Synthesis of (E)-α-Ethynyl-α,β-unsaturated Esters from Allenyl Acetates Catalyzed by DABCO and Their Application to Sonogashira Cross-Coupling Reactions

Abstract

1 PPTS (0.2) CH2Cl2 6 0 2 AcOH (0.2) DMF 12 0 3 Pyridine (0.2) DMF 0.67 75 4 PPh3 (0.2) DMF 0.5 69 5 DABCO (0.2) DMF 0.5 75 6 DABCO (0.2) THF 4.5 50 7 DABCO (0.2) CH3CN 4.5 70 8 DABCO (0.1) DMF 2.5 81 Because synthesis of α-ethynyl-α,β-unsaturated esters is one of the challenging problems in synthetic organic chemistry, many efficient synthetic methods for the preparation of these compounds have been reported. However, the need for a highly selective synthetic method of (E)-α-ethynyl-α,β-unsaturated esters has been remained. Generally, the selective synthesis of these compounds was accomplished by the transition metalcatalyzed cross-coupling reactions of (Z)-α-halo-α,β-unsaturated esters with terminal alkynes through Sonogashira cross-coupling reaction. Nevertheless, this method is limited because the selective synthetic method of (Z)-α-halo-α,β-unsaturated esters is difficult and isomerization is somewhat occurred during the cross-coupling reactions. Although selective synthesis of (Z)α-halo-α,β-unsaturated esters via CrCl2-mediated olefinations of aldehydes with trihaloacetates was reported, the preparation of (Z)-α-halo-α,β-unsaturated esters through bromination-dehydrobromination, rearrangements, alkoxycarbonylation, deoxygenation of glycidic esters, thermal eliminations, or Wittig/Horner-Emmons/Peterson-type condensations often suffer from poor stereoselectivities, unsatisfactory yields, costly reagents, and/or lengthy procedures. Therefore, we tried to prepare selectively (E)-α-ethynyl-α,β-unsaturated esters from another precursor without the use of (Z)-α-halo-α,β-unsaturated esters. As part of our continuing studies into the utility of allene groups, we report herein the preparation of the selective synthesis of (E)-α-ethynyl-α,β-unsaturated esters from allenyl acetates catalyzed by DABCO and their application to Sonogashira cross-coupling reaction (Scheme 1). First, various allenyl acetates were prepared from the reaction of aldehydes with organoindium in situ generated from ethyl 4-bromobutynoate and indium in the presence of lithium iodide in DMF followed by acetylation (Scheme 2). Next, allenyl acetates were treated with various acids or bases (Table 1). Allenyl acetate (1d) did not react with PPTS and AcOH (entries 1 and 2). Surprisingly, treatment of 1d with pyridine (0.2 equiv) in DMF selectively produced ethyl (E)-α-ethynyl cinnamate (2d) in 75% yield (entry 3). E selectivity was determined by the chemical shift of the vinyl proton in 2d. Vinyl proton in E isomer of 2d appeared at upfield due to the shielding effect from the ester group. Encouraged by this result, triphenylphosphine and DABCO were subsequently examined. Use of triphenylphosphine (0.2 equiv) provided 2d in 69%