Origin of chemoselectivity in N-heterocyclic carbene catalyzed cross-benzoin reactions: DFT and experimental insights

The Journal of Organic Chemistry
Steven M LangdonMichel Gravel

Abstract

An exploration into the origin of chemoselectivity in the NHC-catalyzed cross-benzoin reaction reveals several key factors governing the preferred pathway. In the first computational study to explore the cross-benzoin reaction, a piperidinone-derived triazolium catalyst produces kinetically controlled chemoselectivity. This is supported by (1)H NMR studies as well as a series of crossover experiments. Major contributors include the rapid and preferential formation of an NHC adduct with alkyl aldehydes, a rate-limiting carbon-carbon bond formation step benefiting from a stabilizing π-stacking/π-cation interaction, and steric penalties paid by competing pathways. The energy profile for the analogous pyrrolidinone-derived catalyst was found to be remarkably similar, despite experimental data showing that it is less chemoselective. The chemoselectivity could not be improved through kinetic control; however, equilibrating conditions show substantial preference for the same cross-benzoin product kinetically favored by the piperidinone-derived catalyst.

References

Nov 15, 2002·Chemistry : a European Journal·Martina PohlMichael Müller
Jul 10, 2003·Journal of the American Chemical Society·Yoshifumi HachisuKeisuke Suzuki
Apr 14, 2004·Proceedings of the National Academy of Sciences of the United States of America·Travis Dudding, Kendall N Houk
Jan 4, 2006·Angewandte Chemie·Dieter EndersTim Balensiefer
Apr 26, 2006·Angewandte Chemie·Hiroshi TakikawaKeisuke Suzuki
Jun 21, 2007·The Journal of Organic Chemistry·Steven M Mennen, Scott J Miller
Oct 25, 2007·Chemical Reviews·Dieter EndersAlexander Henseler
May 17, 2002·Angewandte Chemie·Dieter Enders, Ulrike Kallfass
Mar 25, 2010·The Journal of Chemical Physics·Giovanni Scalmani, Michael J Frisch
Apr 17, 2010·Journal of the American Chemical Society·Erin R JohnsonWeitao Yang
Aug 28, 2010·The Journal of Physical Chemistry. a·Yunqing He, Ying Xue
Nov 3, 2010·Chemical Communications : Chem Comm·Nadine Kuhl, Frank Glorius
Jan 1, 2009·Synlett : Accounts and Rapid Communications in Synthetic Organic Chemistry·Alex K MathiesKarl A Scheidt
Feb 26, 2011·Angewandte Chemie·Akiomi TakadaKeisuke Suzuki
Apr 26, 2011·Journal of Chemical Theory and Computation·Julia Contreras-GarcíaWeitao Yang
Nov 29, 2011·Angewandte Chemie·André Grossmann, Dieter Enders
Feb 4, 2012·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Luis R DomingoManuel Arnó
Mar 2, 2012·Chemical Society Reviews·Xavier Bugaut, Frank Glorius
Jun 27, 2012·The Journal of Organic Chemistry·Oldamur HollóczkiLászló Nyulászi
Oct 18, 2012·Angewandte Chemie·Javier IzquierdoKarl A Scheidt
Jan 3, 2013·Organic & Biomolecular Chemistry·Christoph R MüllerPablo Domínguez de María
May 9, 2014·Journal of the American Chemical Society·Steven M LangdonMichel Gravel
Jun 27, 2014·Nature·Matthew N HopkinsonFrank Glorius

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Citations

Jun 9, 2016·Journal of the American Chemical Society·Guoxiang ZhangXinqiang Fang
Aug 16, 2017·Organic & Biomolecular Chemistry·Nicoletta Gaggero, Stefano Pandini
Dec 5, 2019·Chemistry : a European Journal·Oldamur Hollóczki
Apr 25, 2015·Chemistry : a European Journal·Eduardo Sánchez-DíezJose L Vicario
May 18, 2016·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Weifang Tang, Ding Du
Aug 23, 2020·Materials·Krzysztof DzieszkowskiZbigniew Rafiński
Nov 27, 2020·Chemical Communications : Chem Comm·Shilpa Barik, Akkattu T Biju
Dec 23, 2020·Organic & Biomolecular Chemistry·Richard S MasseyAnnMarie C O'Donoghue
May 20, 2015·The Journal of Organic Chemistry·Kanchan MalIndrajit Das
Nov 21, 2018·The Journal of Organic Chemistry·Ming-Hsiu HsiehJen-Shiang K Yu
Dec 7, 2018·Chemical Reviews·Shinji Yamada
Sep 16, 2021·Chemistry, an Asian Journal·Kento KimuraSeijiro Matsubara

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