A Facile Route to Bridgehead Disubstituted Bicyclo[1.1.1]pentanes Involving Palladium-Catalyzed Cross-Coupling Reactions

Abstract

3‐Alkylbicyclo[1.1.1]pent‐1‐yl Grignard reagents have been coupled with bromoarenes in the presence of catalytic amounts (0.8–2.0 mol.%) of PdCl2(dppf) in diethyl ether containing 1,4‐dioxane as a co‐solvent at room temperature. The yields of the coupling step range from 73% to 98%. By using di‐ or tribromoarenes, coupling products of types 10 and 11 have been obtained. The X‐ray structures of four model compounds (4a, 4d, 4j, 4n) have been determined, each of which shows a short, nonbonded C1–C3 distance in the bicyclo[1.1.1]pentyl subunit of about 1.89 Å.

Difluoro-Substituted Bicyclo[1.1.1]pentanes for Medicinal Chemistry: Design, Synthesis, and Characterization

“…We next checked whether incorporation of fluorine atoms would have an effect on the geometry of the bicyclo[1.1.1]­pentane skeleton. Fortunately, there are two related nonfluorinated compounds 40 and 41 reported in the literature with known crystallography data . Therefore, we compared geometric parameters of all three molecules 17 , 40 , and 41 (Table ).…”

Nickel-Catalyzed Decarboxylative Cross-Coupling of Bicyclo[1.1.1]pentyl Radicals Enabled by Electron Donor–Acceptor Complex Photoactivation

“…Although considerable advancements have been made in the synthesis of BCP-containing targets, − the methods available to forge BCP–aryl products via direct cross-coupling are somewhat limited. Szeimies and co-workers, de Meijere and co-workers, and Knochel and co-workers have reported Kumada- and Negishi-type couplings between aryl halides and the corresponding BCP organometallic reagents (Figure A). Additionally, Kanazawa, Uchiyama, and co-workers reported a Suzuki-type coupling using 1,3-difunctional silyl BCP boronates.…”

Direct Diazoarylation of [1.1.1]Propellane with Arenediazonium Salts: A Modular Assembly of Arylated Diazo Bicyclo[1.1.1]pentanes

“…9 Aggarwal reported a similar strategy with arylmagnesium halides and organoboronic esters under a transition-metal-free condition. 10 The groups of Szeimies, 11 de Meijere, 12 and Knochel 13 harnessed the addition of alkyl organometallic reagents to facilitate the ring opening of [1.1.1]propellane, generating BCP Grignard or zinc nucleophiles. These nucleophiles were subsequently subjected to cross-coupling with aryl halides under palladium or nickel catalysis.…”