Asymmetric syntheses of (R)-4-halo-6,6a,7,8,9,10-hexahydro-5H-pyrazino[1,2-a][1,n]naphthyridines,important 5-HT2C agonist precursors

Asymmetric syntheses of N-protected (R)-4-halo-6,6a,7,8,9,10-hexahydro-5H-pyrazino[1,2-a][1,n]naphthyridines, advanced intermediates for the synthesis of highly potent and selective 5-HT_2C agonists, are described. The key transformation involves ring opening of N-protected bicyclic sulfamidate (R)-hexahydro-3H-pyrazino[1,2-c][1,2,3]oxathiazine 1,1-dioxide with (4-halo-2-fluoropyridin-3-yl)lithiums or (3-bromo-5-fluoropyridin-4-yl)lithium. In situ hydrolyses of the resultant sulfamic acids and subsequent intramolecular nucleophilic aromatic substitutions (S_NAr) produce the enantiopure tricycles. The two step procedure represents new methodology for the stereoselective syntheses of tetrahydronaphthyridines.     

A Metal–Organic Framework with Cooperative Phosphines That Permit Post‐Synthetic Installation of Open Metal Sites

PCM‐101 is a phosphine coordination material comprised of tris(p‐carboxylato)triphenylphosphine and secondary pillaring groups coordinated to [M₃(OH)]⁵⁺ nodes (M=Co, Ni). PCM‐101 has a unique topology in which R₃P: sites are arranged directly trans to one another, with a P???P separation distance dictated by the pillars. Post‐synthetic coordination of soft metals to the P: sites proceeds at room temperature to provide X‐ray quality crystals that permit full structural resolution. Addition of AuCl groups forces a large distortion of the parent framework. In contrast, CuBr undergoes insertion directly between the trans‐P sites to form dimers that mimic solution‐phase complexes, but that are geometrically strained due to steric pressure exerted by the MOF scaffold. The metalated materials are active in heterogeneous hydroaddition catalysis under mild conditions, yielding different major products compared to their molecular counterparts.     

Toeplitz operators with noncommuting symbols

LetM be a von Neumann algebra with a faithful normal tracial state and letH be a finite maximal subdiagonal subalgebra ofM. LetH ² be the closure ofH in the noncommutative Lebesgue spaceL ²(M). We consider Toeplitz operators onH ² whose symbol belong toM, and find that they possess several of the properties of Toeplitz operators onH ²( ) with symbol fromL ( ), including norm estimates, a Hartman-Wintner spectral inclusion theorem, and a characterisation of the weak^* continuous linear functionals on the space of Toeplitz operators.     

Geometry and bond‐length alternation in nonlinear optical materials. II. Effects of donor strength in two push–pull molecules

The compounds N‐[2‐(4‐cyano‐5‐dicyanomethylene‐2,2‐dimethyl‐2,5‐dihydrofuran‐3‐yl)vinyl]‐N‐phenylacetamide, C₂₀H₁₆N₄O₂,(I), and 2‐{3‐cyano‐5,5‐dimethyl‐4‐[2‐(piperidin‐1‐yl)vinyl]‐2,5‐dihydrofuran‐2‐ylidene}malononitrile 0.376‐hydrate, C₁₇H₁₈N₄O·0.376H₂O, (II), are novel push–pull molecules. The significant bonding changes in the polyene chain compared with the parent molecule 2‐dicyanomethylene‐4,5,5‐trimethyl‐2,5‐dihyrofuran‐3‐carbonitrile are consistent with the relative electron‐donating properties of the acetanilido and piperidine groups. The packing of (I) utilizes one phenyl–cyano C—H...N and two phenyl–carbonyl C—H...O hydrogen bonds. Compound (II) crystallizes with a partial water molecule (0.376H₂O), consistent with cell packing that is dominated by attractive C—H...N(cyano) interactions. These compounds are precursors to novel nonlinear optical chromophores, studied to assess the impact of donor strength and the extent of conjugation on bond‐length alternation, crystal packing and aggregation.     

'Lock and key' control of optical properties in a push-pull system

We report the modulation of the absorbance of a flavin push-pull derivative through specific recognition by a complementary diamidopyridine (DAP), shifting the flavin intramolecular charge transfer band by approximately 30 nm.     

Tuneable pseudorotaxane formation between a biotin-avidin bioconjugate and CBPQT4+

A biotinylated 1,5-dialkoxynaphthalene derivative has been shown to have the ability to bind strongly to avidin and thus act as an artificial binding site for cyclobis(paraquat-p-phenylene) thereby facilitating the formation of a tuneable pseudorotaxane-based bioconjugate.     

