- One-Pot Synthesis of Primary and Secondary Aliphatic Amines via Mild and Selective sp3 C?H Imination
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The direct replacement of sp3 C?H bonds with simple amine units (?NH2) remains synthetically challenging, although primary aliphatic amines are ubiquitous in medicinal chemistry and natural product synthesis. We report a mild and selective protocol for preparing primary and secondary aliphatic amines in a single pot, based on intermolecular sp3 C?H imination. The first C?H imination of diverse alkanes, this method shows useful site-selectivity within substrates bearing multiple sp3 C?H bonds. Furthermore, this reaction tolerates polar functional groups relevant for complex molecule synthesis, highlighted in the synthesis of amine pharmaceuticals and amination of natural products. We characterize a unique C?H imination mechanism based on radical rebound to an iminyl radical, supported by kinetic isotope effects, stereoablation, resubmission, and computational modeling. This work constitutes a selective method for complex amine synthesis and a new mechanistic platform for C?H amination.
- Comito, Robert J.,Ghosh, Subrata K.,Hu, Mengnan
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supporting information
p. 17601 - 17608
(2021/11/03)
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- Synthesis of α-Substituted Primary Benzylamines through Copper-Catalyzed Cross-Dehydrogenative Coupling
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A copper-catalyzed route to α-substituted, primary benzylamines by C-H functionalization of alkylarenes is described. The method directly affords the amine hydrochloride salt. Catalyst loadings down to 0.1 mol % in combination with scalability, insensitivity to air and moisture, and no need for column chromatography makes the procedure highly practical. The facile synthesis of the racemate of a blockbuster drug highlights the relevance for the development of pharmaceuticals. Preliminary mechanistic data are also included.
- Kramer, S?ren
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supporting information
p. 65 - 69
(2019/01/04)
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- Synthesis of potential inhibitors of squalenepoxidase with conformationanl fixation of the structural elements of Butenafine
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The synthesis of the naphthalinemethanamines 6b-h is reported. To obtain products with conformative rigidity, substituents with gradually increased space demand were placed into the α-position. Since the direct reductive amination of the naphthylalkanones 3 with the amines 9 or 10 was only of very limited use the α-substituted naphthalinmethanamines 2 and 4 were synthesized as useful intermediates by various methods and the desired N-substitution pattern of the target compounds was subsequently built up applying - mostly reductive - alkylation methods.
- Stanetty,Wallner
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p. 341 - 350
(2007/10/02)
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