[structure: see text]. A new method for easy removal of ruthenium from metathesis reactions by using a polar isocyanide is reported. This protocol removed most ruthenium byproducts from a variety of synthetically useful metatheses. Moreover, the isocyanide-promoted carbene insertion results in rapid destruction of carbene reactivity, demonstrated in the commonly used first- and second-generation Grubbs' carbenes.

To extend the versatility of the ruthenium carbene-promoted enyne metathesis, it was combined with an Ireland ester enolate Claisen rearrangement. This reaction sequence provided conjugated dienes of higher substitution pattern than that obtained through a cross-enyne metathesis alone. The Ireland-Claisen was conducted across both acyclic and cyclic dienes produced from cross-metathesis and methylene-free enyne metathesis, respectively. In the case of cyclodienes, the Ireland-Claisen rearrangement produced s-trans locked dienes which underwent mode-selective ene reaction. The tandem, sequential use of the Ireland-Claisen rearrangement also proved suitable for chirality transfer originating from chiral propargylic alcohols. Last, the tandem metathesis/Ireland-Claisen was utilized to access 4-substituted-3,5-cyclohexadiene diol derivatives, which are valuable chiral intermediates for natural product synthesis. The combination of this pericyclic reaction with a catalytic metathesis reaction extends the versatility of cross-metathesis since additional diene motifs can be accessed.

The "one-pot" synthesis of nitrogen heterocycles and an oxygen heterocycle by enyne metathesis and in situ cyclization is reported.

No abstract

All reactions were conducted under an argon atmosphere unless otherwise noted. Dichloromethane (CH 2 Cl 2 ) (alumina), benzene and toluene (alumina + Q5) were drawn from a solvent purifier immediately prior to use. Dry tetrahydrofuran (THF) was obtained from a still (Na/benzophenone). Reagent S2 grade methanol was used for trituration and the cycloaddition reaction. Ruthenium [1,3-bis-(2,4,6-trimethylphenyl)-2-imidazolidinylidine]dichloro (phenylmethylene)(tricyclohexylphosphine) (Grubbs' second generation catalyst) was obtained from Materia Inc. (Pasadena, CA). 1,5-Cyclooctadiene (COD) was distilled from sodium prior to use. Amines were purchased from Aldrich and distilled from CaH 2 and stored over KOH. Polymer grade ethylene gas was obtained from Matheson Tri-gas. Triethylchlorosilane was obtained from Gelest, Inc. and distilled under reduced pressure prior to use. N,N-dimethylaminopyridine was obtained from Acros. The remaining reagents were purchased from Aldrich and distilled when applicable. Column chromatography was carried out on Bodman industries silica gel 60 (230 -400 mesh). Thin layer chromatography was developed on glass-backed EM science F254 silica plates and made visible with UV light, iodine, 1.7% KMnO 4 solution in water or Hanessian's stain (5 % w/v cerium molybdate in 0.72 M H 2 SO 4 ). 1 H-NMR spectra were recorded at 500 MHz and 13 C-NMR spectra at 125 MHz in CDCl 3 . 1 H-NMR spectra were referenced on the TMS signal for CDCl 3 . The 13 C-NMR spectra were referenced at 77.0 ppm for CDCl 3 . High resolution mass spectra were obtained using a ThermoFinnigan MAT95XL. Gas chromatography was performed on a Shimadzu GC-17A FID Gas chromatograph (thermal program: 40 °C, 4 min; 25 °C/min to 280 °C; 280 °C, 16.4 min) using an Agilent Technologies 19091J-433 capillary column (30m X 0.250 mm, 0.25 micron). FT-IR spectra were recorded on a Nicolet Impact series 420 IR. Optical rotations were measured on a Jasco DIP-370 polarimeter using the sodium D line at 589 nm in a 50 mm cell held at 25 °C. S3Table 1 Acyclic Diene/Ireland Claisen Rearrangement (E)-2-Methylene-1-phenyl-oct-3-enyl acetate (2B, metathesis step, entry 1). As reported in the literature: 1 To an oven-dried 50 mL Schlenk tube was added 500 mg of alkyne 2A (2.87 mmol), 3.2 mL of 1-hexene (9 equiv, 25.86 mmol), and 3 mL of dichloromethane. The clear solution was stirred for 5 min and 122 mg Grubbs' catalyst 1 (0.14 mmol, 5 mol%) was added as a single portion. Then reaction was heated at reflux for 18 h, cooled to room temperature, concentrated in vacuo (rotary evaporator), and loaded directly onto a silica gel column (3 X 15 cm). Elution with 5% ethyl acetate/hexane gave 500 mg of 2B (68%) as a clear oil. Analytical TLC (10% ethyl acetate/hexane) R f 0.36. 1