Iron‐Catalyzed Cross‐Coupling of Propargyl Ethers with Grignard Reagents for the Synthesis of Functionalized Allenes and Allenols

Abstract

Herein we disclose an iron‐catalyzed cross‐coupling reaction of propargyl ethers with Grignard reagents. The reaction was demonstrated to be stereospecific and allows for a facile preparation of optically active allenes via efficient chirality transfer. Various tri‐ and tetrasubstituted fluoroalkyl allenes can be obtained in good to excellent yields. In addition, an iron‐catalyzed cross‐coupling of Grignard reagents with α‐alkynyl oxetanes and tetrahydrofurans is disclosed herein, which constitutes a straightforward approach towards fully substituted β‐ or γ‐allenols, respectively.

Recent Advances in Non-Precious Metal Catalysis

“…Backvall and co-workers disclosed a stereospecific Fecatalyzed cross-coupling reaction of propargyl ethers with Grignard reagents to obtain tri-and tetrasubstituted fluoroalkyl allenes in good to excellent yields. 98 By screening various leaving groups on the propargyl ether (R = Me) in the presence of Fe(acac) 3 and MeMgBr, the trifluoromethyl allene product was obtained in high yield (91%) without a detectable amount of gem-difluoro-1,3-enyne as a side product. Crosscoupling was also found to be effective on nonfluorinated substrates to provide the desired allenes in good yields.…”

Regio- and Stereoselective Addition to gem-Difluorinated Ene–Ynamides: Access to Stereodefined Fluorinated Dienes

“…A typical way to introduce a gem -difluorinated unit into a molecule is to use Ichikawa’s S N 2′-type reaction on trifluoromethylated alkenes . The defluorinative alkylation protocol has been employed to install numerous complex fragments from conjugated trifluoromethylenynes through nucleophilic addition, electrochemical, and photocatalytic processes as well as radical transformations (Scheme , d). Base-promoted defluorination of α-trifluoromethylated alkynyl derivatives constitutes a metal-free way to obtain alkynyl difluorovinyl compounds (Scheme , e).…”

Nickel-Catalyzed Deaminative Allenylation of Amino Acid Derivatives: Catalytic Activity Enhanced by an Amide-Type NN2 Pincer Ligand

“…Accordingly, enormous efforts have been devoted to the development of efficient methods for the synthesis of allenes . Among these established methodologies, transition metal-catalyzed/mediated cross-coupling of electrophilic propargyl derivatives with various nucleophiles has emerged as one of the most popular and reliable approaches for constructing the core structure of allene moieties . However, the requirements of harsh reaction conditions and multistep operations for preparing the elaborated alkyne-based reagents have stimulated chemists to devise novel and streamlined strategies for the preparation of allenes from readily available starting materials.…”