Synthesis of primary amines
Treatment of ketones with ammonia in ethanol and titanium(IV) isopropoxide, followed by in situ reduction with sodium borohydride allows a highly chemoselective reductive mono-alkylation of ammonia. A simple workup afforded primary amines in good to excellent yields. Reductive alkylation of ammonia with aldehydes afforded the corresponding symmetrical secondary amines selectively.
B. Miriyala, S. Bhattacharyya, J. S. Williamson, Tetrahedron, 2004, 60, 1463-1471.
By optimizing the metal hydride/ammonia mediated reductive amination of aldehydes and hemiacetals, primary amines were selectively prepared with no or minimal formation of the usual secondary and tertiary amine byproduct. The methodology was performed on a range of functionalized aldehyde substrates, including in situ formed aldehydes from a Vasella reaction.
E. M. Dangerfield, C. H. Plunkett, A. L. Win-Mason, B. L. Stocker, M. S. M. Timmer, J. Org. Chem., 2010, 75, 5470-5477.
Cp*Ir complexes bearing a 2-picolinamide moiety effectively catalyze a direct reductive amination of ketones to give primary amines under transfer hydrogenation conditions using ammonium formate as both the nitrogen and hydrogen source.
K. Tanaka, T. Miki, K. Murata, A. Yamaguchi, Y. Kayaki, S. Kuwata, T. Ikariya, M. Watanabe, J. Org. Chem., 2019, 84, 10962-10977.
An efficient, metal and base-free, chemoselective reaction of boronic acids with cyanamidyl/arylcyanamidyl radicals provides primary aryl-, heteroaryl-, and alkyl amines at ambient temperature within 1 h. The reaction is mediated by PIFA and NBS.
N. Chatterjee, M. Arfeen, P. V. Bharatam, A. Goswami, J. Org. Chem., 2016, 81, 5120-5127.
A bench-stable NH-oxaziridine reagent enables a primary electrophilic amination of primary, secondary, and tertiary organometallic substrates. This facile and highly chemoselective transformation occurs in a single step without transition metal catalysts at ambient temperature. A convenient extractive work-up provides alkylamine products.
N. E. Behnke, R. Kielawa, D.-H. Kwon, D. H. Ess, L. Kürti, Org. Lett., 2018, 20, 8064-8068.
The use of aqueous ammonia is essential for a palladium-catalyzed allylic amination for the preparation of primary amines. It is noteworthy that ammonia gas did not react at all. The first catalytic asymmetric synthesis using aqueous ammonia as a nitrogen source has also been demonstrated.
T. Nagano, S. Kobayashi, J. Am. Chem. Soc., 2008, 131, 4200-4201.
An experimentally simple Microwave-assisted reductive alkylation of methyl carbamate with a range of aldehydes provides, after basic work-up, structurally diverse primary amines. This method is particularly amenable to high-throughput synthesis.
F. Lehmann, M. Scobie, Synthesis, 2008, 1679-1681.
The synthesis of free α-chiral amines by a one-pot multicomponent procedure involves the formation of N-diphenylphosphinoylimines from commercially available starting materials and the subsequent enantioselective addition of diakylzinc reagents using an air-stable precatalyst complex.
Cote, A. B. Charette, J. Org. Chem., 2005, 70, 10864-10867.
An oxime reagent as an amino group source achieves a direct conversion from acetyl arenes and alkanes to primary amines with C-C bond cleavage via domino transoximation/Beckmann rearrangement/Pinner reaction. The method was also applied to the synthesis of γ-aminobutyric acids, such as rolipram and baclophen.
K. Hyodo, G. Hasegawa, H. Maki, K. Uchida, Org. Lett., 2019, 21, 2818-2822.
An electrophilic amination of Grignard reagents with 4,4,5,5-tetramethyl-1,3-dioxolan-2-one O-phenylsulfonyloxime followed by acidic hydrolysis of the resulting imines gives primary amines.
M. Kitamura, T. Suga, S. Chiba, K. Narasaka, Org. Lett., 2004, 6, 4619-4621.
Cp*Ir complexes bearing a chiral N-(2-picolyl)sulfonamidato catalyze a convenient asymmetric reductive amination of benzylic ketones using readily available β-amino alcohols as chiral aminating agents. The amino alcohol-derived chiral auxiliary was easily removed by mild periodic oxidants, leading to optically active primary β-arylamines without erosion of the optical purity.
T. Kawada, K. Yabushita, T. Yasuda, T. Ohta, T. Yajima, K. Tanaka, N. Utsumi, M. Watanabe, K. Murata, Y. Kayaki, S. Kuwata, T. Katayama, J. Org. Chem., 2022, 87, 8458-8468.