Reaction of [Ru3(CO)12] with tri(2-furyl)phosphine: Di- and tri-substituted triruthenium and phosphido-bridged diruthenium complexes

Reaction of [Ru₃(CO)₁₂] with tri(2-furyl)phosphine, P(C₄H₃O)₃, at 40 °C in the presence of a catalytic amount of Na[Ph₂CO] furnishes two triruthenium complexes [Ru₃(CO)₁₀{P(C₄H₃O)₃}₂] (1) and [Ru₃(CO)₉{P(C₄H₃O)₃}₃] (2) with the ligand coordinated through the phosphorus atom. Treatment of 1 and 2 with Me₃NO at 40 °C affords the dinuclear phosphido-bridged complexes [Ru₂(CO)₆(μ-η¹,η²-C₄H₃O){μ-P(C₄H₃O)₂}] (3) and [Ru₂(CO)₅(μ-η¹,η²-C₄H₃O){μ-P(C₄H₃O)₂}{P(C₄H₃O)₃}] (4), respectively, that are formed via phosphorus–carbon bond cleavage of a coordinated phosphine followed by coordination of the dissociated furyl moiety to the diruthenium center in a σ,π-alkenyl mode. Reaction of [Ru₃(CO)₁₂] with tri(2-furyl)phosphine in refluxing benzene gives, in addition to 3 and 4, low yields of the cyclometallated complex [Ru₃(CO)₉{μ-η¹,η¹-P(C₄H₃O)₂(C₄H₂O)}₂] (5). Treatment of 3 with EPh₃ (E = P, As, Sb) at room temperature yields the monosubstituted derivatives [Ru₂(CO)₅(μ-η¹,η²-C₄H₃O){μ-P(C₄H₃O)₂}(EPh₃)] (E = P, 8; E = As, 9; E = Sb, 10). Similar reactions of 3 with P(C₄H₃O)₃, P(OMe)₃ and Bu^tNC yield 4, [Ru₂(CO)₅(μ-η¹,η²-C₄H₃O){μ-P(C₄H₃O)₂}{P(OMe)₃}] (11) and [Ru₂(CO)₅(μ-η¹,η²-C₄H₃O){μ-P(C₄H₃O)₂}(NCBu^t)] (12), respectively. The molecular structures of complexes 3, 4 and 8 have been elucidated by single crystal X-ray diffraction studies. Each complex contains a bridging σ,π-alkenyl group and while in 4 the phosphine is bound to the σ-coordinated metal atom, in 8 it is at the π-bound atom. Protonation of 3 and 4 gives the hydride complexes [(μ-H)Ru₂(CO)₆(μ-η¹,η²-C₄H₃O){μ-P(C₄H₃O)₂}]⁺ (6) and [(μ-H)Ru₂(CO)₅(μ-η¹,η²-C₄H₃O){μ-P(C₄H₃O)₂}{P(C₄H₃O)₃}]⁺ (7), respectively, while heating 3 with dimethylacetylenedicarboxylate (DMAD) in refluxing toluene gives the cyclotrimerization product, C₆(CO₂Me)₆.     

Experimental Confirmation of a Predicted Porous Hydrogen-Bonded Organic Framework

Hydrogen-bonded organic frameworks (HOFs) with low densities and high porosities are rare and challenging to design because most molecules have a strong energetic preference for close packing. Crystal structure prediction (CSP) can rank the crystal packings available to an organic molecule based on their relative lattice energies. This has become a powerful tool for the a priori design of porous molecular crystals. Previously, we combined CSP with structure-property predictions to generate energy-structure-function (ESF) maps for a series of triptycene-based molecules with quinoxaline groups. From these ESF maps, triptycene trisquinoxalinedione (TH5) was predicted to form a previously unknown low-energy HOF (TH5-A) with a remarkably low density of 0.374 g cm⁻³ and three-dimensional (3D) pores. Here, we demonstrate the reliability of those ESF maps by discovering this TH5-A polymorph experimentally. This material has a high accessible surface area of 3,284 m² g⁻¹, as measured by nitrogen adsorption, making it one of the most porous HOFs reported to date.     

Density functional theory calculations of novel Rh(I) diphosphinite catalysts

Novel Rh(I) diphosphinite catalysts [Rh((R,R)-3,4-(bis(O-diphenylphosphino)-1,2,5,6-tetra-O-methyl-chiro-inositol)]+ ([Rh-CANDYPHOS]+) and [Rh((R,R)-3,4-(bis(O-diphenylphosphino)-1,2,5,6-tetra-O-ethyl-chiro-inositol)]+ ([Rh-EtCP]+) have been prepared utilizing naturally-occurring resources. Potential energy surfaces for the catalyzed asymmetric hydrogenation of the prochiral enamides methyl-(Z)-α-acetamido cinnamate, methyl-(Z)-α-acetamido cinnamic acid and dimethyl itaconate have been surveyed using density function theory (DFT) methods. Key transition states were identified from previous [Rh((R,R)-DUPHOS)]+ studies for the two diastereoisomeric manifolds 1 and 2. Transition state energies were found starting from models based on (1) the X-ray structure of the active complex (CANDYPHOS)(η⁴-(Z,Z)-cyclo-octa-1,5-diene)-rhodium(I) tetrafluoroborate CHCl₃ solvate [3] and (2) models in which the complex (without substrate) started with C2 molecular symmetry. The difficulties encountered in calculations of the transition state energies of large cations are outlined and limitations noted. Transition state enthalpy values are compared with the observed experimental free energy differences results and previous studies 1 and 2. The predictive aspects of the calculations appear to be limited with the starting models playing an important part in the absolute value of the final energies.