Synthesis of Methylene‐ and Alkylidenecyclopropane Derivatives

Abstract

Since the methylenecyclopropane moiety is found in many biologically active natural substances, the synthesis of methylene-and alkylidenecyclopropanes remains a considerable challenge. In addition, an attractive feature is their surprising stability, accompanied by a high level of strain, conferring on them an otherwise unattainable chemical reactivity. The growing interest in the chemistry of these compounds has in its turn stimulated the development of alternative approaches to their skeleton, aimed at selectively introducing structural and chemical diversification. The three principal methods to synthesize these important compounds are based on the formation of the cyclopropane ring, the use of preformed cyclopropanes, and the use of preformed methyleneand alkylidenecyclopropanes.

Gold(i)-catalyzed cycloisomerization of vinylidenecyclopropane-enes via carbene or non-carbene processes

“… 6 However, to the best of our knowledge, there are barely any reports on one precursor being able to rapidly generate molecular complexity 7 via either carbene or non-carbene pathways in gold catalysis. 8 On the basis of our ongoing investigation on metal-catalyzed transformations of vinylidenecyclopropanes (VDCPs), 9 we envisaged that VDCPs could be excellent candidates for the exploration of new reaction modes in gold catalysis because of their multiple reaction sites. Previously, Toste and co-workers reported novel intramolecular cyclopropanation and allyl-transfer, both through gold carbene intermediates ( Scheme 2 ).…”

Gold‐Catalyzed Intermolecular Anti‐Markovnikov Hydroamination of Alkylidenecyclopropanes

“…Cyclopropyl rings are structural and/or reactive components of a large number of naturally occurring and biologically active molecules including potential therapeutics and are employed as mechanistic probes for use in chemical biology and enzymology. [1] Alkylidenecyclopropanes (ACPs) represent attractive substrates for the synthesis of functionalized cyclopropanes owing to the strain-driven reactivity [2][3][4] and synthetic accessibility [5,6] of ACPs. Indeed, ACPs have been employed widely as building blocks in organic synthesis, [6][7][8] and in this context, transition-metal-catalyzed methods have attracted particular attention.…”

Gold‐Catalyzed Intermolecular Anti‐Markovnikov Hydroamination of Alkylidenecyclopropanes

“…Cyclopropyl rings are structural and/or reactive components of a large number of naturally occurring and biologically active molecules including potential therapeutics and are employed as mechanistic probes for use in chemical biology and enzymology 1. Alkylidenecyclopropanes (ACPs) represent attractive substrates for the synthesis of functionalized cyclopropanes owing to the strain‐driven reactivity2–4 and synthetic accessibility5, 6 of ACPs. Indeed, ACPs have been employed widely as building blocks in organic synthesis,6–8 and in this context, transition‐metal‐catalyzed methods have attracted particular attention 8.…”