Abstract
We have investigated the stereoselectivity and reactivity of the sodium borohydride reduction of 2-X-cyclohexanones (X=H, Cl, Br) using a combined approach of competitive experiments and density functional theory calculations. Our results show that the hydride addition proceeds via a late transition state in which the C–H bond is nearly formed, consistent with the mild reducing power of NaBH4. The reaction barrier decreases from the 2-halocyclohexanones to the unsubstituted cyclohexanone, in line with relative reactivities observed in the competitive experiments. Furthermore, we provide a protocol to solve the longstanding issue of properly modelling the axial–equatorial facial selectivity of hydride addition to the carbonyl group substituted with a vicinal polar group. The inclusion of implicit solvation in combination with an explicit solvent molecule is crucial to reproduce the stereoselective formation of the cis product observed experimentally.
Original language | English |
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Article number | e4556 |
Number of pages | 8 |
Journal | Journal of Physical Organic Chemistry |
Volume | 36 |
Issue number | 10 |
Early online date | 23 Jun 2023 |
DOIs | |
Publication status | Published - Oct 2023 |
Bibliographical note
Funding Information:The authors are thankful to the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—CAPES (funding code: 001), the Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq (grant number: 306830/2021‐3), the Fundação de Amparo à Pesquisa do Estado de Minas Gerais—FAPEMIG (grant number: APQ‐00383/15), the Fundação de Amparo à Pesquisa do Estado de São Paulo—FAPESP (grant number: 2018/03910‐1), the Fundo de Apoio ao Ensino, Pesquisa e Extensão—FAEPEX (grant number: 2466/20), and the Netherlands Organization for Scientific Research (NWO) for the financial support of this research. This work was carried out on the Dutch national e‐infrastructure with the support of SURF Cooperative.
Publisher Copyright:
© 2023 John Wiley & Sons, Ltd.
Funding
The authors are thankful to the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—CAPES (funding code: 001), the Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq (grant number: 306830/2021-3), the Fundação de Amparo à Pesquisa do Estado de Minas Gerais—FAPEMIG (grant number: APQ-00383/15), the Fundação de Amparo à Pesquisa do Estado de São Paulo—FAPESP (grant number: 2018/03910-1), the Fundo de Apoio ao Ensino, Pesquisa e Extensão—FAEPEX (grant number: 2466/20), and the Netherlands Organization for Scientific Research (NWO) for the financial support of this research. This work was carried out on the Dutch national e-infrastructure with the support of SURF Cooperative. The authors are thankful to the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—CAPES (funding code: 001), the Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq (grant number: 306830/2021‐3), the Fundação de Amparo à Pesquisa do Estado de Minas Gerais—FAPEMIG (grant number: APQ‐00383/15), the Fundação de Amparo à Pesquisa do Estado de São Paulo—FAPESP (grant number: 2018/03910‐1), the Fundo de Apoio ao Ensino, Pesquisa e Extensão—FAEPEX (grant number: 2466/20), and the Netherlands Organization for Scientific Research (NWO) for the financial support of this research. This work was carried out on the Dutch national e‐infrastructure with the support of SURF Cooperative.
Funders | Funder number |
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Fundo de Apoio ao Ensino, Pesquisa e Extensão | |
SURF Cooperative | |
Fundação de Amparo à Pesquisa do Estado de São Paulo | 2018/03910‐1 |
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior | 001 |
Nederlandse Organisatie voor Wetenschappelijk Onderzoek | |
Conselho Nacional de Desenvolvimento Científico e Tecnológico | 306830/2021‐3 |
Fundação de Amparo à Pesquisa do Estado de Minas Gerais | APQ‐00383/15 |
Fundo de Apoio ao Ensino, à Pesquisa e Extensão, Universidade Estadual de Campinas | 2466/20 |
Keywords
- density functional computations
- halogens
- reactivity
- solvation
- stereoselectivity