Stereospecific Isomerization of Allylic Halides via Ion Pairs with Induced Noncovalent Chirality.

Samuel Martinez-Erro,Amparo Sanz-Marco,Víctor García-Vázquez,Belén Martín-Matute

doi:10.1021/acs.orglett.0c01200

Abstract

A regioselective protocol for the synthesis of substituted allylic chlorides, bromides, and fluorides has been established. Remarkably, the method can be applied to the enantioselective synthesis of challenging chiral allylic chlorides. When the allylic halides are treated with the base triazabicyclodecene as the catalyst, a [1,3]-proton shift takes place, giving the corresponding vinyl halides in excellent yields with excellent Z:E ratios. Furthermore, the [1,3]-proton shift takes place with an outstanding level of chirality transfer from chiral allylic alcohols (≤98%) to give chiral trifluoromethylated vinyl chlorides.

Highlights

A regioselective protocol for the synthesis of substituted allylic chlorides, bromides, and fluorides has been established
A relevant example of this class of reaction is the isomerization of allylic alcohols into carbonyl compounds, a synthetic transformation in organic chemistry.[3]
Because of the stepwise nature of the catalytic [1,3]hydrogen shift reactions, stereospecific examples of this transformation are rare.[9−11] In 2012, Cahard and co-workers reported an outstanding stereospecific isomerization of enantiopure β-trifluoromethylated allylic alcohols catalyzed by an achiral ruthenium complex.10a In 2016, we reported the stereospecific isomerization of electron-deficient allylic alcohols and ethers mediated by a simple guanidine-type base, triazabicyclodecene (TBD), in the absence of a metal catalyst.[11]

Summary

Corresponding Author

Previously observed in related suprafacial proton shifts.[11,12] We carried out parallel isomerization reactions of 2a and 2a-d1 and observed a large kinetic isotope effect of 5.4 ± 0.6 (see the Supporting Information). This suggests that the deprotonation of C1 is the rate-determining step of the reaction. The high stereospecificity of the reaction indicates a highly efficient transfer of chirality from the starting chiral allylic chloride to the ion pair intermediate. As long as the ion pair remains tight, the chirality can be further transferred stereospecifically to the final product upon protonation of C3 (Figure 1).

■ ACKNOWLEDGMENTS

■ REFERENCES

Catalytic Enantioselective Synthesis of the Endothelin Receptor

Example of Nucleophilic Substitution at Vinylic Carbon with