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Flow chemistry has gained considerable recognition as a simple, efficient, and safe technology for the synthesis of many types of organic and inorganic molecules ranging in scope from large complex natural products to silicon nanoparticles. In this paper we describe a method that adapts flow chemistry to the synthesis of libraries of compounds using a fluorous immiscible solvent as a spacer between reactions. The methodology was validated in the synthesis of two small heterocycle containing libraries. The reactions were performed on a 0.2 mmol scale, enabling tens of milligrams of material to be generated in a single 200 mL reaction plug. The methodology allowed library synthesis in half the time of conventional microwave synthesis while maintaining similar yields. The ability to perform multiple, potentially unrelated reactions in a single run is ideal for making small quantities of many different compounds quickly and efficiently.

A novel matrix metalloproteinase inhibitor, ABT-518, [S-(R*, R*)]-N-[1-(2, 2-dimethyl-1,3-dioxol-4-yl)-2-[[4-[4-(trifluoromethoxy)-phenoxy]phenyl]sulfonyl]ethyl]-N-hydroxyformamide, was labeled with tritium in two phenyl rings in a seven-step synthesis. The overall radiochemical yield of [3H]ABT-518 in seven steps starting from 1-(methylsulfonyl)-4-[4-(trifluoromethoxy)phenoxy]benzene was 6.2% with the radiochemical purity of 99.4%. Copyright © 2009 John Wiley & Sons, Ltd.

The additions of various five-membered ring aminoheterocycles to α-cyanocinnamonitriles were studied. Regiochemistry of product formation can in most cases be controlled by choosing the appropriate electrophile. An α-cyanocinnamonitrile with an additional β-leaving group normally provides products arising from initial attack of the ring amino group, while exo attack predominates in the case of the parent α-cyanocinnamonitrile. Aminopyrazole and aminoindazole provide only exo products with either electrophile. Product assignments were made via X-ray and 2D NMR methods; these assignments serve as a benchmark to several literature references and to future investigations of conjugate additions of these nucleophiles.

Reaction of Tp′W(O)(CO)(I) (1) with silver trifluoromethanesulfonate (silver triflate, AgOTf) in dichloromethane generates Tp′W(O)(CO)(OTf) (2) with triflate in the coordination sphere. Dissolution of neutral triflate adduct 2 in acetonitrile immediately produces the cationic tungsten(IV) nitrile complex [Tp′W(O)(NCMe)(CO)][OTf] (3). Exchange of the triflate anion in 3 for the large, non-coordinating tetrakis[3,5-bis(trifluoromethyl)phenyl]borate anion, [BAr′4]−, produces the isolable salt [Tp′W(O)(NCMe)(CO)][BAr′4] (4). Photolysis of Tp′W(O)(CO)(I) complex (1) in acetonitrile promotes loss of carbon monoxide and generates the neutral tungsten(IV) nitrile complex Tp′W(O)(I)(NCMe) (5). Spectroscopic data for 5 is consistent with formation of an η2-bound nitrile ligand. Chromatography of complex 5 on alumina led to oxidation to form an acylimido complex, Tp′W(O)(I)(NC(O)Me) (6). A dimeric complex, Tp′(O)(I)W(NC(Me)C(Me)N)W(I)(O)Tp′ (7) resulting from reductive coupling of two nitrile ligands was also isolated following alumina chromatography. Methylation of η2-nitrile complex 5 by MeOTf generates the cationic η2-iminoacyl complex [Tp′W(O)(I)(MeNCMe)][OTf] (9).

Reaction of Tp‘W(O)(I)(CO) (1; Tp‘ = hydridotris(3,5-dimethylpyrazolyl)borate) with MeLi followed by trapping of the resultant anion by ClSiPh2Me leads to the formation of a single isomer of the tungsten(VI) heteroatom-substituted carbene complex Tp‘W(O)(I)(C(Me)OSiPh2Me) (5a). The connectivity of complex 5a was confirmed by X-ray crystallography and spectral data. The acyl intermediate in the reaction, [Tp‘W(O)(I)(C(O)Me)][Li] (6), was observed by spectroscopic techniques. Trapping of the acyl intermediate 6 with H+ yields the neutral hydroxy carbene complex Tp‘W(O)(I)(C(Me)OH) (5c). Reaction of complex 1 with PhLi generates the anionic phenyl−acyl complex [Tp‘W(O)(I)(C(O)Ph)][Li] (8), which may be trapped with ClSiPh2Me, yielding the phenyl carbene complex Tp‘W(O)(I)(C(Ph)OSiPh2Me) (7). Carbene complex 5a reacts with AgSO3CF3 to form silver iodide and a coordinated triflate complex, Tp‘W(O)(OSO2CF3)(C(Me)OSiPh2Me) (9). In contrast to the acyl product formed with MeLi and 1, combining LiCuMe2 with 1 lead...

The Ollis–Sweeney ammonium ylid rearrangement has been effectively utilized to provide access to hitherto unknown hybrid privileged structural motifs. The rearrangement of didehydropiperidinium salts containing tethered olefins at the 4-position afforded, after subsequent ring closing metathesis, novel spirocyclic scaffolds suitable for further elaboration and incorporation of final structures into HTS sets.

The relative deuterium concentration and specific deuterium-site locations in a molecule can be determined using Site-Specific Natural Isotope Fractionation-Nuclear Magnetic Resonance (SNIF-NMR). For a given compound (e.g., ethanol) SNIF-NMR can provide information about the chemical pathway of formation and, in some cases, information about the geographic origin of a sample can also be discerned. SNIF-NMR has been applied to the analysis of wines and other alcoholic beverages. In this work, data were collected on samples of apple brandy, tequila, rum, potato vodka, cognac, and synthetic ethanol. Signal-to-noise considerations limit the samples that can be studied without preconcentration to those with relatively high alcohol contents.

Herein we report a concise protocol for the diastereoselective synthesis of novel bridged bicyclic lactams from commercially available components by the sequence of Ugi, ring-closing metathesis (RCM), and Heck reactions. X-ray diffraction studies revealed that the bicyclic products contain varying degrees of pyramidalization of the bridgehead nitrogen atom.

This paper presents the theory of operation, configuration, laboratory and ound test results obtained with an helicopter airborne laser positioning system developed by Princeton University.Unfortunately, due to time constraints, flight data could not be completed for presentation at this time. The system measures the relative position between two aircraft in three dimensions using two orthogonal fan-shaped laser beams sweeping across an array of four detectors. Specifically, the system calculates the relative range, elevation, and azimuth between an observation aircraft and a test helicopter with a high degree of accuracy. The detector array provides a wide field of view in the presence of solar interference due to compound parabolic concentrators and spectral filtering of the detector pulses. The detected pulses and their associated time delays are processed by the electronics and are sent as position errors to the helicopter pilot who repositions the aircraft as part of the closed loop system. Accuracies obtained in the laboratory at a range of 80 ft in the absence of sunlight were ±1° in elevation; +0.5° to -1.5° in azimuth; +0.5 to -1.0 ft in range; while elevation varied from 0 to +28° and the azimuth varied from 0 to ±45°. Accuracies in sunlight were approximately the same for a range of 80 ft, except that the field of view was reduced to approximately 40° (±20°) in direct sunlight.