Synthesis of benzylic amines
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 highly active Mn(I) pincer catalyst enables an atom-economic and highly efficient N-alkylation of amines with alcohols utilizing the borrowing hydrogen methodology. A broad range of anilines and more challenging aliphatic amines were alkylated with primary and secondary alcohols. The reaction offers low catalyst loadings and mild reaction conditions.
L. Homberg, A. Roller, K. C. Hultzsch, Org. Lett., 2019, 21, 3142-3147.
Well-defined Co(II) complexes stabilized by a PCP ligand catalyze efficient alkylations of aromatic amines by primary alcohols into mono-N-alkylated amines in very good yields. The inexpensive, earth-abundant nonprecious metal catalysts make this acceptorless alcohol dehydrogenation concept environmentally benign.
M. Mastalir, G. Tomsu, E. Pittenauer, G. Allmaier, K. Kirchner, Org. Lett., 2016, 18, 3462-3465.
Commercially available [(PPh3)2NiCl2] is an efficient catalyst for the mono-N-alkylation of (hetero)aromatic amines, employing alcohols to deliver diverse secondary amines in excellent yields via the borrowing hydrogen strategy. The catalyst system can also be used for accessing various quinoline derivatives following the acceptorless dehydrogenation pathway.
S. N. R. Donthireddy, V. K. Pandey, A. Rit, J. Org. Chem., 2021, 86, 6994-7001.
Imines and secondary amines were synthesized selectively by a Pd-catalyzed one-pot reaction of benzyl alcohols with primary amines. The reactions did not require any additives and were effective for a wide range of alcohols and amines.
M. S. Kwon, S. Kim, S. Park, W. Bosco, R. K. Chidrala, J. Park, J. Org. Chem., 2009, 74, 2877-2879.
The addition of 4 Å molecular sieves enables an efficient cobalt(II)-catalyzed N-alkylation of both aromatic and aliphatic amines with alcohols with high chemoselectivity (amines vs imines). A hydrogen-borrowing mechanism is responsible for the tandem acceptorless dehydrogenation/condensation/hydrogenation process.
G. Zhang, Z. Yin, S. Zheng, Org. Lett., 2016, 18, 300-303.
A Chan-Lam coupling reaction of benzylic and allylic boronic esters with primary and secondary anilines provides valuable alkyl amine products. Both secondary and tertiary boronic esters can be used as coupling partners, with mono-alkylation of the aniline occurring selectively.
J. D. Grayson, F. M. Dennis, C. C. Robertson, B. M. Partridge, J. Org. Chem., 2021, 86, 9883-9897.
A catalytic system generated in situ from a tetranuclear Ru-H complex with a catechol ligand enables a direct deaminative coupling of two primary amines to form secondary amines. The analogous coupling of aniline with primary amines formed aryl-substituted secondary amines.
P. T. K. Arachchige, H. Lee, C. S. Yi, J. Org. Chem., 2018, 83, 4932-4947.
A monobenzylation of aromatic amines with benzylic alcohols in good yields proceeds under MW conditions in the presence of SmI2 as a catalyst with the generation of water as the sole byproduct. This reaction offers a broad substrate scope and good functional-group tolerance.
J. Gour, S. Gatadi, S. Malasala, M. V. Yaddanpudi, S. Nanduri, J. Org. Chem., 2019, 84, 7488-7494.
The use of 1,2-benzisoxazole as a practical electrophilic primary amine source enables a mild and general copper-hydride-catalyzed hydroamination of alkenes and alkynes to form primary amines. This method provides access to a broad range of chiral α-branched primary amines and linear primary amines.
S. Guo, J. C. Yang, S. L. Buchwald, J. Am. Chem. Soc., 2018, 140, 15976-15984.
A protocol for the dehydrative amination of alcohols in water using a water-soluble calixresorcinarene sulfonic acid as a reusable multifunctional catalyst allows an environmentally benign synthesis of benzylic and allylic amines. The aqueous phase containing the catalyst can be readily recycled.
