Scope and Mechanistic Study of the Coupling Reaction of α,β-Unsaturated Carbonyl Compounds with Alkenes: Uncovering Electronic Effects on Alkene Insertion vs Oxidative Coupling Pathways

Abstract

The cationic ruthenium-hydride complex [(C6H6)(PCy3)(CO)RuH]+BF4− (1) was found to be a highly effective catalyst for the intermolecular conjugate addition of simple alkenes to α,β-unsaturated carbonyl compounds to give (Z)-selective tetrasubstituted olefin products. The analogous coupling reaction of cinnamides with electron-deficient olefins led to the oxidative coupling of two olefinic C–H bonds in forming (E)-selective diene products. The intramolecular version of the coupling reaction efficiently produced indene and bicyclic fulvene derivatives. The empirical rate law for the coupling reaction of ethyl cinnamate with propene was determined as: rate = k[1]1[propene]0[cinnamate]−1. A negligible deuterium kinetic isotope effect (kH/kD = 1.1±0.1) was measured from both (E)-C6H5CH=C(CH3)CONHCH3 and (E)-C6H5CD=C(CH3)CONHCH3 with styrene. In contrast, a significant normal isotope effect (kH/kD = 1.7±0.1) was observed from the reaction of (E)-C6H5CH=C(CH3)CONHCH3 with styrene and styrene-d10. A pronounced carbon isotope effect was measured from the coupling reaction of (E)-C6H5CH=CHCO2Et with propene (13C(recovered)/13C(virgin) at Cβ = 1.019(6)), while a negligible carbon isotope effect (13C(recovered)/13C(virgin) at Cβ = 0.999(4)) was obtained from the reaction of (E)-C6H5CH=C(CH3)CONHCH3 with styrene. Hammett plots from the correlation of para-substituted p-X-C6H4CH=CHCO2Et (X = OCH3, CH3, H, F, Cl, CO2Me, CF3) with propene and from the treatment of (E)-C6H5CH=CHCO2Et with a series of para-substituted styrenes p-Y-C6H4CH=CH2 (Y = OCH3, CH3, H, F, Cl, CF3) gave the positive slopes for both cases (ρ = +1.1±0.1 and +1.5±0.1, respectively). Eyring analysis of the coupling reaction led to the thermodynamic parameters, Δ H‡ = 20±2 kcal mol−1 and S‡ = −42±5 e.u. Two separate mechanistic pathways for the coupling reaction have been proposed on the basis of these kinetic and spectroscopic studies.

Relay Catalysis To Synthesize β-Substituted Enones: Organocatalytic Substitution of Vinylogous Esters and Amides with Organoboronates

“…Kinetic studies suggested that the reaction rate is increased by electron-rich β-substituents that stabilize developing cationic charge at the β-carbon . In light of that observation, we hypothesized that resonance electron donor substituents, ethers and amines, would make the enone even more reactive. , This paradigm would reverse that of nearly all conjugate addition reactions, for which vinylogous esters and amides are too electron-rich to be competent substrates . Precedence for such conjugate additions is limited to a few reports of palladium catalysis to add aryl boronic acids to vinylogous amides .…”

Aerobic Oxidative Cross-Coupling of Substituted Acrylamides with Alkenes Catalyzed by an Electron-Deficient CpRhIII Complex

“…A 1,3-butadiene scaffold is a useful building block for organic synthesis and is often present in natural products and bioactive molecules . As one of the most atom- and step-economical synthesis of 1,3-butadienes, large numbers of transition-metal-catalyzed C–H/C–H coupling reactions between two alkenes have been developed. − For example, the oxidative cross coupling of acrylamides with alkenes via directed vinylic C–H bond cleavage of the acrylamides selectively produces (2 Z ,4 E )-dienamides (Scheme a). − Glorius first reported this transformation by using a cationic Cp*Rh III catalyst . Subsequently, a Ru­(II)-catalyzed variant of this transformation and expansion of the substrate scope (coupling partner, aliphatic alkene (2-allylisoindoline-1,3-dione); directing groups, Weinreb amides) were reported.…”

“…However, these reactions required a high reaction temperature (120–140 °C) and a stoichiometric amount of a Cu­(II) oxidant. With respect to the reaction temperature, low-temperature (50–60 °C) reactions were accomplished by using a cationic Ru­(II) hydride complex as a catalyst or an N -methoxycarbamoyl group as a directing group . However, these reactions still required stoichiometric amounts of external or internal oxidants (excess alkenes or the N -methoxycarbamoyl group), and the available directing groups were strictly limited to secondary amides (NHMe and NHOMe).…”

Direct Intramolecular Conjugate Addition of Simple Alkenes to α,β-Unsaturated Carbonyls Catalyzed by Cu(OTf)2

“…In 2008, Jamison and Ogoshi independently reported the addition of an unactivated alkene to enones under the catalysis of Ni(0). Yi has advanced ruthenium catalysts , for this reaction to synthesize tetrasubstituted olefins. In an early work, Snider and co-workers reported that a stoichiometric amount of a Lewis acid catalyzed the addition of alkenes to α,β-enones .…”