Whitby group

To a stirring solution of N-benzyl-N-(3-heptynyl)amine (309, 1.0 g, 4.8 mmol), K₂CO₃ (1.2 g, 12.0 mmol) and MeCN (10.0 mL), benzenesulfonate (307, 1.33 g, 5.0 mmol) was added dropwise.  The reactants were refluxed for 24 hrs then quenched using NaOH (6M, 30.0 mL).  The product was extracted into diethyl ether (3 x 100 mL), the combined organic layer washed with water (3 x 100 mL), brine (50.0 mL), dried over MgSO₄, filtered and the solvent removed under reduced pressure.  Column chromatography (SiO₂, 0-100 % Et₂O:petroleum including 5 % Et₃N) afforded the title compound as a viscous clear oil (1.3 g, 4.4 mmol, 88 %).

General procedure C (see below) with N-(Dec-9-en-3-yn-1-yl)-N-(hex-1-yn-1-yl)-4-methylbenzenesulfonamide  (372 mg, 1.0 mmol).  Purification by column chromatography (SiO₂, hexane/Et₂O 9:1) gave the title compound as the minor product as a pale yellow oil (119 mg, 32%).

 The minor product was (E)‑N‑(hex‑1‑yn‑1‑yl)‑4‑methyl‑N‑(3‑(2‑methylcyclohexylidene)propyl)benzenesulfonamide (136b) obtained as a pale yellow oil (102 mg, 26%).  

General procedure C: zirconocene mediated cocyclisation of ynamides

n-BuLi (0.88 mL of a 2.5 M solution in hexanes, 2.2 mmol) was added dropwise to a solution of Cp₂ZrCl₂ (322 mg, 1.1 mmol) in dry THF (5.0 mL) at −78 °C.  A solution of the appropriate ynamide (1.0 mmol) in dry THF (3.0 mL) was added dropwise at −78 °C.  The reaction mixture was warmed to room temperature and stirred for 5 h.  The reaction mixture was cooled to −78 °C and MeOH (10.0 mL) added.  After stirring at −78 °C for 1 h the reaction mixture was stirred at room temperature for 16 h.  The reaction mixture was poured into water (100 mL) and extracted with ether (3 × 50 mL).  The organic extracts were combined, washed sequentially with water (2 × 100 mL) and brine (100 mL), dried (MgSO₄), filtered and the solvent removed in vacuo to give the crude product, which was purified as described.

General procedure C (see below) with N-(Dec-9-en-3-yn-1-yl)-N-(hex-1-yn-1-yl)-4-methylbenzenesulfonamide  (372 mg, 1.0 mmol).  Purification by column chromatography (SiO₂, hexane/Et₂O 9:1) gave the title compound as the minor product as a pale yellow oil (119 mg, 32%).

General procedure C: zirconocene mediated cocyclisation of ynamides

n-BuLi (0.88 mL of a 2.5 M solution in hexanes, 2.2 mmol) was added dropwise to a solution of Cp₂ZrCl₂ (322 mg, 1.1 mmol) in dry THF (5.0 mL) at −78 °C.  A solution of the appropriate ynamide (1.0 mmol) in dry THF (3.0 mL) was added dropwise at −78 °C.  The reaction mixture was warmed to room temperature and stirred for 5 h.  The reaction mixture was cooled to −78 °C and MeOH (10.0 mL) added.  After stirring at −78 °C for 1 h the reaction mixture was stirred at room temperature for 16 h.  The reaction mixture was poured into water (100 mL) and extracted with ether (3 × 50 mL).  The organic extracts were combined, washed sequentially with water (2 × 100 mL) and brine (100 mL), dried (MgSO₄), filtered and the solvent removed in vacuo to give the crude product, which was purified as described.

General procedure C (see below) with N-(Hex-1-yn-1-yl)-4-methyl-N-(non-8-en-3-yn-1-yl)benzenesulfonamide (372 mg, 1.0 mmol).  Purification by column chromatography (SiO₂, hexane/Et₂O 9:1) gave the product as a pale yellow oil (119 mg, 32%).

The major product (title compound) was (E)‑N‑(hex‑1‑yn‑1‑yl)‑4‑methyl‑N‑(3‑(2‑methylcyclopentylidene)propyl)benzenesulfonamide (136a) obtained as a pale yellow oil (150 mg, 40%)

General procedure C: zirconocene mediated cocyclisation of ynamides

n-BuLi (0.88 mL of a 2.5 M solution in hexanes, 2.2 mmol) was added dropwise to a solution of Cp₂ZrCl₂ (322 mg, 1.1 mmol) in dry THF (5.0 mL) at −78 °C.  A solution of the appropriate ynamide (1.0 mmol) in dry THF (3.0 mL) was added dropwise at −78 °C.  The reaction mixture was warmed to room temperature and stirred for 5 h.  The reaction mixture was cooled to −78 °C and MeOH (10.0 mL) added.  After stirring at −78 °C for 1 h the reaction mixture was stirred at room temperature for 16 h.  The reaction mixture was poured into water (100 mL) and extracted with ether (3 × 50 mL).  The organic extracts were combined, washed sequentially with water (2 × 100 mL) and brine (100 mL), dried (MgSO₄), filtered and the solvent removed in vacuo to give the crude product, which was purified as described.

General procedure C (see below) with N-(Hex-1-yn-1-yl)-4-methyl-N-(non-8-en-3-yn-1-yl)benzenesulfonamide (372 mg, 1.0 mmol).  Purification by column chromatography (SiO₂, hexane/Et₂O 9:1) gave the title compound as the minor product as a pale yellow oil (119 mg, 32%).

General procedure C: zirconocene mediated cocyclisation of ynamides

n-BuLi (0.88 mL of a 2.5 M solution in hexanes, 2.2 mmol) was added dropwise to a solution of Cp₂ZrCl₂ (322 mg, 1.1 mmol) in dry THF (5.0 mL) at −78 °C.  A solution of the appropriate ynamide (1.0 mmol) in dry THF (3.0 mL) was added dropwise at −78 °C.  The reaction mixture was warmed to room temperature and stirred for 5 h.  The reaction mixture was cooled to −78 °C and MeOH (10.0 mL) added.  After stirring at −78 °C for 1 h the reaction mixture was stirred at room temperature for 16 h.  The reaction mixture was poured into water (100 mL) and extracted with ether (3 × 50 mL).  The organic extracts were combined, washed sequentially with water (2 × 100 mL) and brine (100 mL), dried (MgSO₄), filtered and the solvent removed in vacuo to give the crude product, which was purified as described.