Palladium(I)-Iodide-Catalyzed Deoxygenative Heck Reaction of Vinyl Triflates: A Formate-Mediated Cross-Electrophile Reductive Coupling with cine-Substitution

Abstract

The first deoxygenative Heck reactions are described, as illustrated by formate-mediated cine-substitutions of vinyl triflates with aryl iodides. The collective data corroborate a mechanism in which Pd­(OAc)2 and Bu4NI form the dianionic iodide-bridged dimer [Pd2I6]­[NBu4]2, which, under reducing conditions, serves as a precursor to the palladium­(I) complex [Pd2I4]­[NBu4]2. Dinculear oxidative addition of aryl iodide forms [Pd2I5(Ar)]­[NBu4]2, which dissociates to the monometallic complex [PdI2(Ar)]­[NBu4]. Vinyl triflate migratory insertion–sulfonate elimination delivers a palladium­(IV) carbene, which upon β-hydride elimination/C–H reductive elimination gives the product of cine-substitution. These processes are the first efficient formate-mediated cross-electrophile reductive couplings beyond carbonyl addition.

Formate-Mediated Aryl Halide Reductive Cross-Coupling Catalyzed by Iodide-Bridged Palladium(I) Dimers: Experi-mental and Computational Studies

“…As Pd(OAc)2 is converted to the Pd(I) dimer [Pd(I)(P t Bu3)]2 upon exposure to formate, Bu4NI and P t Bu3•HBF4 (eq. 1), 13 use of Pd(OAc)2 as a precatalyst in the coupling of 1a with 2a was explored in the presence and absence of P t Bu3 (eq. 2).…”

“…Our DFT calculations indicate dissociation of the dimeric oxidative addition complexes 5a and 5b to form monomeric anionic T-shaped Pd(II) complexes is highly endergonic (Figure S3), although such species could be present in small concentrations. 13,28 An equilibrium between 5a and 5b with several aryl Pd(II) iodide dimers (6a-1, 6a-2, 6a-3) via exchange and isomerization is more facile (Figure 5). The most stable isomer 6a-1 involves chelation of the pyridine nitrogen to the adjacent Pd center (2.10 Å) (Figure S7), accounting for the unusual facility of couplings adjacent to heteroaromatic ring nitrogen atoms.…”

“…11 In connection with this work, rhodiumcatalyzed formate-mediated aryl iodide-aldehyde and vinyl halide-aldehyde reductive couplings 12b,c were recently reported, as were palladium-catalyzed formate-mediated deoxygenative Heck-type reactions of vinyl triflates. 13 The ability to promote formate-mediated reductive couplings of aryl halides impelled efforts to develop formate-mediated biaryl crosscouplings; 9,10 however, using homogenous rhodium or heterogenous palladium catalysts, low yields and narrow scope were observed. 9 High-throughput experimentation (HTE) in collaboration with Genentech was applied to the optimization of this process, which has culminated in the first efficient conditions for formate-mediated aryl halide reductive cross-coupling, including challenging 2-pyridyl systems.…”

Cine-Substitution of Enolates: Enolate Dance/Coupling of Cycloalkenyl Pivalates by Nickel Catalysis

“…5,6 In another notable example, by harnessing a deoxygenative Mizoroki−Heck process, the Krische group demonstrated that Pd(I)species can catalyze a cine-substitution of cycloalkenyl triflates with aryl iodides. 7 Despite their uniqueness, these reactions have been primarily limited to carbamoylation and arylation. Furthermore, they require the use of an expensive palladium as a catalyst.…”

Cine-Substitution of Enolates: Enolate Dance/Coupling of Cycloalkenyl Pivalates by Nickel Catalysis

“…5 In another notable example, by harnessing a deoxygenative Mizoroki-Heck process, the Krische group demonstrated that Pd(I)species can catalyze a cine-substitution of cycloalkenyl triflates with aryl iodides. 6 Despite their uniqueness, these reactions have been primarily limited in carbamoylation and arylation. Furthermore, they require the use of expensive palladium as a catalyst.…”