Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Nov 6;135(44):16288-91.
doi: 10.1021/ja408561b. Epub 2013 Oct 28.

Nickel/bis(oxazoline)-catalyzed asymmetric Negishi arylations of racemic secondary benzylic electrophiles to generate enantioenriched 1,1-diarylalkanes

Hien-Quang Do  1 , E R R Chandrashekar, Gregory C Fu
Affiliations

Nickel/bis(oxazoline)-catalyzed asymmetric Negishi arylations of racemic secondary benzylic electrophiles to generate enantioenriched 1,1-diarylalkanes

Hien-Quang Do et al. J Am Chem Soc. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

References

    1. For reviews and leading references, see: Khouzam HR, Ernes R, Gill T, Roy R. Comprehensive Therapy. 2003;29:47–53.Salvatore S, Serati M, Bolis P. Expert Opinion on Pharmacotherapy. 2008;9:1249–1255.Stayrook KR, Carson MW, Ma YL, Dodge JA. In: Vitamin D. Feldman D, Pike JW, Adams JS, editors. Elsevier; London: 2011. pp. 1497–1508.

    1. For examples and leading references, see: Woodmansee DH, Pfaltz A. Chem Commun. 2011;47:7912–7916.Tolstoy P, Engman M, Paptchikhine A, Bergquist J, Church TL, Leung AWM, Andersson PG. J Am Chem Soc. 2009;131:8855–8860. This reference includes a discussion of other approaches to the synthesis of 1,1-diarylalkanes.

    1. For example, see: Paquin J-F, Defieber C, Stephenson CRJ, Carreira EM. J Am Chem Soc. 2005;127:10850–10851.

    1. For recent reports and leading references, see: Maity P, Shacklady-McAtee DM, Yap GPA, Sirianni ER, Watson MP. J Am Chem Soc. 2013;135:280–285.Zhou Q, Srinivas HD, Dasgupta S, Watson MP. J Am Chem Soc. 2013;135:3307–3310.Harris MR, Hanna LE, Greene MA, Moore CE, Jarvo ER. J Am Chem Soc. 2013;135:3303–3306. (doubly benzylic electrophiles)

    1. For an example of an umpolung process that employs an enantioenriched benzylic nucleophile, see: Imao D, Glasspoole BW, Laberge VS, Crudden CM. J Am Chem Soc. 2009;131:5024–5025.

Publication types