Facile Preparation of (2Z,4E)-Dienamides by the Olefination of Electron-deficient Alkenes with Allyl Acetate

Summary

The ruthenium-catalyzed olefination of electron-deficient alkenes with allyl acetate is described here. By using aminocarbonyl as a directing group, this external oxidant-free protocol has high efficiency and good stereo- and regioselectivity, opening a novel synthetic route to (Z,E)-butadiene skeletons.

Abstract

Direct cross-coupling between two alkenes via vinylic C-H bond activation represents an efficient strategy for the synthesis of butadienes with high atomic and step economy. However, this functionality-directed cross-coupling reaction has not been developed, as there are still limited directing groups in practical use. In particular, a stoichiometric amount of oxidant is usually required, producing a large amount of waste. Due to our interest in novel 1,3-butadiene synthesis, we describe the ruthenium-catalyzed olefination of electron-deficient alkenes using allyl acetate and without external oxidant. The reaction of 2-phenyl acrylamide and allyl acetate was chosen as a model reaction, and the desired diene product was obtained in 80% isolated yield with good stereoselectivity (Z,E/Z,Z = 88:12) under optimal conditions: [Ru(p-cymene) Cl₂]₂ (3 mol %) and AgSbF₆ (20 mol %) in DCE at 110 ºC for 16 h. With the optimized catalytic conditions in hand, representative α- and/or β-substituted acrylamides were investigated, and all reacted smoothly, regardless of aliphatic or aromatic groups. Also, differently N-substituted acrylamides have proven to be good substrates. Moreover, we examined the reactivity of different allyl derivatives, suggesting that the chelation of acetate oxygen to the metal is crucial for the catalytic process. Deuterium-labeled experiments were also conducted to investigate the reaction mechanism. Only Z-selective H/D exchanges on acrylamide were observed, indicating a reversible cyclometalation event. In addition, a kinetic isotope effect (KIE) of 3.2 was observed in the intermolecular isotopic study, suggesting that the olefinic C-H metalation step is probably involved in the rate-determining step.

Introduction

Butadienes are widely occurring and are commonly found in many natural products, drugs, and bioactive molecules¹. Chemists have made intense efforts to develop an efficient, selective, and practical synthetic methodology for the synthesis of 1,3-butadienes^2,3_. Recently, direct cross-couplings between two alkenes via double vinylic C-H bond activation was developed, representing an efficient strategy for the synthesis of butadienes, with high atomic and step economy. Among them, the palladium-catalyzed cross-coupling of two alkenes has attracted much attention, provid....

Protocol

Caution: Please consult all relevant material safety data sheets (MSDS) before use. All cross-coupling reactions should be performed in vials under a sealed argon atmosphere (1 atm).

1. Preparation of Butadienes by the Olefination of Acrylamides with Allyl Acetate

1. Dry a screw-cap vial (8 mL) with a compatible magnetic stir bar in an oven at 120 °C for over 2 h. Cool the hot vial to room temperature by blowing on it with inert gas before use.
2. Use an analytical balance and weigh 3.7 mg (~3 mol %, ~0.005 mmol) of [Ru(p-cymene)Cl₂]₂ (brown powder) and 13.7 mg (20 mol%, 0.04 mmol) of AgSb....

Results

Our efforts were focused on the preparation of 1,3-butadiene from acrylamide and allyl acetate.

Table 1 illustrates the optimization of conditions, including the screening of various additives and solvents, using [Ru(p-cymene)Cl₂]₂ as the catalyst. After screening a series of representative solvents, we were pleased to find that the product yield dramatically improved to 80%, with .......

Discussion

[Ru(p-cymene)Cl₂]₂ is a cheap, easily accessible, air-stable, and highly active Ru-based catalyst with excellent functional group tolerance that efficiently operates under mild reaction conditions to give C-H/C-H coupling butadiene products. Silver salt AgSbF₆ was used as an additive that may abstract the chloride of [Ru(p-cymene)Cl₂]₂ to generate a cationic ruthenium complex for the following C-H bond activation. However, only α-subst.......

Materials

Name	Company	Catalog Number	Comments
Allyl Acetate	TCI	A0020	> 98.0%(GC), 25 mL package
Dichloro(p-cymene)ruthenium(II) dimer	TCI	D2751	> 95.0%(T), 5 g package
Silver hexafluoroantimonate	TCI	S0463	> 97.0%(T),  5 g package
1,2-Dichloroethane	TCI	D0364	> 99.5%(GC), 500 g package
Rotavapor	EYELA	N-1200A	Use to dry solvent
Silica gel	Merck	107734	Silica gel 60 (0.063-0.2 mm), for column chromatoraphy