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.

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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 μL 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.

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Reaction of Tp′W(O)(I)(CO) (1; Tp′ ) hydridotris(3,5-dimethylpyrazolyl)borate) with MeLi followed by trapping of the resultant anion by ClSiPh 2 Me leads to the formation of a single isomer of the tungsten(VI) heteroatom-substituted carbene complex Tp′W(O)(I)(dC(Me)-OSiPh 2 Me) (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)(dC(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 ClSiPh 2 Me, yielding the phenyl carbene complex Tp′W(O)(I)(dC(Ph)-OSiPh 2 Me) (7). Carbene complex 5a reacts with AgSO 3 CF 3 to form silver iodide and a coordinated triflate complex, Tp′W(O)(OSO 2 CF 3 )(dC(Me)OSiPh 2 Me) (9). In contrast to the acyl product formed with MeLi and 1, combining LiCuMe 2 with 1 leads to the replacement of iodide by a methyl group to form Tp′W(O)(Me)(CO) (2). Protonation of this methyl tungsten complex (2) in CH 2 Cl 2 in the presence of acetonitrile yields methane and the cationic nitrile adduct [Tp′W(O)(CO)(NCMe)] + (3), while protonation of 2 in neat acetonitrile produces a cationic hydroxy carbene complex, [Tp′W(O)(NCMe)(dC(Me)OH)] + (4).