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.
The first trans‐selective cyanoboration reaction of an alkyne, specifically a 1,3‐enyne, is described. The reported palladium‐catalyzed cyanoboration of 1,3‐enynes is site‐, regio‐, and ...diastereoselective, and is uniquely enabled by the 1,4‐azaborine‐based Senphos ligand structure. Tetra‐substituted alkenyl nitriles are obtained providing useful boron‐dienenitrile building blocks that can be further functionalized. The utility of our method has been demonstrated with the synthesis of Satigrel, an anti‐platelet aggregating agent.
A trans‐selective alkyne cyanoboration debuts! A Pd complex supported by an 1,4‐azaborine‐derived phosphine ligand is uniquely capable to transform 1,3‐enynes into tetra‐substituted borylated dienenitriles with high site‐, regio‐, and trans‐diastereoselectivity.
Recent Advances in Azaborine Chemistry Campbell, Patrick G.; Marwitz, Adam J. V.; Liu, Shih-Yuan
Angewandte Chemie,
June 18, 2012, Letnik:
51, Številka:
25
Journal Article
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The chemistry of organoboron compounds has been primarily dominated by their use as powerful reagents in synthetic organic chemistry. Recently, the incorporation of boron as part of a functional ...target structure has emerged as a useful way to generate diversity in organic compounds. A commonly applied strategy is the replacement of a CC unit with its isoelectronic BN unit. In particular, the BN/CC isosterism of the ubiquitous arene motif has undergone a renaissance in the past decade. The parent molecule of the 1,2‐dihydro‐1,2‐azaborine family has now been isolated. New mono‐ and polycyclic B,N heterocycles have been synthesized for potential use in biomedical and materials science applications. This review is a tribute to Dewar’s first synthesis of a monocyclic 1,2‐dihydro‐1,2‐azaborine 50 years ago and discusses recent advances in the synthesis and characterization of heterocycles that contain carbon, boron, and nitrogen.
Ring around the boron: The BN/CC isosterism of arenes, which results in azaborine structures, has emerged as a viable strategy to increase the range of compounds relevant to biomedical research and materials science. As a tribute to Dewar's first synthesis of a monocyclic 1,2‐azaborine 50 years ago, this review summarizes recent advances in the synthesis and characterization of carbon(C)–boron(B)–nitrogen(N)‐containing heteroaromatics.
We provide a seminal example of the utility of the 1,2‐azaborine motif as a 4C+1N+1B synthon in organic synthesis. Specifically, conditions for the practically scalable photoisomerization of ...1,2‐azaborine in a flow reactor are reported that furnish aminoborylated cyclobutane derivatives. The C−B bonds could also be functionalized to furnish a diverse set of highly substituted cyclobutanes.
Squaring up: A continuous‐flow approach has been developed to photoisomerize 1,2‐azaborines to cis‐1,2‐aminoborylated cyclobutanes and analogues bearing quaternary carbon centers. Further derivatizations at the borylated position led to a series of 2‐functionalized aminocyclobutanes. FG=functional group.
The first example of a BN‐doped cycloparaphenylene BN‐10CPP was synthesized and characterized. Its reactivity and photophysical properties were evaluated in direct comparison to its carbonaceous ...analogues Mes‐10CPP and 10CPP. While the photophysical properties of BN‐10CPP remains similar to its carbonaceous analogues, the electronic structure changes associated with the introduction of a 1,2‐azaborine BN heterocycle into a CPP scaffold enables facile and selective late‐stage functionalizations that cannot be accomplished with carbonaceous CPPs. Specifically, Ir‐catalyzed hydrogenation of BN‐10CPP selectively reduces the BN heterocyclic ring, which upon hydrolysis produces a rare example of a macrocyclic paraphenylene 6 incorporating the versatile ketone functionality within the macrocyclic ring.
The introduction of a 1,2‐azaborine ring into a CPP scaffold enables new chemical reactivity associated with the BN heterocycle that cannot be accomplished with carbonaceous CPP compounds.
