Propargylic alcohols trimerization

In the presence of suitable nickel or cobalt complexes, propargyl alcohol trimerizes to a mixture of l,3,5-ben2enetrimethanol [4464-18-0] and 1,2,4-trimethanol [25147-76-6] hen-zene (28). 

Nickel halide complexes with amines give mixtures of linear polymer and cychc trimers (30). Nickel chelates give up to 40% of linear polymer (31). When heated with ammonia over cadmium calcium phosphate catalysts, propargyl alcohol gives a mixture of pyridines (32). 

The general mechanistic picture presented above applies to a number of synthetically useful systems including the first to be discovered, in which trimerization of acetylene to benzene, and propargyl alcohol to a 1 1 mixture of 1,2,4- and 1,3,5-trisubstituted benzene derivatives was catalyzed by (Ph3P)2Ni(CO)2. Phosphine nickel carbonyls are usually much more highly regioselective for 1,2,4-... 

The strong forward donation-back donation of electrons (i.e., the Chatt model) between alkynes and ruthenium makes such a bond a very good ligand for Ru. Hence it is not surprising that reactions involving ruthenacyclopentadienes as intermediates, notably in the trimerization of alkynes to benzenes, occur readily. Intercepting the ruthenacyclopentadiene prior to its reaction with an additional alkyne, however, is rather rare. A unique juxtaposition of functionality occurs when a propargyl alcohol is the alkyne partner which allows such a diversion as shown in Scheme 1.3. 

Chiral 3-substituted phthalides are an important core structure in a number of biological compounds (85-87). The synthesis of chiral phthalides has been achieved by Witulski and Zimmerman starting from optically pure propargylic alcohols 76 and acids 75 (Scheme 40) (88). The chiral ester-linked diynes 77 were trimerized with acetylene using RhCKPPhsls as the catalyst to afford the optically pure phthalides 78 in good yields. However, the major drawback of this reaction is the low yield in the esterification step. This reaction is also difficult to apply to the synthesis of 3,3-disubstituted phthalides due to the difficulties in the preparation of optically pure tertiary propargylic alcohols. 

---