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Synlett 2011(6): 805-808  
DOI: 10.1055/s-0030-1259718
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of ‘Spacer’-Naproxen [2-(6-Methoxybiphenylen-2-yl)propanoic Acid] and -Isonaproxen [2-(7-Methoxybiphenylen-2-yl)propanoic Acid]

Juan A. González Gómez, James R. Green, K. Peter C. Vollhardt*
Department of Chemistry, University of California at Berkeley, Berkeley, CA 94720-1460, USA
Fax: +1(510)6435208; e-Mail: kpcv@berkeley.edu;
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Publikationsverlauf

Received 28 January 2011
Publikationsdatum:
08. März 2011 (online)

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Abstract

The CpCo(CO)2-catalyzed cocyclization of 1,2-diethynyl-4-methoxybenzene with alkynes can be applied to the synthesis of ‘spacer’-naproxen [2-(6-methoxybiphenylen-2-yl)propanoic acid] and its 7-methoxy isomer, ‘spacer’-isonaproxen. While unsymmetrical alkynes are incorporated without regioselectivity, the methoxy group in 6-methoxy-2,3-bis(trimethylsilyl)biphenylene directs electrophiles to C-3, thus allowing for regiochemical differentiation between the 2- and 3-positions.

Key words

alkynes - cobalt - cyclization - carbocycles - regioselectivity

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14

The structures of all new compounds (SciFinder) were in accord with their analytical and/or spectroscopic properties; see Supporting Information.