Additive-Free Pd-Catalyzed α-Allylation of Imine-Containing Heterocycles.

Marko Kljajic,Rolf Breinbauer,Hansjörg Weber,Johannes G Puschnig

doi:10.1021/acs.orglett.6b03407

Abstract

An additive-free Pd-catalyzed α-allylation of different imino-group-ontaining heterocycles is reported. The activation of α-CH pronucleophiles (pKa (DMSO) > 25) occurs without the addition of strong bases or Lewis acids using only the Pd/Xantphos catalyst system. The reaction scope has been studied for various 5- and 6-membered nitrogen-containing heterocycles (yields up to 96%). Mechanistic investigations suggest an initial allylation of the imine-N followed by a Pd-catalyzed formal aza-Claisen rearrangement.

Highlights

O ver the past decade, the transition-metal-catalyzed CH functionalization of heterocycles has expanded the organic tool box with efficient means to form C−C bonds without apparent leaving groups on the heterocycle substrate.[1,2]. Among these the allylation of heterocycles at the sp2-hybridized carbon under CH-activation has been described by using various transition metals as catalysts.[3]
We report a new method for the additive-free α-allylation of several heterocycles with allyl acetate under mild conditions (Scheme 1), which complements the existing work on various nucleophiles.[8]
In our ongoing efforts to use the Tsuji−Trost allylation[9] for the synthesis of biologically active molecules,[10] we have observed that, when DBN is used as base additive, under certain circumstances the formation of allylated 1,8-diazabicyclonon-5-ene (3) could be observed

Summary

Introduction

O ver the past decade, the transition-metal-catalyzed CH functionalization of heterocycles has expanded the organic tool box with efficient means to form C−C bonds without apparent leaving groups on the heterocycle substrate.[1,2] Among these the allylation of heterocycles at the sp2-hybridized carbon under CH-activation has been described by using various transition metals as catalysts.[3]. This reaction aroused our interest as it appeared to have proceeded under direct C−H allylation in an α-position to an amidine moiety[2] whereas comparable N-heterocycles could only be activated with strong bases and additives (Scheme 2).[6] In order to prevent a possible self-deprotonation, which could be the case for bases like DBN, we used the readily available oxazoline 4 as a suitable test substrate to study the Scheme 1.

Results

Conclusion