Intermolecular Alkyne Hydroacylation. Mechanistic Insight from the Isolation of the Vinyl Intermediate That Precedes Reductive Elimination

Abstract

The isolation of the branched alkenyl intermediate that directly precedes reductive elimination of the final α,β-unsaturated ketone product is reported for the hydroacylation reaction between the alkyne HCCArF (ArF = 3,5-(CF3)2C6H3) and the β-S-substituted aldehyde 2-(methylthio)benzaldehyde: [Rh(fac-κ3-DPEphos)(C(CH2)ArF)(C(O)C6H4SMe)2][CB11H12]. The structure of this intermediate shows that, in this system at least, hydride migration rather than acyl migration occurs. Kinetic studies on the subsequent reductive elimination to form the crystallographically characterized ketone-bound product [Rh(cis-κ2-DPEphos)(η2:η2,κ1-H2CC(ArF)C(O)(C6H4SMe)][CB11H12] yield the following activation parameters for reductive elimination, which follows first-order kinetics (k obs = (6.14 ± 0.04) × 10–5 s–1, 324 K): ΔH ⧧ = 95 ± 2 kJ mol–1, ΔS ⧧ = −32 ± 7 J K–1 mol–1, ΔG ⧧(298 K) = 105 ± 4 kJ mol–1. Mechanistic studies, including selective deuteration experiments, show that hydride insertion is not reversible and also reveal that an interesting isomerization process is occurring between the two branched alkenyl protons that is suggested to occur via a metallocyclopropene intermediate. During catalysis, the consumption of substrates and evolution of products follow pseudo zero-order kinetics. The observation of both linear and branched products under stoichiometric and catalytic regimes, in combination with kinetic modeling, allows for an overall mechanistic scheme to be presented. Partitioning of linear and branched pathways at the hydride insertion step occurs with an approximate 2:1 selectivity, while reductive elimination of the linear product is at least 3 orders of magnitude faster than that from the branched. An explanation for the large difference in rate of reductive elimination in this system, as recently outlined by Goldman, Krogh-Jespersen, and Brookhart, is that steric crowding in branched intermediates can slow C–C reductive elimination even though such species are higher in energy than their linear analogues, if the rotation of the vinyl group to the appropriate orientation is inhibited by steric crowding in the branched isomers.

Well‐Defined and Robust Rhodium Catalysts for the Hydroacylation of Terminal and Internal Alkenes

“…13b H/D exchange was observed into free 4 a during catalysis, suggesting reversible aldehyde and alkene binding. The measured KIE is similar to other systems in which reductive elimination is proposed to be turnover‐limiting,8b, 13 rather than irreversible CH activation (KIE ≈2.57c, 18), and is likely an equilibrium isotope effect 21. Addition of just 1‐octene to 3 a results in isomerization to give a mixture of internal alkenes, that are not seen during catalysis when 4 a is also present.…”

Ortho-aryl substituted DPEphos ligands: rhodium complexes featuring C–H anagostic interactions and B–H agostic bonds

“…11,[15][16][17][18][19] The cationic Schrock-Osborn [Rh(chelating-phosphine)] + system is a widely used one in catalysis and synthesis, 20, 21 and the active species are often accessed via hydrogenation of a suitable diene precursor, such as [Rh(chelatingphosphine)(NBD)][anion] (NBD = norbornadiene), in a coordinating solvent such as acetone. We have particular interest in such systems with the DPEphos ligand, with regard to their use as pre-catalysts for amine-borane dehydropolymerisation, 22,23 alkene and alkyne hydroacylation, [24][25][26] and alkyne carbothiolation, 27 amongst other applications. We now report the synthesis of new Schrock-Osborn systems with ortho-substituted DPEphos ligands, including a new i Prsubstituted ligand (Figure 2).…”

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

“…Although Weller and co-workers have elegantly demonstrated hydride migration, rather than the alternative carbometalation, occurs during rhodium-catalyzed intermolecular alkyne hydroacylation [ 78 ], no such experiment has been carried out under iridium catalysis. As such, we set out to explore the possibility acyl migration is favored over hydride migration in iridium-catalyzed hydroacylation reactions ( Figure 2 ).…”