A concise synthesis of monobenzofused 1,4-azaborine phosphine ligands (Senphos) is described. These Senphos ligands uniquely support Pd-catalyzed trans-selective hydroboration of terminal and ...internal 1,3-enynes to furnish corresponding dienylboronates in high efficiency and diastereoselectivity. X-ray structural analysis of the Senphos–Pd(0) complex reveals a κ2-P-η2-BC coordination mode, and this isolated complex has been shown to serve as a competent catalyst for the trans-hydroboration reaction. This work demonstrates that the expanded chemical space provided by the BN/CC isosterism approach translates into the functional space in the context of stereoselective catalytic transformations.
A new family of carbon‐bound boron enolates, generated by a kinetically controlled halogen exchange between chlorocatecholborane and silylketene acetals, is described. These C−boron enolates are ...demonstrated to activate 1,3‐enyne substrates in the presence of a Pd0/Senphos ligand complex, resulting in the first examples of a carboboration reaction of an alkyne with enolate‐equivalent nucleophiles. Highly substituted dienyl boron building blocks are produced in excellent site‐, regio‐, and diastereoselectivity by the described catalytic cis‐carboboration reaction.
A new family of carbon‐bound boron enolates, in cooperation with a Pd complex supported by an 1,4‐azaborine‐derived phosphine ligand, transforms enynes into highly substituted dienyl boronates in exquisite site‐, regio‐, and cis‐diastereoselectivity.
The regioregular synthesis of the first azaborine oligomers and a corresponding conjugated polymer was accomplished by Suzuki–Miyaura coupling methods. An almost perfectly coplanar syn arrangement of ...the heterocycles was deduced from an X‐ray crystal structure of the dimer, which also suggested that NH⋅⋅⋅π interactions play an important role. Computational studies further supported these experimental observations and indicated that the electronic structure of the longer azaborine oligomers and polymer resembles that of poly(cyclohexadiene) more than poly(p‐phenylene). A comparison of the absorption and emission properties of the polymer with those of the oligomers revealed dramatic bathochromic shifts upon chain elongation, thus suggesting highly effective extension of conjugation.
A BN serial: A regioregular conjugated polymer and short model oligomers constructed solely from 1,2‐azaborine units by Suzuki–Miyaura cross‐coupling have been synthesized and found to adopt an unusual syn conformation stabilized by NH⋅⋅⋅π interactions. The optoelectronic properties of the polymer more closely resemble the computationally predicted properties of poly(cyclohexadiene) rather than those of poly(p‐phenylene). pin=pinacol.
Cation-π binding ability of BN indole Boknevitz, Katherine; Darrigan, Clovis; Chrostowska, Anna ...
Chemical communications,
03/2020, Letnik:
56, Številka:
26
Journal Article
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A BN indole-containing aromatic scaffold has been synthesized and the cation-π binding ability characterized by nuclear magnetic resonance (NMR) monitored titrations. The resulting chemical shifts ...were analyzed using a non-linear curve fitting procedure and the extracted association constants (Ka's) compared with the natural indole scaffold. Computations were also performed to support our findings. This work shows that incorporation of a B-N bond in place of a C-C bond in an aromatic system slightly lowers the cation-π binding ability of the arene's π-system with simple cations.
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is a major advance in treating NSCLC with EGFR-activating mutations. However, acquired resistance, due partially to secondary ...mutations limits their use. Here we report that NSCLC cells with acquired resistance to gefitinib or osimertinib (AZD9291) exhibit EMT features, with a decrease in E-cadherin, and increases in vimentin and stemness, without possessing any EGFR secondary mutations. Knockdown of E-cadherin in parental cells increased gefitinib resistance and stemness, while knockdown of vimentin in resistant cells resulted in opposite effects. Src activation and Hakai upregulation were found in gefitinib-resistant cells. Knockdown of Hakai elevated E-cadherin expression, attenuated stemness, and resensitized the cells to gefitinib. Clinical cancer specimens with acquired gefitinib resistance also showed a decrease in E-cadherin and an increase in Hakai expression. The dual HDAC and HMGR inhibitor JMF3086 inhibited the Src/Hakai and Hakai/E-cadherin interaction to reverse E-cadherin expression, and attenuated vimentin and stemness to restore gefitinib sensitivity. The EMT features of AZD9291-resistant H1975 cells were related to the upregulation of Zeb1. Both gefitinib and AZD9291 sensitivity was restored by JMF3086 through reversing EMT. Our study not only revealed a common mechanism of EMT in both gefitinib and AZD9291 resistance beyond EGFR mutations per se, but also provides a new strategy to overcome it.
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