Bidentate Phosphorus Baskets by Intramolecular Phosphinidene Addition

Assema, S.G.A. van; Ehlers, Andreas W.; Kanter, Frans J. J. de; Schakel, Marius; Spek, Anthony L.; Lutz, Martin; Lammertsma, Koop

doi:10.1002/chem.200501531

Cited by 19 publications

(14 citation statements)

References 31 publications

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“…Based on this hypothesis, we sought to simplify the phosphine ligand while maintaining the P-olefin binding motif that conferred the unique activity of 23 through the use of ( Z )-2,3,6,7-tetrahydrophosphepines (Figure 7). 41…”

Section: Rh-catalyzed Direct Arylation Of Heterocyclesmentioning

confidence: 99%

Direct Functionalization of Nitrogen Heterocycles via Rh-Catalyzed C−H Bond Activation

2008

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Conspectus Nitrogen heterocycles are present in many compounds of enormous practical importance, ranging from pharmaceutical agents and biological probes to electroactive materials. Direct functionalization of nitrogen heterocycles through C-H bond activation constitutes a powerful means of regioselectively introducing a variety of substituents with diverse functional groups onto the heterocycle scaffold. Working together, our two groups have developed a family of Rh-catalyzed heterocycle alkylation and arylation reactions that are notable for their high level of functional-group compatibility. This Account describes our work in this area, emphasizing the relevant mechanistic insights that enabled synthetic advances and distinguished the resulting transformations from other methods. We initially discovered an intramolecular Rh-catalyzed C-2-alkylation of azoles by alkenyl groups. That reaction provided access to a number of di-, tri-, and tetracyclic azole derivatives. We then developed conditions that exploited microwave heating to expedite these reactions. While investigating the mechanism of this transformation, we discovered that a novel substrate-derived Rh-N-heterocyclic carbene (NHC) complex was involved as an intermediate. We then synthesized analogous Rh–NHC complexes directly by treating precursors to the intermediate [RhCl(PCy3)2] with N-methylbenzimidazole, 3-methyl-3,4-dihydroquinazoline, and 1-methyl-1,4-benzodiazepine-2-one. Extensive kinetic analysis and DFT calculations supported a mechanism for carbene formation in which the catalytically active RhCl(PCy3)2 fragment coordinates to the heterocycle before intramolecular activation of the C-H bond occurs. The resulting Rh-H intermediate ultimately tautomerizes to the observed carbene complex. With this mechanistic information and the discovery that acid co-catalysts accelerate the alkylation, we developed conditions that efficiently and intermolecularly alkylate a variety of heterocycles, including azoles, azolines, dihydroquinazolines, pyridines, and quinolines, with a wide range of functionalized olefins. We demonstrated the utility of this methodology in the synthesis of natural products, drug candidates, and other biologically active molecules. In addition, we developed conditions to directly arylate these heterocycles with aryl halides. Our initial conditions that used PCy3 as a ligand were successful only for aryl iodides. However, efforts designed to avoid catalyst decomposition led to the development of ligands based on 9-phosphabicyclo[4.2.1]nonane (Phoban) that also facilitated the coupling of aryl bromides. We then replicated the unique coordination environment, stability, and catalytic activity of this complex using the much simpler tetrahydrophosphepine ligands and developed conditions that coupled aryl bromides bearing diverse functional groups without the use of a glovebox or purified reagents. With further mechanistic inquiry, we anticipate that researchers will better understand the details of the aforementioned Rh-catalyzed C-H b...

