Intramolecular Cyclopropanation and C–H Insertion Reactions with Metal Carbenoids Generated from Cyclopropenes

Activation of unsaturated carbon–carbon bonds by means of transition metal catalysts is an exceptionally active research field in organic synthesis. In this context, due to their high ring strain, cyclopropenes constitute an interesting class of substrates that displays a versatile reactivity in the presence of transition metal catalysts. Metal complexes of vinyl carbenes are involved as key intermediates in a wide variety of transition metal-catalyzed ring-opening reactions of cyclopropenes. Most of the reported transformations rely on intermolecular or intramolecular addition of nucleophiles to these latter reactive species. This Account focuses specifically on the reactivity of carbenoids resulting from the ring-opening of cyclopropenes in cyclopropanation and C–H insertion reactions, which are arguably two of the most representative transformations of metal complexes of carbenes. Compared with the more conventional α-diazo carbonyl compounds, the use of cyclopropenes as precursors of metal carbenoids in intramolecular cyclopropanation or C–H insertion reactions has been largely underexploited. One of the challenges is to devise appropriately substituted and readily available cyclopropenes that would not only undergo regioselective ring-opening under mild conditions but also trigger the subsequent desired transformations with a high level of chemoselectivity and stereoselectivity. These goals were met by considering several substrates derived from the readily available 3,3-dimethylcyclopropenylcarbinols or 3,3-dimethylcyclopropenylcarbinyl amines. In the case of 1,6-cyclopropene-enes, highly efficient and diastereoselective gold­(I)-catalyzed ring-opening/intramolecular cyclopropanations were developed as a route to diversely substituted heterocycles and carbocycles possessing a bicyclo[4.1.0]­heptane framework. The use of rhodium­(II) catalysts enabled us to widen the scope of this transformation for the synthesis of medium-sized heterocyclic scaffolds incorporating an eight-membered ring. The reactivity of rhodium­(II) carbenoids generated from 3,3-dimethylcyclopropenylcarbinols was also investigated in intramolecular C­(sp3)–H insertions. Despite their low electrophilic character, these purely donor rhodium­(II) carbenoids underwent remarkably efficient diastereoselective 1,5- or 1,6-C–H insertions allowing access to a wide variety of substituted cyclopentanols, cyclohexanols, bicycloalkanols, and tetrahydropyrans with high level of diastereoselectiv