Intramolecular trans‐Dicarbofunctionalization of Alkynes by a Formal anti‐Carbopalladation/Stille Cascade

Abstract

An intramolecular Pd-catalyzed trans-dicarbofunctionalization of internal alkynes using aryl bromides and aryl stannanes is presented. Tetrasubstituted double bonds embedded in an oligocyclic ring system are obtained in a regio- and diastereoselective fashion. The transformation features a broad substrate scope and functional-group tolerance.

Direct C–H Alpha Arylation of Enones with ArI(O2CR)2 Reagents

“…18 With regards to the aryl moiety, alkyl groups at the ortho-, meta-, and para-position relative to the iodide were well tolerated giving a-(2-iodoaryl)enones 15-19 in good to excellent yields. Both an electron-donating methoxy (20) and electron-withdrawing ester (21) could be incorporated, however more strongly electron-withdrawing groups such as -NO2 (22) or -CN (23) led to significant drops in yield. Iterative halogen substitution at the o-, m-, and p-positions was then examined using chlorine, bromine, and fluorine as these products would provide several orthogonal functional handles and be challenging to synthesize using traditional metal catalyzed cross couplings.…”

“…Turning to nitrogen-containing scaffolds, conversion to the nitro derivative 43 was of particular interest as this functionality has been utilized in the synthesis of indole natural products and related scaffolds. 3a-3j Initial screening found that typical nitration procedures led to degradation of the enone moiety, 20 however conversion of 12 to the diaryliodonium salt (not shown, see Supporting Information) followed by treatment with KNO2 gave 43 in good yields. 22 Mechanistically, the results are consistent with our initial proposal of an "umpoled" enolonium species which undergoes nucleophilic arylation in the C-C bond forming step (see Scheme 3A), analogous to other recent…”

Direct C–H Alpha Arylation of Enones with ArI(O2CR)2 Reagents

“…18 With regards to the aryl moiety, alkyl groups at the ortho-, meta-, and para-position relative to the iodide were well tolerated giving a-(2-iodoaryl)enones 15-19 in good to excellent yields. Both an electron-donating methoxy (20) and electron-withdrawing ester (21) could be incorporated, however more strongly electron-withdrawing groups such as -NO2 ( 22) or -CN ( 23) led to significant drops in yield. Iterative halogen substitution at the o-, m-, and p-positions was then examined using chlorine, bromine, and fluorine as these products would provide several orthogonal functional handles and be challenging to synthesize using traditional metal catalyzed cross couplings.…”

“…Turning to nitrogen-containing scaffolds, conversion to the nitro derivative 43 was of particular interest as this functionality has been utilized in the synthesis of indole natural products and related scaffolds. 3a-3j Initial screening found that typical nitration procedures led to degradation of the enone moiety, 20 however conversion of 12 to the diaryliodonium salt (not shown, see Supporting Information) followed by treatment with KNO2 gave 43 in good yields. 22 Mechanistically, the results are consistent with our initial proposal of an "umpoled" enolonium species which undergoes nucleophilic arylation in the C-C bond forming step (see Scheme 3A), analogous to other recent reports of reductive [3,3] iodonium-Claisen reactions.…”

Intramolecular Pd‐Catalyzed Formal anti‐Carboalkoxylation of Alkynes: Access to Tetrasubstituted Enol Ethers

“…[13] It is important to use as ubstituent at the triple bond that does not allow b-hydride elimination, since this pathway is fastert han the internal isomerization.I na ll previous reports, the reactive anti-configured Pd species was intercepted by nucleophilic carbon moieties such as olefins, [15] or stannylateda renes. [16] However,t he use of nucleophilic heteroatomic speciess uch as hydroxy units [17] would allow af acile generationo ft etrasubstituted enol ethers startingf rom internal alkynes. Couplingp artners wouldb eaC ÀBr bond for the first side of the triple bond and aliphatic alcohols or phenolsf or the opposite side, leading to HBr as the only side product.…”