Mechanism of Pd/Senphos-Catalyzed trans-Hydroboration of 1,3-Enynes: Experimental and Computational Evidence in Support of the Unusual Outer-Sphere Oxidative Addition Pathway

Abstract

The reaction mechanism of the Pd/Senphos-catalyzed trans-hydroboration reaction of 1,3-enynes was investigated using various experimental techniques, including deuterium and double crossover labeling experiments, X-ray crystallographic characterization of model reaction intermediates, and reaction progress kinetic analysis. Our experimental data are in support of an unusual outer-sphere oxidative addition mechanism where the catecholborane serves as a suitable electrophile to activate the Pd 0bound 1,3-enyne substrate to form a Pd-η 3 -π-allyl species, which has been determined to be the likely resting state of the catalytic cycle. Double crossover labeling of the catecholborane points toward a second role played by the borane as a hydride delivery shuttle. Density functional theory calculations reveal that the rate-limiting transition state of the reaction is the hydride abstraction by the catecholborane shuttle, which is consistent with the experimentally determined rate law: rateThe computed activation free energy ΔG ‡ = 17.7 kcal/mol and KIE (k H /k D = 1.3) are also in line with experimental observations. Overall, this work experimentally establishes Lewis acids such as catecholborane as viable electrophilic activators to engage in an outer-sphere oxidative addition reaction and points toward this underutilized mechanism as a general approach to activate unsaturated substrates.

Distinguishing Competing Mechanistic Manifolds for C(acyl)–N Functionalization by a Ni/N-Heterocyclic Carbene Catalyst System

“…We next assessed the reactivity of single-component Ni(0) precatalyst 6 toward representative twisted amide substrates across a range of amidicities (Scheme A). ,, Amides 1b – d underwent clean conversion to the corresponding SIPr-supported Ni­(II) acyl products, which were isolated in 43–81% yield and characterized by SC-XRD (Figure ), confirming their composition and connectivity. Although no oxidative addition products were detected with substrates lacking a carbamate directing group (e.g., 1a ), a crossover experiment between 1a and fluorine-tagged substrate 1e provided support for their kinetic accessibility (Scheme B). − …”

A syn outer-sphere oxidative addition: the reaction mechanism in Pd/Senphos-catalyzed carboboration of 1,3-enynes

“…In our recently reported trans -hydroboration 15 and trans -cyanoboration 16 of 1,3-enynes catalyzed by a Pd 0 /Senphos ligand complex, an unusual “outer-sphere” oxidative addition mechanism featuring a Pd-π-allyl intermediate is proposed. 17,18 Our initial mechanistic hypothesis was analogous (Scheme 2a): the presence of Senphos ligand L enables (COD)Pd(CH 2 TMS) 2 to reductively eliminate 1,2- bis(trimethylsilyl)-ethane to form the active LPd 0 species I , 19 which then binds to the 1,3-enyne. The resulting LPd 0 –enyne complex II is then activated by the Lewis acidic C–boron enolate to furnish the outer-sphere oxidative adduct III .…”

Asymmetric Friedel−Crafts reaction of unsaturated carbonyl-tethered heteroarenes via vinylogous activation of Pd0-π-Lewis base catalysis

“…Recently, our group and others uncovered that Pd 0 could chemoselectively form η 2 -complexes with the alkene moiety of 1,3-enynes. 7 As a result, the alkyne group could be HOMO (the Highest Occupied Molecular Orbital)-raised upon π-Lewis base activation of Pd 0 , and undergo vinylogous nucleophilic attack towards electrophiles, even enantioselectively. Density functional theory (DFT) also supported that regioselective dihapto-coordination to the alkene group by Pd 0 was favoured, as outlined in Scheme 1b .…”