CH2Cl2-triethylamine mixture

To a solution of the above compound (2.5 g, 7.43 mmol) in CH2Cl2 (50 ml) was added triethylamine (2.1 ml, 14.9 mmol) followed by addition of benzyl chloroformate (1.2 ml, 8.1 mmol). The mixture was allowed to stir at ambient temperature for 6 h. The solution was diluted with 1 L of CH2CI2 and washed with water. The organics were dried over anhydrous MgS04, concentrated... 

To a solution of Grubbs catalyst G1 (943 mg, 1.15 mmol, 0.4 equiv) in CH2C12 (900 mL) was added a solution of enyne 51 (2.00 g, 2.86 mmol, 1.0 equiv) in toluene (100mL). The reaction was purged with ethylene and stirred at 45 °C under an atmosphere of ethylene for 40 h. The crude mixture was treated with ethyl vinyl ether (1 mL) and concentrated to a black oil. Purification by silica gel chromatography (doped with triethylamine, 5-6% in CH2Cl2/hexane) afforded cyclophane 53 (624 mg, 31%). 

The Step 2 product (6.55 g) was dissolved in 50 ml DMF, then treated with 7.9 ml triethylamine followed by t-butyl 2-bromoethylcarbamate (4.3 g) dissolved in 5 ml DMF. The mixture was stirred 3 days at ambient temperature and was then diluted with EtOAc and water. The organic phase was dried and concentrated to a gum. The gum was purified by chromatography using CH2Cl2/methyl alcohol, 95 5, and 5.7 g product isolated as a gum. 

The Step 6 product (0.3 g) and A,ALcarbonyldiimidazole (0.19 g) were dissolved in 20 ml DMF and stirred 1 hour at ambient temperature. The mixture was then treated with the Step 4 product (0.42 g) and 0.32ml triethylamine and stirred 20 hours. The solution was then diluted with water and diethyl ether, the organic phase separated, dried, and concentrated to a gum. The residue was purified by chromatography using CH2Cl2/methyl alcohol, 93 7, and 0.38 g product isolated, mp = 139—140°C. 

A mixture of chlorotrimethylsilane (0.205 mmol) was added to a suspension of n. v-3-aminocyclohexanecarboxylic acid (0.205 mmol) suspended in 500 ml CH2Cl2/acetonitrile, 5 1, and refluxed for 2 hours. Once cooled, triethylamine (0.410 mmol) was added dropwise to the mixture followed immediately by the portionwise addition of triphenylmethyl chloride (0.205 mmol). The mixture was stirred 18 hours and sufficient methyl alcohol was added to dissolve the vessel contents. The solution was concentrated and the residue was partitioned between 800 ml diethyl ether/10% citric acid, 1 1. The ether layer was collected and combined with a 150 ml diethyl ether extraction from the citric acid layer. Combined fractions were extracted three times with 250 ml 2 M NaOH and once with 100 ml water. These layers were washed twice with 150 ml diethyl ether, cooled to 0°C, acidified to pH 7 with 12 M HC1, and re-extracted three times with 200 ml EtOAc. The extract was dried over MgS04, then concentrated, and the product isolated in 85% yield as a white foam. 

A O.IM CH2CI2 solution of the Step 4 product (1 eq) and triethylamine (2 eq) was treated with triphosgene (0.3 eq) at 0°C. The mixture was stirred for 1 hour at ambient temperature and concentrated the residue was extracted with EtOAc. The extract was filtered was re-concentrated, the residue re-crystallized in CH2Cl2/pentanes, and the product was isolated as a white solid. 

The Step 10 product (0.848 mmol), Al,A-dimethylaminopyridine (0.017 mmol), and triethylamine (1.7 mmol) were dissolved in 30 ml of CH2CI2 and then treated with phthalic anhydride (1.06 mmol). The mixture was next stirred at ambient temperature for 12hours. The solution was washed with IM of HCl solution, extracted with CH2CI2, and washed with NaHCOs solution and water. The mixmre was purified by flash chromatography using CH2Cl2/acetone, 2.5 1, respectively, and the product was isolated in 73% yield. 

Isobutyryl chloride (0.18 mmol) was added to a solution of triethylamine (0.18 mmol) containing the product from Step 2 (0.164 mmol) and the mixture stirred at ambient temperature 2 hours. It was then diluted with CH2CI2, washed with water and brine, dried, and concentrated. The residue was purified by chromatography using silica gel with 0.5-1% methyl alcohol/CH2Cl2 and the product isolated. MS data supplied. 

A reactor was charged with paraformaldehyde (30.5 g), N-methyl-N -nitroguanidine (20 g), triethylamine (17 g) and 100 ml apiece toluene and dioxane, and the mixture refluxed 16 hours. Thereafter, the solvent was evaporated, the residue purified by column chromatography on silica using CH2Cl2/methyl alcohol, 95 5, and the product isolated, mp= 137-139 °C. 