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Section: Rh-catalyzed Direct Arylation Of Heterocyclesmentioning

confidence: 99%

Direct Functionalization of Nitrogen Heterocycles via Rh-Catalyzed C−H Bond Activation

2008

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“…Similarly, the diphosphane baskets 69b,c were obtained (Scheme 29). [40] Scheme 26. Synthesis of 66 and 67.…”

Section: Electrophilic Phosphinidene Complexesmentioning

confidence: 99%

Phospha‐ and Arsaalkenes RE=C(NMe₂)₂ (E = P, As) as Novel Phosphinidene‐ and Arsinidene‐Transfer Reagents

Weber

2007

Eur J Inorg Chem

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Phosphinidenes (phosphanylidenes) (RP) are electronically and coordinatively unsaturated phosphorus compounds, which, as six-electron species, are formally analogous to the more familiar carbenes and nitrenes. In contrast to carbenes (CR 2 ), the extremely reactive phosphinidenes cannot be isolated without decomposition. Thus, our knowledge on phosphinidenes is mainly limited to trapping reactions and quantum-chemical calculations. There are a number of synthetic methods for phosphinidenes available, for example photolysis or thermolysis of cyclic phosphanes and oligophosphanes,

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“…17 Recently, Lammertsma and coworkers published the synthesis of (Z)-1-phenyl-2,3,6,7-tetrahydrophosphepine, but used the material in situ to generate a variety of interesting Mo-phosphepine complexes and did not isolate the free ligand. 18 We utilized a modified version of the Lammertsma procedure in order to prepare a small set of phosphepine ligands (Scheme 1). 19 Specifically, a three step procedure, involving addition of two equivalents of 3-butenylmagnesium bromide to the appropriate phosphine chloride followed by an alcohol quench, peroxide oxidation, aqueous workup, and olefin metathesis was developed to construct the substituted 2,3,6,7-tetrahydrophosphepine ring with only a single purification after the final step.…”

Section: Synthesis and Evaluation Of (Z)-2367-tetrahydrophosphepinesmentioning

confidence: 99%

Rh(I)-Catalyzed Arylation of Heterocycles via C−H Bond Activation: Expanded Scope through Mechanistic Insight

et al. 2008

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A practical, functional group tolerant method for the Rh-catalyzed direct arylation of a variety of pharmaceutically important azoles with aryl bromides is described. Many of the successful azole and aryl bromide coupling partners are not compatible with methods for the direct arylation of heterocycles using Pd(0) or Cu(I) catalysts. The readily prepared, low molecular weight ligand, Z-1-tert-butyl-2,3,6,7-tetrahydrophosphepine, which coordinates to Rh in a bidentate P-olefin fashion to provide a highly active yet thermally stable arylation catalyst, is essential to the success of this method. By using the tetrafluoroborate salt of the corresponding phosphonium, the reactions can be assembled outside of a glove box without purification of reagents or solvent. The reactions are also conducted in THF or dioxane, which greatly simplifies product isolation relative to most other methods for direct arylation of azoles employing high-boiling amide solvents. The reactions are performed with heating in a microwave reactor to obtain excellent product yields in two hours.

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Bidentate Phosphorus Baskets by Intramolecular Phosphinidene Addition

Cited by 19 publications

References 31 publications

Direct Functionalization of Nitrogen Heterocycles via Rh-Catalyzed C−H Bond Activation

Direct Functionalization of Nitrogen Heterocycles via Rh-Catalyzed C−H Bond Activation

Phospha‐ and Arsaalkenes RE=C(NMe₂)₂ (E = P, As) as Novel Phosphinidene‐ and Arsinidene‐Transfer Reagents

Rh(I)-Catalyzed Arylation of Heterocycles via C−H Bond Activation: Expanded Scope through Mechanistic Insight

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Bidentate Phosphorus Baskets by Intramolecular Phosphinidene Addition

Cited by 19 publications

References 31 publications

Direct Functionalization of Nitrogen Heterocycles via Rh-Catalyzed C−H Bond Activation

Direct Functionalization of Nitrogen Heterocycles via Rh-Catalyzed C−H Bond Activation

Phospha‐ and Arsaalkenes RE=C(NMe2)2 (E = P, As) as Novel Phosphinidene‐ and Arsinidene‐Transfer Reagents

Rh(I)-Catalyzed Arylation of Heterocycles via C−H Bond Activation: Expanded Scope through Mechanistic Insight

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Phospha‐ and Arsaalkenes RE=C(NMe₂)₂ (E = P, As) as Novel Phosphinidene‐ and Arsinidene‐Transfer Reagents