Synthesis of β-Amino ketones, esters, nitriles and related compounds
An efficient and very simple conjugate addition of aromatic and aliphatic amines to α,β-unsaturated carbonyl compounds under solvent-free conditions in the presence of catalytic amount of silicon tetrachloride gave the corresponding Michael adducts with very good yields.
N. Azizi, R. Baghi, H. Ghafuri, M. Boloutchian, M. Hashemi, Synlett, 2010, 379-382.
Ceric ammonium nitrate efficiently catalyzes the aza-Michael reaction of amines with α,β-unsaturated carbonyl compounds in water to produce the corresponding β-amino carbonyl compounds in very good yields under mild conditions. The reaction is procedurally simple and offers limited chemoselectivity, as aromatic amines were found to be unreactive.
R. Varala, N. Sreelatha, S. R. Adapa, Synlett, 2006, 1549-1553.
The addition of primary and secondary amines to α,β-unsaturated esters, nitriles, amides, and ketones mediated by solid lithium perchlorate gave the corresponding saturated amines under solvent-free and environmentally friendly conditions at room temperature.
N. Azizi, M. R. Saidi, Tetrahedron, 2004, 60, 383-387.
Cellulose-supported copper(0) efficiently catalyzes aza-Michael reactions of N-nucleophiles, such as amines and imidazoles with α,β-unsaturated compounds to produce the corresponding β-amino compounds and N-substituted imidazoles in excellent yields. The recovered catalyst can be used for several cycles with consistent activity.
K. R. Reddy, N. S. Kumar, Synlett, 2006, 2246-2250.
A mild palladium-catalyzed conjugate addition of a carbamate nucleophile to an enone provides β-amido ketones in very good yields. The regiocontrol, neutral conditions, and lack of preactivation of the nucleophile are attractive features of this transformation.
M. J. Gaunt, J. B. Spencer, Org. Lett., 2001, 3, 25-28.
A highly efficient and mild conjugate addition reaction of aromatic amines and aromatic aza-heterocycles to α,β-unsaturated olefins is promoted by 3-7 mol % of a Cu complex generated in situ from a mixture of inexpensive CuCl, a readily available phosphine or imidazolium salt, and KOtBu at ambient temperature. A wide range of β-amino sulfone, β-amino nitrile, and β-amino carbonyl compounds is selectively synthesized in high yields.
S. Kim, S. Kang, G. Kim, Y. Lee, J. Org. Chem., 2016, 81, 4048-4057.
The use of readily available and stable Weinreb amides enables a mild and efficient sequential synthesis of β-aminoketones or their derivatives ( e.g., pyrazolines). The reaction proceeds in good to excellent yields for a variety of amides, vinyl Grignard reagents and N-nucleophiles.
A. Gomtsyan, R. J. Koenig, C.-H. Lee, J. Org. Chem., 2001, 66, 3613-3616.
A sequential nucleophilic substitution at the carbonyl group of amides by vinylmagnesium bromide followed by Michael reaction after quench by water provides β-aminoketones.
A. Gomtsyan, Org. Lett., 2000, 2, 11-13.
A gold-catalyzed hydroamination of propargylic alcohols with anilines provides 3-hydroxyimines. A subsequent reduction gives 1,3-amino alcohols with high syn selectivity. By using a catalytic amount of aniline, 3-hydroxyketones can be obtained in high yield directly from propargylic alcohols. And a selective formation of 3-aminoketones via a rearrangement/hydroamination pathway is also described.
V. Laserna, M. J. Porter, T. D. Sheppard, J. Org. Chem., 2019, 84, 11391-11406.
1,4-diazobicyclo[2.2.2]octane (DABCO) based ionic liquids were used as recyclable catalysts for the aza-Michael addition at room temperature without any organic solvent. A low loading of the very efficient [DABCO-PDO][OAc] catalyzed reactions of various amines with a wide range of α,β-unsaturated amides to afford products in very good yields within hours. Moreover, the catalyst could be reused up to eight times.
