Metal Triflate-Promoted Allylic Substitution Reactions of Cinnamyl Alcohol in the Presence of Orthoesters and Acetals.

Dawn R Chaffey,Nicholas C O Tomkinson,Stuart H Taylor,Andrew E Graham,Carla Alamillo-Ferrer,Thomas E Davies

doi:10.1021/acsomega.9b02059

Dawn R Chaffey, Nicholas C O Tomkinson + Show 4 more

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https://doi.org/10.1021/acsomega.9b02059

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Abstract

The product distribution of ethers formed from the reaction of cinnamyl alcohol with orthoesters in the presence of indium (III) triflate (InOTf)3 is dependent on both the reaction temperature and catalyst loading. Carrying out the reaction at room temperature under low loadings of the catalyst leads to a facile reaction generating the unexpected secondary allyl ether as the major product. In contrast, carrying out the reaction under higher catalyst loadings at elevated temperatures provides the expected primary linear ether in high yield and with excellent selectivity. The etherification reaction is also effective in the presence of acetals and ketals in place of orthoesters and allows for the development of the procedure to encompass a telescoped etherification protocol in which the acetal is generated in situ.

Highlights

The continuing interest in the development of transition metal-catalyzed processes involving allylic substrates is testimony to the versatility and utility in this area of chemistry
The synthesis of allyl ether products remains an area of considerable interest due to their diverse reactivity, which makes them highly versatile synthetic intermediates, in natural product synthesis.[10−13] While extensive work has demonstrated the facile reactions of carbon and nitrogen nucleophiles in transition metal-catalyzed allylic substitution reactions, the corresponding formation of carbon−oxygen bonds from both derivatized and underivatized allylic substrates remains a considerable challenge due to the low nucleophilicity of alcohols.[14,15]
The direction of the equilibrium for allylic alcohols bearing phenyl substituents, such as 1, is dictated by thermodynamic considerations favoring the formation of the more conjugated linear products.[21,25−27] allylic substrates derived from the corresponding secondary alcohol typically give primary addition products as the major component of substitution reactions, except in special circumstances.[14,28,29]

Summary

Introduction

The continuing interest in the development of transition metal-catalyzed processes involving allylic substrates is testimony to the versatility and utility in this area of chemistry.

Methods

Results

Conclusion