the reaction . the protodeauration was found to be very exergonic and thus irreversible , and it results in the formation of complex int4(z ) , with aucl coordinated to the double bond of intermediate 5z . to close the catalytic cycle for thiophenol addition overall , the formation of intermediate 5z is calculated to be exergonic by 11.1 kcal mol . in the second part of the reaction , intermediate 5 rearranges to the final product , aldehyde 3 i. the isomerization of allylic alcohols to the corresponding ketones is known to be catalyzed by complexes of transition metals such as ru , rh , and fe . however , to the best of our knowledge , no examples of gold - catalyzed isomerization of allylic alcohols have been reported . interestingly , the above - mentioned reactions usually follow a redox pathway involving intermediate formation of metal hydride and ,-unsaturated ketone , and result in an intra- or intermolecular 1,3-hydride transfer to the 3-position of the product . in contrast , the gold - catalyzed process described here results in a selective intramolecular 1,2-hydride shift ( schemes 7 and 8) . the dissimilarity in hydride transfer and the fact that this process requires the presence of both aucl and a proton source ( table 5 ) suggests that this gold - catalyzed isomerization of 5 to 3 i follows a different mechanistic route compared with previous reactions catalyzed by other metals . we have evaluated theoretically a number of possible mechanisms for the isomerization of 5 to 3 i which comply with the results of the experimental investigations discussed above . the calculations show that the only pathway that has plausible barriers is initiated by protonation of allylic alcohol 5 by an external proton source activated with aucl ( figure 3 ) . all of the other alternative mechanisms tested , such as those involving hydride shift promoted by coordination of aucl to the double bond of 5 or intramolecular protonation of the double bond by the aucl - activated hydroxyl group , were found to proceed via high - energy routes with barriers exceeding 30 kcal mol ( see supporting information for details ) . free - energy profile for the gold - catalyzed isomerization of allylic alcohol 5 to aldehyde 3 i. the catalytic cycle for the rearrangement of 5z into 3 i starts with complex int4(z ) . under the normal reaction conditions thiophenol 2 a is present in the reaction mixture in excess and may act as a proton donor . thus , in the first step of the reaction , 2 a , acidified by coordination of aucl to the sulfur atom , protonates the double bond of allylic alcohol 5z at the 3-position ( ts4(z ) , see figure 4 for the optimized structure ) . the calculated barrier is 16.4 kcal mol relative to int4(z ) , and the resulting dissociated ion - pair intermediate int5 lies 7.0 kcal mol higher than int4(z ) ( see figure 3 for the free - energy diagram ) . since the transition state for the following step of the catalytic cycle ( ts5 ) is higher in energy than ts4(z ) optimized transition - state structures for the key steps of the gold - catalyzed isomerization of allylic alcohol 5 to aldehyde 3 i. importantly , the intermediate int5 can undergo rotation around the c  c single bond and a subsequent reprotonation via ts4(e ) , which results in the formation of the isomeric int4(e ) . hence , although the preceding hydrothiolation reaction delivers the z - configured allylic alcohol 5z exclusively , as discussed above , it may interconvert with 5e under the reaction conditions to afford the experimentally observed mixture of isomers . the calculated energy difference between free 5e and 5z is 0.5 kcal mol in favor of 5e . this corresponds to a 5e:5z ratio of about 2:1 , which differs slightly from the experimentally observed 2:7 mixture , which corresponds to 0.8 kcal mol in favor of 5z . the subsequent step of the reaction is the key 1,2-hydride shift ( ts5 ) , driven by the electron - deficient character at the 2-position in int5 . this takes place via ts5 with an overall barrier of 24.3 kcal mol relative to int4(z ) . interestingly , although both int5 preceding ts5 and the resulting int6 were found to be more stable as dissociated ion pairs , the transition state has slightly lower energy as an associated ion pair . this is due to the interaction between the gold center and the hydride ( figure 4 ) , that is , gold assists the hydride shift . after the hydride shift , the proton is returned to the thiophenol ( ts6 , see figure 4 for the optimized structure ) and a complex of aucl with the product is formed ( int7 ) . the calculated barrier for this is very low , only 3.3 kcal mol relative to int6 . to close the catalytic cycle , product 3 i is released and int4 regenerated . the latter ligand