A. Ying, Z. Li, J. Yang, S. Liu, S. Xu, H. Yan, C. Wu, J. Org. Chem., 2014, 79, 6510-6516.
A highly enantio- and regioselective Ni-catalyzed hydroamination of readily available unactivated alkenes bearing weakly coordinating native amides or esters provides β- or γ-amino acid derivatives and 1,2- or 1,3-diamines for both terminal and internal unactivated alkenes and a broad amine coupling partner scope. The mild reaction is well suited for late-stage functionalization.
C. Lee, H.-J. Kang, H. Seo, S. Hong, J. Am. Chem. Soc., 2022, 144, 9091-9100.
The efficiency of a CeCl3·7H2O-NaI system supported on silica gel in conjugate addition of secondary amines to α,β-enones is remarkable: no inert conditions are required, since oxygen and moisture are tolerated. The mildness of the reaction conditions and simplicity of operation make the reaction highly synthetically useful.
G. Bartoli, M. Bosco, E. Marcantoni, M. Petrini, L. Sambri, E. Torregiani, J. Org. Chem., 2001, 66, 9052-9055.
CeCl3 • 7H2O/NaI supported on neutral alumina (Al2O3) promotes heteroatom Michael additions under solvent-free conditions. The CeCl3 • 7H2O/NaI/Al2O3 system works well for hetero-Michael additions of weak nucleophiles such as imidazoles and carbamates to various acceptors.
G. Bartoli, M. Bartolacci, A. Giuliani, E. Marcantoni, M. Massaccesi, E. Torregiani, J. Org. Chem., 2005, 70, 169-174.
A versatile RuCl3-catalyzed 1,4-conjugate addition of primary, secondary and aromatic amines, thiols, and carbamates to α,β-unsaturated compounds in poly(ethylene glycol) (PEG) provides the desired β-substituted carbonyls in high yields. RuCl3-PEG offers low sensitivity toward moisture and oxygen, high tolerance of different functional groups, and efficient recyclability.
H. Zhang, Y. Zhang, L. Liu, H. Xu, Y. Wang, Synthesis, 2005, 2129-2136.
A copper-catalyzed electrophilic amination of cyclopropanols with O-benzoyl-N,N-dialkylhydroxylamines enables the synthesis of various β-aminoketones via C-C bond cleavage and Csp3-N bond formation. The mild reaction conditions tolerate several functional groups including benzoate, tosylate, expoxide, and α,β-unsaturated carbonyls.
Z. Ye, M. Dai, Org. Lett., 2015, 17, 2190-2193.
In a palladium-catalyzed intermolecular aminocarbonylation of alkenes, the use of hypervalent iodine reagent can accelerate the reaction. The current transformation presents a convenient method to generate β-amino acid derivatives from simple alkenes.
J. Cheng, X. Qi, M. Li, P. Chen, G. Liu, J. Am. Chem. Soc., 2015, 137, 2480-2483.
A general alkylamination of vinylarenes and an unprecedented diastereoselective anti-carboamination of unsaturated esters provide amines and unnatural β-amino acids. This alkylamination is enabled by an iron catalyst and alkyl diacyl peroxides, that serve as both alkylating reagents and internal oxidizing agents.
B. Qian, S. Chen, T. Wang, X. Zhang, H. Bao, J. Am. Chem. Soc., 2017, 139, 13076-13082.
A combined amino- and N-heterocyclic carbene (NHC)-catalyzed one-pot reaction sequence using commercially available catalysts at low catalyst loadings gives β-hydroxy and β-amino esters in high yield and excellent enantiopurity. The generation of quaternary stereocenters and application in gram-scale synthesis were also realized, with no requirements of inert or anhydrous reaction conditions.
H. Jiang, B. Gschwend, Ł. Albrecht, K. A. Jørgensen, Org. Lett., 2010, 12, 5052-5055.
The regio- and stereoselective aminochlorination of α,β-unsaturated ketones with N,N-dichloro-p-toluenesulfonamide (4-TsNCl2) and CuOTf as catalyst provides an easy access to vicinal haloamino ketones, with excellent regioselectivity and good yields. Aromatic and aliphatic enones give opposite regioselectivity.
D. Chen, C. Timmons, S. Chao, G. Li, Eur. J. Org. Chem., 2004, 3097-3101.