Mechanism of Ti-Catalyzed Oxidative Nitrene Transfer in [2+2+1] Pyrrole Synthesis from Alkynes and Azobenzene
Abstract
A combined computational and experimental study on the mechanism of Ti-catalyzed formal [2 + 2 + 1] pyrrole synthesis from alkynes and aryl diazenes is reported. This reaction proceeds through a formally TiII/TiIV redox catalytic cycle as determined by natural bond orbital (NBO) and intrinsic bond orbital (IBO) analysis. Kinetic analysis of the reaction of internal alkynes with azobenzene reveals a complex equilibrium involving Ti=NPh monomer/dimer equilibrium and Ti=NPh + alkyne [2 + 2] cycloaddition equilibrium along with azobenzene and pyridine inhibition equilibria prior to rate-determining second alkyne insertion. Computations support this kinetic analysis, provide insights into the structure of the active species in catalysis and the roles of solvent, and provide a new mechanism for regeneration of the Ti imido catalyst via disproportionation. Reductive elimination from a 6-membered azatitanacyclohexadiene species to generate pyrrole-bound Tiπ is surprisingly facile and occurs through a unique electrocyclic reductive elimination pathway similar to a Nazarov cyclization. The resulting Tiπ species are stabilized through backbonding into the $π*$ of the pyrrole framework, although solvent effects also significantly stabilize free Tiπ species that are required for pyrrole loss and catalytic turnover. Further computational and kinetic analysis reveals that in complex reactions with unysmmetric alkynes the resultingmore »
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC); Univ. of California, Oakland, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC)
- OSTI Identifier:
- 1543723
- Grant/Contract Number:
- AC02-05CH11231
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of the American Chemical Society
- Additional Journal Information:
- Journal Volume: 140; Journal Issue: 23; Journal ID: ISSN 0002-7863
- Publisher:
- American Chemical Society (ACS)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Chemistry
Citation Formats
Davis-Gilbert, Zachary W., Wen, Xuelan, Goodpaster, Jason D., and Tonks, Ian A. Mechanism of Ti-Catalyzed Oxidative Nitrene Transfer in [2+2+1] Pyrrole Synthesis from Alkynes and Azobenzene. United States: N. p., 2018.
Web. doi:10.1021/jacs.8b03546.
Davis-Gilbert, Zachary W., Wen, Xuelan, Goodpaster, Jason D., & Tonks, Ian A. Mechanism of Ti-Catalyzed Oxidative Nitrene Transfer in [2+2+1] Pyrrole Synthesis from Alkynes and Azobenzene. United States. https://doi.org/10.1021/jacs.8b03546
Davis-Gilbert, Zachary W., Wen, Xuelan, Goodpaster, Jason D., and Tonks, Ian A. Tue .
"Mechanism of Ti-Catalyzed Oxidative Nitrene Transfer in [2+2+1] Pyrrole Synthesis from Alkynes and Azobenzene". United States. https://doi.org/10.1021/jacs.8b03546. https://www.osti.gov/servlets/purl/1543723.
@article{osti_1543723,
title = {Mechanism of Ti-Catalyzed Oxidative Nitrene Transfer in [2+2+1] Pyrrole Synthesis from Alkynes and Azobenzene},
author = {Davis-Gilbert, Zachary W. and Wen, Xuelan and Goodpaster, Jason D. and Tonks, Ian A.},
abstractNote = {A combined computational and experimental study on the mechanism of Ti-catalyzed formal [2 + 2 + 1] pyrrole synthesis from alkynes and aryl diazenes is reported. This reaction proceeds through a formally TiII/TiIV redox catalytic cycle as determined by natural bond orbital (NBO) and intrinsic bond orbital (IBO) analysis. Kinetic analysis of the reaction of internal alkynes with azobenzene reveals a complex equilibrium involving Ti=NPh monomer/dimer equilibrium and Ti=NPh + alkyne [2 + 2] cycloaddition equilibrium along with azobenzene and pyridine inhibition equilibria prior to rate-determining second alkyne insertion. Computations support this kinetic analysis, provide insights into the structure of the active species in catalysis and the roles of solvent, and provide a new mechanism for regeneration of the Ti imido catalyst via disproportionation. Reductive elimination from a 6-membered azatitanacyclohexadiene species to generate pyrrole-bound Tiπ is surprisingly facile and occurs through a unique electrocyclic reductive elimination pathway similar to a Nazarov cyclization. The resulting Tiπ species are stabilized through backbonding into the $π*$ of the pyrrole framework, although solvent effects also significantly stabilize free Tiπ species that are required for pyrrole loss and catalytic turnover. Further computational and kinetic analysis reveals that in complex reactions with unysmmetric alkynes the resulting pyrrole regioselectivity is driven primarily by steric effects for terminal alkynes and inductive effects for internal alkynes.},
doi = {10.1021/jacs.8b03546},
journal = {Journal of the American Chemical Society},
number = 23,
volume = 140,
place = {United States},
year = {Tue May 15 00:00:00 EDT 2018},
month = {Tue May 15 00:00:00 EDT 2018}
}
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