A Convergent, Modular Approach to Functionalized 2,1-Borazaronaphthalenes from 2-Aminostyrenes and Potassium Organotrifluoroborates

Abstract

Azaborines are an important class of compounds with applications in both medicinal chemistry and materials science. 2-Chloro-2,1-borazaronaphthalene was the first borazaronaphthalene reported in 1959; however, access to more highly functionalized substructures has been limited because of the harsh reaction conditions required to displace the chloride on boron. A convergent approach has been developed to synthesize disubstituted 2,1-borazaronaphthalenes from N-substituted 2-aminostyrenes and potassium organotrifluoroborates, where the potassium organotrifluoroborate is converted to the active R-BX2 species (X = Cl or F) in situ by addition of a fluorophile. Starting from aryl-, heteroaryl-, alkynyl-, alkenyl-, and alkyltrifluoroborates, a library of highly functionalized 2,1-borazaronaphthalenes are synthesized in one step under mild, transition-metal free conditions.

Method for Accessing Nitrogen-Containing, B-Heteroaryl-Substituted 2,1-Borazaronaphthalenes

“…Using the standard reaction conditions previously developed by our group for accessing the 2,1-borazaronaphthalene core, 4 initial attempts to condense nitrogen-containing trifluoroborates with o -aminostyrene derivatives were met with no success. To understand what caused nitrogen heterocyclic trifluoroborates to be incompatible with the reported conditions, pyridine was added in increasing amounts to the reaction of 2-aminostyrene ( 1 ) with phenyltrifluoroborate ( 2 ) (Table 1).…”

“…3b This specific class of azaborines has been investigated for their utility mainly because of the simple and robust method for their synthesis, which begins with a highly versatile condensation between 2-aminostyrenes and potassium organotrifluoroborates. 4 Furthermore, the myriad recent methods for functionalizing this core extends the potential for additional applications of the 2,1-borazaronaphthalene substructure. 5 However, one deficiency within the initial synthetic scope for accessing the 2,1-borazaronaphthalene core was the lack of nitrogen-containing heterocyclic functional units, particularly substituted off of boron.…”

“…5 However, one deficiency within the initial synthetic scope for accessing the 2,1-borazaronaphthalene core was the lack of nitrogen-containing heterocyclic functional units, particularly substituted off of boron. 4 Azaborine subunits containing N -heterocyclic scaffolds at this position would be of particular value, especially considering the diverse use of heterocycles and their recognition as “privileged structures” for modulation of biological systems. 6 A recent solution to address this problem was reported by Rombouts et al using microwave (μW) conditions (eq 1), which allowed the annulation of pyridyl styrenes in high yields.…”

Improving Transformations Through Organotrifluoroborates

“…The developed method boasts a large functional group tolerance, allowing the presence of aryl nitro, nitrile, and ester substituents as well as alkyl bromide and iodide moieties. These structures have been shown to undergo halogenation reactions and subsequent cross-couplings, allowing formation of a large library of functionalized isosteres of naphthalene cores (Scheme 75) [114]. Organotrifluoroborates have found use in several useful niches in synthetic organic chemistry.…”

Accessing Elaborated 2,1-Borazaronaphthalene Cores Using Photoredox/Nickel Dual-Catalytic Functionalization

“…Therefore, a series of 3-bromo-2-phenyl-2,1-borazaronaphthalene derivatives were prepared in high yield via selective electrophilic bromination (Scheme 3). 4 …”