NR transfer reactivity of azo-compound I of P450. How does the nitrogen substituent tune the reactivity of the species toward C-H and C=C activation?
We studied electronic structures and reactivity patterns of azo-compound I species (RN-Cpd I) by comparison to O-Cpd I of, e.g., cytochrome P450. The study shows that the RN-Cpd I species are capable of C=C aziridination and C-H amidation, in a two-state mechanism similar to that of O-Cpd I. However, unlike O-Cpd I, here the nitrogen substituent (R) exerts a major impact on structure and reactivity. Thus, it is demonstrated that Fe=NR bonds of RN-Cpd I will generally be substantially longer than Fe=O bonds; electron-withdrawing R groups will generate a very long Fe=N bond, whereas electron-releasing R groups should have the opposite effect and hence a shorter Fe=N bond. The R substituent controls also the reactivity of RN-Cpd I toward C=C and C-H bonds by exerting steric and electronic effects. Our analysis shows that an electron-releasing substituent will lower the barriers for both bond activation reactions, since the electronic factor makes the reactions highly exothermic, while an electron-withdrawing one should raise both barriers. The steric bulk of the substituent is predicted to inhibit more strongly the aziridination reactions. It is predicted that electron-releasing substituents with small bulk will create powerful aziridination reagents, whereas electron-withdrawing substituents like MeSO(2) will prefer C-H bond activation with preference that increases with steric bulk. Finally, the study predicts (i) that the reactions of RN-Cpd I will be less stereospecific than those of O-Cpd I and (ii) that aziridination will be more stereoselective than amidation.
Moreau
Yohann
Y
Department of Organic Chemistry and the Lise Meitner-Minerva Center for Computational Quantum Chemistry, The Hebrew University of Jerusalem, Givat Ram Campus, 91904 Jerusalem, Israel.
Chen
Hui
H
Derat
Etienne
E
Hirao
Hajime
H
Bolm
Carsten
C
Shaik
Sason
S
D000475:Alkenes / Q000737:chemistry; D000577:Amides / Q000737:chemistry; D001388:Aziridines / Q000737:chemistry; D001391:Azo Compounds / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry*; D004583:Electrons; D006860:Hydrogen Bonding; D007097:Imines / Q000737:chemistry; D007501:Iron / Q000737:chemistry; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry*; D013816:Thermodynamics
D000475:Alkenes; D000577:Amides; D001388:Aziridines; D001391:Azo Compounds; D007097:Imines; C017621:phenylnitrene; C033132:aziridine; D002244:Carbon; D003577:Cytochrome P-450 Enzyme System; C013658:propylene; D007501:Iron; D009584:Nitrogen