Ynamides react with ketenes in [2+2] cycloadditions leading to a variety of substituted 3-aminocyclobut-2-en-1-ones. The ynamides employed in these reactions are readily available via the copper-promoted N-alkynylation of carbamates and sulfonamides with alkynyl bromides and iodides. The scope of the [2+2] cycloaddition with regard to both the ketene and ynamide component is described.

A 250-mL, three-necked, round-bottomed flask equipped with a magnetic stir bar, an argon gas inlet tube, a rubber septum, which is pierced with a Teflon-coated thermocouple, and a 200-mL pressure-equalizing addition funnel fitted with a rubber septum (Note 2) is charged via syringe through the septum with allylamine (1) (14.0 mL, 10.68 g, 187 mmol, 2.1 equiv) (Note 3) and 100 mL of dichloromethane (Note 4). The solution is cooled to 0 °C (internal temperature) in an ice-water bath and a solution of methyl chloroformate (7.0 mL, 8.6 g, 91 mmol) (Note 5) in 30 mL of dichloromethane is added dropwise via the addition funnel over 10 min. The resulting white mixture is allowed to warm to room temperature over 30 min and then transferred to a 500-mL separatory funnel and extracted with 50 mL of aqueous 1M HCl solution, 50 mL of saturated aqueous NaHCO 3 solution, and 50 mL of saturated aqueous NaCl solution. The organic phase is dried over MgSO 4 , filtered, and concentrated by rotary evaporation (23 °C, 16 mmHg) to afford 10.12-10.26 g (97-98%) of carbamate 2 as a colorless oil (Note 6).Checked by Scott E. Denmark and Xiaorong Liu. 1 t-Butyl and ethyl N-allylcarbamate are commercially available. The method described here for the synthesis of the methyl derivative 2 illustrates a general procedure for the preparation of carbamates which usually delivers the desired compounds in near-quantitative yield and in a state of high purity, suitable for use in the N-alkynylation reaction without further purification. 2 The apparatus was flame-dried under reduced pressure (0.08 mmHg) and then maintained under an atmosphere of argon during the course of the reaction. 3 Allylamine (98%) was purchased from Alfa Aesar and used without purification. 4 Dichloromethane was purified by pressure filtration under argon through activated alumina. 5 Methyl chloroformate (99%) was obtained from Aldrich Chemical Company, Inc. and used as received. NIH Public Access

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n ‐Butylamine 1‐Octyne Vinylidene chloride 2‐Chloro‐1‐decen‐3‐yne Copper (I) iodide 1, 3‐Decadiyne Diisopropylamine