S. Shirakawa, S. Shimizu, Synlett, 2008, 1539-1542.
A catalytic amount of manganese dioxide and solvent-free conditions under air enabled a practical and efficient N-alkylation method for a variety of sulfonamides and amines using alcohols as green alkylating reagents.
X. Yu, C. Liu, L. Jiang, Q. Xu, Org. Lett., 2011, 13, 6184-6187.
Halogen bonding induces an intermolecular Csp3-H amination and even enables a hydrogen atom transfer relay strategy to access privileged pyrrolidine structures directly from alkanes. Mechanistic studies support the presence of multiple halogen bond interactions.
F. Wu, J. P. Ariyarathna, N. Kaur, N.-E. Alom, M. L. Kennell, O. H. Bassiouni, W. Li, Org. Lett., 2020, 22, 2135-2140.
A base-catalyzed/promoted transition-metal-free direct alkylation of amines with either aromatic or aliphatic alcohols provides the desired amines in good yields.
Q.-Q. Li, Z.-F. Xiao, C.-Z. Yao, H.-X. Zheng, Y.-B. Kang, Org. Lett., 2015, 17, 5328-5331.
A highly enantio- and regioselective copper-catalyzed hydroamination reaction of alkenes with hydroxylamine esters in the presence of diethoxymethylsilane enables the conversion of a wide variety of substituted styrenes, including trans-, cis-, and β,β-disubstituted styrenes, to yield α-branched amines. In addition, aliphatic alkenes gave exclusively the anti-Markovnikov hydroamination products.
S. Zhu, N. Niljianskul, S. L. Buchwald, J. Am. Chem. Soc., 2013, 135, 15746-15749.
A CuH-catalyzed hydroamination of alkenes using an amine transfer reagent and a silane provides chiral amines with high efficiency and stereoselectivity. However, the current technology has been limited to dialkylamine transfer reagents (R2NOBz). A modified type of monoalkylamine transfer enabled the synthesis of chiral secondary amines, including those derived from amino acid esters, carbohydrates, and steroids.
D. Niu, S. L. Buchwald, J. Am. Chem. Soc., 2015, 137, 9716-9721.
Benzylic hydrocarbons are selectively converted to the corresponding sulfonamides by the [Cu(CH3CN)4]PF6-catalyzed reaction with anhydrous TolSO2NNaCl (chloramine-T). Under the same conditions, representative ethers and olefins are also amidated.
R. Bhuyan, K. M. Nicholas, Org. Lett., 2007, 9, 3957-3959.
A palladium complex generated in situ from [Pd(η3-C3H5)(cod)]BF4 and DPPF is a good catalyst for benzylations of malonates with a wide range of benzyl methyl carbonates. The DPEphos ligand is superior to DPPF in the case of palladium-catalyzed benzylic amination of benzylic esters.
R. Kuwano, Y. Kondo, Y. Matuyama, J. Am. Chem. Soc., 2003, 125, 12104-12105.
A Mannich-like zinc-mediated three-component reaction of aromatic halides, amines, and paraformaldehyde allows the straightforward synthesis of a range of functionalized tertiary benzylamines. This procedure involves the in situ formation of arylzinc reagents.
E. Le Gall, A. Decompte, T. Martens, M. Troupel, Synthesis, 2010, 249-254.
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.
The use of an oxazaborolidine-BH3 complex enables a simple and efficient copper-catalyzed selective transfer hydrogenation of nitriles to primary amine-boranes and secondary amines in good yields. The selectivity control was achieved under mild conditions by switching the solvent and the copper catalysts.
H. Song, Y. Xiao, Z. Zhang, W. Xiong, R. Wang, L. Guo, T. Zhou, J. Org. Chem., 2022, 87, 790-800.
A metal bis(trimethylsilyl)amide/Cs2CO3 co-catalyzed benzylation of in situ generated N-(trimethylsilyl) aldimines with toluene derivatives provides a diverse array of bioactive 1,2-diarylethylamines with excellent efficiency and broad functional group tolerance. The catalyst exhibits high chemoselectivity for deprotonation of toluenes at the benzylic position.
