The alkali-metal salts (potassium and sodium) of a large number of aryl-and heteroarylsilanols undergo efficient cross coupling with a wide range of aromatic bromides and chlorides under mild conditions to form polysubstituted biaryls. The critical feature for the success of these coupling reactions and their considerable scope is the use of bis(tri-tert-butylphosphine)palladium. Under the optimized conditions, electron-rich, electron-poor, and sterically hindered arylsilanolates afford cross-coupling products in good yields. Many functional groups are compatible with the coupling conditions such as esters, ketones, acetals, ethers, silyl ethers, and dimethylamino groups. Two particularly challenging substrates, (2-benzofuranyl)dimethylsilanolate and (2,6-dichlorophenyl) dimethylsilanolate prepared as their sodium salts showed excellent activity in the coupling reactions, in the former case also with aromatic chlorides. General methods for the efficient synthesis of a wide range of aromatic silanols are also described.

This paper describes the fluorination of nitrogen heterocycles using anhydrous NBu4F. Quinoline derivatives as well as a number of 3- and 5-substituted pyridines undergo high-yielding fluorination at room temperature using this reagent. These results with anhydrous NBu4F compare favorably to traditional halex fluorinations using alkali metal fluorides, which generally require temperatures of ≥100 °C.

A general strategy for the construction of macrocyclic lactones containing conjugated Z,Z-1,3-diene subunits has been is described. The centerpiece of the strategy is a sequential ring-closing metathesis that forms an unsaturated siloxane ring followed by an intramolecular cross-coupling reaction with a pendant alkenyl iodide. A highly modular assembly of the various precursors allowed the preparation of unsaturated macrolactones containing 11-, 12-, 13-and 14-membered rings. Although the ring closing metathesis process proceeded uneventfully, the intramolecular cross-coupling required extensive optimization of palladium source, solvent, fluoride source and particularly fluoride hydration level. Under the optimal conditions (including syringe pump high dilution), the macrolactones were produced in 53-78% yield as single stereoisomers. A benzo fused 12-membered ring macrolactone containing an E,Z-1,3-diene unit was also prepared by the same general strategy. The E-2-styryl iodide was prepared by a novel Heck reaction of an aryl nonaflate with vinyltrimethylsilane followed by iododesilylation with ICl.

Optimization of the route to the sap-feeding insecticidal candidate tyclopyrazoflor featuring [3 + 2] cyclization of 3-hydrazinopyridine·2HCl and methyl acrylate is described. The key impurities in the [3 + 2] cyclization were identified and successfully controlled after optimization. The hazards associated with oxidation of an intermediate pyrazolidin-3-one using the incompatible combination of potassium persulfate and N,N-dimethylformamide (DMF) were avoided by using potassium ferricyanide in the presence of potassium hydroxide in water. The two elimination impurities in the ethylation step to produce tyclopyrazoflor were successfully minimized using ethyl iodide in the presence of cesium carbonate in DMF at 0 °C. The overall yield for this seven-step synthesis of tyclopyrazoflor was improved from 10% to 41% after the optimization detailed herein.

The total syntheses of marine natural products belonging to the kainoid family, isodomoic acids G and H are described. The strategic connection involves a sequential silylcarbocyclization/siliconbased cross-coupling process. These total syntheses were achieved efficiently via a twelve and a thirteen step, longest-linear sequence, respectively. The key transformations include a diastereoselective rhodium-catalyzed carbonylative silylcarbocyclization reaction of a (L)-vinylglycine-derived 1,6-enyne, a desilylative iodination reaction, as well as an alkenyl-alkenyl silicon-based cross-coupling reaction. The mechanistic insight garnered during the investigation of the iododesilylation reaction enabled stereocontrolled introduction of the iodine with either inversion or retention of double bond configuration. The invertive desilylative iodination leads to the total synthesis of isodomoic acid H, while its congener, isodomoic acid G, was obtained via a retentive iododesilylation.Isodomoic acids G (1) and H (2) were isolated in 1997 by Arakawa from red alga Chondria armata. 1 They belong to the family of kainoid amino acids, that includes kainic acid, domoic acid, and isodomoic acids, a series of structurally related natural products bearing a 3-carboxymethylproline moiety and a side-chain on C(4). These compounds differ in the position and configuration of the double bond at C(4). 2 Kainoid amino acids have long been recognized as neuroexcitatory agents, and their high potency makes them extremely valuable as research tools in neuroscience as well as medicinal chemistry. 3 In fact, in 2000 the shortage of kainic acid threatened to hamper research projects in neurodegenerative diseases and a call for new supplies for isolation or synthesis was issued. 4a Even now, the price of kainic acid remains extremely high and other kainoid derivatives are obtained in only minute quantities from natural sources. 4b In response, many syntheses of kainic acid have been reported, whereas sdenmark@illinois.edu. Supporting Information Available: Full experimental procedures and characterization data for intermediates and synthetic natural product described. This material is available free of charge via the Internet at http://pubs.acs.org. Our interest in developing a new synthetic route to these natural products stems from the desire (1) to showcase the synthetic utility of the sequential silylcarbocyclization/silicon-based crosscoupling technology recently developed in these laboratories and (2) to potentially provide access to various analogues by a modular approach. 6 We describe herein efficient, stereoselective total syntheses of 1 and 2 via a common intermediate. 7 NIH Public AccessAn obvious disconnection of 1 and 2 is the division into the substituted proline core and sidechain fragments at C(1′)-C(2′) (Scheme 1). The construction of the conjugated diene would involve the silicon-based cross-coupling reaction of silanol 3 8 with iodide 4 or 5, both of which would be derived from aldehyde 6 via a stereo-divergent iodode...