Synfacts 2014; 10(3): 0283
DOI: 10.1055/s-0033-1340728
Metal-Catalyzed Asymmetric Synthesis and Stereoselective Reactions
© Georg Thieme Verlag Stuttgart · New York

Trisubstituted Monofluoroalkenes via Rh-Catalyzed Allylic C–F Bond Activation

Contributor(s):
Mark Lautens
,
Marcel Sickert
Zhang H, Lin J.-H, Xiao J.-C, * Gu Y.-C. Shanghai Institute of Organic Chemistry, P. R. of China and Syngenta, Bracknell, UK
Rh-Catalyzed Allylic C–F Bond Activation: The Stereoselective Synthesis of Trisubstituted Monofluoroalkenes and a Mechanism Study.

Org. Biomol. Chem. 2014;
12: 581-588
Further Information

Publication History

Publication Date:
17 February 2014 (online)

 

Significance

Fluorinated organic molecules are of particular interest to the pharmaceutical, agrochemical, and polymer industry as a consequence of the unique properties of carbon–fluorine bonds, where the replacement of C–H or C–OH bonds is usually exploited to adjust acidity, lipophilicity, and (metabolic) stability. As a result, new methodologies to introduce fluorine into complex organic molecules are necessary to satisfy the continuously growing demand. Herein, the authors report the stereoselective synthesis of trisubstituted monofluoroalkenes via a rhodium-catalyzed Csp3–F bond activation of allylic difluorohomo­allylic alcohols.


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Comment

Under the optimized conditions, the reaction exhibited a substrate scope that included aromatic and heteroaromatic substituents. Interestingly, the selectivity of the reaction depends strongly on the electronic nature of the substituents, where reactions of halogen-, ester-, and sulfonate-substituted substrates have furnished the Z-configured products with selectivities up to >99:1. Initial mechanistic studies were conducted and support a C–F activation mode. However, isomerization studies have also shown that the stereoselectivity is controlled predominately by Ph3P via a rhodium-independent pathway.


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Review

For an account on C(sp3)–F activation, see: M. F. Kuehnel, D. Lentz, T. Braun Angew. Chem. Int. Ed. 2013, 52, 3328–3348.


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