A practical procedure of propargylation of aldehydes

Palladium-Catalyzed One-Pot Conversion of Aldehydes and Ketones into 4-Substituted Homopropargyl Alcohols and 5-En-3-yn-1-ols

“…Thus, 2,3dibromopropene (16) [or 2,3-dichloropropene (15)] was treated with tert-BuLi, at −78 °C, to promote metal−halogen exchange and generate 2-bromo-3-lithiopropene (17) (or 3bromo-2-lithiopropene) that could undergo 1,2-elimination to generate allene (6), the treatment of which with n-BuLi was expected to produce 1,3-dilithiopropyne (5) as in method A (Scheme 2). The efficiency of this procedure was indirectly corroborated by reacting intermediate 5 with benzophenone (10) to obtain the corresponding homopropargyl alcohol 14 (Scheme 4)…”

“…This protocol was performed under different conditions, all of which produced alcohol 14 in very poor yields (Table 2). In all cases, reduction of benzophenone (10) produced benzhydrol (21) as a major byproduct (Table 2). An additional common byproduct was 1,1-diphenylpentan-1-ol (22) obtained from the addition of remnant n-BuLi to benzophenone (10).…”

“…In all cases, reduction of benzophenone (10) produced benzhydrol (21) as a major byproduct (Table 2). An additional common byproduct was 1,1-diphenylpentan-1-ol (22) obtained from the addition of remnant n-BuLi to benzophenone (10). The presence of the latter compound ( 22) was an indication of the incomplete metalation of allene (6) with n-BuLi or the incomplete metal−halogen exchange of 16 (or 15) with t-BuLi, which would result in a low yield of allene (6) (Scheme 4).…”

“…Propargylation, a three-carbon homologation, is a very useful chemical transformation often employed in isoprenoid-related syntheses . However, it is frequently difficult to accomplish cleanly, and mixtures of allenic and acetylenic products are generally obtained . An indirect procedure employing 3-lithio-1-trimethylsilylpropyne initially produces the trimethylsilyl-protected acetylene, from which the required homologated alkyne is liberated by reaction with ethanolic silver nitrate followed by sodium cyanide …”

“…9 However, it is frequently difficult to accomplish cleanly, and mixtures of allenic and acetylenic products are generally obtained. 10 An indirect procedure employing 3-lithio-1-trimethylsilylpropyne initially produces the trimethylsilylprotected acetylene, from which the required homologated alkyne is liberated by reaction with ethanolic silver nitrate followed by sodium cyanide. 11 We previously reported 12 the preparation of the operational equivalent of the propargyl dianion (5) from treatment of allene (6) with 2 equiv of n-BuLi (Scheme 2).…”