Stereoselective synthesis of hex-2-(E)-en-4-yn-1,6-dioates and E,Z-muconic acid diesters via organo-catalyzed self-coupling of propiolates

Tetrahedron Letters Tetrahedron Letters 46 (2005) 2547–2549 Stereoselective synthesis of hex-2-(E)-en-4-yn-1,6-dioates and E,Z-muconic acid diesters via organo-catalyzed self-coupling of propiolates P. Veeraraghavan Ramachandran,* Michael T. Rudd and M. Venkat Ram Reddy Department of Chemistry, 560 Oval Drive, Purdue University, West Lafayette, IN 47907-2084, USA Received 31 January 2005; revised 14 February 2005; accepted 16 February 2005 Abstract—Alkyl propiolate couples with itself in the presence of catalytic DABCO under very mild conditions to provide a quantitative yield of E-hex-2-en-4-yne dioates. Hydrogenation of these enyne dioates using Lindlar catalyst provides the corresponding E,Z-diene dioate, a common structural motif found in an array of natural products. Ó 2005 Elsevier Ltd. All rights reserved. We had reported that, while attempting a Baylis–Hillman reaction of ethyl acrylate with a-acetylenic ketones, we stumbled upon a novel 1,4-diazabicyclo[2.2.2]octane (DABCO)-catalyzed coupling of acetylenic ketones via a carbon–oxygen bond yielding divinyl ethers.1 This organo-catalysis reaction is feasible only when the terminus of the acetylene is free. We could extend this reaction to include the cross-condensation of terminal and internal acetylenic ketones under carefully controlled conditions (Scheme 1).1 When we undertook to cross couple 4-phenyl-3-butyn-2one with ethyl propiolate, we encountered an instantaneous, quantitative, and stereodefined self-condensation of the ester via a carbon–carbon bond to form diethyl E2-en-4-yn-1,6-dioate (Scheme 2). O Ph N N (10%) 0.5M, CH2Cl2 0° C, rt, 1 h O DABCO (1%) O OEt EtO 0.5 M, CH2Cl2 0° C, 0.2%.3 These diacids are also useful as cross-linking agents for OH-containing materials, such as cellulose, and as intermediates for insecticides.3 Accordingly, several syntheses of muconic acid diesters have been reported.4 A literature search revealed a stoichiometric reaction of methyl propiolate with triethylamine, N-methylpiperidine, or N-methylpyrrolidine to form the enyne dioate in moderate to high yields.5 A patent also disclosed the dimerization of propiolate esters in the presence of 10% of a tertiary amine at temperatures ranging from À10 to 100 °C for several hours.3,6 Numerous amines, including DABCO, pyridine and picoline were reported to be effective. It is surprising that there has been no earlier reference to this patent, although several applications of muconic acid esters have since been reported. Our experiments established that long reaction times and extreme conditions are not necessary for the coupling. This study focused on the limitations of the instantaneous and catalyzed reaction. No influence of solvents was observed. Various amines, aromatic and aliphatic, were tested as organic catalysts. Differing from the claim in the patent, pyridine and picoline were ineffective for catalysis. TMEDA compares well with the efficacy of DABCO. However, DBU failed to catalyze the reaction (Table 1). tion. Decreasing the catalyst further results in an incomplete reaction. We chose 1% catalyst at 0 °C as the standard condition for the reaction with the catalyst being removed at the end of the reaction by filtration through a pad of silica. We prepared a series of aromatic and aliphatic propiolate esters via DCC mediated esterification of propiolic acid, including esters from chiral alcohols. In all of the cases, we experienced no difficulty in forming the enyne diesters (Scheme 3). In fact, the reactions of aromatic esters were highly instantaneous and exothermic and were carried out under controlled conditions at low temperature. The proposed mechanism of the catalytic cycle is as follows (Scheme 4). We converted a representative enyne diester, diethyl 2Een-4-yn-1,6-dioate, to (E,Z)-muconic acid diester (Scheme 5). Hydrogenation using Lindlar catalyst provided the corresponding E,Z-diene dioate. Selective enzymatic hydrolysis of the E,Z-diester and conversion to various other difunctionalized dienes is known.7 This diene has also been applied in Diels–Alder reactions.8 A typical experimental procedure for the preparation of diisopinocampheyl hex-2-(E)-en-4-yn-1,6-dioate and the corresponding E,Z-dienoate is as follows. To a solution Examination of the catalytic turnover revealed that 0.1 mol % of DABCO is sufficient to catalyze the reac- O COOR OR O H Catalyst % Catalyst Solvent Reaction time 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 DABCO DABCO DABCO DABCO DABCO DABCO Et3N TMEDA DBU Pyridine Picoline DABCO DABCO DABCO DABCO 10 10 10 10 10 10 10 10 10 10 10 1 0.1 0.01 0.001 CH2Cl2 Hexane EtOAc CH3CN Toluene THF CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 THF THF