DABO Boronates: Stable Heterocyclic Boronic Acid Complexes for Use in Suzuki-Miyaura Cross-Coupling Reactions

Abstract

Diethanolamine-complexed heterocyclic boronic acids (DABO boronates) are air-stable reagents that can be used directly in Suzuki-Miyaura reactions in the presence of water or a protic co-solvent. Interestingly, heterocyclic DABO boronates can be stored for extended periods of time at room temperature with no noticeable degradation, unlike their boronic acid counterparts. Heterocyclic DABO boronates constitute an operationally simple and efficient alternative to other boronic acid derivatives as coupling partners in palladium-catalyzed cross-coupling reactions under standard ­Suzuki-Miyaura conditions.

Key words

Suzuki-Miyaura reaction - cross-coupling - palladium catalysis - heterocyclic boronate - aryl boronate

References

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20

MIDA is over 100 times more expensive. KHF₂ is similarly priced, but 3.0 equiv are required for the synthesis of heterocyclic potassium trifluoroborates. Pinacol is about 10 times more expensive than DEA. Prices were obtained from the Sigma-Aldrich online catalogue.

21

2-Methoxyphenylboronic acid and 2-furyl DABO boronate 7 were mixed at r.t. in THF for 3 h to give an equilibrium mixture of both boronic acids and their DABO counterparts. A similar product mixture was observed beginning with 2-methoxyphenyl DABO boronate 4 and 2-furylboronic acid.

24

Excess diethanolamine can be removed by triturating the crude solid in EtOAc and filtering. DABO complexes could not be characterized by HRMS, and unidentifiable boron-containing masses were observed by electron ionization. Elemental analysis was attempted, but the carbon percentage was consistently below the theoretical value by about 10.

25

No decomposition of 2-furyl DABO boronate 7 was observed by NMR analysis after 72 d of storage in open vials at r.t. The average temperature and humidity were 24 ˚C and 65%, respectively, during this period. In contrast, the commercial 2-furylboronic acid completely decomposed in less than one week under these conditions. We recommend storing DABO boronates at r.t. in a closed vial.