The State of the Art in Azaborine Chemistry: New Synthetic Methods and Applications

Abstract

Boron-nitrogen heteroarenes hold great promise for practical application in many areas of chemistry. Enduring interest in realizing this potential has in turn driven perennial innovation with respect to these compounds' synthesis. This Perspective discusses in detail the most recent advances in methods pertaining to the preparation of BN-isosteres of benzene, naphthalene, and their derivatives. Additional focus is placed on the progress enabled by these syntheses toward functional utility of such BN-heterocycles in biochemistry and pharmacology, materials science, and transition-metal-based catalysis. The prospects for future research efforts in these and related fields are also assessed.

Figure 1.

Three possible boron-nitrogen isosteres of benzene.

Figure 2.

Examples of BN-polyaromatic compounds synthesized by Dewar.

Scheme 1.. Synthesis of an Azaborine-Containing CDK2 Inhibitor (6) through Rh-Catalyzed B-arylation^,,a

^a Abbreviations: BIPHEP = 2,2’-bis(diphenylphosphmo)-1,1’-biphenyl; CDMT = 2-chloro-4,6-dimethoxy-1,3,5-triazine; NMM = N-methylmorpholine; TBAF = tetra-n-butylammonium fluoride.

Scheme 2.. Negishi Cross-Coupling of C(3)-Brominated Azaborine (Top) and Derivatization of a C(3)-Vinylated Azaborine into BN-Naphthalene 7 and BN-Indenyl Anion 8 (Bottom)

Scheme 3.. Ir-Catalyzed C(6)-Selective Borylation, Followed by Pd-Catalyzed (Hetero)arylation^,a

^a Abbreviations: cod = 1,5-cyclooctadiene; dtbpy = 4,4’-di-tert-butyl-2,2’-bipyridine; MTBE = methyl tert-butyl ether.

Scheme 4.. Dimerization (Top) and Polymerization (Bottom) of Azaborine Monomers through Suzuki-Miyaura Coupling^,a

^a Abbreviations: dppf = 1,1’-bis(diphenylphosphino)ferrocene; MTBE = methyl tert-butyl ether.

Scheme 5.. Selective Photoisomerization of Azaborine 1 Conducted in a Neon Matrix (4 K)

Figure 3.

Carbonyl A₁ vibrational IR frequencies for various bisphosphine-ligated molybdenum complexes.

Scheme 6.. Ring Expansion of Boroles into Hexasubstituted 1,2-Azaborines

Scheme 7.. Fang’s Synthesis and Subsequent Derivatization of 8a-Azonia-4a-boratanaphthalene (15)^,

Scheme 8.. Palladium-Catalyzed Suzuki-Miyaura Coupling Reactions of Electron-Deficient Aryl Chlorides Using 17 as a Ligand^,a

^a Yields in parentheses are from reactions using 5 mol % PPh₃ as a ligand.

Scheme 9.. Cui’s Synthesis of 2-Azonia-1-boratanaphthalenes Starting from Aryl Ketimines

Scheme 10.. Liu’s Synthesis of 8a-Azonia-1-boratanaphthalene (18) Starting from 2-Vinylpyridine

Scheme 11.. Molander’s Synthesis of 1-Azonia-2-boratanaphthalenes from 2-Aminostyrenes and Potassium Trifluoroborate Salts^,a

^a Abbreviations: CPME = cyclopentyl methyl ether.

Scheme 12.. Synthesis and Derivatization of 2-(Chloromethyl)-1-azonia-2-boratanaphthalenes^,a

^a Abbreviations: CPME = cyclopentyl methyl ether; Pd-G2 = chloro[2-(2’-amino-1,1’-biphenyl)]palladium(II), RuPhos = 2-dicyclohexylphosphino-2’,6’-diisopropoxybiphenyl; XPhos = 2-dicyclohexylphopshmo-2’,4’,6’-triisopropylbiphenyl.

Scheme 13.. C(3)-Selective Bromination of 1-Azonia-2-boratanaphthalenes and Subsequent Functionalization^,a

^a Abbreviations: bpy = 2,2’-bipyridine; CPME = cyclopentyl methyl ether; dppf = 1,1’-bis(diphenylphosphino)ferrocene; dtbpy = 4,4’-di-tert-butyl-2,2’-bipyridine; Pd-G2 = chloro[2-(2’-amino-1,1’ -biphenyl)]palladium(II); SPhos = 2-dicyclohexylphosphino-2’,6’-dimethoxybiphenyl.

Scheme 14.. Synthesis of 1,3-Azaborine 24

Scheme 15.. 1,3-Azaborine Boron Substituent Exchange under Acidic (Top) and Basic (Bottom) Conditions^,a

^a Abbreviations: TMS = trimethylsilyl.

Scheme 16.. Regioselective Electrophilic Aromatic Substitution of 24 with Böhme’s Salt

Figure 4.

UV-PE spectra of toluene (left), 26 (middle), and 27 (right). Energy values are reported as the negative of the experimentally determined ionization energy (-IE). The depicted molecular orbitals are the top seven occupied orbitals associated with the energy levels observed for each molecule. Spectral data and orbital calculations originally reported in ref .

Scheme 17.. Rhodium-Catalyzed Cycloaddition of Iminoborane 28 with Acetylene

Scheme 18.. Synthesis of C(2)-Substituted 1,4-Azaborines through Stoichiometric η⁴-1,2-Azaborete Rhodium Complexes^,a

^a Abbreviations: Fc = ferrocenyl; TAA = 4-(N,N-bis(4-methoxyphenyl)amino)phenyl.

Scheme 19.. Synthesis of Bis- and Tris-1,4-azaborines Using Diyne (Top) and Triyne (Bottom) Starting Materials

Scheme 20.. Synthesis of 3,5-Dimethyl-1,4-azaborines

Scheme 21.. Diversification of the B(4) Substituent Starting from 32

Figure 5.

Normalized absorption (solid lines) and emission (dotted traces) spectra for 33 (green) and 34 (red) and their carbonaceous analogues 33-c (black) and 34-c (purple) in THF at 1 × 10⁻⁵ M. Spectral data originally reported in ref .

Scheme 22.. Calculated Relative Thermodynamic Stabilities of 1, 2, and 3^a

^a ΔE_rel values (kcal mol⁻¹) are from ref .

Scheme 23.. Complexation of 1,4-BN-Naphthalene 35 with Neutral and Cationic Platinum(II) Sources^a

^a Crystal structure information originally provided in ref .

Scheme 24.. Synthesis of κ²-P-η²-BC Ligands 36 and 37^,a

^a Abbreviations: PMHS = polymethylhydrosiloxane

Scheme 25.. Palladium-Catalyzed trans-Hydroboration of Terminal (Top) and Internal (Bottom) 1,3-Enynes Using 36 and 37, Respectively, as Ligand

Figure 6.

Frontiers for future discoveries in azaborine chemistry.