Diethyl(3-pyridyl)borane is a typical organoboron reagent. Its molecular structure contains a pyridine ring and a diethylborane group, combining the reactivity of both heterocycles and organoboron compounds. It is a key building block in the Suzuki -Miyaura coupling reaction, and can be used to form carbon–carbon bonds and synthesize multi-substituted pyrimidine compounds. Additionally, diethyl(3-pyridyl)borane serves as a key intermediate in the production of the anticancer drug abiraterone and is also used in the preparation of potential antitumor candidate molecules such as ATR kinase inhibitors. It is widely applied in the synthesis of pharmaceutical intermediates and the construction of complex organic molecules.

Structure and Properties of Diethyl(3-pyridyl)borane

Synthesis of diethyl(3-pyridyl)borane(D3PB) was initially reported by Terashima et al.,  who then developed a coupling reaction using it as the starting material.  This material, now commercially available from Aldrich Chemical Co., is notable for its stability under ambient conditions, in spite of little steric hindrance on boron. The authors ascribed the stability to the depression of both the nucleophilicity of the nitrogen atom and the electrophilicity of the boryl group, caused by the donation of π electrons in the pyridine ring to the vacant p-orbital of the boron atom. However, since pyridine is known to be highly deactivated toward electrophilic substitution, the pyridine ring in diethyl(3-pyridyl)borane would not act effectively as a π donor. Furthermore the boron is electropositive, and thus, significant stabilization would not arise from delocalization of the π electron onto this atom. Our studies  support this consideration:? the boron atom in 6-phenylborepino[4,5-c]thiophene, 6-phenylborepino[4,5-b]thiophene, or 2-methyl-6-phenylborepino[4,5-c]pyrrole forms the coordination bond with the nitrogen atom of various amines in spite of formal conjugation with strong π-electron donors, such as heteroles. Hence, it would be suggested that the boron and nitrogen atoms in diethyl(3-pyridyl)borane should act as a Lewis acid and Lewis base, respectively, to form the intermolecular boron?nitrogen coordination bond. [1]

The 1H NMR spectra of the mixture of diethyl(3-pyridyl)borane and bases such as pyridine (as solvent), piperidine (in deuteriodichloromethane), or quinuclidine (in deuteriodichloromethane) left standing at room temperature for several days, remained unchanged. The fact shows that the concentration of the open-chain oligomer, which has a boron atom free from the coordination, is quite low, since the basicity of the nitrogen atom in pyridine should be comparable to that of D3PB. The spectrum of the mixture of equimolar amounts of D3PB and N,N-dimethylaminopyridine displayed proton signals due to the tetramer of diethyl(3-pyridyl)borane and some sharp doublets having the same coupling constants as that of N,N-dimethylaminopyridine at higher positions, indicating that some molecules of N,N-dimethylaminopyridine are coordinated with the boron atom and, namely, several open-chain oligomers of D3PB involving the coordination bond with the pyridine are formed. Integration of the signal showed that 17.5% of the tetramer of D3PB had not decomposed. Interestingly, upon heating, only the signals due to open-chain oliogomers were broadened at 90 °C and signals due to the tetramer of diethyl(3-pyridyl)borane remained unchanged. The mixture of 3-(2-methoxyethoxy)-5-(diethylboryl)pyridine and N,N-dimethylaminopyridine exhibited similar behavior. At room temperature 33.3% of the tetramer of D3PB remained intact and broadening of signals due to open-chain oligomers involving N,N-dimethylaminopyridine occurred at 90 °C. Though signals due to open-chain oligomers partly started to coalesce at 100 °C, the signals of both tetramers of D3PB and 3-(2-methoxyethoxy)-5-(diethylboryl)pyridine remained unchanged. In conclusion, 3-(diethylboryl)pyridines comprise the cyclic tetramer via the coordination bonds, the cooordination bond of which is stable at ambient temperature and in aerated organic solvents with high water content. The marked thermal stability and the intriguing structure should be of use both in consideration of the reactivity of diethyl(3-pyridyl)borane and in construction of the artificial self-assembly systems with novel functionality.

References

[1]Sugihara Y, Takakura K, Murafuji T, Miyatake R, Nakasuji K, Kato M, Yano S. Structure and Properties of 3-(Diethylboryl)pyridines(1). J Org Chem. 1996 Oct 4;61(20):6829-6834. doi: 10.1021/jo960825k. PMID: 11667577.