Regiodivergent Hydroborative Ring Opening of Epoxides via Selective C-O Bond Activation.

Marc Magre,Luigi Cavallo,Eva Paffenholz,Magnus Rueping,Bholanath Maity

doi:10.1021/jacs.0c05917

Abstract

A magnesium-catalyzed regiodivergent C–O bond cleavage protocol is presented. Readily available magnesium catalysts achieve the selective hydroboration of a wide range of epoxides and oxetanes yielding secondary and tertiary alcohols in excellent yields and regioselectivities. Experimental mechanistic investigations and DFT calculations provide insight into the unexpected regiodivergence and explain the different mechanisms of the C–O bond activation and product formation.

Highlights

The broad presence of hydroxyl moieties in pharmaceuticals, agrochemicals, and fragrance chemistry have led to the development of efficient protocols for their synthesis.[1]
We explored the scope and limitations of the MgBu2-catalyzed regioselective hydroboration of epoxides (Scheme 2) starting with monosubstituted terminal epoxides, which lead to secondary alcohols (2a−2h)
The most stable geometry is A7, in which two THF molecules are coordinated to Mg, and we considered it as the starting state in the catalytic cycle

Summary

■ INTRODUCTION

The broad presence of hydroxyl moieties in pharmaceuticals, agrochemicals, and fragrance chemistry have led to the development of efficient protocols for their synthesis.[1]. Different from the MgBu2-catalyzed mechanism, the formation of the Mg−H complex is unfeasible because of the very high endergonicity associated with the transfer of a hydride from HBpin to Mg (ΔG⧧ = 37.8 kcal/mol, Scheme S1 in the Supporting Information). The step is ring opening of the epoxide by nucleophilic attack via the SN2-type transition state TS5 (Figure 4) This step requires the overcoming of a free energy barrier of 29.2 kcal/mol from B1 and leads to the formation of the intermediate B2, a charge-separated species. Hydride transfer from the electron rich HBpin in B4 to the coordinated C O of 5, occurs via transition state TS8 and leads to intermediate B6 This step requires the overcoming of an overall free energy span of 25.0 kcal/mol from the reference structures B1+5. Energetics for the Step of Racemization of Mg(NTf2)2-Catalyzed Reaction inversion of configuration is observed at the chiral center in the resulting intermediate, emerging a pathway toward the formation of enantiomer of PB

■ CONCLUSIONS

■ ACKNOWLEDGMENTS

■ REFERENCES