C–H and C–F bond activation of fluorinated propenes at Rh: enabling cross-coupling reactions with outer-sphere C–C coupling

The reaction of [Rh{(E)-CF 
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Created by potrace 1.16, written by Peter Selinger 2001-2019
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 CHCF3}(PEt3)3] with Zn(CH3)2 results in the methylation of the alkenyl ligand to give [Rh{(E/Z)-C(CH3)CHCF3}(PEt3)3]. Variable temperature NMR studies allowed the identification of a heterobinuclear rhodium–zinc complex as an intermediate, for which the structure [Rh(CH3)(ZnCH3){(Z)-C(CH3)CHCF3}(PEt3)2] is proposed. Based on these stoichiometric reactions, unique Negishi-type catalytic cross-coupling reactions of fluorinated propenes by consecutive C–H and C–F bond activation steps at room temperature were developed. The C–H bond activation steps provide a fluorinated ligand at Rh and deliver the fluorinated product, whereas the C–F bond activation and C–C coupling occur via outer-sphere nucleophilic attack at the fluorinated alkenyl ligand.


EDGE ARTICLE
Herein studies on catalytic C-C coupling reactions at uorinated alkenyl ligands are described.Stoichiometric model reactions give an insight into a possible reaction mechanism.Unprecedented rhodium catalyzed Negishi-type cross-coupling reactions of uorinated olens have been developed, based on both C(sp 2 )-F and C(sp 2 )-H bond activation and, remarkably, involving a C-C coupling step in the outer coordination sphere.4) and an unknown product in a ratio of 3 : 0.7 : 2.5 : 1, respectively.When the reaction was run in the presence of one equivalent of PEt 3 , a mixture of complexes 2 and Z-3 in a 1 : 17 ratio was observed aer 10 minutes.The preferential formation of the Z-3 isomer might indicate a diminished role of 2 for the reaction mechanism in this case.When the reaction was monitored at 253 K by NMR spectroscopy, aer 4 h 75% conversion of complex 1 was observed to give complex 2 and a second complex (ratio 9 : 1), which is possibly an isomer of 2, together with the release of triethylphosphine (Scheme 2).The rhodium-zinc heterobimetallic complex 2 is not stable at low temperatures, and aer one day, reductive elimination of Zn(CH 3 ) 2 took place followed by coordination of phosphine to rhodium leading to the Z/E-3 isomers in a 1 : 4 ratio.Treatment of the product mixture with Z-1,3,3,3-tetrauoropropene (5a) led then to the regeneration of complex 1 and release of E-1,1,1-triuorobut-2-ene (6a) by C-H bond activation and formation (Scheme 2).This step comprises the replacement of a lower uorinated ligand by a higher uorinated ligand by C-H bond activation as a higher degree of uorination oen leads to stronger bonds. 34As previously reported, complex 1 is not stable and aer a dehydrouorination step complex 4 is obtained. 33n an alternative approach in which complex 1 was treated with LiCH 3 instead of Zn(CH 3 ) 2 , a mixture of complexes (Z/E)-3 and 4 was also obtained.However, in this case a heterobinuclear intermediate similar to 2 was not observed.][37][38][39] The formation of 2 followed by the generation of E/Z-3 from complex 1 can be considered as a case for a rare outer-sphere reaction where a nucleophile attacks the uorinated ligand bonded at rhodium.Note that the attack of a uorosilicate at the carbon atom of a uorinated pyridyl ligand has been proposed at rhodium. 40The attack of PEt 3 at the b-carbon atom of a peruorovinyl ligand at nickel was also described. 41In addition, outer-sphere electrophilic uorination was reported by Lynam, Slattery and co-workers. 42,43The rearrangements of the alkenyl ligands for the conversion of 2 into E-3, 1 into 2 and E-3 into 6a comprise an isomerization at the double bond.This might involve an intermediate vinylidene complex that can be formed by a reversible migration of a methyl group from the alpha carbon to the metal center.5][46] In addition, a negative hyperconjugation of the p-electron density into antibonding orbitals at the CF 3 group might weaken the C]C double bond and allow for an isomerization of the alkenyl ligands.Note that Ojima et al. proposed a zwitterionic carbene-rhodium complex as an intermediate for such a cis/trans rearrangement. 47However, another alternative route for the isomerization to give complexes 2 or E-3 could imply a rearrangement during the nucleophilic substitution.Aer addition of CH 3 − to Ca, the bcarbanion formed could show a free rotation about Ca-Cb.A Lewis-acidic cation of the type [ZnMe] + would then abstract the uoride forming the oligomeric [ZnFMe] n .

