Synthesis of Highly Functionalized Triarylbismuthines by Functional Group Manipulation and Use in Palladium- and Copper-Catalyzed Arylation Reactions

Abstract

Organobismuthines are an attractive class of organometallic reagents that can be accessed from inexpensive and nontoxic bismuth salts. Triarylbismuthines are particularly interesting due to their air and moisture stability and high functional group tolerance. We report herein a detailed study on the preparation of highly functionalized triarylbismuth reagents by triple functional group manipulation and their use in palladium- and copper-catalyzed C-, N-, and O-arylation reactions.

Synthesis of Highly Functionalized Diaryl Ketones by Palladium‐Catalyzed Carbonylative Cross‐Coupling Reaction Between Triarylbismuthines and Aryl(Heteroaryl) Iodides

“…To demonstrate the triarylbismuth scope and evaluate the tolerance to substitution and functionalities, we then performed the carbonylative cross‐coupling reaction on methyl 4‐iodo benzoate 4 a using various triarylbismuthines 2 (Table ). Triarylbismuthines were easily prepared from the corresponding organomagnesium reagents using methods that we previously published . As expected, substitution at the para and meta position was well tolerated (entry 1 and 2).…”

“…We began our investigation by attempting the carbonylative cross‐coupling reaction between tris( para ‐tolyl)bismuthine 2 a and methyl 4‐iodobenzoate 4 a using conditions that we previously reported for the cross‐coupling of triarylbismuthines with aryl halides and triflates (Table ) . To that end, using 0.4 equivalents of tris( para ‐tolyl)bismuthine 2 a , 5 mol% of tetrakis(triphenylphosphine)palladium(0), 2.0 equivalents of lithium chloride, 2.0 equivalents of rubidium carbonate in DMF under 1 atmosphere of carbon monoxide at 80 °C for 3 hours, the desired diaryl ketone 5 a was obtained in 73 % yield along with 18 % of the corresponding biaryl side product 6 a (entry 1).…”

“…These copper and palladium‐catalyzed reactions operate under mild conditions, show high functional group compatibility and allow the installation of alkyl and aryl groups on medicinally relevant scaffolds. We recently reported a procedure for the cross‐coupling reaction of functionalized triarylbismuthines 2 with aryl bromides, iodides and triflates 1 and showed that the use of LiCl as an additive and rubidium carbonate as a base leads to higher yields of the desired cross‐coupling product (Scheme A) . In light of our interest in palladium‐catalyzed cross‐coupling reactions involving organobismuth reagents, we sought to develop a procedure for the carbonylative version of that reaction (Scheme C).…”

Evaluation of dispersion type metal···π arene interaction in arylbismuth compounds – an experimental and theoretical study

“…6). While our work was in progress, Gagnon and co-workers reported the crystal structure of 3 , which exhibits very similar lattice parameters [64]. However, the packing structure has not been discussed in detail and thus its description is given here.…”

Copper‐Promoted O‐Arylation of the Phenol Side Chain of Tyrosine Using Triarylbismuthines

“…In 2014, we disclosed a highly efficient protocol for the O‐arylation of phenols using triarylbismuth reagents and hypothesized that the reaction proceeds through a copper(III) species where the metal center is simultaneously bound to the phenoxide and the aryl group (Scheme d ) . In contrast to Barton's O‐phenylation procedure, this reaction operates directly from triarylbismuthines, a class of reagents which can be easily prepared by the addition of Grignard species to bismuth trichloride and where the functional groups can be modified directly on the bismuth species …”