Generation of Medium-Ring Cycloalkynes by Ring Expansion of Vinylogous Acyl Triflates

Abstract

Reductive cyclization of aryl and vinyl iodides tethered to vinylogous acyl triflates (VATs) induces a ring-expanding fragmentation to provide cyclic alkynyl ketones, including strained nine-membered cycloalkynes, in fair to excellent yield. The tandem cyclization/C-C bond-cleavage is initiated under carefully optimized conditions by halogen-metal exchange in the presence of carbonyl and vinyl triflate functionality. A modified protocol for alkylation of 1,3-cyclohexanedione is described for preparing the relevant VAT substrates.

Toward an integrated route to the vernonia allenes and related sesquiterpenoids

“…This transformation appears well-suited for access to the vernonia targets and related compounds [15]. The method relies on suitably functionalized vinyl triflates [39–41]. In general, C–C fragmentation reactions appear to be sensitive to the precise structure of the cyclic system involved, and small, apparently minor, structural changes may severely retard the reaction [38].…”

9‐Membered Carbocycles: Strategies and Tactics for their Synthesis

“…In this domino reaction, samarium(III) alkoxide 23 was formed by a samarium diioide‐mediated intramolecular cyclization of δ‐iodoketone 22 , which then fragmented to afford cyclononene 24 (Scheme a). In a conceptually related approach, the Dudley group accessed highly strained cycloalkynes of medium ring size . The first step was an iodine‐lithium exchange of a vinyl or phenyl iodide 25 with n‐ butyllithium, followed by an intramolecular 1,2‐addition of the generated organolithium species to the ketone (Scheme b).…”

“…In ac onceptually related approach, the Dudley group accessed highly strained cycloalkynes of medium ring size. [23] The first step was an iodine-lithium exchange of av inyl or phenyli odide 25 with n-butyllithium, followed by an intramolecular 1,2-addition of the generated organolithium species to the ketone (Scheme7b). An ensuing alkynogenic fragmentation of the resultant lithium alkoxide 26 afforded the cycloalkynes 27.T he formation of these strained products was likely driven by the release of at riflate anion.…”

6.19 Fragmentation Reactions

“…Reese later revisited the Eschenmoser-Tanabe method for the synthesis of medium-ring cycloalkynes (equation 46). 63 Dudley 64 and Brewer 65 have likewise developed ring-expansion analogs of their alkynogenic fragmentation processes (equations 47 and 48, respectively). Kuwajima generated both cyclic alkynes and cyclic allenes by thermal fragmentation of regioisomeric enol triflates 29 and 30 (equations 49 and 50).…”