G. Liu, P. J. Walsh, J. Mao, Org. Lett., 2019, 21, 8514-8518.
A simple Re2O7-catalyzed direct dehydrative coupling between π-activated alcohols with electron-deficient amines has been achieved under mild and open flask conditions. The protocol alows the conversion of allylic, benzylic, and propargylic alcohols. The mechanistic proof for the SN1-type process has also been provided.
B. G. Das, R. Nallagonda, P. Ghorai, J. Org. Chem., 2012, 77, 5577-5583.
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.
Manganese dioxide is employed as an in situ oxidant for the one-pot conversion of alcohols into imines. In combination with polymer-supported cyanoborohydride (PSCBH), a one-pot oxidation-imine formation-reduction sequence enables alcohols to be converted directly into both secondary and tertiary amines.
L. Blackburn, R. J. K. Taylor, Org. Lett., 2001, 3, 1637-1639.
Treatment of methylarenes with 1,3-dibromo-5,5-dimethylhydantoin or N-bromosuccinimide and a catalytic amount of 2,2′-azobis(isobutyronitrile) followed by a reaction with a nucleophile, such as benzoic acid, p-toluenethiol, sodium p-toluenesulfinate, aqueous dimethylamine, or succinimide, provides the corresponding benzylated products in good yields.
H. Shimojo, K. Moriyama, H. Togo, Synthesis, 2015, 47, 1280-1290.
A Lewis acid palladium-catalyzed reaction of amides, aryl aldehydes, and arylboronic acids enables a practical and general synthesis of α-substituted amides from simple, readily available building blocks.
T. Beisel, G. Manolikakes, Org. Lett., 2013, 15, 6046-6049.
A palladium-catalyzed, enantioselective three-component reaction of sulfonamides, aldehydes, and arylboronic acids generates a wide array of α-arylamines with high yields and enantioselectivities. Notably, this process tolerates air and moisture and provides an operationally simple approach for the synthesis of chiral α-arylamines.
T. Beisel, G. Manolikakes, Org. Lett., 2015, 17, 3162-3165.
Aromatic aldehydes can be converted to α-amino anion equivalents via amination with 2,2-diphenylglycine and subsequent decarboxylation. These in situ generated α-imino anions are highly reactive for Pd-catalyzed allylation to give homoallylic amines in high yields with excellent regioselectivity.
L. Ding, J. Chen, Y. Hu, J. Xu, X. Gong, D. Xu, B. Zhao, H. Li, Org. Lett., 2014, 16, 720-723.
A one-pot catalyst-free chemoselective synthesis of N-benzyl propargylamines with good functional group compatibility involves in situ formation of an active amine through Petasis reaction of primary amines, formaldehyde solution, and boronic acids, which reacts in a decarboxylative coupling reaction with propiolic acids to give products in high yields.
H. Feng, H. Jia, Z. Sun, J. Org. Chem., 2014, 79, 11812-11818.
A wide range of chiral propargylamines can be prepared in a one-pot three-component reaction between an alkyne, an aldehyde and a secondary amine at room temperature in the presence of CuBr and (R)-quinap in good yield and good enantioselectivity.
N. Gommermann, C. Koradin, K. Polborn, P. Knochel, Angew. Chem., 2003, 115, 5941-5944.
The regioselective opening of Bn2N-α-methylserine-β-lactone with organocuprates gave enantiopure α-methyl amino acids in excellent yields.
N. D. Smith, A. M. Wohlrab, M. Goodman, Org. Lett., 2005, 7, 255-258.
A Cu-catalyzed regioselective and stereospecific aminoboration of styrenes with bis(pinacolato)diboron and O-benzoyl-N,N-dialkylhydroxylamines delivers β-aminoalkylboranes in good yields. The Cu catalysis enables introduction of both amine and boron moieties to C-C double bonds simultaneously in a syn fashion. Moreover, the use of a chiral biphosphine ligand, (S,S)-Me-Duphos, provides optically active β-aminoalkylboranes.
N. Matsuda, K. Hirano, T. Satoh, M. Miura, J. Am. Chem. Soc., 2013, 135, 4934-4937.