Categories: C-N Bond Formation >
Synthesis of urea derivatives
Structurally and functionally diverse N-carbamoylamino acids were obtained through the alkylation of monosubstituted parabanic acids followed by hydrolysis of the intermediate products in very good yields and excellent purity.
A. V. Bogolubsky, S. V. Ryabukhin, G. G. Pakhomov, E. N. Ostapchuk, A. N. Shivanyuk, A. A. Tolmachev, Synlett, 2008, 2279-2282.
An efficient method for palladium-catalyzed cross-coupling of aryl chlorides and triflates with sodium cyanate allows the synthesis of unsymmetrical N,N′-di- and N,N,N′-trisubstituted ureas in one pot and is tolerant of a wide range of functional groups. Insight into the mechanism of aryl isocyanate formation was gleaned through studies of the transmetalation and reductive elimination steps of the reaction.
E. V. Vinogradova, B. P. Fors, S. L. Buchwald, J. Am. Chem. Soc., 2012, 134, 11132-11135.
Pd-catalyzed arylation of ureas enables a facile synthesis of an array of unsymmetrical N,N′-diarylureas in good to excellent yields from benzylurea via a one-pot arylation-deprotection protocol, followed by a second arylation.
S. Breitler, N. J. Oldenhuis, B. P. Fors, S. L. Buchwald, Org. Lett., 2011, 13, 3262-3265.
Palladium-catalyzed amidation allows the preparation of unsymmetrically substituted ureas. Both aryl bromides and chlorides, as well as heteroaryl chlorides, have been coupled to aryl, benzyl, and aliphatic ureas by using a novel nonproprietary bipyrazole ligand (bippyphos).
B. J. Kotecki, D. P. Fernando, A. R. Haight, K. A. Lukin, Org. Lett., 2009, 11, 947-950.
Hydroxamic acids were synthesized from carboxylic acids and hydroxylamine hydrochloride in the presence of ethyl 2-cyano-2-(4-nitrophenylsulfonyloxyimino)acetate (4-NBsOXY). 4-NBsOXO also promotes the Lossen rearrangement of hydroxamic acids in the presence of amines to yield ureas. The reactions are compatible with common N- and O-protecting groups and prevent racemization.
K. Thalluri, S. R. Manne, D. Dev, B. Mandal, J. Org. Chem., 2014, 79, 3765-3775.
The arylation of N-H and O-H containing compounds at room temperature with phenylboronic acids is promoted in the presence of cupric acetate and a tertiary amine. Substrates include phenols, amines, anilines, amides, imides, ureas, carbamates, and sulfonamides.
D. M. T. Chan, K. L. Monaco, R.-P. Wang, M. P. Winteres, Tetrahedron Lett., 1998, 39, 2933-2936.
A mild, ruthenium-catalyzed anti-Markovnikov addition of secondary amides, anilides, lactames, ureas, bislactames, and carbamates to terminal alkynes has been developped. Two complementary protocols provide either the E or the Z isomers.
L. J. Goossen, J. E. Rauhaus, G. Deng, Angew. Chem. Int. Ed., 2005, 44, 4042-4045.
Imidazolidin-2-ones are prepared in two steps from readily available N-allylamines. Addition of the amine starting materials to isocyanates affords N-allylureas, which are converted to imidazolidin-2-ones with generation of two bonds and up to two stereocenters in the presence of aryl bromides, a catalytic amount of Pd2(dba)3/Xantphos and NaOtBu.
J. A. Fritz, J. S. Nakhla, J. P. Wolfe, Org. Lett., 2006, 8, 2531-2534.
A palladium-catalyzed carbonylation of urea derivatives with aryl iodides and bromides afforded N-benzoyl ureas in very good yields using near-stoichiometric amounts of carbon monoxide generated from the decarbonylation of 9-methylfluorene-9-carbonyl chloride as CO precursor. The synthetic protocol displayed good functional group tolerance. The methodology is also highly suitable for 13C isotope labeling.
K. Bjerglund, A. T. Lindhardt, T. Skrydstrup, J. Org. Chem., 2012, 77, 3793-3799.