üBER DIE INSERTION VON RPS2 IN DIE PN-BINDUNG VON AMINOPHOSPHINEN

Abstract

Aminophosphine des Typs R_n P(NR′₂)_3-n (n= 2, 1, 0; R = Ph, c-Hex, (-)Men, t-Bu; R′= Me, Et, n-Bu) reagieren mit 2, 4-Bis(aryl)-1, 3, 2, 4-dithiadiphosphetan-2, 4-disulfiden (ArPS₂)₂(Ar: Ph, 4-Methoxyphenyl = An, Naphthyl, Thienyl) unter formaler Insertion monomerer {ArPS₂)-Einheiten in eine oder in zwei der λ³-P—N-Bindung zu chiralen Organophosphorverbindungen Ar(R′₂N)P(S)—S—PR_n (NR′₂)_2-n(n = 2, 1, 0) und [Ar(R′₂N)P(S)—]₂PR₂(NR′₂)_1-n (n = 1.0). In diesen werden bei Raumtemperatur bevorzugt die λ³—P—N—und λ³—P—S-Bindungen durch H₂O oder Methanol unter Bildung von Produktgemischen solvolysiert. Mit Chlorwasserstoff bildet sich aus An(Et₂N)P(S)—S—PPh(NEt₂) das An(Et₂ N)P(S)—S—PPh(C1). Addition von Schwefel führt zu Ar(R′₂N)P(S)—S—P(S)R_n (NR′)_2-n (n=2, 1). Die Stereoisomerenbildung der neuen Verbindungen wird besprochen und ihre Struktur sowie die Zusammensetzung der Reaktionsmischungen aus den ³¹P-Spektren hergeleitet.

Aminophosphines R_n P(NR′₂)_3-n (n = 2, 1, 0; R = Ph. c-Hex, (-)Men, t-Bu; R′= Me, Et, n-Bu) react with 2, 4-Bis(aryl)-1, 3, 2, 4-dithiadiphosphetane-2, 4-disulfides (ArPS₂)₂ (Ar: Ph, 4-Methoxyphenyl = An, Naphthyl, Thienyl) under formal insertion of monomeric {ArPS₂)-units in one or in two of the λ³-P—N-bonds to yield chiral organophosphorus compounds Ar(R′₂N)P(S)—S—]₂PR_n (NR′₂)₂ (n = 2, 1, 0) and [Ar(R′₂N)P(S)—S—]₂ PR₂ (NR′₂)_2-n (n = 1, 0). At room temperature chiefly the A—P—N and A³—P—S-bonds in these products are solvolyzed by H, O or methanol with formation of mixtures of compounds. With hydrogen chloride An(Et₂N)P(S)—S—PPh(NEt₂) is converted into An(Et₂N)P(S)—S—PPh(Cl). Addition of sulfur yields Ar(R′₂N)P(S)—S P(S)R_n (NR′₂)_2-n (n = 2, 1). Stereoisomerism of the new compounds is discussed and their structures as well as the composition of reaction mixtures are deduced from “P-NMR-spectra”.     

Stress-Strain Behavior of Shape Memory Polymers by 1WE Method: Application to Tecoflex®

Thermomechanical cycles including programming, cooling, unloading and heating to trigger the 1WE were examined for a shape memory polymer (SMP), Tecoflex® (TFX EG-72D). Cycles were performed at 60°C with 50% and 225% strains and the recovery time of 10 min. Strains evolving with time were estimated during the thermomechanical treatments for the total 44 cycles using 50% strains and the total 50 cycles using 225% strains. Recovery ratios for 50% strains and 225% were also estimated. It turns out that programming, cooling, unloading and heating to trigger the 1WE causes an increase of irreversible strain and is associated with a corresponding decrease of the intensity of the 1WE in particular during the first thermomechanical cycles. In parallel scanning electron microscopic study using secondary electron imaging shows a very slight wavy surface structure evolved during cycling.     

Multi-purpose functionality for the structural elaboration of the piperazine-2,5-dione motif

Mild methods for controlled C- and N-alkylation of 3-benzyloxycarbonylpiperazine-2,5-diones are reported. The benzyloxylcarbonyl substituent can also serve as latent functionality for N-acyliminium ion formation and subsequent trapping enables installation of new carbon and/or heteroatom substituents.     

Polymer-supported pyridine-bis(oxazoline). Application to ytterbium-catalyzed silylcyanation of benzaldehyde

[reaction: see text] Terminal acetylenes containing hydroxy and carboxylic acid groups were subjected to Sonogashira coupling with 4-bromo-2,6-bis[(R)-4-phenyloxazolin-2-yl]pyridine and the resulting pybox derivatives were immobilized on Tentagel resins. Ytterbium(III) chloride complexes of the polymeric ligands catalyzed the addition of trimethylsilyl cyanide to benzaldehyde with 80-81% ee. The ligands were reused more than 30 times without any loss in selectivity or activity, and the metal complexes could be recovered and reused at least four times, although with slightly decreasing activity.     

