Mechanistic Understanding of the Pd(0)-Catalyzed Coupling Cyclization of 1,2-Allenyl Ketones with Aryl Halides: A Computational Study

Abstract

The Pd­(0)-catalyzed coupling cyclization of 1,2-allenyl ketones with aryl halides to construct multisubstituted furan derivatives has been developed. Nevertheless, the detailed mechanism of this reaction, proceeding via either the Pd­(II)-carbenoid or the π-allyl-Pd­(II) intermediate, still remains debatable. Herein, computational studies were performed to provide mechanistic insights into the reactions, and substituent-dependent mechanistic pathways were revealed. Computational results suggest that the substituents, R1–R3 attached to 1,2-allenyl ketones and R4 attached to the aryl moiety of aryl halides, could play significant roles in the variation of the mechanistic pathway. It would be favorable to form the Pd­(II)-carbenoid intermediate when R1 is an aryl/alkyl group or steric hindrance is present between R2 and R3. For the substrate of aryl halide, the aryl moiety bearing electron-donating group (R4) at the para position is more ready to undergo migratory insertion to form the π-allyl-Pd­(II) intermediate than that with electron-withdrawing group. The factors responsible for the formation of both Pd­(II)-carbenoid and π-allyl-Pd­(II) intermediates are discussed.

DFT computational insight into Pd(0)-catalyzed oxidative cross-coupling of 1,2-allenyl ketones and aryl boronic acids: Pd(ii)-carbenoid intermediate versus π-allyl-Pd(ii) intermediate

“…The above results indicate that for the substituted 1,2-allenyl ketone, the π-allyl-Pd( ii ) intermediate mechanism with an energy barrier of 27.7 kcal mol −1 may mainly contribute to the formation of the product and the Pd( ii )-carbenoid intermediate mechanism also makes partial contributions. This situation is different from the reactions of the substituted 1,2-allenyl ketones with aryl halides reported recently by Bao et al , 28 who showed that the Pd( ii )-carbenoid intermediate mechanism is beneficial when the aryl reagent is aryl iodide rather than the present aryl boronic acid.…”

“…To account for these intra-and intermolecular crosscoupling reactions, the previous reports have proposed two different mechanistic pathways, which can be referred to as the metal-carbene intermediate mechanism [18][19][20] and the π-allyl-metal intermediate mechanism. 26,27 Bao et al 28 have reported an elegant DFT-based computational study on the cross-coupling reaction of 1,2-allenyl ketones with iodobenzene, one of the most commonly used aryl halides. It is found that the viable mechanistic pathway depends on the substituents on either 1,2-allenyl ketones or iodobenzene.…”

DFT calculations in solution systems: solvation energy, dispersion energy and entropy

“…Sakaki et al employed this method to calculate the free-energy profiles of a series of transition metal catalytic reactions, e.g., the migratory insertion reactions CO 2 , 185,186 borylation, 187,188 [2 + 2] and [4+2] oxidative cyclization reactions, 189,190 and oxidative addition/reductive elimination reactions. [191][192][193][194][195] In addition, Guan,196,197 Bao, [198][199][200] Huang, 201 and Lei 202 applied this model to investigate the reaEction mechanisms and free-energy profiles of catalytic reactions.…”

Highlighting the Rich Chemistry of the Allenone Moiety

“…On the other hand, electron-donating aryl halides favour the π-allyl reaction intermediates 164, producing same intermediates 165 after oxycyclization (Scheme 32b). [110] A related palladium carbene intermediate 169 has been also proposed to explain the cross-coupling reaction of allenones 2 and boronic acids 167 to synthesize 3-substituted furans 168 (Scheme 33a). [111] Both aryl and allyl boronic acids have provided good results, and allenones showing a wide range of substitution pattern have been effective for this transformation, building highly substituted furans with good yields (Scheme 33a).…”

“…Allenones 2 exhibiting alkyl or aryl substituents at the terminal allenic position, or showing steric hindrance in R 2 or R 3 positions are more likely to evolve through a palladium carbenoid intermediate 164 , which generates the observed furans after migratory insertion building dihydrofurans 165 and eventual β‐elimination. On the other hand, electron‐donating aryl halides favour the π‐allyl reaction intermediates 164 , producing same intermediates 165 after oxycyclization (Scheme 32b) [110] …”