B. Morandi, E. Carreira
Mar 23, 2012
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Influential Citations
150
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Quality indicators
Journal
Science
Abstract
Tamer Triangulations Diazomethane is a broadly useful precursor to carbene (CH2), which, in turn, reacts with olefins to form triangular carbon cycles known as cyclopropanes. These small rings are of fundamental interest for their strained bonds and turn up periodically in natural products, as well as in pharmaceutical and agrochemical research. Unfortunately, the flip side of diazomethane's facile reactivity is its dangerous tendency to explode—a hazard exacerbated by the need to isolate the compound after its preparation in highly basic water before it can be reacted with hydrophobic olefins. Morandi and Carreira (p. 1471) now show that an iron cyclopropanation catalyst can circumvent the need for the isolation step, inducing reaction of the hazardous compound in a biphasic aqueous/organic medium immediately after its generation. A robust catalyst circumvents the need to isolate a common reagent that is toxic and explosive. Diazomethane is a common and versatile reagent in organic synthesis whose broader use is generally impeded by its explosiveness and toxicity. Here we report that a simple iron porphyrin complex catalyzes the cyclopropanation of styrenes, enynes, and dienes under the demanding conditions [aqueous 6 molar potassium hydroxide (KOH) solution, open to air] necessary for the in situ generation of diazomethane from a water-soluble diazald derivative. A biphasic reaction medium arising from the immiscibility of the olefin substrates with water appears essential to the overall efficiency of the process. The work we describe highlights an approach to catalysis with untoward reactive intermediates, in which the conditions for their generation under operationally safe regimes dictate catalyst selection.