Synthesis of chromans and flavanes
A convergent three-step method provides 2-substituted chromans via Heck coupling of readily accessible allylic alcohols and 2-iodophenols, followed by reduction and Mitsunobu cyclization. The utility and generality of this method is demonstrated through the synthesis of a series of 2-aryl-, 2-heteroaryl- and 2-alkylchromans, as well as an azachroman derivative. A Noyori-catalyzed ketone reduction enables an asymmetric version.
R. K. Orr, L.-C. Campeau, H. R. Chobanian, H. M. McCabe Dunn, B. Pio, C. W. Plummer, A. Nolting, R. T. Ruck, Synthesis, 2017, 49, 657-666.
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.
Rh-catalyzed asymmetric transfer hydrogenation enables a straightforward access to enantiomerically enriched cis-3-benzyl-chromanols from (E)-3-benzylidene-chromanones in the presence of HCO2H/DABCO as the hydrogen source.
R. M. Betancourt, P. Phansavath, V. Ratovelomanana-Vidal, Org. Lett., 2021, 23, 1621-1625.
Cooperative asymmetric catalysis with hydrogen chloride (HCl) and chiral dual-hydrogen-bond donors (HBDs) enables a highly enantioselective Prins cyclization of a wide variety of simple alkenyl aldehydes. The optimal chiral catalysts withstand the strongly acidic reaction conditions and induce rate accelerations of 2 orders of magnitude over reactions catalyzed by HCl alone.
D. A. Kutateladze, E. N. Jacobsen, J. Am. Chem. Soc., 2021, 143, 20077-20083.
A Ru-catalyzed asymmetric transfer hydrogenation of 2,3-disubstituted flavanones provides chiral flavanols with three contiguous stereocenters with excellent ees and drs. The reaction proceeds via a base-catalyzed retro-oxa-Michael addition to racemize two stereogenic centers simultaneously in concert with a highly enantioselective ketone transfer hydrogenation step.
Q.-X. Xie, L-X. Liu, Z.-H. Zhu, C.-B. Yu, Y.-G. Zhou, J. Org. Chem., 2022, 87, 7521-7530.