Cascade Claisen Rearrangement: Rapid Synthesis of Polysubstituted Salicylaldehydes and Total Syntheses of Hemigossypol and Gossypol

Abstract

A cascade Claisen rearrangement of a well-organized maltol propargyl ether for the construction of polysubstituted salicylaldehydes is reported. This reaction features high atom economy (100 %), as well as catalyst-free and gram-scale conditions. Based on this novel methodology, the total synthesis of hemigossypol, gossypol, and their analogues has been realized.

Deconstructive Reorganization: De Novo Synthesis of Hydroxylated Benzofuran

“…After the deprotection of 2l and 2aj,the tetraphenolic Alfafuran [21] (14)a nd triphenolic Wittifuran X [22] (15) were afforded in 86 %and 54 %yield, respectively.Coumestrol (16), aproliferate inhibitor of ovarian and breast cancer, [2] could be obtained in 11 %total yield from 2ab via asequence of formylation, Pinnick oxidation, demethylation, and automatic esterification. Moracin M [23] (17), aphosphodiesterase-4i nhibitor,w as also accessible from 2ac after simple transformation [24] in 88 %y ield. Through esterification with propargylic acid and palladium-catalyzed cyclization, [25] 2af could advance to anhydromarmesin (18)in39%yield.…”

“…II could then engage in an aldol cyclization,followed by adehydration process to finally deliver benzofuran III (Scheme 2d). As part of our continuous endeavours to develop new dearomatic cascade rearrangement of pyrones, [17] we herein report an unprecedented deconstructive reorganization strategy for the de novo synthesis of hydroxylated benzofuran from kojic acid-or maltol-derived alkynes (Scheme 2d). In this reaction, both the benzene and furan rings were simultaneously established via an arene cycloisomerizaiton tandem reaction.…”

Cascade Claisen Rearrangement: Rapid Synthesis of Polysubstituted Salicylaldehydes and Total Syntheses of Hemigossypol and Gossypol

“…Investigation of the substituent effect at C2-position. ForXray data [20] please see the SupportingInformation.…”

“…[b] Estrone-derived styrene (0.2 mmol) and 1a (0.7 mmol). ForX-ray data [20] please see the SupportingInformation.…”

A one-pot diastereoselective synthesis of 1,3-diols and 1,3,5-triols via cascade reactions of arylalkynyl Grignard reagents with enol esters

“…In recent years, significant advances in cascade reactions involving Grignard reagent-mediated rearrangements have been reported. [22][23][24][25][26] In addition, nucleophilic addition of Grignard reagents to esters is one of the methods for the synthesis of tertiary alcohols. Initially, Zwahlen et al 27 reported a nucleophilic/rearrangement/nucleophilic addition cascade between a Grignard reagent and an enol lactone to afford a 1,3-diol compound.…”