Direct α-Benzylation of Methyl Enol Ethers with Activated Benzyl Alcohols: Its Rearrangement and Access to (±)-Tetrahydronyasol, Propterol A, and 1,3-Diarylpropane

Abstract

Herein, we report a one-pot Lewis acid mediated synthesis of bi-and triarylpropanal derivatives and their corresponding isomeric ketones from aromatic enol ethers. This transformation takes place via nucleophilic attack of enol ethers to electron-rich benzyl alcohols. The substrate scope of this indicates that it might proceed via quinomethoxy methide as a key intermediate leading to propanal derivatives, and their Wagner−Meerwein rearrangement afforded isomeric ketones. Further, this methodology was applied for the synthesis of (±)-tetrahydronyasol, propterol A, and 1,3diarylpropane.

One‐Pot Transition‐Metal‐Free Synthesis of Polysubstituted Fused Benzene Derivatives from Methyl Enol Ethers and Alkynes

“…Synthesis of methyl enol ethers ( 1 a – 1 q , 4 and 9 ). All methyl enol ethers 1 a – 1 q , 4 and 9 are known compounds except 1 l and prepared by Wittig reaction of corresponding carbonyl compounds using following literature protocols [13–16,20,21] …”

“…Recently, our group reported a direct α‐benzylation method using methyl enol ethers leading to synthesis of (±)‐tetrahydronyasol, propterol‐A natural products [14] . Also, new strategies for the synthesis of indole, thiazole and thiazoline derivatives from MEE have been disclosed [15,16] .…”

Alkyl Enol Ethers: Development in Intermolecular Organic Transformation

“…The most common method for the preparation of alkyl enol ethers is the Wittig reaction of the corresponding aldehyde or ketone derivatives in the presence of a base. Different aliphatic or aromatic aldehydes or ketones 24 can be converted into their corresponding enol ethers 25 using Wittig condition via one‐carbon elongation [2b,19] . In this method, the ylide was prepared in situ from the salt (methoxymethyl)triphenylphosphonium chloride along with a base.…”

“…Recently, our group have developed a Lewis acid‐catalyzed α‐benzylation of aromatic enol ethers 25 by using activated benzyl alcohol 45 to afford bi‐and tribenzyl‐carbonyl derivatives 46 and their analogous isomeric ketones 46 a (Scheme 19). [2b] The synthesis of compound 46 proceeds via formation of quinomethoxy methide as an intermediate followed by nucleophilic attack of enol ethers through Zn‐catalyst, and then Wagner‐Meerwein rearrangement led to isomeric ketones 46 a in the presence of BF 3 .Et 2 O in 1, 2‐DCE at 50 °C. This strategy is further used for the preparation of natural products.…”

Boron Trifluoride Etherate-Controlled Reactions of Methyl Enol Ethers: Selective Synthesis of Dihydrofuro[3,2-c]chromenone and Furo[3,2-c]chromenone Derivatives

“…Recently, our group reported a direct α-benzylation strategy using MEE to access (±)-tetrahydronyasol, propterol-A natural products. 14 Also, new efficient methods for the synthesis of thiazole, thiazoline, and indole derivatives from MEE have been disclosed. 15,16 Our ongoing research interest on diverse reactivity of methyl enol ethers (MEEs) provoked us to explore reactions of MEEs with an electrophilic or nucleophilic partner.…”