Six-membered Phosphorus Heterocycles Research Articles

Boundaries of the Hyperconjugation from π-Extended Six-Membered Phosphorus Heterocycles.

In the context of materials science, six-membered phosphorus heterocycles are intriguing building blocks due to their tunable properties through phosphorus post-functionalization and their unique hyperconjugative effects arising from the phosphorus substituents that contribute to further tuning the optoelectronic properties of the system. Seeking for the discovery of improved materials, the latter features have triggered an astonishing evolution of molecular architectures based on phosphorus heterocycles. Theoretical calculations showed that the hyperconjugation causes a reduction in the S0-S1 gap, which strongly depends on the nature of both the P-substituent and the π-conjugated core, but where are the limits? Outlining the hyperconjugative effects of six-membered phosphorus heterocycles would allow scientists to know how to design next-generation organophosphorus systems with enhanced properties. Herein, we discovered that, in cationic six-membered phosphorus heterocycles, an increase in the hyperconjugation does not affect the S0-S1 gap anymore; i.e., quaternizing the phosphorus atoms leads to properties that go beyond those provoked by hyperconjugative effects. DFT calculations revealed that the latter is particularly marked in phosphaspiro derivatives. Our detailed investigations spotlight the potential of π-extended systems based on six-membered phosphorus spiroheterocycles for accessing properties beyond those achieved to date through hyperconjugative effects, thus laying the groundwork for new research possibilities toward improved organophosphorus systems.

Luminescent Pyrrole-Based Phosphaphenalene Gold Complexes: Versatile Anticancer Tools with Wide Applicability.

Brain cancer, one of the most lethal diseases, urgently requires the discovery of novel theranostic agents. In this context, molecules based on six‐membered phosphorus heterocycles – phosphaphenalenes – are especially attractive; they possess unique characteristics that allow precise chemical engineering. Herein, we demonstrate that subtle structural modifications of the phosphaphenalene‐based gold(I) complexes lead to modify their electronic distribution, endow them with marked photophysical properties and enhance their efficacy against cancer. In particular, phosphaphenalene‐based gold(I) complexes containing a pyrrole ring show antiproliferative properties in 14 cell lines including glioblastomas, brain metastases, meningiomas, IDH‐mutant gliomas and head and neck cancers, reaching IC50 values as low as 0.73 μM. The bioactivity of this new family of drugs in combination with their photophysical properties thus offer new research possibilities for both the fundamental investigation and treatment of brain cancer.

Oxophosphonium-Alkyne Cycloaddition Reactions: Reversible Formation of 1,2-Oxaphosphetes and Six-membered Phosphorus Heterocycles.

While the metathesis reaction between alkynes and carbonyl compounds is an important tool in organic synthesis, the reactivity of alkynes with isoelectronic main-group R2E═O compounds is unexplored. Herein, we show that oxophosphonium ions, which are the isoelectronic phosphorus congeners to carbonyl compounds, undergo [2 + 2] cycloaddition reactions with different alkynes to generate 1,2-oxaphosphete ions, which were isolated and structurally characterized. The strained phosphorus-oxygen heterocycles open to the corresponding heterodiene structure at elevated temperature, which was used to generate six-membered phosphorus heterocycles via hetero Diels-Alder reactions. Insights into the influence of the substituents at the phosphorus center on the energy profile of the oxygen atom transfer reaction were obtained by quantum-chemical calculations.

Gold(i) complexes based on six-membered phosphorus heterocycles as bio-active molecules against brain cancer.

π-Systems based on six-membered phosphorus heterocycles possess structural and electronic characteristics that clearly distinguish them from the rest of the organophosphorus molecules. However, their use in cancer therapy has been uninvestigated. In particular, glioblastoma is one of the most lethal brain tumors. The development of novel and more efficient drugs for the treatment of glioblastoma is thus crucial to battle this aggressive disease. Herein, we report a new family of gold(i) complexes based on six-membered phosphorus heterocycles as a promising tool to investigate brain cancer. We discovered that the latter complexes inhibit the proliferation, sensitize to apoptosis and hamper the migration of not only conventional but also stem-like glioblastoma cells. Our results unveil thus new research opportunities for the treatment of glioblastoma.

Organophosphorus-B(C6F5)3 adducts: towards new solid-state emitting materials.

The coordination of B(C6F5)3 to materials based on six-membered phosphorus heterocycles via P[double bond, length as m-dash]O bonds tunes their physicochemical properties both in solution and in the solid state, remarkably improving their performances in light-emitting layers.

Diphosphahexaarenes as Highly Fluorescent and Stable Materials.

Oligoarenes are regarded as subunits of π-extended carbon nanoforms, such as graphene and nanotubes, with exceptional technological importance. Fused arenes can thus provide fundamental insight into the nature of the electronic properties of fused polyaromatic rings and pave the way for the design of extended graphene-like materials. However, large π-extended arenes often show low stability. Herein we report the straightforward preparation of linearly fused diphosphahexaarenes containing two six-membered phosphorus heterocycles. They are highly stable towards air, water, and light over months in both solution and the solid state. Single-crystal X-ray crystallography confirmed the molecular structure of all derivatives. Investigations of their optoelectronic properties revealed that the diphosphahexaarenes exhibit ambipolar redox behavior and high fluorescence quantum yields. Embedding six-membered phosphorus rings into large acenes thus opens up new opportunities for the investigation of polyaromatic systems.

