Palladium-Mediated CO₂ Extrusion Followed by Insertion of Allenes: Translating Mechanistic Studies to Develop a One-Pot Method for the Synthesis of Alkenes

Abstract

= H) is reported. This is an isoelectronic variant of CO 2 extrusion−insertion (ExIn) reactions previously developed using heterocumulenes for the synthesis of thioamides (from isothiocyanates, RNCS), amidines (from carbodiimides, RNCNR), and amides (from isocyanates, RNCO). Evidence that the key aryl-palladium intermediate reacts to form a stable allyl-palladium product via insertion of the allene at the C2 position that enables the synthesis of alkenes was provided by a combination of gas-phase multistage mass spectrometry (MS n ) experiments and condensed-phase monitoring using 1 H NMR spectroscopy as well as theoretical computational data. Isolation and X-ray crystallographic analysis of the salt [(phen)Pd(CH 2 CH(Ar)CHPh)] + (CF 3 CO 2 − ) (where Ar = 2,6dimethoxyphenyl) confirmed insertion of the allene at the C2 position and revealed a syn relationship between the two aryl groups. A survey of different hydrogen sources to promote the removal of palladium from the alkene product revealed that NaBH 4 provides the highest yield and with the Z-alkene as the major isomer.

Why does the synthesis of N-phenylbenzamide from benzenesulfinate and phenylisocyanate via the palladium-mediated Extrusion–Insertion pathway not work? A mechanistic exploration

“…While we have observed the protodecarboxylation side reaction in our previous studies of ExIn reactions involving the 2,6-dimethoxybenzoic acid substrate, [25][26][27][28] we never observed the formation of the biaryl side product. Thus we were interested in establishing the energetics of the biaryl side reaction relative to the insertion of phenylisocyanate (Fig.…”

“…These studies involve palladium-mediated/catalysed extrusion of CO 2 to form an organopalladium intermediate followed by insertion of an appropriate (hetero)cumulene (Scheme 1b). [25][26][27][28] Given that these synthetic methods were limited to the use of 2,6-dimethoxybenzoic acid as a substrate, we recently explored the use of silver carbonate for the synthesis of N-phenyl-benzamide starting from benzoic acid and phenyl isocyanate. [29] While the desired ExIn mechanism operates in the gas-phase (Scheme 1c, Eqns 1, 2), a different base-catalysed condensation mechanism not requiring silver operates in solution.…”

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

“…Scheme 5 below summarises the key aspects that underpinned the development of ExIn reactions. 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.…”

“…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.…”

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

“…Our initial report on transformation of the anionic copper acetate complex [(CH 3 )Cu(O 2 CCH 3 )] − to the anionic copper(I) dithioacetate complex [(CH 3 )Cu(S 2 CCH 3 )] − [17] convinced us that guided by mechanistic studies, these extrusion-insertion (ExIn) reactions could potentially be harnessed for one-pot organic synthetic methods for a wide range of new species including thioamides, amidines, amides, alkenes and ketones (Eqn 1, Scheme 1a). [18][19][20][21][22][23][24] In potential competition with the desired products is the protodecarboxylation side reaction (Eqn 2, Scheme 1a and Cycle B, Scheme 1b). [25,26] Fortunately, comprehensive investigations by Kozlowski's group into the scope of the palladium-catalysed protodecarboxylation side reaction identified potential solvent and additives that suppress this reaction, [25] which provided a valuable starting point in our solution-phase investigations.…”