Asymmetric Synthesis of α,β-Unsaturated δ-Lactones through Copper(I)-Catalyzed Direct Vinylogous Aldol Reaction

Journal of the American Chemical Society
Hai-Jun Zhang, Liang Yin

Abstract

A simple methodology for the asymmetric synthesis of chiral α,β-unsaturated δ-lactones was achieved by copper(I)-catalyzed direct vinylogous aldol reaction (DVAR) of β,γ-unsaturated esters and various aldehydes, including aromatic aldehydes, heteroaromatic aldehydes, α,β-unsaturated aldehydes, and aliphatic aldehydes. For aromatic and heteroaromatic aldehydes, a one-pot reaction consisting of DVAR, isomerization of the unsaturated carbon-carbon double bond from ( E)-form to ( Z)-form, and subsequent intramolecular transesterification was required to get the lactones in moderate to high yields with high enantioselectivity. For α,β-unsaturated and aliphatic aldehydes, the DVAR proceeded directly to afford the lactones in moderate yields with high enantioselectivity. In the DVAR, various functional groups were well tolerated. Moreover, the methodology was nicely applicable to the aldehyde group distributed in natural products, derivatives of natural product, and derivatives of drug molecules (atomoxetine and naproxen). The mechanism studies revealed that α-addition was reversible and not favored, which accounted for the excellent regioselectivity in the DVAR. The copper(I)-dienolate species generated through deprotonation was prop...Continue Reading

References

Jun 9, 2001·The Journal of Organic Chemistry·G Bluet, J M Campagne
Feb 6, 2002·Chembiochem : a European Journal of Chemical Biology·M KalesseW Beil
Jun 26, 2003·Journal of the American Chemical Society·Scott E Denmark, Gregory L Beutner
Dec 18, 2003·Journal of the American Chemical Society·Suzanne B BuckDale L Boger
Mar 18, 2005·Journal of the American Chemical Society·Scott E DenmarkMartin D Eastgate
May 19, 2005·Journal of the American Chemical Society·Xavier MoreauJean-Marc Campagne
Jun 9, 2005·Angewandte Chemie·Scott E DenmarkGregory L Beutner
Jan 26, 2006·Journal of the American Chemical Society·Scott E Denmark, John R Heemstra
Nov 9, 2006·Journal of the American Chemical Society·Dongbo ZhaoMasakatsu Shibasaki
Jun 23, 2007·The Journal of Organic Chemistry·Scott E Denmark, John R Heemstra
Sep 25, 2007·Organic Letters·Lars V Heumann, Gary E Keck
Dec 7, 2007·Organic Letters·Serkan SimsekMarkus Kalesse
Feb 14, 2009·Journal of the American Chemical Society·Ryo YazakiMasakatsu Shibasaki
Oct 23, 2009·Chemical Society Reviews·Timothy NewhouseReinhard W Hoffmann
Mar 17, 2010·Chemistry : a European Journal·Marcus FringsCarsten Bolm
Apr 13, 2010·Bioorganic & Medicinal Chemistry Letters·Jean-Yves WachKarl Gademann
Jun 25, 2010·Chemical Communications : Chem Comm·Chong Huang, Bo Liu
Jun 25, 2010·Chemical Communications : Chem Comm·Marcus FringsCarsten Bolm
Jun 30, 2010·Journal of the American Chemical Society·Ravi P SinghLi Deng
Jul 2, 2010·The Journal of Organic Chemistry·Yang YangXiaoming Feng
Nov 12, 2010·Chemical Communications : Chem Comm·Sunil V Pansare, Eldho K Paul
Mar 26, 2011·Chemical Reviews·Giovanni CasiraghiFranca Zanardi
Apr 9, 2011·Organic Letters·Marc T Gieseler, Markus Kalesse
Jul 7, 2011·Chemistry : a European Journal·Sunil V Pansare, Eldho K Paul
Dec 1, 2011·Journal of the American Chemical Society·Hyun-Suk YeomSeunghoon Shin
Dec 14, 2011·Organic Letters·Jeffrey A GazailleTarek Sammakia
Mar 10, 2012·Organic Letters·Gerrit Symkenberg, Markus Kalesse
Oct 19, 2012·Organic Letters·Carlo Cassani, Paolo Melchiorre
Dec 13, 2012·Angewandte Chemie·Xuan HuangBo Liu
Dec 25, 2012·Organic Letters·David BastidaPaolo Melchiorre

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Citations

Oct 6, 2018·Chemical Communications : Chem Comm·Chang-Yun ShiLiang Yin
Aug 5, 2020·Nature Communications·Tengfei KangXiaoming Feng
Nov 22, 2020·Angewandte Chemie·Si-Qing WangLiang Yin
Feb 12, 2021·Journal of the American Chemical Society·Jun-Jie TianXiao-Chen Wang
Mar 30, 2021·Chemistry : a European Journal·Baptiste LecacheyJean-Marc Campagne
May 8, 2021·Chemistry : a European Journal·Mikel Oiarbide, Claudio Palomo
Jun 5, 2020·Organic Letters·Guang-Yao RanYing-Chun Chen
Dec 16, 2021·Organic Letters·Atanu MondalS S V Ramasastry

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