Synthesis of Trisubstituted Furans via Copper(I)-Catalyzed Strain-Driving Cycloisomerization/Annulative Fragmentation

Abstract

The in situ formed furan-fused cyclobutenes via Cu(I)-catalyzed cycloisomerization of readily available allenyl ketones bearing a cyclopropyl moiety are a highly reactive and powerful species, which undergo annulative fragmentation with terminal ynones to afford a wide variety of functional furans in moderate to high yields. This ring-distortion protocol features an unprecedented strain-controlled cycloisomerization/Diels−Alder/retro-Diels−Alder (CDRD) sequence under mild conditions.involving furan-fused cyclobutenes to create structurally new molecules are currently being pursued in our laboratory. ■ ASSOCIATED CONTENT * sı Supporting InformationThe Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.orglett.2c00578.Experimental procedures and copies of 1 H and 13 C NMR spectra for all new compounds; crystallographic data for compounds 3a-tosylhydrazone and 3abtosylhydrazone (PDF)Accession Codes CCDC 2150987−2150988 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk

Intermolecular Allene–Alkyne Coupling: A Significantly Useful Synthetic Transformation

“…Exploiting the cyclization ability of neighboring carbonyl functionality of allenyl ketones to achieve AA cross-coupling, Yao, Miao, and co-workers studied the reactivity of substrates bearing a strain-ring cyclopropyl moiety ( 57a ) (Scheme ). This study showcased that using an electrophilic Cu­(I) catalyst, the in-situ-generated furan-fused cyclobutene 57d is highly reactive and powerful species, which undergo annulative fragmentation with terminal ynones ( 57b ) to afford a functionalized furan derivatives ( 57c ). The authors proposed that the Cu­(I) catalyst is only responsible for the first cycloisomerization event forming the key furan-fused cyclobutene intermediate through strain-driven ring expansion of tethered cyclopropyl moiety.…”

Highlighting the Rich Chemistry of the Allenone Moiety

“…[118] In a different approach and taking advantage of the cycloisomerization of cyclopropylidene allenones 119 to build furan fused-cyclobutenes (see Scheme 23), a cascade cycloisomerization/Diels-Alder reaction/retro Diels-Alder process has been performed, yielding substituted furan systems 195 in the presence of terminal alkynones and copper catalysts (Scheme 38b). [119] Same starting materials 119 in the presence of stoichiometric CuI and molecular iodine evolve through a tandem cycloisomerization/ ring opening process providing iodofuran molecules 196 (Scheme 38c). [120,121] Although scarcely reported, cross-coupling reactions involving the oxycyclization of allenones in the presence of gold catalysts are also feasible.…”

“…Arene‐tethered propargyl allenones 93 undergo a tandem 5‐ endo ‐oxycyclization/6π electrocyclization reaction providing the skeleton of naphtho[1,2‐ b ]furan in compounds 193 employing platinum chloride as catalyst (Scheme 38a) [118] . In a different approach and taking advantage of the cycloisomerization of cyclopropylidene allenones 119 to build furan fused‐cyclobutenes (see Scheme 23), a cascade cycloisomerization/Diels‐ Alder reaction/retro Diels‐Alder process has been performed, yielding substituted furan systems 195 in the presence of terminal alkynones and copper catalysts (Scheme 38b) [119] . Same starting materials 119 in the presence of stoichiometric CuI and molecular iodine evolve through a tandem cycloisomerization/ring opening process providing iodofuran molecules 196 (Scheme 38c) [120,121] …”

Synthesis of Polysubstituted Furans: An Update Since 2019

“…Yao et al in 2022 exposed a strategy for the synthesis of trisubstituted furans 76 via Cu(I)-catalyzed cycloisomerization/Diels-Alder/retro-Diels-Alder (CDRD) cascade reaction of allenyl ketones bearing a cyclopropyl moiety 72 and terminal ynones 73 under mild conditions in good to excellent yields. [62] First of all, allene ketones 72 processed a cycloisomerization reaction, leading to ring expansion allenyl ketone substrate, which has aromatic ring substituents including methyl, methoxy, bromo, and fluoro can yield moderately desired furans. When solvents such as acetonitrile, ethylacetate, dichloromethane, 1, 1-dichloroethane, and toluene are employed, the reaction's yield is very low (Scheme 11).…”

“…Yao et al. in 2022 exposed a strategy for the synthesis of trisubstituted furans 76 via Cu(I)‐catalyzed cycloisomerization/Diels‐Alder/retro‐Diels‐Alder (CDRD) cascade reaction of allenyl ketones bearing a cyclopropyl moiety 72 and terminal ynones 73 under mild conditions in good to excellent yields [62] . First of all, allene ketones 72 processed a cycloisomerization reaction, leading to ring expansion of a cyclopropyl moiety to afford key furan‐fused cyclobutenes intermediate 74 in the presence of copper (I) salts.…”