The accessible scope of palladium-catalyzed diazo cross-coupling reactions has been expanded to include aryl chlorides by controlled diazo slow addition. The success of this strategy is based on manipulating speciation within the catalytic cycle through starvation of the diazo reagent to make the Pd­(II) oxidative intermediate the resting state. The strategy is also applicable to cross-coupling reactions with aryl bromides and, in combination with safe, on-demand flow generation of nonstabilized diazo reagents, has been used to greatly expand the scope of applicable diazo compounds for this chemistry as well. Lastly, DFT calculations have provided insight into the mechanism and support for the proposed explanation for success of the slow addition strategy.

The design of novel xylo-like nucleoside analogues bearing a C3' all-carbon quaternary center and a C2'hydroxy substituent is described. Synthesis of this scaffold makes use of highly diastereoselective transformations on acyclic substrates. Central to the approach is formation of a 2,4-syn cyanohydrin from cyanide addition onto an aldehyde through a proposed seven-membered ring chelate using a bidentate Lewis acid. In addition, a highly diastereoselective Mukaiyama aldol reaction, an intramolecular radical atom cyclization, and thioaminal formation are used to generate this novel molecule. A series of related nucleoside analogues are being tested as antiviral and anticancer agents.

A range of methods has been investigated recently for the arylation of weakly acidic C(sp 3 )−H bonds, primarily exploiting directed metalation with a transition metal catalyst or radical formation via hydrogen atom transfer. In this work, a classical basemediated approach is taken, exploiting the ability of organometallic superbases to metalate very weakly acidic (pK a > 40) C−H bonds. Conditions are developed with either n-BuLi/diamine or n-BuLi/ KOtBu superbases to enable metalation to occur with high selectivity. Organolithium nucleophiles can be directly used in cross-coupling, or organozincs can be formed to enable reactions with functional groupdense organohalides.