Nickel/Bis(oxazoline)-Catalyzed Asymmetric Negishi Arylations of Racemic Secondary Benzylic Electrophiles to Generate Enantioenriched 1,1-Diarylalkanes
A tertiary stereogenic center that bears two different aryl substituents is found in a variety of bioactive compounds, including medicines such as Zoloft and Detrol. We have developed an efficient method for the synthesis of enantioenriched 1,1-diarylalkanes from readily available racemic benzylic a...
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American Chemical Society (ACS)
2018
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| Online Access: | http://hdl.handle.net/1721.1/113309 |
| _version_ | 1826205313623130112 |
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| author | Do, Hien-Quang Chandrashekar, E. R. R. Fu, Gregory C |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Do, Hien-Quang Chandrashekar, E. R. R. Fu, Gregory C |
| author_sort | Do, Hien-Quang |
| collection | MIT |
| description | A tertiary stereogenic center that bears two different aryl substituents is found in a variety of bioactive compounds, including medicines such as Zoloft and Detrol. We have developed an efficient method for the synthesis of enantioenriched 1,1-diarylalkanes from readily available racemic benzylic alcohols. Formation of a benzylic mesylate (which is not isolated), followed by treatment with an arylzinc reagent, LiI, and a chiral nickel/bis(oxazoline) catalyst, furnishes the Negishi cross-coupling product in high ee and good yield. A wide array of functional groups (e.g., an aryl iodide, a thiophene, and an N-Boc-indole) are compatible with the mild reaction conditions. This method has been applied to a gram-scale synthesis of a precursor to Zoloft. |
| first_indexed | 2024-09-23T13:10:43Z |
| format | Article |
| id | mit-1721.1/113309 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T13:10:43Z |
| publishDate | 2018 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1133092022-10-01T13:35:02Z Nickel/Bis(oxazoline)-Catalyzed Asymmetric Negishi Arylations of Racemic Secondary Benzylic Electrophiles to Generate Enantioenriched 1,1-Diarylalkanes Do, Hien-Quang Chandrashekar, E. R. R. Fu, Gregory C Massachusetts Institute of Technology. Department of Chemistry Chandrashekar, E. R. R. Fu, Gregory C A tertiary stereogenic center that bears two different aryl substituents is found in a variety of bioactive compounds, including medicines such as Zoloft and Detrol. We have developed an efficient method for the synthesis of enantioenriched 1,1-diarylalkanes from readily available racemic benzylic alcohols. Formation of a benzylic mesylate (which is not isolated), followed by treatment with an arylzinc reagent, LiI, and a chiral nickel/bis(oxazoline) catalyst, furnishes the Negishi cross-coupling product in high ee and good yield. A wide array of functional groups (e.g., an aryl iodide, a thiophene, and an N-Boc-indole) are compatible with the mild reaction conditions. This method has been applied to a gram-scale synthesis of a precursor to Zoloft. National Institute of General Medical Sciences (U.S.) (Grant R01-GM62871) 2018-01-26T16:08:35Z 2018-01-26T16:08:35Z 2013-10 2013-08 2018-01-24T15:12:24Z Article http://purl.org/eprint/type/JournalArticle 0002-7863 1520-5126 http://hdl.handle.net/1721.1/113309 Do, Hien-Quang et al. “Nickel/Bis(oxazoline)-Catalyzed Asymmetric Negishi Arylations of Racemic Secondary Benzylic Electrophiles to Generate Enantioenriched 1,1-Diarylalkanes.” Journal of the American Chemical Society 135, 44 (October 2013): 16288–16291 © 2013 American Chemical Society http://dx.doi.org/10.1021/JA408561B 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 | Do, Hien-Quang Chandrashekar, E. R. R. Fu, Gregory C Nickel/Bis(oxazoline)-Catalyzed Asymmetric Negishi Arylations of Racemic Secondary Benzylic Electrophiles to Generate Enantioenriched 1,1-Diarylalkanes |
| title | Nickel/Bis(oxazoline)-Catalyzed Asymmetric Negishi Arylations of Racemic Secondary Benzylic Electrophiles to Generate Enantioenriched 1,1-Diarylalkanes |
| title_full | Nickel/Bis(oxazoline)-Catalyzed Asymmetric Negishi Arylations of Racemic Secondary Benzylic Electrophiles to Generate Enantioenriched 1,1-Diarylalkanes |
| title_fullStr | Nickel/Bis(oxazoline)-Catalyzed Asymmetric Negishi Arylations of Racemic Secondary Benzylic Electrophiles to Generate Enantioenriched 1,1-Diarylalkanes |
| title_full_unstemmed | Nickel/Bis(oxazoline)-Catalyzed Asymmetric Negishi Arylations of Racemic Secondary Benzylic Electrophiles to Generate Enantioenriched 1,1-Diarylalkanes |
| title_short | Nickel/Bis(oxazoline)-Catalyzed Asymmetric Negishi Arylations of Racemic Secondary Benzylic Electrophiles to Generate Enantioenriched 1,1-Diarylalkanes |
| title_sort | nickel bis oxazoline catalyzed asymmetric negishi arylations of racemic secondary benzylic electrophiles to generate enantioenriched 1 1 diarylalkanes |
| url | http://hdl.handle.net/1721.1/113309 |
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