title: Sequential catalytic role of bifunctional bicyclic guanidine in asymmetric phospha-Michael reaction.
abstract: The catalytic mechanism and origin of enantioselectivity of bicyclic guanidine-catalyzed phospha-Michael reaction between diphenyl phosphine oxide and β-nitrostyrene were investigated by DFT calculations at M06-2X/cc-pVTZ//M06-2X/cc-pVDZ level in conjunction with the implicit SMD solvation method. The catalyst is found to be involved in all 3 steps of the proposed catalytic cycle, namely (1) tautomerization of phosphine oxide, (2) C-P bond formation and (3) concerted hydrogen transfer. The bifunctional role of the guanidine catalyst is clearly demonstrated in all 3 key steps. Due to the geometry of the bicyclic guanidine catalyst, the preferred orientation of the reactants in the transition state of enantioselective C-P bond forming step favours the R enantiomer, in excellent accord with the observed enantioselectivity. Analysis of various transition states suggests that the asymmetric C-P bond formation is controlled by the hydrogen bonding interaction and steric effect between the catalyst and substrate. Various weaker C-H···X (X = N, O and π) interactions also play a role in stabilizing the key transition states.
authors.affiliation: Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore, 117543.
authors.forename: Bokun
authors.initials: B
authors.lastname: Cho
authors.forename: Choon-Hong
authors.initials: CH
authors.lastname: Tan
authors.forename: Ming Wah
authors.initials: MW
authors.lastname: Wong
mesh_terms: D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D002384:Catalysis; D002625:Chemistry, Organic; D018360:Crystallography, X-Ray; D019791:Guanidine / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry; D006860:Hydrogen Bonding; D008958:Models, Molecular; D010647:Phenyl Ethers / Q000737:chemistry*; D010720:Phosphines / Q000737:chemistry*; D011789:Quantum Theory; D013237:Stereoisomerism; D013343:Styrenes / Q000737:chemistry*
chemical_list: D001643:Bridged Bicyclo Compounds; D010647:Phenyl Ethers; D010720:Phosphines; D013343:Styrenes; C011955:beta-nitrostyrene; D006859:Hydrogen; C044646:phosphine; D019791:Guanidine