Palladium-mediated CO2 extrusion followed by insertion of ketenes: translating mechanistic studies to develop a one-pot method for the synthesis of ketones

Abstract

Multistage mass spectrometry (MSn) experiments were used to explore extrusion–insertion (ExIn) reactions of the palladium complex [(phen)Pd(O2CPh)]+ (phen, 1,10-phenanthroline). Under collision-induced dissociation (CID) conditions, the organopalladium cation [(phen)Pd(Ph)]+ was formed via decarboxylation and was found to react with phenylmethylketene to yield the enolate [(phen)Pd(CPhMeC(O)Ph)]+ via an insertion reaction. A further stage of CID revealed that the enolate fragments via loss of styrene to form the acyl complex [(phen)Pd(C(O)Ph)]+. Formation of both the coordinated enolate and acyl anions is supported by density functional theory (DFT) calculations. Attempts to develop a palladium-mediated one-pot synthesis of ketones from 2,6-dimethoxybenzoic acid as the key substrate and the ketene substrates R1R2C═C═O (R1 = Ph, R2 = Me; R1 = R2 = Ph) proved challenging owing to low yields and side product formation.

Bringing a Mechanistic Lens to the Development of New Transfer Hydroarylation Isodesmic Reactions for the Synthesis of Amides, Thioamides, Amidines, Alkenes and Ketones from Carboxylic Acids via Extrusion and Insertion Elementary Steps

“…We have used a mechanisms-based approach to study a total of five different ExIn reactions for the synthesis of thioamides, [87] amidines, [115] amides, [137] alkenes [138] and ketones (Scheme 5a). [139] The desired ExIn catalytic process, eq. 2, (cycle A of Scheme 5b) is potentially in competition with the unwanted protodecarboxylation side reaction, eq.…”

“…À 46.1 (À 62.1) iPrNCNiPr (b), [115] N 0.7 (À 16.6) À 35.1 (À 52.7) PhNCO (b), [137] N À 4.1 (À 18.2) [138] PhCH to give cis-29 À 14.6 (À 30.2) [138] PhCH to give trans-29 [138] CH 2 to give cis-29 À 13.5 (À 27.9) [138] CH 2 to give trans-29 À 15.0 (À 29.7) À 63.4 (À 78.4) PhCMeCO (b), [139] PhCMe À 12.2 (À 27.9) Table 3. DFT calculated energetics (ΔG(ΔH)) in kcal mol À 1 of condensed-phase insertion of (hetero)cumulenes (step 2a of cycle A) versus protodepalladation of arylpalladium complex (step 2b of cycle B) -see Figure 6 for numbering of species.…”