Cycloisomerization of Hydroxyalkynes

The formation of reactive intermediates provides possible opportunities for new reaction design. An attractive highly reactive intermediate, carbenes, which demonstrate numerous useful synthetic pathways, most notably by addition to alkenes and alkynes and also insertion into X-H bonds, where X is both carbon and heteroatoms, suffers from problems associated with their accessibility. Undoubtedly, the most useful class of precursor is the diazo compounds, whose safety problems restrict their use. For the specific case of vinylidenes, an attractive possibility is a terminal alkyne which is isomeric with a vinylidene. Although the thermolysis appears to effect this transformation (Equation 1.1, path a), the extraordinarily high temperatures required make the prospect of a transition metal-catalyzed version (Equation 1.1, path b) attractive. The early studies of Werner [6] using Rh and Bruce and co-workers [7] using Ru proved the facility with which such species would form however, the studies focused on the formation and isolation of the vinylidene-metal complexes and their stoichiometric reactions. 

While the presence of propargylic hydroxy groups has proven problematic (see below), the presence of a propargylic N-tosylamido group is tolerated (Equation 1.3). 

Interestingly, the presence of a bis-homopropargylic secondary amide does not lead to insertion into the N-H (as happens with a tungsten catalyst [8c]) competing with formation of the dihydropyran as shown in Equation 1.4 [10]. This reaction extends to the insertion into a phenolic OH to form benzofurans (Equation 1.5). In this case, the presence of an amine such as n-butylamine or pyridine appears to be required [11]. It should be noted that insertion into the benzylic OH to form the pyran system does not compete. 

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