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Synfacts 2011(4): 0351-0351  
DOI: 10.1055/s-0030-1259592
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart ˙ New York

Asymmetric Synthesis of 1,1-Diarylethane Drugs

Contributor(s):Philip Kocienski
B. L. H. Taylor, E. C. Swift, J. D. Waetzig, E. R. Jarvo*
University of California, Irvine, USA
Stereospecific Nickel-Catalyzed Cross-Coupling Reactions of Alkyl Ethers: Enantioselective Synthesis of Diarylethanes
J. Am. Chem. Soc.  2011,  133:  389-391  
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Publication History

Publication Date:
18 March 2011 (online)

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Key words

asymmetric addition - chiral chaperones - nickel-catalyzed cross-coupling - arylzinc reagents

Significance

Syntheses of the sleep-inducing H1-antihistamine K and the tubulin polymerization inhibitor N exemplify a general enantioselective synthesis of 1,1-diarylethanes using the stereo­specific nickel-catalyzed cross-coupling reactions of alkyl ethers with methylmagnesium iodide. Further seven examples are reported giving yields of 70-96% and ee values of 85-99%.

Comment

The chiral diarylcarbinols (for example, E) were constructed via enantioselective addition of Et2Zn to aryl aldehydes catalyzed by Ti(Oi-Pr)4 and ent-BINOL (A. S. C. Chan and co-workers Tetrahedron: Asymmetry 1997, 8, 585) or by addition of arylzinc reagents catalyzed by ent-(1-methylpyrrolidin-2-yl)diphenylmethanol (A. L. Braga et al. J. Org. Chem. 2008, 73, 2879).

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