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Synthesis of 2,3-Dihydrobenzofurans

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A unique Rh(III)-catalyzed C-H activation of N-phenoxyacetamides followed by carbooxygenation of 1,3-dienes enables the construction of dihydrobenzofurans. This redox-neutral [3 + 2] annulation offers chemoselectivity, good substrate/functional group compatibility, and profound synthetic potentials. An asymmetric approach has also been demonstrated.
L. Wu, L. Li, H. Zhang, H. Gao, Z. Zhou, W. Yi, Org. Lett., 2021, 23, 3844-3849.


A highly enantioselective Pd/TY-Phos-catalyzed Heck/Tsuji-Trost reaction of o-bromophenols with various 1,3-dienes provides chiral substituted 2,3-dihydrobenzofurans with excellent regio- and enantiocontrol, high functional group tolerance, and easy scalability. The construction of optically pure natural products (R)-tremetone and fomannoxin is highlighted.
Y. Tu, B. Xu, Q. Wang, H. Dong, Z.-M. Zhang, J. Zhang, J. Am. Chem. Soc., 2023, 145, 4378-4383.


A bifunctional aminoboronic acid facilitates intramolecular aza- and oxa-Michael reactions of α,β-unsaturated carboxylic acids. The combination of an arylboronic acid with a chiral aminothiourea enables enantioselective conversions to afford the desired heterocycles in high yields and ee’s (up to 96% ee).
T. Azuma, A. Murata, Y. Kobayashi, T. Inokuma, Y. Takemoto, Org. Lett., 2014, 16, 4256-4259.


A highly enantioselective and straightforward intramolecular asymmetric addition of aryl halides to unactivated ketones provides chiral 3-hydroxy-2,3-dihydrobenzofurans with a chiral tertiary alcohol at the C-3 position in good yields and excellent enantioselectivities.
Y. Li, W. Li, J. Tian, G. Huang, H. Lv, Org. Lett., 2020, 22, 5353-5357.


A highly enantioselective palladium-catalyzed iodine atom transfer cycloisomerization of olefin-tethered aryl iodides provides optically active 2,3-dihydrobenzofurans, indolines and chromanes bearing an alkyl iodide group in good yields. The reaction offers use of readily available starting materials, a broad substrate scope, high selectivity, and mild conditions.
Z.-M. Zhang, B. Xu, L. Wu, L. Zhou, D. Ji, Y. Liu, Z. Li, H. Zhang, J. Am. Chem. Soc., 2019, 141, 8110-8115.


A phosphorus(III)-mediated formal [4+1]-cycloaddition of 1,2-dicarbonyls and o-quinone methides provides 2,3-dihydrobenzofurans. Subtle steric interactions involved in the [4+1]-cycloannulation have an impact on yield and stereoselectivity in dihydrobenzofuran formation.
K. X. Rodriguez, J. D. Vail, B. L. Ashfeld, J. Zhu, Org. Lett., 2016, 18, 4514-4517.


Fluoride-induced desilylation of 2-bromo-1-{2-[(triisopropylsilyl)oxy]phenyl}ethyl nitrate enables a regioselective one-pot synthesis of 3-substituted 2,3-dihydrobenzofurans via generation of o-quinone methides followed by Michael addition of different C, N, O, and S nucleophiles, and intramolecular 5-exo-tet elimination of a bromide anion. The method has potential synthetic applications in drug discovery.
A. k. Shaikh, G. Varvounis, Org. Lett., 2014, 16, 1478-1481.