- One-Pot Synthesis of Primary and Secondary Aliphatic Amines via Mild and Selective sp3 C?H Imination
-
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
-
supporting information
p. 17601 - 17608
(2021/11/03)
-
- Development of an in situ-Product Crystallization (ISPC)-Concept to Shift the Reaction Equilibria of Selected Amine Transaminase-Catalyzed Reactions
-
The synthesis of enantiopure amines via amine transaminases involves several challenges including unfavorable reaction equilibria and product inhibition. Described here is a non-catalytic approach to overcome such problems by using an in situ-product crystallization (ISPC) to selectively remove a targeted product amine from an amine transaminase-catalyzed reaction. The continuous removal of the product amine from its reaction solution as a barely soluble salt effectively yields a displacement of the reaction equilibrium towards the products and facilitates a simple downstream processing approach via filtration. The targeted product amine is eventually obtained from the salt, while the counterion compound can be easily recycled.
- Hülsewede, Dennis,T?nzler, Marco,Süss, Philipp,Mildner, Andrea,Menyes, Ulf,von Langermann, Jan
-
p. 2130 - 2133
(2018/05/31)
-
- Synthesis of primary sec-alkylamines via nucleophilic ring-opening of N-phosphorylated aziridines
-
The novel ring-opening reaction of various 2-alkyl- and 2,2-dimethyl-N-(diethoxyphosphoryl)aziridines (1) and (10) with copper-modified Grignard reagents proceeds regiospecifically at the less hindered carbon. The diethyl N-sec-alkylphosphoramidates (2) thus obtained may efficiently be converted to primary sec-alkylamine hydrochlorides (3) by refluxing with 20% hydrochloric acid. 2,3-Disubstituted N-phosphorylated aziridines except N-phosphorylated cyclohexenimine (4) do not react under the described conditions. Copper-mediated reaction of 2-phenyl-N-(diethoxyphosphoryl)aziridine (7) with Grignard reagents affords a mixture of regioisomers (8) and (9) but still with the preference of ring-opening at the carbon of lesser substitution.
- Gajda, Tadeusz,Napieraj, Anna,Osowska-Pacewicka, Krystyna,Zawadzki, Stefan,Zwierzak, Andrzej
-
p. 4935 - 4946
(2007/10/03)
-