Highlights on π-systems based on six-membered phosphorus heterocycles.

π-Extended molecules based on six-membered phosphorus heterocycles are exceptional systems due to their unique structural and chemical properties. Even though the first six-membered phosphorus heterocycles were synthesized in the 1950s-1960s, their chemistry is currently experiencing a renaissance with the focus on materials science. In this perspective, we highlight relevant systems that emphasize the potential of these particular organophosphorus materials for different fields of research, from bio- to optoelectronic applications. We also discuss their properties and outline our personal outlook on the future efforts toward the next generation of improved organophosphorus materials.

A Guide for the Design of Functional Polyaromatic Organophosphorus Materials.

The impact of integrating six-membered phosphorus heterocycles into a poly(hetero)aromatic materials is investigated. Mechanistic studies reveal the key synthetic requirements to embed the latter phosphorus heterocycles in polyaromatic molecules. DFT calculations indicate that introducing six-membered phosphorus rings into π-extended molecules induces a particular electron distribution over the π-extended system. Electrochemical investigations confirm that inserting six-membered phosphacycles into polyaromatics triggers ambipolar redox behavior. Steady-state spectroscopy reveals that fusing pyrroles with phosphorus-containing polyaromatic molecules induces fluorescence quantum yields as high as 0.8, whereas transient absorption spectroscopy demonstrates that fusing thiophenes promote the formation of non-emissive triplet-excited states. As a whole, the optoelectronic properties of fused phosphorus-containing materials give rise to promising performances in photoelectrochemical cells. Moreover, X-ray analyses confirm that the 3D arrangement in the solid state of polyaromatic systems containing six-membered phosphorus rings can be tailored through post-functionalization of the phosphorus center. Altogether, this investigation sets the bedrock for the design of a new generation of highly functional polyaromatic organophosphorus materials, keeping control over their electrochemical properties, fluorescence features, photo-induced excited states, and 3D molecular arrangement.

ChemInform Abstract: Paving the Way to Novel Phosphorus‐Based Architectures: A Noncatalyzed Protocol to Access Six‐Membered Heterocycles.

Phosphorus-based heterocycles provide access to materials with properties that are inaccessible from all-carbon architectures. The unique hybridization of phosphorus gives rise to electron-accepting capacities, a large variety of coordination reactions, and the possibility of controlling the electronic properties through phosphorus postfunctionalization. Herein, we describe a new noncatalyzed synthetic protocol to prepare fused six-membered phosphorus heterocycles. In particular, we report the synthesis of novel phosphaphenalenes. These fused systems exhibit the benefits of both five- and six-membered phosphorus heterocycles and enable a series of versatile postfunctionalization reactions. This work thus opens up new horizons in the field of conjugated materials.

Paving the Way to Novel Phosphorus-Based Architectures: A Noncatalyzed Protocol to Access Six-Membered Heterocycles.

Phosphorus-based heterocycles provide access to materials with properties that are inaccessible from all-carbon architectures. The unique hybridization of phosphorus gives rise to electron-accepting capacities, a large variety of coordination reactions, and the possibility of controlling the electronic properties through phosphorus postfunctionalization. Herein, we describe a new noncatalyzed synthetic protocol to prepare fused six-membered phosphorus heterocycles. In particular, we report the synthesis of novel phosphaphenalenes. These fused systems exhibit the benefits of both five- and six-membered phosphorus heterocycles and enable a series of versatile postfunctionalization reactions. This work thus opens up new horizons in the field of conjugated materials.

Sodium Phosphaethynolate as a Building Block for Heterocycles

Phosphorus-containing heterocycles have evolved from laboratory curiosities to functional components, such as ligands in catalytically active metal complexes or molecular constituents in electronic devices. The straightforward synthesis of functionalized heterocycles on a larger scale remains a challenge. Herein, we report the use of the phosphaethynolate (OCP)(-) anion as a building block for various sterically unprotected and functionalized hydroxy substituted phosphorus heterocycles. Because the resulting heterocycles are themselves anions, they are building blocks in their own right and allow further facile functionalization. This property may be of interest in coordination chemistry and material science.

Resolution of 5- and 6-Membered P-Heterocycles: Racemic and Optically Active Platinum(II)-3-Phospholene Complexes

Methods were developed for the resolution of several five- and six-membered phosphorus heterocycles (1c-e, 2, 4). It was investigated if the optical activity is preserved during the 1a→2→3→4 reaction sequence. Racemic and optically active 1b-e 3-phospholene 1-oxides were converted to the corresponding platinum-complexes (10b-e), which are potential catalysts.

