Palladium Catalyzed Carbonylative Coupling of Alkyl Boron Reagents with Bromodifluoroacetamides

Abstract

A catalytic protocol for the preparation of α,α-difluoro-β-alkyl-β-ketoamides is developed employing a Pd-mediated carbonylative Suzuki coupling between alkylboron reagents and bromodifluoroacetamides with COgen as the CO source. The reaction reveals good functional group tolerance providing a broad selection of α,α-difluoro-β-alkyl-β-ketoamides in moderate to good yields, which represent useful precursors for further synthetic manipulation. Finally, the methodology is amenable to 13C-isotope labeling at the ketone carbon applying 13C-COgen.

Radical Carbonylation under Low CO Pressure: Synthesis of Esters from Activated Alkylamines at Transition Metal‐Free Conditions

“…A variety of Katritzky salts derived from amines were tested firstly and led to the corresponding esters in moderate to excellent yields (Scheme 2, 3-13). Cyclic, chain, and phenyl-containing amine derivatives were well-tolerated in this transformation (3)(4)(5)(6)(7)(8)(9)(10)(11). When the Radical Carbonylation under Low CO Pressure Chin.…”

“…[4] In general, there are two accepted pathways for the radical carbonylative transformations: (1) One is trapping the radical by (noble) metal center to form an organometallic intermediate followed by CO insertion (Scheme 1a, path a). [5] However, this process is usually limited by the slow oxidative addition and/or rapid β-hydride elimination. [6] (2) The other pathway is capture of the CO by radicals to generate acyl radicals directly (Scheme 1a, path b).…”

The Fascinating Chemistry of α‐Haloamides

“…Very recently, Skrydstrup et al have successfully employed alkyl-9-BBN B as suitable partners of both tertiary and secondary bromodifluoroacetamides A in their Pd-mediated carbonylative Suzuki coupling method (Scheme 199). [221] Thus, a variety of α,α-difluoro-β-alkyl-β-ketoamides C were produced in moderate to good yields by using a wide range of boron reagents B. The latter were in turn easily prepared by hydroboration of terminal alkenes with the 9-BBN dimer.…”

Developments in the Chemistry of α‐Carbonyl Alkyl Bromides

“…By using Pd(PPh 3 ) 4 as the catalyst and Xantphos as al igand, as elective carbonylation of alkyl boron reagents with bromodifluoroacetamides has been achieved in moderate to good yields by the Skrydstrup group (Scheme 50). [46] Avariety of amides and esters containing fluoroalkylated chains could be synthesized. Moreover,d ifluoro-substitutedh eterocycles have been successfully applied to the synthesis of other corresponding products.…”