To the crude product from Step 1 (6.96 g) dissolved in 30 ml triethylamine and 6 ml dimethylformamide at ambient temperature was added 3 ml trimethylsilylacetylene, Cul (150 mg) and bis(triphenyl-phosphine)palladium(II)chloride (300 mg). The mixture was heated 1 hour to 50-60°C, an additional 0.3 ml trimethylsilylacetylene added, and heating continued 30 minutes. The cooled mixture was diluted with 250 ml water, extracted with 250 ml diethyl ether, separated, dried, and concentrated. The material was purified by chromatography on silica gel using CH2Cl2/hexane, 1 1, re-crystallized from diethyl ether/hexane, and the product isolated, mp = 181-182°C. H-NMR, MS, and elemental analysis data supplied. 

The product from Step 3 (0.11 mol) was suspended in 500ml of CHjClj containing 17.4 ml triethylamine, the mixture cooled to -70 °C, trifluoromethanesulphonic anhydride (0.12 mol) added, and the reaction stirred 1 hour at ambient temperature. Thereafter, it was washed with 200 ml water and 100 ml ice cold 1M HCl solution. The organic phase was dried, concentrated, purified by chromatography on a silica gel using CH2Cl2/methyl alcohol, 98 2, and the product isolated in 98% yieid, mp = 68-70 °C. 

A solution of 4-(2-chloroethylsulfonyl)phenol (24.4 mmol) dissolved in 50 ml CH2CI2 was treated at 37°C with triethylamine (26.4 mmol), stirred for 3.25 hour, and the product from Step 5 (22.0 mmol) dissolved in 40 ml CH2CI2 added. The mixture was stirred at 37 °C 3 hours, cooled to room temperature, and treated with 80 ml water and solid NaCl. The mixture was extracted 3 times with 70 ml CH2CI2, dried, concentrated to 70 ml, treated with 75 ml toluene, and concentrated to 100 ml. After 3 days at 0°C the suspension was concentrated to 50 ml, filtered, and crude product isolated as white crystals. They were purified by chromatography on silica gel using CH2Cl2/t- butylmethyl ether, 19 1, and the product isolated in 87.1% yield, mp = 155.5-156.2°C. MS Data supplied. 

Typical procedure, as exemplified by the preparation of 307b [195] To a stirred solution of 4.0-TAPP (67 mg, 0.10 mmol) and triethylamine (89 mg, 0.88 mmol) in dichloromethane (50 mL) under N2 was added triphosgene (39 mg, 0.13 mmol). The reaction mixture was stirred at room temperature for 1 h, and then piperidine (43 mg, 0.50 mmol) was added and stirring was continued for a further 1 h. The solvent was removed in a rotary evaporator, and the residue was chromatographed on silica gel (eluent MeOH/CH2Cl2, 1 100) to give 307b (94%). 

Typical procedure. N-Carboxy-ji-cMoro-L-alanme anhydride [821] To a solution of N-Boc-yS-chloro-L-alanine (400 mg, 1.8 mmol) and tert-butyldimethylsilyl chloride (283 mg, 1.9 mmol) in ethyl acetate (2 mL) at 0 °C was added triethylamine (244 pL, 1.8 mmol). Triethylamine hydrochloride was immediately precipitated, and after stirring for 30 min at 0 °C, it was filtered off (244 mg, 100%). The filtrate was then concentrated in vacuo to leave an oil, which was redissolved in dichloromethane (3.0 mL). After chilling to 0 °C, oxalyl chloride (195 pL, 2.25 mmol) was added, followed by 2-3 drops of DMF. Once gas evolution had subsided (approximately 2 min), additional DMF (2 drops) was added and the reaction mixture was allowed to warm to room temperature. Further DMF was added dropwise until no further gas was evolved (approximately 10 min). The solution was then diluted with THF (ca. 10 mL) and concentrated once more. This routine ensures removal of any unreacted oxalyl chloride. The flask containing the resulting oil was placed on a vacuum line, and evaporation of the DMF (over about 2 h) afforded white needles. Recrystallization from CH2Cl2/hexane gave the desired NCA in quantitative yield (270 mg). 

Typical procedure for the synthesis of benzo[Z ]furan. To a screw-capped vial with a stir bar were added 2-iodophenol (110 mg, 0.5 mmol), phe-nylacetylene (56.2 mg, 0.55 mmol), PS-PdONPs (2.9 mg, 1.5 mol% of Pd), triethylamine (152 mg, 1.5 mmol), and H2O (1.0 mL). After stirring at 80 °C for 20 h, the reaction mixture was cooled to room temperature by immediately immersing the vial in water ( 20 °C) for about 10 min. Subsequently, the aqueous phases were removed, and the recovered catalyst was washed with H2O (5x3.0 mL) and diethyl ether (5x3.0 mL), which were then added to the aqueous phase. The aqueous phase was extracted eight times with diethyl ether. The combined organic extracts were dried over MgS04 and concentrated under reduced pressure. The recovered PS-PdONPs was dried in vacuo and reused. The resulting product was purified by PTLC (hexane-CH2Cl2). 

---