Categories: Synthesis of N-Heterocycles, Synthesis of O-Heterocycles > Synthesis of Cyclic Amines, Synthesis of Cyclic Ethers >
Synthesis of morpholines
Recent Literature
A tandem sequential one-pot reaction employing both hydroamination and
asymmetric transfer hydrogenation reactions enables an efficient and practical
enantioselective synthesis of 3-substituted morpholines from aminoalkyne
substrates. A wide range of functional groups is tolerated. Hydrogen-bonding
interactions between the oxygen and the [(S,S)-Ts-DPEN] ligand of the Ru
catalyst are crucial for obtaining high ee's.
Y. Y. Lau, H. Zhai, L. L. Schafer, J. Org. Chem.,
2016, 81, 8696-8709.
A scalable, photocatalytic coupling of silicon amine protocol (SLAP) reagents
and aldehydes provides substituted morpholines, oxazepanes, thiomorpholines, and
thiazepanes under continuous flow conditions in the presence of an inexpensive
organic photocatalyst (TPP) and a Lewis acid additive.
M. K. Jackl, L. Legnani, B. Morandi, J. W. Bode, Org. Lett.,
2017, 19, 4696-4699.
Boron trifluoride etherate mediates an intramolecular hydroalkoxylation/hydrothioalkoxylation
of nitrogen-tethered alkenes providing five-membered thiazolidine, six-membered
1,4-oxazines (morpholines) and tetrahydro-2H-1,4-thiazines (thiomorpholines),
and seven-membered 1,4-oxazepanes in good yields.
M. J. Deka, K. Indukuri, S. Sultana, M. Borah, A. K. Saikia, J. Org. Chem.,
2015,
80, 4349-4359.
The reaction of 1,2-amino alcohols or diamines with an α-phenylvinylsulfonium
salt enables a concise synthesis of stereodefined C-substituted morpholines and
piperazines in very good yields. Factors affecting regio- and diastereocontrol
are discussed. Azepines and oxazepines can also be prepared in moderate yields.
J. V. Matlock, T. D. Svejstrup, P. Songara, S. Overington, E. M. McGarrigle, V.
K. Aggarwal, Org. Lett.,
2015,
17, 5044-5047.
Use of a base-free Pd(DMSO)2(TFA)2 catalyst enables the
synthesis of six-membered nitrogen heterocycles via a Wacker-type aerobic
oxidative cyclization of alkenes. Various heterocycles, including morpholines,
piperidines, piperazines and piperazinones, are accessible by this method.
Z. Lu, S. S. Stahl, Org. Lett., 2012,
14, 1234-1237.
Iron(III) catalyzes a diastereoselective synthesis of 2,6- and 3,5-disubstituted
morpholines from 1,2-amino ethers and 1,2-hydroxy amines substituted by an
allylic alcohol. The morpholines were obtained either by C-O or C-N bond
formation.
T. Aubineau, A. Dupas, T. Zeng, J. Cossy, J. An, Synlett, 2021,
32,
525-531.
A Pd(0)-catalyzed Tsuji-Trost reaction of vinyloxiranes with amino-alcohols
followed in situ by a Fe(III)-catalyzed heterocyclization provides 2,6-, 2,5-,
and 2,3-disubstituted as well as 2,5,6- and 2,3,5-trisubstituted morpholines in
very good yields and diastereoselectivities.
T. Aubineau, J. Cossy, Org. Lett.,
2018, 20, 7419-7423.
4-CN-pyridine is an effective cyanation reagent under catalyst-free,
paired electrochemical reaction conditions. Mechanistic studies support a nucleophilic reaction pathway,
and the cyanation protocol can be applied to diverse substrates including N,N-dialkyl
anilines, indole derivatives and amino acids (via decarboxylative cyanation).
G. S. Kumar, P. S. Shinde, H. Chen, K. Muralirajan, R. Kancherla, M. Rueping, Org. Lett.,
2022, 24, 6357-6363.