Categories: C-H Bond Formation >
Reduction of amides to amines
A nickel-catalyzed reduction of secondary and tertiary amides provides amines. The reaction transforms various amide substrates, proceeds in the presence of esters and epimerizable stereocenters, and can be used to achieve the reduction of lactams. Moreover, this methodology provides a simple tactic for accessing medicinally relevant α-deuterated amines.
B. J. Simmons, M. Hoffmann, J. Hwang, M. K. Jackl, N. K. Garg, Org. Lett., 2017, 19, 1910-1913.
1,1,3,3-tetramethyldisiloxane and 1,2-bis(dimethylsilyl)benzene are found to be effective reducing agents for a platinum-catalyzed reduction of carboxamides to amines. The reaction tolerates other reducible functional groups such as NO2, CO2R, CN, C═C, Cl, and Br. The product is obtained by simple extraction.
S. Hanada, E. Tsutsumi, Y. Motoyama, H. Nagashima, J. Am. Chem. Soc., 2009, 131, 15032-15040.
A zinc-catalyzed reduction of tertiary amides shows remarkable chemoselectivity and substrate scope tolerating ester, ether, nitro, cyano, azo, and keto substituents.
S. Das, D. Addis, S. Zhou, K. Junge, M. Beller, J. Am. Chem. Soc., 2010, 132, 1770-1771.
The combination of amide activation by Tf2O with B(C6F5)3-catalyzed hydrosilylation with TMDS enables a one-pot reduction of secondary amides to amines under mild conditions with broad applicability and excellent chemoselectivity for many sensitive functional groups.
P.-Q. Huang, Q.-W. Lang, Y.-R. Wang, J. Org. Chem., 2016, 81, 4235-4243.
Diethylzinc (Et2Zn) is an efficient and chemoselective catalyst for the reduction of tertiary amides under mild reaction conditions employing polymeric silane (PMHS) as a cost-effective hydride source. Crucial for the catalytic activity was the addition of a substoichiometric amount of lithium chloride. A series of amides containing different additional functional groups were reduced to their corresponding amines in very good yields.
O. O. Kovalenko, A. Volkov, H. Adolfsson, Org. Lett., 2015, 17, 446-449.
Tris(pentafluorophenyl)boron B(C6F5)3 is an effective catalyst for the reduction of tertiary and N-phenyl secondary amides in the presence of a silane. Various amides can be reduced in near quantitative yield, with minimal purification, at low temperatures, and with short reaction times. This reduction tolerates alkenes, nitro groups, and aryl halides, including aryl iodides.
R. C. Chadwick, V. Kardelis, P. Lim, A. Adronov, J. Org. Chem., 2014, 79, 7728-7733.
Reduction of secondary amides to imines and secondary amines has been achieved using low catalyst loadings of readily available iridium catalysts such as [Ir(COE)2Cl]2 with diethylsilane as reductant. The stepwise reduction to secondary amine proceeds through an imine intermediate that can be isolated when only 2 equiv of silane is used. This system shows high efficiency and an appreciable level of functional group tolerance.
C. Cheng, M. Brookhart, J. Am. Chem. Soc., 2012, 134, 11304-11307.
An expeditious and practical method for the reduction of various amides and lactams to amines in good to excellent yields is consisted of activation with Tf2O followed by reduction with sodium borohydride in THF at room temperature. This method offers TBDPS-group tolerance, short reaction time, and a simple workup.
S.-H. Xiang, J. Xu, H.-Q. Yuan, P.-Q. Huang, Synlett, 2010, 1829-1832.
A chemoselective activation of a secondary amide with triflic anhydride in the presence of 2-fluoropyridine enables a mild reduction using triethylsilane, a cheap and rather inert reagent. Imines can be isolated after a basic workup or readily transformed to the aldehydes following an acidic workup. The amine moiety can be accessed by addition of Hantzsch ester to the reaction mixture.
G. Pelletier, W. S. Bechara, A. B. Charette, J. Am. Chem. Soc., 2010, 132, 12817-12819.
A triruthenium cluster catalyzes the reaction of secondary amides with hydrosilanes, yielding a mixture of secondary amines, tertiary amines, and silyl enamines. Production of secondary amines with complete selectivity is achieved by the use of higher concentration of the catalyst and bifunctional hydrosilanes such as 1,1,3,3-tetramethyldisiloxane followed by acidic workup.
S. Hanada, T. Ishida, Y. Motoyama, H. Nagashima, J. Org. Chem., 2007, 72, 7551-7559.
Phenol carbamates undergo an anionic ortho-Fries rearrangement to their corresponding amides in the presence of LDA. Sterically hindered substrates can be converted with s-BuLi/TMEDA at -90°C. The amides can be efficiently reduced with lithium aluminum hydride to the corresponding Mannich bases.
N. Assimomytis, Y. Sariyannis, G. Stavropoulos, P. G. Tsoungas, G. Varvounis, P. Cordopatis, Synlett, 2009, 2777-2782.
Odorless Dod-S-Me and MMS are developed as efficient borane carriers. The yields of hydroborations and reductions with the borane complex of Dod-S-Me are very high. The recovery of Dod-S-Me after the reaction is quantitative.
P. K. Patra, K. Nishide, K. Fuji, M. Node, Synthesis, 2004, 1003-1006.