Job/Unit: O51046 /KAP1 Date: 22-09-15 14:25:04 Pages: 6 FULL PAPER DOI: 10.1002/ejoc.201501046 Ruthenium-Catalyzed Atom-Economical Stereo- and Regioselective Synthesis of Long-Chain Fatty Acid Enol Esters Rajesh K. Jena [a] and Manish Bhattacharjee* [a] Keywords: Alkynes / Ruthenium / Enols / Esters / Phosphine complexes / Fatty acids The ruthenium(II) complex [Ru(dppp) 2 (CH 3 CN)Cl][BPh 4 ] {dppp = diphenylphosphinopropane} is an efficient catalyst Introduction Recently, a biosynthetic gene cluster, known as fee (fatty acid enol esters) was isolated from cultured bacteria that produces long-chain fatty acid enol esters. [1] This study was followed by a report on the synthesis of fatty acid enol es- ters from substituted acetaldehydes and long-chain acid chlorides. [2] However, the enol esters were obtained as 1:1 mixtures of cis and trans products. Additions of carboxylic acids to alkynes afford enol es- ters. The first report on the addition of a carboxylic acid to an alkyne using Ru 3 (CO) 12 as catalyst was by Rotem and Shvo. [3] This was followed by a series of reports on ruth- enium-catalyzed addition of carboxylic acid to alkynes. [4,5] Addition of carboxylic acids to alkynes affords three pos- sible isomers and most of the reported reactions afford more than one isomer. Compounds of the type RuCl x (p- cymene)(triazol-5-ylidene) have been found to be effective catalysts for the addition of carboxylic acids to alkynes. [6] However, the regio- and stereoselectivity were found to be very poor. [6] Enol formation catalyzed by a cationic vinyl- idene ruthenium complex [7] has also been reported and the nature of the product was found to be dependent on the type of acid; again, a mixture of products was obtained. Notably, most of the catalytic systems afford Markovnikov addition products. Ruthenium-catalyzed addition reactions of carboxylic acids have been studied extensively by Dixneuf and co-workers [8,5c,5e] and by Mitsudo and co- workers, [5a,5d] and catalytic systems for anti-Markovnikov addition as well as Markovnikov addition products have been developed. [8] For anti-Markovnikov addition, the cata- [a] Department of Chemistry, Indian Institute of Technology, Kharagpur 721302, India E-mail: mxb@iitkgp.ac.in http://www.chemistry.iitkgp.ac.in/~mxb/ Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/ejoc.201501046. Eur. J. Org. Chem. 0000, 0–0 © 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 1 for the synthesis of enol esters of long-chain acids from reac- tion of alkynes with long-chain fatty acids. lysts used were synthesized from sensitive organometallic compounds such as bis(cyclootadienyl)ruthenium [5a,5b] or bis(2-methylpropenyl)(cylooctadienyl)ruthenium. [8] Re- cently, Goossen et al. reported the anti-Markovnikov ad- dition of carboxylic acids to alkynes using [(p-cumene)- RuCl 2 ] 2 and phosphenes such as PPh 3 , P(Fur) 3 , or P(p- ClC 6 H 4 ) 3 in the presence of organic bases such as pyridine or (4-dimethylamino)pyridine. [4b] We have been interested in the synthesis of simple catalytically active ruthenium(II) cationic compounds containing phosphine ligands and la- bile N-donor ligands, which can easily afford 16-electron species in solution. Recently, we have reported the synthesis, structure, and catalytic properties of the cationic complex [(PPh 3 ) 2 Ru- (CH 3 CN) 3 Cl][BPh 4 ]. [9] The cationic complex was found to be an active catalyst for condensation of carboxylic acids and alkynes in the presence of a catalytic amount of BF 3 ·Et 2 O. [9d] The major product was found to be the Mar- kovnikov addition product. In another report, we described Z-selective anti-Markovnikov addition of alkynes to carb- oxylic acids catalyzed by trans-[Ru(dppe) 2 (CH 3 CN)Cl]- [BPh 4 ], [10] and we have recently described the synthesis and structure of [Ru(dppp) 2 (CH 3 CN)Cl][BPh 4 ] {dppp = diphenylphosphinopropane}, which can catalyze oxidative coupling of terminal alkynes in the presence of a catalytic amount of Ag(NO 3 ). [11] In a preliminary communication, we have recently reported the synthesis and structure of [Ru(dppe)(PPh 3 )(CH 3 CN) 2 Cl][BPh 4 ] {dppe = diphenyl- phosphinoethane} and shown that this can catalyze the ad- dition of terminal alkynes to azoles in a highly regiospecific as well as stereoselective manner to give the E-addition products primarily. [12] In a continuation of our studies, we have shown that [Ru(dppp) 2 (CH 3 CN)Cl][BPh 4 ] can catalyze the addition of alkynes to azoles to give cis-N-vinyl azoles selectively. [13] Thus, we anticipated that [Ru(dppp) 2 - (CH 3 CN)Cl][BPh 4 ](1) could be used as a catalyst for the selective addition of long-chain fatty acids to alkynes. Herein, we report the addition of fatty acids to alkynes cat- alyzed by 1 and describe the selectivity of this reaction.