Results and discussion
The suggested structure of complex 2 is supported by NMR spectroscopic data, in part based on the data for the 13 C labeled derivative [Rh( 13 CH 3 )(Zn 13 CH 3 ){(Z)-C( 13 CH 3 )]CHCF 3 }(PEt 3 ) 2 ] (2 0 ) (see ESI ‡).Thus, in the 1 H NMR spectrum of complex 2 0 a resonance for the rhodium-bound methyl ligand is observed at −0.42 ppm as a doublet of triplets with coupling constants of 121.1 and 4.6 Hz due to the coupling to the carbon atom and the two phosphine ligands.In addition, a resonance at −0.21 ppm is assigned to the methyl group at the Zn atom.It appears as a doublet coupled with 1 J H-C = 123.2Hz.The 13 C{ 1 H} NMR displays two resonances at −27.5 and −9.2 ppm for the rhodium-and zinc-bonded methyl moieties, respectively.The former exhibits a doublet of pseudo quartets as a result of the coupling to rhodium (9.3 Hz), the two phosphorus atoms and the carbon atom bonded to zinc with a coupling constant of 5.2 Hz.The latter signal also shows the 5.2 Hz carbon-carbon coupling together with the extra coupling to rhodium resulting in a pseudo triplet.In addition, the geometry of complex 2 was optimized by DFT calculations using toluene as a solvent (BP86/ def2-SVP, see ESI ‡).The complex exhibits a tetragonal pyramidal structure at rhodium in which the methylzinc group is at the apical position.The distance between the Zn nucleus and one of the uorine atoms of the CF 3 moiety of 2.747 Å is shorter than the sum of van der Waals radii which might be the reason for the favored cis arrangement of the Zn center and the CF 3 group at the moiety containing the double bond.In fact, this product is 7.4 kJ mol −1 more stable than the corresponding trans isomer.
Complex [Rh{(E)-CF]CHCF 3 }(PEt 3 ) 3 ] ( 1) is synthesized by C-H bond activation of 5a using [Rh(CH 3 )(PEt 3 ) 3 ] (7). 33Therefore, complex 7 was also tested as a pre-catalyst and full conversion to compound 6a was obtained aer 1 h using only 5 mol% of catalyst (Scheme 3, Table 1, entry 2).Remarkably the transformation occurs at room temperature within 1 h.Note that Zn(CH 3 ) 2 does not react with the olen in the absence of a rhodium catalyst.
The formation of 9a should take place through a comparable mechanism as for the generation of 6a, leading to a Rh-Zn bimetallic intermediate which would bear an ethyl group at the olen and an ethyl ligand bound to rhodium.This intermediate can produce ethene together with [Rh(H)(PEt 3 ) 3 ] by b-H elimination.The rhodium hydrido complex would then react with 5a to give 3,3,3-triuoropropene and complex [Rh{(E)-CF] CHCF 3 }(PEt 3 ) 3 ] (1) as described before in the literature. 33he scope of the rhodium deuorinative methylation was then investigated using other olenic substrates and complex [Rh(CH 3 )(PEt 3 ) 3 ] (7) as a catalyst (Table 2, see also the ESI ‡ for further optimizations).Thus, E-1,3,3,3-tetrauoropropene (5b) was converted into compound 6a with 95% conversion.Higher uorinated derivatives were also attempted and both Z-Scheme 3 Catalytic Negishi cross-coupling reaction of 5a.1,2,3,3,3-pentauoropropene (5c) and peruoropropene (5d) were used.In the rst case Z-1,1,1,2-tetrauorobut-2-ene (6c) was identied in 25% conversion as the main product, while in the second case a mixture of Z/E-1,2,3,3,3-pentauorobut-2-ene isomers (6d) in a 1 : 0.9 ratio was formed (10% conversion).The latter stoichiometric conversion and decrease in reactivity for the peruorinated substrate could be due to the preference of complex 7 for the activation of C-H over C-F bonds. 67Then, 2,3,3,3-tetrauoropropene (HFO-1234yf, 5e) was used as a substrate, but only 11% conversion was achieved to form 6c and unidentied compounds.Finally, to investigate the inuence of a CF 3 group on the catalytic methylation of uo-roolens, 1,1-diuoroethane (5f) and triuoroethane (5g) were employed as reagents.While 5f yielded only traces of the methylated product 2-uoropropene (6f) even at 60 °C, compound 5g provided a mixture of E-1,2-diuoropropene (6g) and an unknown compound in a 5 : 1 ratio with 17% conversion.These results also suggest a preference of the rhodium system for olens with a geminal CHF group facilitating the initial C-H bond activation.

71 Table 2
unprecedented reaction pathway: (I) the C-F bond activation and C-C coupling steps occur by an outer-sphere nucleophilic attack at the uorinated alkenyl ligand.(II) Another crucial step comprises C-H bond activation to convert the olenic substrate into a Rh derivative, whereas at the same time the lower-uorinated olenic product is released.Stoichiometric model reactions give insight into key-steps of a putative catalytic cycle.A heterobinuclear Rh/Zn complex might play a certain role for the C-C coupling step.Note that in the past Rh-catalyzed hydrodeuorination, germylation, silylation and borylation reactions of uorinated olens were studied, but cross coupling reactions were elusive.65-Negishicross-coupling methylation of fluorinated olefins (R F = F and/or CF 3 )

Table 1
Catalyst and methyl source screening to obtain 6a Conversion based on the consumption of Zn(CH 3 ) 2 and determined by 1 H NMR spectroscopy.b 1 h reaction time, 5 mol% of complex 7. a