An alkyne hydroacylation route to highly substituted furans.

transforming relatively complex starting materials into substituted heterocycles, and for the functionalization of existing heterocycles, there is less precedent for methodology which involves the direct, regiodefined synthesis of highly substituted heterocycles from simple starting materials. As such, new methods for the synthesis of substituted heterocycles (or their precursors) are potentially of significant value. This is particularly true if such methods do not suffer from the same drawbacks as the traditional syntheses of 1,4-dicarbonyl compounds, the classic substrates for the preparation of furans, thiophenes, and pyrroles; these syntheses are often either stepor atom-inefficient. The recent advances achieved in intermolecular alkene and alkyne hydroacylation chemistry means that these transformations are now ideal methods to exploit for the synthesis of heterocyclic molecules, because they employ simple substrates and commercially available catalyst systems, and generate no by-products because of their 100% atom-economy. In addition, a broad range of aldehydes can now be employed, and particularly in the case of alkyne hydroacylation, significant substitution of the unsaturated component can be tolerated, thus allowing for the regioselective production of highly substituted complex molecules in one catalytic intermolecular carbon–carbon bond forming step. Herein, we demonstrate the utility of intermolecular alkyne hydroacylation in the efficient synthesis of diand trisubstituted furans and related heterocycles. g-Hydroxy-a,b-enones are known to undergo acid-catalyzed dehydrative cyclization to form furans, and this transformation has been exploited by several research groups, most notably in the recent work from Donohoe et al. The intermolecular hydroacylation of an aldehyde with readily available propargylic alcohols would permit the synthesis of g-hydroxy-a,b-enones with 100% atom efficiency; coupling this carbon–carbon bond formation with an acid-catalyzed dehydrative cyclization would allow for the regioselective synthesis of dior trisubstituted furans. The associated disconnection is novel for this type of heterocycle (Scheme 2). Our initial investigations to realize the above route to furans focused on the combination of propargyl alcohol 1a