Ag(i)-catalyzed intramolecular transannulation of enynone tethered donor–acceptor cyclopropanes: a new synthesis of 2,3-dihydronaphtho[1,2-b]furans

Abstract

An efficient AgOTf catalyzed tandem intramolecular transannulation of ((2-alkynyl)aryl)cyclopropyl ketones leading to the 2,3-dihydronaphtho[1,2-b]furans has been developed. The reaction features a regioselective alkyne hydration, cyclopropylketone-2,3-dyhydrofuran rearrangement, and benzannulation. The methodology gives direct access to the tricyclic core structure of biologically important 2,3-dihydronaphtho[1,2-b]furan natural products.

Synergistic Lewis–Brønsted Acid Catalysis in Cascade Cyclization of ortho-Alkynylaryl Cyclopropylketones for the Synthesis of 2,3-Dihydronaphtho[1,2-b]furans

“…Interestingly, this protocol could be used with substrate tethered with terminal alkyne 1s′ to give the desired product 2s′ in 38% yield along with a complex reaction mixture. It was important to note that the previously reported method could not be used to prepare this particular product . It was important to note that naphthofuran derivatives 2 could be used as substrates to synthesize 5,6-dihydrotetraphen-7-ol ( 6 ) via acid-activated isomerization by using 2.0 equiv of p -TsOH in DCE at 100 °C overnight as shown in Table .…”

“…We therefore aimed to search for new conditions which could convert substrates 1 to naphthofuran derivatives 2 employing a lower amount of catalyst loading with a shorter reaction time. We discovered that a synergism between AgTFA and (+)-CSA could increase the efficiency of this transformation, providing the desired product in better yields and shorter reaction times compared with the reported method . Moreover, our method used a less expensive catalyst with a lower catalyst loading which could provide several advantages for this transformation.…”

“…Interestingly, 2-alkynylarylcyclopropylketone precursors could also be converted to 2,3-dihydronaphtho­[1,2- b ]­furans which occurred via AgOTf-catalyzed tandem intramolecular transannulation as shown in Table (first column) . However, this method could not be applied to substrates containing terminal alkyne (R = H).…”

Opportunities for the Application and Advancement of the Corey–Chaykovsky Cyclopropanation

“…However, the yields are generally moderate to low, suggesting undesired reactions with the nitro group could still be viable and in some cases competitive (vide supra, Scheme ). Only a moderate yield is obtained when a nitro group is present at a distal position of ester 267 , an alkene acceptor which otherwise would be expected to present minimal challenge and exhibit high yield, suggesting the occurrence of unproductive reactivity (Scheme ). Some reports document the methylation of aromatic rings bearing nitro groups by TMSOI, even at room temperature (see Table ).…”

Synthesis of (Het)aryl 2-(2-hydroxyaryl)cyclopropyl Ketones

“…In addition, D-A cyclopropanes can isomerize to alkenes conjugated to either electron-releasing [29][30][31] or electron-withdrawing groups [29,32,33] and exhibit reactivity of substituted styrenes (or their heterocyclic analogues) [31,[34][35][36][37][38] or Michael acceptors [39][40][41][42][43][44][45], respectively (Scheme 1b). Moreover, D-A cyclopropanes can provide their acceptor [4,[46][47][48] or donor [5,40,42,49] substituents for new bond formations. Among others, D-A cyclopropanes, bearing the hydroxy group at the ortho-position of a donor aromatic substituent, are especially interesting.…”