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Synfacts 2013; 9(9): 0917
DOI: 10.1055/s-0033-1339523
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of a Retinoic Acid Receptor Agonist

Contributor(s):
Philip Kocienski
Wisniewska HM, Swift EC, Jarvo ER * University of California, Irvine, USA
Functional-Group-Tolerant, Nickel-Catalyzed Cross-Coupling Reaction for Enantioselective Construction of Tertiary Methyl-Bearing Stereoisomers.

J. Am. Chem. Soc. 2013;
135: 9083-9090
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Further Information

Publication History

Publication Date:
19 August 2013 (online)

 
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Key words

retinoic acid receptor agonist - nickel-catalyzed cross-coupling - α-(methylthio)acetate esters - dimethylzinc

Significance

The target molecule I is a retinoic acid receptor γ (RARγ) agonist that is of interest for the treatment of acne, psoriasis and melanoma. The synthesis depicted features the first nickel-catalyzed stereospecific Negishi alkyl–alkyl cross-coupling reaction of secondary benzylic α-(methylthio)acetate esters with dimethylzinc.


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Comment

The mild reaction conditions are compatible with a variety of functional groups including alkenes, protected alkynes, acetals, and esters. Heterocycles, amines, and imides are also well tolerated. Cross-coupling with diethylzinc is also possible but the reaction is more complex owing to additional competitive reaction pathways.


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