exchange is slightly endergonic ( by 0.1 and 1.4 kcal mol for int4(z ) and int4(e ) , respectively ) . this means that int4(z ) and int7 are the most stable gold complexes present in the reaction mixture . as discussed above , it was experimentally shown that aucl can promote the isomerization of allylic alcohol 5 to aldehyde 3 i even in the absence of the thiophenol ( table 5 , entry 3 ) . the reaction was , however , inhibited by the addition of 30 mol % of proton sponge ( table 5 , entry 4 ) or molecular sieves ( table 5 , entry 5 ) . from these results , we concluded that the role of the proton donor may also be played by hcl , which could be present in aucl or might be generated under the reaction conditions . therefore , we also calculated the free - energy profile for the reaction involving hcl as the proton source instead of thiophenol . the results indicated that such process is indeed feasible and in fact more energetically favorable than that with thiophenol ( see supporting information ) . however , from the calculations it is difficult to say which of the two alternative pathways is operational under the normal reaction conditions , due to the much higher concentration of 2 a compared to hcl in the reaction mixture . proposed reaction mechanism : on the basis of the experimental and computational studies the following reaction mechanism is proposed for the gold - catalyzed reaction between propargylic alcohols and thiophenols producing -sulfenylated carbonyl compounds . the mechanism consists of two catalytic cycles ( scheme 10 ) , corresponding to the two sequential processes taking place in the course of the reaction : 1 ) hydrothiolation of propargylic alcohol 1 i and 2 ) isomerization of sulfenylated allylic alcohol 5 to the final aldehyde 3 i. proposed reaction mechanism . for the hydrothiolation cycle ( scheme 10 , left part ) , it was established that the initial addition of the thiophenol to the triple bond of the propargylic alcohol proceeds by an outer - sphere mechanism and can occur at both the 2- and 3-positions ( ts1a and ts1b ) , affording both int2a and int2b . however , this step and the subsequent proton transfer ( ts2a and ts2b ) were found to be reversible , and thus the final regioselectivity is determined by the protodeauration . according to the calculations , protodeauration is favored for the -adduct ( ts3a ) , in agreement with the experimental results . once formed , the intermediate sulfenylated allylic alcohol 5 can undergo isomerization to the final product , following the second catalytic cycle ( scheme 9 , right part ) . the first step of the cycle involves protonation of the double bond of 5 by a proton donor ( e.g. , thiophenol 2 a ) , acidified by coordination to aucl . the protonation step was found to be reversible , and this may account for the z e isomerization of allylic alcohol 5 , which is produced in the hydrothiolation step as the z isomer exclusively , whereas a mixture of 5z and 5e was observed experimentally . from int5 a 1,2-hydride shift takes place ( ts5 ) , which is driven by the electron - deficient character at the 2-position . in the final step of the cycle , the gold - catalyzed pathway described here is a new mechanism for the isomerization of allylic alcohols and is distinct from those followed in the presence of other transition metal catalysts . an atom - efficient , gold - catalyzed route to -sulfenylated carbonyl compounds from propargylic alcohols and aromatic thiols was studied . by utilizing this protocol , primary aromatic , secondary aromatic , and secondary aliphatic propargylic alcohols were transformed into -sulfenylated carbonyl compounds in good to excellent yields . when a secondary alcohol was used , an -sulfenylated ketone was generated , and when a primary alcohol was used , an -sulfenylated aldehyde was obtained . the protocol was found to be general with respect to a variety of substituents on the aromatic ring of the alcohols and thiols . experimental and theoretical investigations were performed to elucidate the mechanism and the source of regioselectivity of the reaction . the initial thiol attack at the 2-position of the propargylic alcohol was suggested to be due to a favored protodeauration step via an energetically favored five - membered cyclic transition state , instead of the unfavorable four - membered cyclic transition state found for attack at the 3-position of the triple bond . furthermore , experimental data and calculations showed that protonation of the double bond of the sulfenylated allylic alcohol intermediate in the next step was promoted by a proton - transfer mediator coordinated to gold chloride . 