Patrick McCarren

The origins of reactivity and regioselectivity in nickel-catalyzed reductive coupling reactions of alkynes and aldehydes were investigated with density functional calculations. The regioselectivities of reactions of simple alkynes are controlled by steric effects, while conjugated enynes and diynes are predicted to have increased reactivity and very high regioselectivities, placing alkenyl or alkynyl groups distal to the forming C-C bond. The reactions of enynes and diynes involve 1,4-attack of the Ni-carbonyl complex on the conjugated enyne or diyne. The consequences of these conclusions on reaction design are discussed.

α-Santonin 1 is a naturally occurring sesquiterpene lactone of significant historical interest. Not only is its solid-state photochemistry the oldest documented for an organic compound, but it is also the first drug to have been formulated in the United States. Not surprisingly, while its photochemical behavior in solution has been relatively well-established, its solid-state photoreactivity has not been thoroughly characterized. In this communication, with a combination of polarizing microscopy, single-crystal X-ray diffraction, spectroscopic methods, chemical trapping, and product analyses, we have confirmed a remarkable sequence of events that includes three consecutive solid-state reactions. The first step is a remarkably phase-selective and site-specific single-crystal-to-single photorearrangement of 1 into the previously postulated cyclopentadienone intermediate 2. The second step is a highly stereoselective Diels−Alder reaction to form a transient topochemical dimer, and the third step is an intramolecular 2π + 2π photodimerization to form the cage dimer 4 as the final product. Cyclopentadienone 2 was characterized in situ by single-crystal X-ray diffraction analysis as well as by electronic and vibrational spectroscopies. The intermediate cyclopentadienone 2 was also trapped as the [4π + 2π] cycloadduct 8 by an interfacial solid−liquid reaction between a photoreacted sample and dimethyl acetylene dicarboxylate (DMAD).