γ-Selective Cross-Coupling Reactions of Potassium Allyltrifluoroborates with Haloarenes Catalyzed by a Pd(0)/D-t-BPF or Pd(0)/Josiphos ((R,S)-CyPF-t-Bu) Complex: Mechanistic Studies on Transmetalation and Enantioselection

Abstract

Cross-coupling between bromoarenes and [(E)-CH3CH=CHCH2BF3]K (2a) by a catalyst prepared from Pd(OAc)2 and D-t-BPF selectively provided γ-coupling products via SE2′ substitution. Mechanistic study of transmetalation revealed a heretofore unknown process, namely, formation of a highly electrophilic [Pd(Ar)(D-t-BPF)]+ before transmetalation with 2a. Thus, kinetic data in coupling of 4-substituted bromoarenes with 2a showed a linear positive correlation (ρ = −1.1) accelerated by donating substituents. This rate-determining role of transmetalation was further confirmed by kinetic data between oxidative adducts [Pd(Ar)(Br)(D-t-BPF)] and 2a that exhibited an analogous correlation with a negative ρ-value (−0.50). Theoretical study by density functional theory (DFT) calculation showed that transmetalation between [Ar−Pd]+ and 2a via an SE2′ (open) transition state is a slightly lower energy process than an SE2′ (closed) process. Allylic substitutions with chiral catalysts are the current topics for enantioselective C−C bond formation, but the catalysts that are effective for allylic nucleophiles have remained unexplored. Among the ligands screened, (R,S)-CyPF-t-Bu was found to achieve 77−90% ee for representative para- and meta-substituted bromoarenes and 2-bromo-1-alkenes in refluxing aqueous tetrahydrofuran (THF) or MeOH. To obtain mechanistic information on enantioselection, the mode of substrate coordination to a cationic phenylpalladium intermediate was calculated, that is, the reaction stage directly preceding the stereodetermining insertion step by DFT calculation. A stable adduct between [Pd(CyPF-t-Bu)(Ph)]+ and 2a located at the C−C double bond from its re-face yielding the experimentally observed R-product is preferred thermodynamically rather than the corresponding si-coordination.

Synthesis of chiral heterocycles by ligand-controlled regiodivergent and enantiospecific Suzuki Miyaura cross-coupling

“…33,34 The resulting chiral pyranyl and piperidyl allylic boronates 3 and 4 can lead to either a-or gregioselectivity in a Suzuki Miyaura cross-coupling with organohalide electrophiles (RX). This regioselectivity is tied to the mechanistic nature of the transmetallation step and whether it occurs with or without allylic rearrangement [22][23][24][25][26][27] .…”

“…The ensuing transmetallation may occur through either an S E or S E 0 mechanism. The S E 0 mode of transmetallation is thought to be prevalent with phosphine-ligated Pd(II) species 25,29 . Thus, in these conditions, both XPhos and (4-CF 3 -C 6 H 4 ) 3 P are expected to first provide s-bonded allylic Pd(II) complex B via a syn-S E 0 pathway made favourable through coordination of the electron-deficient Pd(II) to the electron-rich alkene.…”

“…With allylic boronates, the challenge of controlling selectivity is aggravated by the need to address a third type of selectivity arising from the possibility of forming two different regioisomers (Fig. 1c) [22][23][24][25][26][27][28][29] . Regioisoselectivity (or 'site selectivity') tends to be governed by the intrinsic steric and electronic effects dictated by the allylic substrate.…”

Metal-Catalyzed Reactions of Organoboronic Acids and Esters

“…(Scheme 16). 92 Among steps involved in the catalytic cycle of cross-coupling, oxidative addition exhibits a positive correlation accelerated by withdrawing groups. It is also difficult to conclude that it is due to the rate-determining role of reductive elimination.…”

Cross-coupling Reactions of Organoboranes: An Easy Method for C–C Bonding

“…We reported the efficiency of D-t-BPF for £-selective coupling of potassium allyltrifluoroborates with bromoarenes and asymmetric reaction using (R,S)-CyPF-t-Bu as the chiral auxiliary (eq 13). 27 Molander and co-workers reported the use of functional potassium alkyltrifluoroborates, which are stable to air and moisture. 28 As mentioned above, the CB bond of organoboronic acids is totally covalent which is inert to ionic reactions, but nucleophilicity of organic groups on a boronic atom are significantly enhanced by quaternerization by an anionic ligand.…”