Enantioselective Synthesis of Axially Chiral Biaryls by the Pd- Catalyzed Suzuki-Miyaura Reaction: Substrate Scope and Quantum Mechanical Investigations
We report efficient syntheses of axially chiral biaryl amides in yields ranging from 80−92%, and with enantioselectivity in the range 88−94% ee employing an asymmetric Suzuki−Miyaura process with Pd(OAc)[subscript 2] and KenPhos as ligand. These studies demonstrate that electron-rich and electron-de...
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| Format: | Article |
| Language: | en_US |
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American Chemical Society (ACS)
2012
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| Online Access: | http://hdl.handle.net/1721.1/71946 https://orcid.org/0000-0003-1528-6438 https://orcid.org/0000-0003-3875-4775 |
| _version_ | 1826197894924861440 |
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| author | Shen, Xiaoqiang Jones, Gavin O. Watson, Donald A. Bhayana, Brijesh Buchwald, Stephen Leffler |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Shen, Xiaoqiang Jones, Gavin O. Watson, Donald A. Bhayana, Brijesh Buchwald, Stephen Leffler |
| author_sort | Shen, Xiaoqiang |
| collection | MIT |
| description | We report efficient syntheses of axially chiral biaryl amides in yields ranging from 80−92%, and with enantioselectivity in the range 88−94% ee employing an asymmetric Suzuki−Miyaura process with Pd(OAc)[subscript 2] and KenPhos as ligand. These studies demonstrate that electron-rich and electron-deficient o-halobenzamides can be efficiently coupled with 2-methyl-1-naphthylboronic acid and 2-ethoxy-1-naphthylboronic acid. The yields and selectivities of the reactions are independent of the nature of halogen substituent on the benzamide coupling partner. Our investigations demonstrate that axially chiral heterocyclic and biphenyl compounds can also be synthesized with this methodology. We also report computational studies used to determine the origin of stereoselectivity during the selectivity-determining reductive elimination step of the related coupling of tolyl boronic acid with naphthylphosphonate bromide that was reported in a previous publication (J. Am. Chem. Soc. 2000, 122, 12051−12052). These studies indicate that the stereoselectivity arises from a combination of weak -(C)H··O interactions as well as steric interactions between the tolyl and naphthylphosphonate addends in the transition state for C−C coupling. |
| first_indexed | 2024-09-23T10:55:17Z |
| format | Article |
| id | mit-1721.1/71946 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:55:17Z |
| publishDate | 2012 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/719462022-09-27T15:56:14Z Enantioselective Synthesis of Axially Chiral Biaryls by the Pd- Catalyzed Suzuki-Miyaura Reaction: Substrate Scope and Quantum Mechanical Investigations Shen, Xiaoqiang Jones, Gavin O. Watson, Donald A. Bhayana, Brijesh Buchwald, Stephen Leffler Massachusetts Institute of Technology. Department of Chemistry Buchwald, Stephen L. Shen, Xiaoqiang Jones, Gavin O. Watson, Donald A. Bhayana, Brijesh Buchwald, Stephen Leffler We report efficient syntheses of axially chiral biaryl amides in yields ranging from 80−92%, and with enantioselectivity in the range 88−94% ee employing an asymmetric Suzuki−Miyaura process with Pd(OAc)[subscript 2] and KenPhos as ligand. These studies demonstrate that electron-rich and electron-deficient o-halobenzamides can be efficiently coupled with 2-methyl-1-naphthylboronic acid and 2-ethoxy-1-naphthylboronic acid. The yields and selectivities of the reactions are independent of the nature of halogen substituent on the benzamide coupling partner. Our investigations demonstrate that axially chiral heterocyclic and biphenyl compounds can also be synthesized with this methodology. We also report computational studies used to determine the origin of stereoselectivity during the selectivity-determining reductive elimination step of the related coupling of tolyl boronic acid with naphthylphosphonate bromide that was reported in a previous publication (J. Am. Chem. Soc. 2000, 122, 12051−12052). These studies indicate that the stereoselectivity arises from a combination of weak -(C)H··O interactions as well as steric interactions between the tolyl and naphthylphosphonate addends in the transition state for C−C coupling. National Institutes of Health (U.S.) (Grant Number GM-46059) National Natural Science Foundation (National Center for Supercomputing Applications) 2012-08-01T19:43:20Z 2012-08-01T19:43:20Z 2010-07 2010-05 Article http://purl.org/eprint/type/JournalArticle 0002-7863 1520-5126 http://hdl.handle.net/1721.1/71946 Shen, Xiaoqiang et al. “Enantioselective Synthesis of Axially Chiral Biaryls by the Pd-Catalyzed Suzuki−Miyaura Reaction: Substrate Scope and Quantum Mechanical Investigations.” Journal of the American Chemical Society 132.32 (2010): 11278–11287. https://orcid.org/0000-0003-1528-6438 https://orcid.org/0000-0003-3875-4775 en_US http://dx.doi.org/10.1021/ja104297g Journal of the American Chemical Society Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society (ACS) PMC |
| spellingShingle | Shen, Xiaoqiang Jones, Gavin O. Watson, Donald A. Bhayana, Brijesh Buchwald, Stephen Leffler Enantioselective Synthesis of Axially Chiral Biaryls by the Pd- Catalyzed Suzuki-Miyaura Reaction: Substrate Scope and Quantum Mechanical Investigations |
| title | Enantioselective Synthesis of Axially Chiral Biaryls by the Pd- Catalyzed Suzuki-Miyaura Reaction: Substrate Scope and Quantum Mechanical Investigations |
| title_full | Enantioselective Synthesis of Axially Chiral Biaryls by the Pd- Catalyzed Suzuki-Miyaura Reaction: Substrate Scope and Quantum Mechanical Investigations |
| title_fullStr | Enantioselective Synthesis of Axially Chiral Biaryls by the Pd- Catalyzed Suzuki-Miyaura Reaction: Substrate Scope and Quantum Mechanical Investigations |
| title_full_unstemmed | Enantioselective Synthesis of Axially Chiral Biaryls by the Pd- Catalyzed Suzuki-Miyaura Reaction: Substrate Scope and Quantum Mechanical Investigations |
| title_short | Enantioselective Synthesis of Axially Chiral Biaryls by the Pd- Catalyzed Suzuki-Miyaura Reaction: Substrate Scope and Quantum Mechanical Investigations |
| title_sort | enantioselective synthesis of axially chiral biaryls by the pd catalyzed suzuki miyaura reaction substrate scope and quantum mechanical investigations |
| url | http://hdl.handle.net/1721.1/71946 https://orcid.org/0000-0003-1528-6438 https://orcid.org/0000-0003-3875-4775 |
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