An expedient approach for the synthesis and the anti-acetylcholinesterase activity evaluation of 6H-benzimidazol[1,2-c][1,3,2]benzoxazaphosphorine 2-(4-methoxyphenyl)-2-sulfide derivatives from 4-mercapto-2H-chromene-2-thione

A new efficient route for the synthesis of substituted 6H-benzimidazol[1,2-c][1,3,2] benzoxazaphosphorine 2-(4-methoxyphenyl)-2-sulfide from 4-mercapto-2H-chromene-2-thione is described. The anti-acetylcholinesterase activity of the most important synthons is considered. Ways of constructing six-membered phosphorus-heterocycles via cyclization of Lawesson’s reagent with bifunctional substrates are discussed.

Synthesis of Phosphaisoquinolin‐1‐ones by Pd(II)‐Catalyzed Cyclization of o‐(1‐Alkynyl)phenylphosphonamide Monoesters.

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Synthesis of Phosphaisoquinolin-1-ones by Pd(II)-Catalyzed Cyclization of o-(1-Alkynyl)phenylphosphonamide Monoesters

A Pd(II)-catalyzed intramolecular cyclization of o-(1-alkynyl)phenylphosphonamide monoethyl esters was examined, and a new class of six-membered phosphorus heterocycles (phosphaisoquinolin-1-ones) were formed with high regioselectivity and good yields. The present reaction is the first example of intramolecular addition of P-NH to substituted alkynes, which provides a valuable way to synthesize novel phosphorus heterocycles with potential bioactivities.

Cyclic oxyphosphoranes in synthesis. A novel synthesis of oxathiaphospholenes, fused pyrimidines and aminooxyphosphoranes

Trialkyl phosphites induced the condensation of one molecule of 3,5-di-tert-butyl-1,2benzoquinone (1) with two molecules of methyl-, ethyl-, phenyland hexyl iso thiocyanates (6a6d) leading to the formation of quinazoline-2,4-dithione derivatives (12a, 12b, 14, and 15) and trialkyl phosphates. Three steps were involved, and the intermediates could, but need not, be isolated. In the second step, the intermediates, new six-membered phosphorus heterocycles 8a8d were isolated and identified. In contrast, condensation of 4,6-di-tert-butylbenzo-2-methoxy-2oxo-1,3,2-dioxaphosphole (19) with one molecule of 6a-6d afforded the corresponding aminooxyphosphoranes 22a-22d. Allyl iso thiocyanate (16), on the other hand, reacted with 2,2,2-trialkoxy-1,3,2-dioxaphospholenes 3a and 3b to give the phosphates 18a and 18b whereas with 19 spirocyclic oxaphosphole 24 was isolated.

The Synthesis of Phosphaisocoumarins by Cu(I)‐Catalyzed Intramolecular Cyclization of o‐Ethynylphenylphosphonic Acid Monoesters.

Cu(I)-catalyzed intramolecular cyclization of o-ethynylphenylphosphonic acid monoethyl esters was examined, and a new class of six-membered phosphorus heterocycles was formed with high regioselectivity and good yields. The present reaction is the first example of intramolecular addition of P−OH to alkynes, which provides a convenient way to synthesize novel phosphorus heterocycles having potential bioactivities.

The synthesis of phosphaisocoumarins by Cu(I)-catalyzed intramolecular cyclization of o-ethynylphenylphosphonic acid monoesters.

Cu(I)-catalyzed intramolecular cyclization of o-ethynylphenylphosphonic acid monoethyl esters was examined, and a new class of six-membered phosphorus heterocycles was formed with high regioselectivity and good yields. The present reaction is the first example of intramolecular addition of P-OH to alkynes, which provides a convenient way to synthesize novel phosphorus heterocycles having potential bioactivities.

1,3-Diphosphetane-2,4-diyles--Cryptocarbenes?

1,3-Diphosphetane-2,4-diyles ( A ) possess a diradical molecular structure. Experimental studies reveal interconversions of different valence isomers of the diradicals. As a consequence of the facile thermal ring opening of 1,3-diphosphetane-2.4-diyles A , we obtained crypto-phosphinocarbenes ( B ), confirmed by the results of intramolecular rearrangements as well as reactions with multiple bonded systems. A new range of five- and six-membered phosphorus heterocycles are isolated, including transition-metal complexes. The mechanism for the ring-expansion are predicted by quantum chemical calculations.

Conformations of saturated six-membered phosphorus heterocycles. X-ray crystallographic and proton NMR study of cis-2-oxo-2-(dimethylamino)-5-phenyl-1,3,2-oxazaphosphorinane, a cyclophosphamide-like molecule in a twist conformation

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTConformations of saturated six-membered phosphorus heterocycles. X-ray crystallographic and proton NMR study of cis-2-oxo-2-(dimethylamino)-5-phenyl-1,3,2-oxazaphosphorinane, a cyclophosphamide-like molecule in a twist conformationWesley G. Bentrude, Roberta O. Day, Joan M. Holmes, Gyongyi Szakal Quin, William N. Setzer, Alan E. Sopchik, and Robert R. HolmesCite this: J. Am. Chem. Soc. 1984, 106, 1, 106–111Publication Date (Print):January 1, 1984Publication History Published online1 May 2002Published inissue 1 January 1984https://doi.org/10.1021/ja00313a022RIGHTS & PERMISSIONSArticle Views234Altmetric-Citations29LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (747 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts