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The Preparation of 2,3,5‐Tri‐ and 2,3‐Disubstituted Furans by Regioselective Palladium(0)‐Catalyzed Coupling Reactions: Application to the Syntheses of Rosefuran and the F 5 Furan Fatty Acid
Author(s) -
Bach Thorsten,
Krüger Lars
Publication year - 1999
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/(sici)1099-0690(199909)1999:9<2045::aid-ejoc2045>3.0.co;2-6
Subject(s) - regioselectivity , chemistry , furan , medicinal chemistry , catalysis , yield (engineering) , stille reaction , aryl , palladium , alkyl , coupling reaction , organic chemistry , materials science , metallurgy
The 5‐acceptor‐substituted 2,3‐dibromofurans 1 and 2 underwent a regioselective Pd 0 ‐catalyzed coupling reaction at the C‐2 carbon atom. With alkynes the corresponding 2‐alkynylfurans 4 and 5 were accessible (49–97% yield). Alkyl‐, aryl‐, and alkenylzinc reagents gave the 2‐substituted furans 8 starting from compound 2 (66–84% yield). The 2‐allylfurans 8e and 8f were obtained by a regioselective Stille coupling in 79% and 73% yield. The latter reaction was also applied to the parent 2,3‐dibromofuran ( 27 ) and yielded the substitution product 28 (60% yield). Subsequent Pd 0 ‐catalyzed reactions to introduce a methyl group in 3‐position by a methyldebromination were successfully conducted for 2‐alkynyl‐3‐bromofurans with MeZnCl and PdCl 2 (PPh 3 ) 2 as the catalyst in THF (reflux) to yield compounds 13 – 16 and 24 (67–76%) and with SnMe 4 and PdCl 2 [P( o ‐Tol) 3 ] 2 as the catalyst in DMA (90 °C) for the 2‐allyl‐3‐bromofuran 8e to yield 18 (70%). The more facile reaction of the 2‐alkynylfurans relative to those of furans bearing an sp 3 ‐carbon atom at C‐2 appears to be due to steric reasons. Studies on the 2‐alkyl‐3‐bromofuran 20 supported this notion. With the regioselective coupling methodology the terpene rosefuran ( 22 ) was prepared in four steps starting from furan 2 (35% yield overall). The F 5 furan fatty acid ( 26 ) was synthesized from furan 1 in five steps (29% yield overall).