Titanium Salalen Catalyzed Enantioselective Benzylic Hydroxylation

The titanium complex of the cis-1,2-diaminocyclohexane (cis-DACH) derived Berkessel-salalen ligand is a highly efficient and enantioselective catalyst for the asymmetric epoxidation of terminal olefins with hydrogen peroxide (“Berkessel-Katsuki catalyst”). We herein report that this epoxidation catalyst also effects the highly enantioselective hydroxylation of benzylic C−H bonds with hydrogen peroxide. Mechanism-based ligand optimization identified a novel nitro-salalen Ti-catalyst of the highest efficiency ever reported for asymmetric catalytic benzylic hydroxylation, with enantioselectivities of up to 98 % ee, while overoxidation to ketone is marginal. The novel nitro-salalen Ti-catalyst also shows enhanced epoxidation efficiency, as evidenced by e.g. the conversion of 1-decene to its epoxide in 90 % yield with 94 % ee, at a catalyst loading of 0.1 mol-% only.     

Chemical Validation of Mycobacterium tuberculosis Phosphopantetheine Adenylyltransferase Using Fragment Linking and CRISPR Interference**

The coenzyme A (CoA) biosynthesis pathway has attracted attention as a potential target for much-needed novel antimicrobial drugs, including for the treatment of tuberculosis (TB), the lethal disease caused by Mycobacterium tuberculosis (Mtb). Seeking to identify inhibitors of Mtb phosphopantetheine adenylyltransferase (MtbPPAT), the enzyme that catalyses the penultimate step in CoA biosynthesis, we performed a fragment screen. In doing so, we discovered three series of fragments that occupy distinct regions of the MtbPPAT active site, presenting a unique opportunity for fragment linking. Here we show how, guided by X-ray crystal structures, we could link weakly-binding fragments to produce an active site binder with a K_D <20 μM and on-target anti-Mtb activity, as demonstrated using CRISPR interference. This study represents a big step toward validating MtbPPAT as a potential drug target and designing a MtbPPAT-targeting anti-TB drug.     

The closo-Cluster Triad: B9X9, [B9X9]· –, and [B9X9]2– with Tricapped Trigonal Prisms (X = Cl,Br, I). Syntheses,Crystal and Electronic Structures

Halogenation of nido-B₁₀H₁₄ with C₂H₂Cl₄, C₂Cl₆, Br₂, or I₂, produces by cluster degradation the (2 n)-closo-clusters B₉X₉ (X = Cl, Br, I). The synthesis of salts of the perhalogenated radical anions of the type (2 n + 1)-closo-[B₉X₉]^{· –} and of the corresponding dianions (2 n + 2)-closo-[B₉X₉]^2– from neutral B₉X₉ is described [n is the number of cluster atoms; (2 n), (2 n + 1), and (2 n + 2) is the number of cluster electrons]. Molecular and crystal structures of B₉Cl₉, B₉Br₉, [(C₆H₅)₄P][B₉Br₉] · CH₂Cl₂, and [(C₄H₉)₄N]₂[B₉Br₉] · CH₂Cl₂ have been determined via X-ray diffraction. All three oxidation states of the cluster retain the tricapped trigonal prism. The reduction of the clusters B₉X₉ was shown by cyclic voltammetry in CH₂Cl₂ to proceed via two successive one-electron reversible steps, separated by at least 0.4 V. The paramagnetic radical anions [B₉X₉]^{· –} (X = Cl, Br) were further characterized by magnetic susceptibility measurements of [Cp₂Fe][B₉X₉] and [Cp₂Co][B₉X₉], respectively. The EPR spectra of [B₉X₉]^{· –} (X = Cl, Br, I) in glassy frozen CH₂Cl₂ solutions showed increasing g anisotropy for the heavier halogen derivatives, illustrating significant halogen participation at the singly occupied MO. The ¹¹B NMR spectra of CD₂Cl₂ solutions of the neutral clusters B₉X₉ exhibit only one sharp resonance, indicating that the boron atoms are highly fluxional in solution. In contrast, two different boron resonances as expected for a rigid tricapped trigonal prism are clearly observed for the [B₉X₉]^2– dianions in solutions and for solid B₉Br₉ in the ¹¹B MAS NMR spectra. Temperature dependent ¹¹B MAS NMR experiments on B₉Br₉ and [B₉Br₉]^2– in the solid state show a reversible coalescence of the two resonances at higher temperature. ¹¹B MAS NMR spectra and DTA measurements of [B₉Br₉]^2– showed a phase transition.     

A Model for the Cobalamin-Dependent Methionine Synthase

The acid-catalyzed transfer of a Me group from N,N-dimethylaniline ( 6 ) to vitamin-B₁₂-derived Co^I complexes 2a , b was realized (Scheme 3). Hexane-1-thiol ( 8 ) was methylated by the methylcobalt complexes 4a , b in the presence of pyridine. Conditions for the complete cycle, i.e., Me transfer from 6 to 8 with Co^I complexes acting as a nucleophile and a nucleofuge have been established. The importance of Zn²⁺ as activating agent and of the basicity of tertiary amines for the Me transfer has been investigated.