Synthesis of 2,3-dihydrobenzofurans via the palladium catalyzed carboalkoxylation of 2-allylphenols

Abstract

A new Pd-catalyzed alkene carboalkoxylation strategy for the preparation of 2,3-dihydrobenzofurans is described. This method effects the coupling of readily available 2-allylphenol derivatives with aryl triflates to generate a wide range of functionalized 2,3-dihydrobenzofurans in good yields and diastereoselectivities (up to >20:1). Use of newly developed reaction conditions that promote anti-heteropalladation of the alkene is essential in order to generate products in high yield.

Recent Developments in Pd0‐Catalyzed Alkene‐Carboheterofunctionalization Reactions

“…The same conditions that were used to promote alkene-carboamination reactions of relativelye lectron-poor nucleophiles through an anti-aminopalladationp athway have also shown utility for the conversion of 2-allylphenols 102 into substituted dihydrobenzofurans 103 (Scheme 37). [47] Prior studies had illustrated that ar elated conversion of but-3-enylphenols into benzochromans proceeded in good yield, [48] but these conditions were not effective for the reactions of 2-allylphenols (102). In contrast, conditions that favored anti-heteropalladation provided the desired dihydrobenzofuran products in good yields, albeit with modest diastereoselectivities.…”

Functionalized Allyl Aryl Ether Synthesis from Benzoic Acids Using a Dearomatization and Decarboxylative Allylation Approach

“…Among all of the functionalized arenes, allyl aryl ethers particularly draw our attention because they are key precursors used in natural product synthesis . For instance, allyl aryl ethers can undergo aryl-Claisen [3,3]-sigmatropic rearrangements providing ortho -allyl phenols followed by cyclization to give dihydrobenzofurans, which are important backbones in many biologically active molecules . Moreover, isochroman and dioxabicyclooctane scaffolds can be prepared through Friedel–Crafts type cyclizations of allyl aryl ethers …”

Recent Advances in Synthetic Strategies to 2,3-Dihydrobenzofurans

“…A more general Pd-catalyzed alkene carboalkoxylation method by Wolfe and Hutt (2016) effected the coupling of readily available o-allylphenol derivatives with aryl triflates to generate a wide range of functionalized DHBs in good yields and diastereoselectivities (up to >20:1) (Scheme 24, route B). 85 The use of newly developed reaction conditions that promoted anti-heteropalladation of the alkene was essential in order to generate the products in high yield. In the case of 2,3-disubstituted DHBs excellent dr in favor of trans isomers was obtained.…”