Recent Advances in Process Chemistry

http://pubs.acs.org/doi/pdf/10.1021/acs.oprd.6b00012

Lots of good stuff in this one, below is one example.

Synthesis of 2,3,6-Trisubstituted Pyridines from Isoxazolinones

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Substituted pyridines are an important class of organic compounds and ubiquitous in the chemistry world. Various methodologies have been developed to construct substituted pyridine derivatives. Recently, René Peters and co-workers developed a regioselective Pd-catalyzed synthesis of 2,3,6-trisubstituted pyridines from isoxazolinones (Peters, R., et al. J. Org. Chem. 2015, 80, 6822). The protocol involves a regioselective Pd(II)-catalyzed 1,4-addition of isoxazolinones to enones, followed by a Pd(0)-catalyzed dihydropyridine formation and oxidation. The formation of the dihydropyridine is hypothesized via a vinylnitrene-Pd complex species formed by oxidative addition of Pd(0) to the N–O bond of the 1,4-adduct followed by a decarboxylation. This two-step sequence allows a rapid and regioselective entry to substituted pyridines starting from readily accessible isoxazolinones. Despite these advantages, the safety issue needs to be addressed during application of this approach toward large-scale production as the second step required a mixture of hydrogen and air.