Markus K. Kindermann

Sterically and Polarity-Controlled Reactions of tBuLi with P=CH-NR Heterocycles : Novel Heterocyclic P-and P,O-Ligands and Preliminary Tests in Transition-Metal Catalysis

(1R)-1,3-Benzazaphospholes 1 a-c, P=CH-NR heterocycles of the indole type, react with tBuLi in two ways, depending on the steric demand of the N-substituent and the polarity of the medium. The presence of small N-alkyl groups induces CH-deprotonation in the 2-position to give hetaryllithium reagents 2 a and 2 b, whereas bulky N-substituents and nonpolar solvents change the reactivity towards addition at the P=C bond. The preferred regioselectivity is tert-butylation at phosphorus, occurring with excellent diastereoselectivity for trans-adducts 3 b and 3 c, but the inverse tert-butylation at C2 to 5 b was also observed. N-Neopentyl groups, with intermediate steric demand, give rise to formation of mixtures in ethers but allow switching either to selective CH lithiation in THF/KOtBu or to addition in pentane. Bulkier N-adamantyl groups always cause preferred addition. Protonation, silylation, and carboxylation were used to convert the P=CLi-NR, (E)-tBuP-CHLi-NR, and LiP-CH(tBu)-NR species into the corresponding sigma(2)-P or sigma(3)-P compounds 4 b and 6 a,b, 7 b,c, or 8 b-10 b with additional N and/or O donor sites. Slow diffusion-controlled air oxidation of 10 b led to the meso-diphosphine 11 b. Preferred eta(1)-P coordination was shown for an [Rh(cod)Cl] complex 12 b, and the potential of the new ligands 4 b and 7 b in catalysis was demonstrated by examples of Pd-catalyzed C-N coupling and Ni-catalyzed ethylene oligomerization (TON>6300). Crystal structures of 6 b, 11 b, and 12 b are presented.

Bulky N-Substituted 1,3-Benzazaphospholes : Access via Pd-Catalyzed C-N and C-P Cross Coupling, Lithiation, and Conversion to Novel P=C-PtBu2 Hybrid Ligands

The syntheses of novel bulky N-substituted 1,3-benzazaphospholes are presented, together with their reactions with tert-butyllithium and coupling with tBu 2PCl to novel P, P-hybrid ligands that combine the highly basic and bulky di- tert-butylphosphanyl group with pi-acidic low-coordinated phosphorus. The syntheses start with the preparation of new N-secondary 2-bromoanilines 1 by reduction of N-acyl 2-bromoanilides or more generally by Pd-catalyzed selective monoamination of o-dibromobenzene, followed by Pd-catalyzed C-P coupling with P(OEt) 3 to the respective 2-anilino-phosphonates 2. The next steps are reduction to 2-phosphanylanilines 3 and condensation with Me 2NCH(OMe) 2, which leads via phosphaalkenes 4 to the corresponding N-substituted benzazaphospholes 5. The reaction with tBuLi depends on the steric demand of the N substituent. Methyl, neopentyl-, and mesityl-derivatives were converted to P=C Li species 6 and coupled with tBu 2PCl to novel P=C-P tBu 2 ligands 7, whereas N-adamantyl and N-2,6-diisopropylphenyl-derivatives prefer addition of tBuLi at the PC bond to form dihydroderivatives. The chemical shifts of the low-coordinated phosphorus of 5 and 7 were found to reflect electronic and steric effects of the N substituents. The comparison of the crystal structures of N-neopentyl-1,3-benzazaphospholes 5 and 7 gives evidence of steric repulsion between the adjacent di- tert-butyl and neopentyl groups by the preferred anti orientation of the P- tert-butyl groups and moderate deviations of C2 and P3 of 7b from the ring plane.

A new promising application for highly cytotoxic metal compounds: η6-areneruthenium(II) phosphite complexes for the treatment of alveolar echinococcosis.

Two series of η(6)-areneruthenium(II) phosphite complexes were prepared, characterized, and evaluated in vitro for their toxic potential against Echinococcus multilocularis metacestodes. Neutral complexes of general formula [(η(6)-p-cymene)RuCl(2){P(OR)(3)}] (R = Et, (i)Pr, Ph) with two easily exchangable chloride ligands showed only minor toxicity, whereas the substitution of these moieties against a β-diketonate (2,2,6,6-tetramethylheptanedionate) ligand led to hydrolytically stable complex salts of type [(η(6)-p-cymene)Ru(β-diketonate){P(OR)(3)}][BF(4)] (R = Et, (i)Pr, Ph) with comparable in vitro toxicity (50% PGI release at c = 1.4 - 4.7 μM) to the reference drug nitazoxanide (50% PGI release at c = 1.2 μM). In addition, the latter complexes were highly toxic against rat hepatoma cells (IC(50) = 0.40-2.0 μM) and less toxic against human foreskin fibroblasts (IC(50) = 1.1-2.9 μM) and Vero cells (IC(50) = 1.2-8.9 μM). The measured cytotoxicities against mammalian cells are, to the best of our knowledge, among the highest ever observed for ruthenium-based complexes. In conclusion, complex salts of type [(η(6)-p-cymene)Ru(β-diketonate){P(OR)(3)}][BF(4)] might be interesting candidates for further development toward anthelmintic drugs and/or highly cytotoxic metal compounds.

