The three carbon atoms of allene moieties allow unique transformations and rapid generation of complexity. Not surprisingly, allenes became extremely versatile building blocks in organic synthesis. Transition-metal-catalyzed reactions of these cumulene π-systems have been particularly successful, and many applications in the synthesis of complex products have been reported. This review summarizes the palladium-catalyzed transformation of allenes published during the last decade. Many of the examples presented are impressive multicomponent processes or cascade reactions involving two or more steps leading to molecular complexity in simple one-pot operations. Consequently, several reactions have been developed with the goal of delivering new synthetic routes to natural products.

In this report we describe the synthesis of differentially functionalized pyridine derivatives 3 and the related 3-bromo-substituted pyridines 11. Dissociation of 6H-1,2-oxazine precursors (1a, 1b, 5, 6, or 12) in situ, mediated by boron trifluoride–diethyl ether, generates the azapyrylium intermediates A, which undergo hetero-Diels–Alder reactions with various mono- and disubstituted alkynes 2. In general, these pyridine syntheses proceeded with high efficiencies and were very flexible with respect to all positions in the pyridine cores. For the 3-phenyl-substituted pyridine derivatives 3a–3j and 11a–11f the best results were obtained by a new microwave-assisted protocol, which is clearly superior to the previously used conventional procedure at low temperature in dichloromethane. Furthermore, 3-(trifluoromethyl)- and 3-acryloyl-substituted 6H-1,2-oxazines reacted cleanly under microwave irradiation conditions to furnish the expected pyridine derivatives 3k and 3l in respectable yields. The 3-bromo-substituted pyridines 11 were further functionalized through palladium-catalyzed couplings such as Suzuki or Sonogashira reactions, which led smoothly to tri- or tetrasubstituted pyridine derivatives such as 19–21 and 23. Reductive debromination of 11e afforded the pyridine 17 in excellent yield, whereas oxidation of the pyridinyl thioether 3g with oxone led to the corresponding sulfoxide 24. Our method thus establishes a new and versatile approach to highly substituted pyridine derivatives.