Synthesis and reactivity of furoquinolines bearing an external methylene-bond: access to reduced and spirocyclic structures

Abstract

A family of furoquinolines were efficiently obtained through a tandem acetalization/cycloisomerization process catalyzed by (5 mol%) silver imidazolate polymer and triphenylphosphine, and diversity was brought by the use of 7 different alcohol groups. From these furoquinolines, 3 examples of reduced derivatives could be obtained (d.r. up to 94 : 6), 10 different spiroketal derivatives by hetero-Diels-Alder reaction (d.r. up to 20 : 1), 8 hetero-[5,5]-spirocycles by cycloaddition with dibromoformaldoxime (d.r. up to 86 : 14) and finally 6 hetero-[5,6]-spirocycles by [4 + 2] cycloaddition with ethyl 3-bromo-2-(hydroxyimino)propanoate (d.r. up to 90 : 10).

Discovery of a Phosphine-Mediated Cycloisomerization of Alkynyl Hemiketals: Access to Spiroketals and Dihydropyrazoles via Tandem Reactions

“…A number of methods for the synthesis of spiroketals have been developed. − They were inspired by the challenge of natural product total synthesis, physical investigations into the fundamental principles governing spiroketal configuration, and the biological activities associated with spiroketal-containing natural products. Representative examples of natural product spiroketals are oligomycin B ( 1 ), − berkelic acid ( 2 ), − and reveromycin A ( 3 ) (Figure ). − Among the structures in Figure , oligomycin B is noteworthy because it contains a ketone α to the spiroketal which parallels the organization of functionality that develops in the new tandem reaction reported here.…”

Synthesis of unnatural α-amino esters using ethyl nitroacetate and condensation or cycloaddition reactions

“…It started with the preparation of the methylene-bearing dipolarophile 25 from propargylamide 24 using gold(I) chemistry, which turned out to be tolerant to a wide variety of dry solvents (dichloromethane, tetrahydrofuran, toluene, dimethylformamide, or acetonitrile) [26–27]. As for a related report [28] describing [2 + 3] cycloadditions between chlorooxime 26 and other methylene-bearing compounds, its reaction with compound 25 gave the spiroacetal 27 . However, in the present case this cycloadduct was only detectable by 1 H NMR analysis of the crude reaction mixture.…”

Synthesis of 5,6- and 6,6-Spirocyclic Compounds

“…This strategy has been demonstrated most recently by Belmont et al [163], where HDA between a variety of furoquinolines 313 and acrolein affords the spiroacetals 314 in good yield and selectivity (Scheme 77).…”

“…An initial report [164] of the HDA between an o-QM and chroman-derived enol ethers 315 required high temperature and pressure to afford 6,6-bis(benzannulated) spiroacetals (Scheme 78). Unfortunately, the corresponding 5,6-spiroacetals could not be accessed using this method due to the difficulty in obtaining the requisite enol ether 318, which under methylenation conditions Scheme 77 Belmont et al's HDA approach to mono(benzannulated) spiroacetals [163] isomerized to the endocyclic isomer exclusively. Similarly, Pettus and coworkers [154] were only able to obtain bis(benzannulated) spiroacetal 320 in poor yield when using enol ether 318 as the dienophile.…”