The key to this approach is the treatment of aldehydes with benzoyl bromide (BzBr) in the presence of a ZnBr2 catalyst at –10 °C to prepare α-OBz bromide compounds which can be used as stable carbene precursors. It is worth noting that this step of the process can be carried out on the scale of tens of grams using recrystallization to isolate the products. The α-OBz bromide compounds are then reacted with Zn as a reductant and LiCl as an activator at room temperature, followed by FeCl2 as a catalyst to form non-stabilized iron carbenes in solution which can react in one pot with alkenes to prepare the desired cyclopropane products. A wide selection of alkenes is tolerated under these conditions, such as styrenes, dienes, enynes, vinyl halides, enols and enamines. Notably, unactivated alkenes as well as endocyclic alkenes (to prepare bicyclic products) and exocyclic alkenes (to prepare spirocyclic compounds) are also viable reaction partners.
The introduction of additives to the reaction mixture, including alkyl halides, internal alkenes and ketones, reveals that this transformation is tolerant of many functional groups; however, it should be noted that some additives, such as phenols, anilines and thiols, are less well tolerated and interfere with the cyclopropanation reaction. Mechanistic studies suggest that these non-stabilized carbenes likely react through a concerted (2 + 1) pathway, affording diastereoselective retention similar to that found with stabilized diazo reagents.
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