4-phenyl-3-(phenylthio)butan-2-one ( 3 a ) : aucl ( 5 mg , 2 mol % ) was transferred to a 5 ml microwave vial with a small magnet in a glove box under nitrogen atmosphere . the cap of the vial was closed tightly and the vial was removed from the glove - box . dry nitromethane ( 2.5 ml ) , alcohol 1 a ( 145 l , 1 mmol ) , and benzenethiol ( 2 a , 154 l , 1.5 mmol ) were added to the vial by syringe and the mixture was stirred with a magnetic stirrer at 65 c for 24 h. after completion of the reaction ( shown by tlc or crude nmr spectroscopy ) , the solvent was evaporated under reduced pressure and the residue was purified by silica - gel ( 100200 mesh ) column chromatography with 3 vol % ethyl acetate / pentane as eluent to yield the desired product 3 a as a pale yellow oil ( 240 mg , 0.94 mmol , 94 % ) . h nmr ( 300 mhz , cdcl3 ) : =2.20 ( s , 3 h , h-1 ) , 3.00 ( dd , j=6.9 hz , 14.4 hz , 1 h , h-4 ) , 3.19 ( dd , j=8.4 hz , 14.1 hz , 1 h , h-4 ) , 3.90 ( dd , j=6.9 hz , 8.4 hz , 1 h , h-3 ) , 7.187.37 ppm ( m , 10 h , h - arom ) . c nmr ( 75 mhz , cdcl3 ) : =28.1 , 36.9 , 59.0 , 127.1 , 128.5 , 128.8 , 129.4 , 133.0 , 133.3 , 138.3 , 204.5 ppm . computational details : the calculations were performed with the m06 functional as implemented in the gaussian 09 package . geometries were optimized by using the def2-svp double- basis set with polarization functions on all atoms . relativistic effects were accounted for by using the relativistic sdd effective core potential for gold . the stationary points were characterized by frequency calculations to confirm their character as minima ( no imaginary frequencies ) or transition states ( one imaginary frequency corresponding to the reaction coordinate ) . the solvation energies were calculated as single - point energy corrections at the same level of theory as the geometry optimization by using the conductor - like polarizable continuum model ( cpcm ) formalism with the parameters for nitromethane ( =36.562 ) . thermal corrections to gibbs free energies were calculated for 338.15 k , which is the temperature at which the reactions were performed experimentally . the final gibbs free energies reported in this article were obtained from single - point calculations with the larger 6 - 311+g(2d,2p ) basis set for h , c , o , s , and cl , and sdd for au , corrected for zero - point and thermal effects , as well as solvation . for comparison , we also reoptimized all of the structures using the b3lyp functional and recalculated the energies with all corrections , including dispersion . some differences were observed , but the results were in general consistent with the m06 results presented here ( see supporting information for details ) . as a service to our authors and readers , this journal provides supporting information supplied by the authors . such materials are peer reviewed and may be re - organized for online delivery , but are not copy - edited or typeset . technical support issues arising from supporting information ( other than missing files ) should be addressed to the authors
gold(i)-chloride - catalyzed synthesis of -sulfenylated carbonyl compounds from propargylic alcohols and aryl thiols showed a wide substrate scope with respect to both propargylic alcohols and aryl thiols . 
 primary and secondary aromatic propargylic alcohols generated -sulfenylated aldehydes and ketones in 6097 % yield . 
 secondary aliphatic propargylic alcohols generated -sulfenylated ketones in yields of 4771 % . 
 different gold sources and ligand effects were studied , and it was shown that gold(i ) chloride gave the highest product yields . 
 experimental and theoretical studies demonstrated that the reaction proceeds in two separate steps . 
 a sulfenylated allylic alcohol , generated by initial regioselective attack of the aryl thiol on the triple bond of the propargylic alcohol , was isolated , evaluated , and found to be an intermediate in the reaction . 
 deuterium labeling experiments showed that the protons from the propargylic alcohol and aryl thiol were transferred to the 3-position , and that the hydride from the alcohol was transferred to the 2-position of the product . 
 density functional theory ( dft ) calculations showed that the observed regioselectivity of the aryl thiol attack towards the 2-position of propargylic alcohol was determined by a low - energy , five - membered cyclic protodeauration transition state instead of the strained , four - membered cyclic transition state found for attack at the 3-position . experimental data and dft calculations supported that the second step of the reaction is initiated by protonation of the double bond of the sulfenylated allylic alcohol with a proton donor coordinated to gold(i ) chloride . 
 this in turn allows for a 1,2-hydride shift , generating the final product of the reaction .