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General Hydroamination of Allenamides: Mechanistic Insights with an Acetate Adduct and 1,1,1,3,3,3-Hexafluoro-2-propanol

Kadiyala Sagar, Tapas R. Pradhan, Abdikani Omar Farah, Henry R. Wise, Bhailal C. Merja, Malempati Srimannarayana*, Paul Ha-Yeon Cheong* and Jin Kyoon Park*

*GITAM University, Telangana, India; Oregon State University, Corvallis, United States; Pusan National University, Busan, Korea, Email: smalempagitam.edu, paulcscience.oregonstate.edu, pjkyoonpusan.ac.kr

K. Sagar, T. R. Pradhan, A. O. Farah, H. R. Wise, B. C. Merja, M. Srimannarayana, P. H.-Y. Cheong, J. K. Park, Org. Lett., 2023, 25, 5574-5578.

DOI: 10.1021/acs.orglett.3c01820



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Abstract

A HFIP-assisted allenamide activation enables metal-free regioselective intermolecular interception of amines to provide 1,3-diamines. Exclusive N-chemoselectivity and regioselectivity were achieved for a broad range of substrates. Experimental mechanistic studies revealed that 1,1,1,3,3,3-hexafluoro-2-propanol mediates the proton transfer for activation of the allenamide.

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Representative procedure for scope study

A screw-capped 7 mL vial (with hole and PTFE/silicone septum) with a magnetic stir bar was charged with allenamide 1 (0.2 mmol), amine 2 (1.3 equiv), and NaOAc (1.0 equiv, 16.4 mg, 0.2 mmol) dissolved in dry dichloromethane (0.12 M, 1.67 mL) under nitrogen atmosphere. After 5 min of stirring, HFIP (5.0 equiv, 105 L, 1 mmol) was added into the above solution following heating of the reaction mixture for 4 h at 45 C by means of a preheated heating block. The reaction was monitored by TLC showing the consumption of starting allenamide. After solvent evaporation to dryness, it was then diluted with dichloromethane (5 mL). Water was added and the organic layer was separated. The aqueous layer was further extracted with dichloromethane (2 X 5 mL). The combined organic layer was dried over sodium sulfate to obtain a reddish-brown crude residue, which when subjected to silica gel column chromatography using hexane: EtOAc (19:1 to 1:1) as eluent afforded the corresponding coupling products in up to 87% isolated yield.


Key Words

allylic amines


ID: J54-Y2023