Efficient Trapping of 1,2‐Cyclohexadienes with 1,3‐Dipoles

Abstract

1,2-Cyclohexadienes are transient intermediates that undergo rapid dimerization and intermolecular trapping with activated olefins and heteroatomic nucleophiles. Fluoride-mediated desilylative elimination of readily accessible 6-silylcyclohexene-1-triflates allows the mild, chemoselective, and functional-group tolerant generation of cyclic allene intermediates, which undergo efficient trapping reactions with stable 1,3-dipoles. The reactions proceed with high levels of both regio- and diastereoselectivity. The reaction of cyclic allenes with azides is accompanied by the facile loss of dinitrogen, resulting in the formation of tetrahydroindoles or polycylic aziridines depending on the azide employed.

Diels–Alder cycloadditions of strained azacyclic allenes

“…When cyclic nitrones 49 and 51 were utilized, tri- and tetracyclic products 50 and 52 were obtained, respectively (entries 3 and 4). Additionally, trapping of the allene intermediate with azomethine imines 19 53 and 55 gave the corresponding pyrazolidine products 54 and 56 (entries 5 and 6). Of note, 56 contains three distinct nitrogen-containing heterocycles: a piperidine, a pyrazolidine and a pyridine ring.…”

“…Of note, 56 contains three distinct nitrogen-containing heterocycles: a piperidine, a pyrazolidine and a pyridine ring. Nitrile oxide 19 57 was also employed as a trapping agent and gave rise to isoxazoline 58 in 81% yield. These reactions (entries 1–7) represent the first [3+ 2] cycloadditions of heterocyclic allenes.…”

“…Over the subsequent five decades, the field of cyclic allene chemistry has been largely driven by theoretical studies of allene structure and chirality 6–11 , in addition to studies of cycloaddition mechanisms 12 . With regard to experiments, various methods to generate cyclic allenes have been developed 11,13,14 , and subsequently used in cycloaddition methodologies of 1,2-cyclohexadienes 15–19 . Taken together, these studies suggest the potential synthetic utility of cyclic allene intermediates.…”

Understanding the 1,3‐Dipolar Cycloadditions of Allenes

“…Lofstrand et al. synthesized and subsequently trapped 1,2‐cyclohexadiene, through a 1,3‐dipolar cycloaddition under mild conditions (Scheme b) . Houk and Garg recently carried out a systematic study on the synthesis of azacyclic allenes as well as their reactivity towards cycloadditions (Scheme c) .…”

Cycloadditions of Oxacyclic Allenes and a Catalytic Asymmetric Entryway to Enantioenriched Cyclic Allenes

“…[10] However,o nly recently has 2 seen synthetic use in cycloadditions. [11] This is largely due to the fact that it can be accessed under mild fluoride-mediated conditions from silyl triflate 3. [12,13] One exciting opportunity in the field of strained cyclic intermediates is the ability to access heterocyclic allenes.…”