Ring Cleavage of Benzofurans and Tetrahydrobenzofurans by m‐Chloroperbenzoic Acid Epoxidation

Abstract

The oxidation of the benzofurans 1a–f (tetrahydrobenzofurans 1g, h) with excess m‐CPBA is reported. The in situ generated, highly reactive benzofuran epoxides 2a–f and their quinone methides 3a–f (cis‐ene diones 3g, h) afford the labile tautomeric peroxy esters 5 and 5′ by nucleophilic addition of the peroxy acid. On elimination of m‐chlorobenzoic acid, the peroxy esters 5/5′ of the benzofuran derivatives 1a–f rearrange thermally to the keto esters 6 by CC cleavage or to the spiro epoxides 7 by CO cleavage. The latter undergo thermal isomerization to the 1,3‐benzodioxoles 8 and Diels‐Alder cycloaddition to the corresponding dimers 9. Independently, the keto esters 6 and the 1,3‐dioxoles 8 were synthesized by thermolysis of the dioxetanes 11. The tautomeric m‐CPBA adducts 5/5′ of the persistent ene diones 3g, h, derived from the tetrahydrobenzofuran derivatives 1g, h, rearrange as well to the spiro epoxides 7g, h. In contrast to the benzofuran derivatives 6a–f, the keto enol ester 6h suffers Baeyer‐Villiger rearrangement with another molecule of m‐CPBA to form the ene diester 10h.

Identification of Gli-mediated transcription inhibitors through synthesis and evaluation of taepeenin D analogues

“…Analogues 8a, b and 10a, b were designed having in mind to investigate, at a later stage, the activity of dimeric or hybrid derivatives. [15][16][17] Derivatives 19a, b and 22a, b (Scheme 4) were targeted seeking to substitute the oxidation prone 18,19 benzofuran moiety of the prototype with a more robust heteroaromatic ring system. To this end, Friedel-Crafts ipso-acylation of dehydroabietate derivative 11 (ref.…”

A Fast Entry to Furanoditerpenoid-Based Hedgehog Signaling Inhibitors: Identifying Essential Structural Features

“…Direct oxidation of this substrate's C(6)−C( 7) double bond employing m-CPBA, dimethyldioxirane, or osmium tetroxide based protocols were unsuccessful, presumably due to the lability of the benzofuran moiety under these conditions. 22 Selective oxidation was accomplished with NBS in THF/H 2 O to produce a mixture of bromohydrins that upon treatment with potassium tert-butoxide at low temperature furnished epoxide 13. 23 Although the 1 H NMR spectrum of the crude epoxide indicated a single diastereomer, its sensitivity hindered rigorous purification/characterization and necessitated immediate use.…”

Photochemistry of Thiarubrine A and Other 1,2-Dithiins: Formation of 2,6-Dithiabicyclo[3.1.0]hex-3-enes

“…We report the direct observation of novel sulfur compounds whose formation provides an explanation for the light-induced conversion of 1,2-dithiins to thiophenes. In particular we find that brief irradiation of 1 with visible light at −60 to −75 °C affords in excellent yields 2,6-dithiabicyclo[3.1.0]hex-3-enes ( 4 ), a previously unknown class of compounds . Matrix isolation and flash photolysis techniques have been used to identify and determine the lifetime in solution of s-cis-s-trans -( Z )-2-butenedithial ( cZt - 3b ), a presumed intermediate in the formation of 4 , and to define alternative low-temperature photochemical pathways available to cZt - 3b .…”