Why Is the Suzuki−Miyaura Cross-Coupling of sp³Carbons in α-Bromo Sulfoxide Systems Fast and Stereoselective? A DFT Study on the Mechanism

Abstract

The stereoselectivity-determining oxidative addition step in the Suzuki-Miyaura cross-coupling of alpha-bromo sulfoxides is analyzed computationally through DFT calculations on a model system defined by Pd(PMe(3))(2) and CH(3)SOCH(2)Br. Both monophospine and bisphosphine complexes have been considered, different reaction pathways being characterized through location of the corresponding transition states. The lowest energy transition states correspond to nucleophilic substitution mechanisms, which imply inversion of configuration at the carbon, in good agreement with experimental data on the process. The energy-lowering and stereodirecting role of the sulfinyl substituent is explained through its attractive interactions with the palladium center, which are only possible in the most favored mechanisms.

Influence of the Ligand of Palladium(0) Complexes on the Rate of the Oxidative Addition of Aryl and Activated Alkyl Bromides: Csp2−Br versus Csp3−Br Reactivity and Selectivity

“…This is in agreement with the DFT calculations that propose the mono‐ligated Pd 0 [P( o ‐Tol) 3 )] as the reactive species in a concerted oxidative addition ,. It is, however, important to point out the significant role of the Pd 0 precursor.…”

“…No DFT calculations have been performed on these substrates, but the effect of the steric hindrance of the ligand on the regioselectivity at the Csp 3 −X position is quite similar. However, the theoretical reasonable explanation proposed above would not perfectly apply to all substrates used in Scheme because Csp 3 −X (X=Br or Cl) positions remain highly reactive in these molecules regardless of the ligand used . Kinetic data on the oxidative addition of palladium(0) complexes to Csp 3 −Br and Csp 2 −Br derivatives or to Csp 3 −Br/Csp 2 −Br in the same molecule would be of great interest to explain the experimental findings and confirm the mechanism proposed from DFT calculations.…”

“…Computational studies by Maseras et al. performed on the oxidative addition (in which regioselectivity occurred) attribute the high regioselectivity to the steric hindrance of the ligand: bis‐ligated complexes Pd 0 L 2 (moderately bulky L such as PPh 3 ) would selectively react at the sp 3 carbon electrophile (oxidative addition through a S N 2‐like mechanism), whereas mono‐ligated complexes Pd 0 L (bulky L such as P( o ‐Tol) 3 ) would selectively react at the sp 2 carbon electrophile (oxidative addition by a concerted mechanism) ,…”

Competitive and Selective Csp3Br versus Csp2Br Bond Activation in Palladium‐Catalysed Suzuki Cross‐Coupling: An Experimental and Theoretical Study of the Role of Phosphine Ligands

“…In spite of this, sp 3 activation is preferred only for bisphosphine systems. Therefore, this palladium-oxygen interaction, which had been suggested by us as critical in the oxidative addition of a-bromo sulfoxides, [21] does not seem to play a key role in the current selectivity problem.…”

Phosphino-(α-sulfinylalkyl)phosphonium ylide complexes (Rh, Pd) with a configurationally stable asymmetric ylidic carbon

“…5). 30 On the basis of natural population analysis (NPA), the Pd-sulfinyl interaction was claimed to be of electrostatic nature and to be responsible for the stabilization of the transition state. Although (S C ,S C )-4b and 5-SN2 have not been studied at the same DFT level, the geometry and atomic charges appear to be similar in both complexes (Fig.…”