Asymmetric Hydroformylation Catalyzed by RhH(CO)₂[(R,S)-Yanphos]: Mechanism and Origin of Enantioselectivity

Abstract

Asymmetric hydroformylation (AHF) catalyzed by transition metal (TM) complexes bearing chiral phosphorus ligands is one of the most powerful synthetic ways that could provide chiral aldehydes directly from alkenes and syngas in one step. Experiments have proved the efficiency of Rh catalyst with hybrid phosphorus ligands owning two different phosphorus moieties in AHF. Herein the origin of enantioselectivity of AHF catalyzed by RhH(CO)2[(R,S)-Yanphos] was studied at M06/BSI level using the density functional theory (DFT) method to unveil a fundamental understanding on factors contributing to the efficiency in AHF. The alkene insertion step is supposed to be the chirality-determining step in the whole catalytic cycle of the Rh-Yanphos system. Four possible pathways of styrene (Sub1) insertion step (pathways R1, S1, R2, and S2) were discussed; the calculated results indicate that pathways R1 and S2 are proposed to be two dominant alkene insertion pathways and that styrene tends to adopt apical coordination mode (A mode) to Rh center in pathways R1 and S2 compared to equatorial coordination mode (E mode) in pathways R2 and S1. The enantioselectivity of AHFs of ten alkene substrates (CH2═CH-R, R═Ph, C(═O)OCH3, Ph-(p)-Me, Ph-(p)-OMe, Ph-(p)-(i)Bu, Ph-(p)-F, Ph-(p)-Cl, Ph-(o)-F, OC(═O)-Ph and O-Ph, corresponding alkenes are abbreviated as Sub1 to Sub10, respectively) were also investigated. The predicted chiralities agree well with experimental results. The present work suggests that the relative stabilities of coordination modes (A/E mode) of alkene to 2 (RhH(CO)[(R,S)-Yanphos]) might be of importance in the enantioselectivity of AHF catalyzed by Rh-Yanphos.

Silicon-oriented regio- and enantioselective rhodium-catalyzed hydroformylation

“…As shown in Fig. 5 , the alkene insertion step was computed to be the rate-determining step, which is in agreement with the previous computational studies 51 – 56 and no observation of the H/D scrambling from the product (Fig. 7 ).…”

“…On the basis of the previous computational and experimental results on other Rh-catalyzed hydroformylation 8 , 51 – 57 , we also carried out DFT calculations (using ( S , R )-( N -Bn)-YanPhos and 1a ) to examine energetics of the whole reaction path for this Rh-catalyzed AHF and understand its regioselectivity and enantioselectivity to gain more insightful understanding (Figs. 5 and 6 ).…”

Substituent effects and chemoselectivity of the intramolecular Buchner reaction of diazoacetamide derivatives catalyzed by the di-Rh(ii)-complex

“…[29][30][31][32][33][34][35][36][37][38][39] The hybrid density functional ωB97X-D method is reliable and has been used in previous studies. [40][41][42] The transition states (TSs) were further confirmed by the vibrational analysis and characterized by only one imaginary vibrational mode. The intrinsic reaction coordinate (IRC) calculations were performed in order to confirm and identify intermediates (INTs) along the reaction pathways.…”

Unraveling the Importance of Noncovalent Interactions in Asymmetric Hydroformylation Reactions

“…For instance, QM/MM computations have been employed to gather qualitative as well as quantitative estimates on the origin of enantioselectivity in catalytic AHF reactions in the recent years. The DFT (M06) studies using simplified models for Rh-YanPhos catalyst suggested that the efficiency of alkene coordination is an important factor that has a bearing on the enantioselectivity . It is important to note that the stereochemical outcome of asymmetric transformations could depend on the catalyst–substrate noncovalent interactions (NCIs) .…”

“…The DFT (M06) studies using simplified models for Rh-YanPhos catalyst suggested that the efficiency of alkene coordination is an important factor that has a bearing on the enantioselectivity. 25 It is important to note that the stereochemical outcome of asymmetric transformations could depend on the catalyst− substrate noncovalent interactions (NCIs). 26 Therefore, the use of QM/MM approaches that typically place the regions of the ligand in the MM framework is likely to be ineffective.…”