Electronic structure of stable benzodiazasilylenes: photoelectron spectra and quantum-chemical investigations

Photoelectron spectra of 2,3-dihydro-1,3-di(neopentyl)-1H-1,3,2-benzodiazasilol-2-ylidene were investigated and compared to those of 2,3-dihydro-1,3-di(tert-butyl)-1H-1,3,2-diazasilol-2-ylidene and the related 2,3-dihydro-1,3-di(neopentyl)-1H-1,3,2-benzodiazasilole. The experimental spectra were assigned with the help of quantum-chemical calculations using the MP2/6-31G* level of theory. Trends in the orbital energies correspond well with the observed ionization energies. A 0.41 eV stabilization of the highest occupied molecular orbital level from the silane to the related silylene derivative indicates the incorporation of the silicon empty out-of-plane orbital into the π system. A good agreement was found between the calculated and experimental geometries. Delocalization stabilization of the investigated molecules is also supported by appropriate isodesmic reactions. The reaction energy indicates significant aromatic stabilization of the silylene derivatives. The stabilization is, however, reduced by a considerable ring strain.

Synthesis of aminotri‐ and aminotetrasilanes by cross‐coupling of aminochlorosilanes with chlorotrimethylsilane

We studied the reductive coupling of aminochlorosilanes and chlorotrimethylsilane by lithium in tetrahydrofuran. Cross-coupling was observed in the case of diaminodichlorosilanes 7 or aminotrichlorosilanes 8 and allows a direct access to 2,2-diamino-hexamethyltrisilanes 9 and amino(tristrimethylsilyl)silanes 10. Me2Si(iPr2N)Cl 3 reacts instead preferentially to the symmetric diaminodisilane 6. Bulkier diamino(chloro)methylsilanes 5 did not undergo the coupling reaction. The cross-coupled aminodi-, -tri- and tetrasilanes are useful starting compounds for other functionally substituted oligosilanes, as was shown by reaction of 9 with HX (X=Cl, Br, I) to 11 and the synthesis of the heterocyclic trisilanes 9d and 9f using 11a. The molecular structure of [(iPr2N)2SiH]2 2a is discussed. NMR data including 1JSiSi coupling constants are given.

Selective palladium-catalysed arylation of 2,6-dibromopyridine using N-heterocyclic carbene ligands

A selective palladium-catalysed arylation of 2,6-dibromopyridine has been developed by employing N-heterocyclic carbene ligands. Selective mono-arylation was performed in water/acetonitrile solvent system at ambient temperature with catalyst loading of 0.1 mol%. This reaction was also found to proceed smoothly in water although at a slightly elevated temperature of 80 °C. 2,6-Disubstituted and diversely substituted 2,6-pyridines were also obtained in high yields which will be of importance to organic and medicinal chemists.

2-Hydroxy- and 2-Amino-Functional Arylphosphines—Syntheses, Reactivity, and Use in Catalysis

We present the synthesis, resolution, structures and catalytic activity of selected representatives of 2-(1S)-camphanoyloxy-phenyl- and biphenylphosphines and the access to novel asymmetric P,N-heterocyclic ethylenebis(phosphine) ligands.

2-Hydroxy-1, 1-Biphenyl- and -Binaphthyl-2′-Phosphines - Synthesis, Structure and Use in Rh-Catalyzed Carbonylation

Abstract Dibenzofuran and dinaphthofuran are cleaved by lithium in presence of electron transfer catalysts to yield C,O-dilithium reagents. These are reacted with chloro- or alkoxyphosphines providing 2-hydroxy-1,l ‘-biphenyl-2’-phosphines and 2-hydroxy-1,‘-binaphthyl-2’-phosphines which form solvent complexes with O…H‒O or P…H‒O bridging bonds. The planes of the benzene rings of the biphenyl units are nearly perpen-dicular in the unit cell. Line form analysis of the temperature dependent solution NMR spectra of diastereoisomeric 2-HO-C6H4-C6H4-P (tBu)Ph revealed a barriere of rotation of Δ H= 12.87 kcal/mol. The respective 0-trimethylsilyl ethers have a higher barrier, and 2-hydroxybinaphthyl-2-phosphines dont racemize after separation by HPLC.