Categories: Synthesis of O-Heterocycles > Lactones >
Synthesis of 5,6-dihydropyran-2-ones
A Cu(I)-catalyzed direct vinylogous aldol reaction (DVAR) of β,γ-unsaturated esters and various aldehydes enables a synthesis of chiral α,β-unsaturated δ-lactones. For aromatic aldehydes, a one-pot reaction consisting of DVAR, isomerization of the unsaturated carbon-carbon double bond, and subsequent intramolecular transesterification was required, whereas for α,β-unsaturated and aliphatic aldehydes, the reaction proceeded directly.
H.-J. Zhang, L. Yin, J. Am. Chem. Soc., 2018, 140, 12270-12279.
The synthesis of α,β-unsaturated lactones from β-acetoxy aldehydes is achieved by reaction with the lithium enolate of methyl acetate. The reaction is relatively insensitive to structural changes in the aldehyde substrates. The process was extended to the synthesis of five-ring lactones from α-acetoxy aldehydes.
G. E. Keck, X.-Y. Li, C. E. Knutson, Org. Lett., 1999, 1, 411-413.
Highly stereoselective 2-oxonia-Cope rearrangement reactions between rationally designed nonracemic vinylogous aldolation synthons and aldehydes provide δ-hydroxy-α,β-unsaturated esters with excellent enantioselectivities and unprecedented Z- and E-selectivities.
A. Padarti, H. Han, Org. Lett., 2018, 20, 1448-1452.
1-Alkoxy-1-amino-1,3-butadienes undergo Diels-Alder (DA) and hetero-Diels-Alder (HDA) reactions under mild reaction conditions with a variety of electron-deficient dienophiles. The hydrolysis of the DA cycloadducts provides 6-substituted and 6,6-disubstituted 2-cylohexenones in good yields with excellent regioselectivities, whereas HDA cycloadducts afford 6-substituted 5,6-dihydropyran-2-ones.
P. K. Elkin, N. D. Durfee, V. H. Rawal, Org. Lett., 2021, 23, 5288-5293.
An AgOTf-catalyzed intramolecular cyclization of phenoxyethynyl diols affords multisubstituted α,β-unsaturated-γ-lactones in good yields under mild conditions. This method was also applicable to the synthesis of α,β-unsaturated-δ-lactones. Replacement of AgOTf with a stoichiometric amount of N-bromosuccinimide furnishes α-bromo-substituted α,β-unsaturated lactones.
M. Egi, Y. Ota, Y. Nishimura, K. Shimizu, K. Azechi, S. Akai, Org. Lett., 2013, 15, 4150-4153.
Highly functionalized δ-lactones were produced in the presence of a catalytic amount of the Cu(OAc)2-DIFLUORPHOS complex through three-component assembly of dialkylzincs, allenic esters, and unactivated ketones. This CAMCR (catalytic asymmetric multicomponent reaction) constructs two C-C bonds and one tetrasubstituted chiral center simultaneously.
K. Oisaki, D. Zhao, M. Kanai, M. Shibasaki, J. Am. Chem. Soc., 2007, 129, 7439-7443.
In a construction of 6-substituted 3-fluoro-5,6-dihydropyran-2-ones under mild conditions, the key step is a Julia-Kocienski olefination.
S. K. Mandal, A. Sarkar, P. Chakraborty, A. P. Chattoapdhyay, Synlett, 2018, 29, 75-78.
A mild, enantioselective hetero-Diels-Alder (HDA) reaction of the Brassard diene with aldehydes in the presence of a chiral titanium(IV) tridentate Schiff-base complexe has been developed. The mechanism is discussed.
Q. Fan, L. Lin, J. Liu, Y. Huang, X. Feng, Eur. J. Org. Chem., 2005, 3542-3552.