A Tandem Conjugate Addition–Intramolecular Horner–Wadsworth–Emmons Olefination Approach to the Synthesis of Cyclopentene[c]chroman-2-ones and Cyclopent-1-enecarboxylates

Abstract

A strategically new approach to cyclopentene[c]chroman-2-ones and cyclopent-1-enecarboxylates by tandem MichaelHorner-Wadsworth-Emmons reaction of 2,5-hexanedione with 3-(diethoxyphosphoryl)coumarins is described. The products were obtained as single diastereoisomers in high yields. The cyclopent-1-enecarboxylate moiety is present in many biologically active natural products. 1 Within this class of compounds the cyclopenta[c]tetrahydropyran-2-one ring system is incorporated in the reduced or modified form into natural products such as neonepetalactone (1) In recent years considerable research activity has been directed toward the synthesis of cyclopentene-fused chroman-2-ones. The synthetic strategies include [3+2] cycloaddition of allenoates with 3-alkoxycarbonylcoumarin, 3a intramolecular [3+2] cycloaddition of 2-styrenyl allenoates, 3b annulation of 3-acetylcoumarin with allenylboronic esters, 3c and [3+2] cycloaddition of 3-acetylcoumarin with cyclopropenone acetals. 3d Palladiumcatalyzed [3+2] cycloaddition of 2-(trimethylsilylmethyl)-allyl acetates with coumarins has been used to install a cyclopentane ring containing an exo-methylene group. 3e Despite its potential utility, the approach based on a Michael addition of homoenolate anion equivalents to α-dialkoxyphosphoryl-α,β-unsaturated lactones followed by an intramolecular Horner-Wadsworth-Emmons (HWE) reaction of the resulting 2-phosphono-6-oxoalkanoates has been exploited only rarely for the preparation of cyclopentene annulated γ-and δ-lactones. Minami et al. reported that the tandem Michael-intramolecular HWE reaction of diethyl 2-oxoalkylmalonates with α-phosphoryl-α,β-unsaturated-γ-lactones provided cyclopentenefused γ-lactones. 4a Bestmann et al. reported that Michael addition of [2-(1,3-dioxolan-2-yl)ethyl]magnesium bromide to 3-(diethoxyphosphoryl)coumarin followed by deprotection of the aldehyde group and an intramolecular HWE reaction led to cyclopentene-annulated chromanones. 4b In the course of our earlier studies we have reported that the above [3+2] annulation strategy could be extended for the preparation cyclopent-1-enecarboxylates from the corresponding tert-butyl (E)-2-(diethoxyphosphoryl)alk-2-enoates. 4c In spite of these advances, it is evident that methods to access cyclopentannulated lactones, particularly via conceptually different approaches are still of significant interest. It is worthy of note that 1,4-diketones are known to be potent homoenolate equivalents. 5a Surprisingly, a strategy for [3+2] cyclopentannulation that utilizes homoenolates generated from 1,4-diketones (γ-oxoketone enolates) as three-carbon fragments has not been exploited. 5 In this letter we report the first examples of a tandem Michael-intramolecular HWE reaction of 2,5-hexanedione (8) with 3-(diethoxyphosphoryl)coumarins 7a-c in which the dione serves as a γ-oxoketone enolate equivalent. This approach expands greatly the scope of the conjugate addition involving coumarins 7 6 and provides a new and prac-

An efficient synthesis of 3-diethoxyphosphoryl-4-(1H-indol-3-yl)-3,4-dihydrocoumarins: a convenient approach to 3-methylene-4-(indol-3-yl)-3,4-dihydrocoumarins

“…39,40 We envisioned that the use of the same approach would allow Michael addition of indole to 3-(diethoxyphosphoryl)coumarins. Herein, this challenge has been addressed and we present the efficient synthesis of 3-diethoxyphosphoryl-4-(indol-3-yl)-3,4-dihydrocoumarins by an unprecedented TBD-mediated reaction of indoles with 3-(diethoxyphosphoryl)coumarins.…”

Synthesis of cyclopent-1-enecarbonitriles via a tandem Giese/HWE reaction initiated by visible light

“…7 In 2008, we demonstrated the application of 2-diethoxyphosphoryl-6-oxohexanoates, in the intramolecular Horner–Wadsworth–Emmons reaction leading to the preparation of 5-substituted tert -butyl cyclopent-1-enecarboxylates (Scheme 2). 8…”