Categories: C-N Bond Formation > Amines > Synthesis of primary amines >

Synthesis of protected primary amines

Related:
carbamates
sulfonamides
sultams

Name Reactions

Recent Literature

A low catalyst loading of [Cp*IrCl₂]₂ in the presence of t-BuOK enables a simple and versatile N-alkylation of sulfonamides with various alcohols based on a catalytic hydrogen transfer reaction. Various N-alkylated sulfonamides were prepared in good to excellent yields. Key catalytic species is a sulfonylimido-bridged unsaturated diiridium complex [(Cp*Ir)₂(μ-NTs)₂].
M. Zhu, K.-i. Fujita, R. Yamaguchi, Org. Lett., 2010, 12, 1336-1339.

A borrowing hydrogen approach using a well-defined and bench-stable Mn(I) PNP pincer precatalyst enables an efficient manganese-catalyzed N-alkylation of sulfonamides with benzylic and simple primary aliphatic alcohols as alkylating agents. A diverse range of aryl and alkyl sulfonamides undergoes mono-N-alkylation in excellent yields.
B. G. Reed-Berendt, L. C. Morrill, J. Org. Chem., 2019, 84, 3715-3724.

A new, simple method for the conversion of alcohols to tosylamides is presented.
M. C. Marcotullio, V. Campagna, S. Sternativo, F. Costantino, M. Curini, Synthesis, 2006, 2760-2766.

A copper-based photoredox catalyst, bearing a tridentate carbazolide/bisphosphine ligand, that can be activated upon irradiation by blue LEDs, achieves the coupling of a range of primary carbamates with unactivated secondary alkyl bromides at room temperature.
J. M. Ahn, J. C. Peters, G. C. Fu, J. Am. Chem. Soc., 2017, 139, 18101-18106.

A direct, stereospecific amination of alkylboronic and borinic esters can be accomplished by treatment with methoxyamine and potassium tert-butoxide. In addition, this process also enables the direct amination of tertiary boronic esters in an efficient fashion.
E. K. Edelstein, A. C. Grote, M. D. Palkowitz, J. P. Morken, Synlett, 2018, 29, 1749-1752.

The direct amination of alkyl and aryl pinacol boronates with lithiated methoxyamine provides aliphatic and aromatic amines, stereospecifically, and without preactivation of the boronate substrate.
S. N. Mlynarski, A. S. Karns, J. P. Morken, J. Am. Chem. Soc., 2012, 134, 16449-16451.

Hypervalent Iodine(III)-Mediated Decarboxylative Ritter-Type Amination Leading to the Production of α-Tertiary Amine Derivatives
K. Kiyokawa, T. Watanabe, L. Fra, T. Kojima, S. Minakata, J. Org. Chem., 2017, 82, 11711-11720.

An intramolecular decarboxylation of readily prepared alkanoyloxycarbamates enables a general and effective synthesis of primary and secondary alkylamines. The reaction tolerates a broad range of functional groups and the corresponding products were obtained in good yields under mild conditions.
P. Li, N. Ma, Z. Wang, Q. Dai, C. Hu, J. Org. Chem., 2018, 83, 8233-8240.

Half-sandwich ruthenium complexes activate terminal alkynes toward anti-Markovnikov hydration and reductive hydration under mild conditions. Propargylic alcohols can be converted to 1,3-diols in high yield and with retention of stereochemistry at the propargylic position. The method is also amenable to formal anti-Markovnikov reductive amination and oxidative hydration reactions to access linear amines and carboxylic acids, respectively.
M. Zeng, S. B. Herzon, J. Org. Chem., 2015, 80, 8604-8618.

A three-component condensation of aldehydes, benzyl carbamate and allyltrimethylsilane, which affords corresponding protected homoallylic amines in excellent yields, is catalyzed by iodine.
P. Phukan, J. Org. Chem., 2004, 69, 4005-4006.

A safe alternative to the Curtius rearrangement, that employs a copper catalyst in combination with blue-LED irradiation, achieves a decarboxylative coupling of readily available aliphatic N-hydroxyphthalimide esters to afford protected amines under mild conditions. This C-N bond-forming process is compatible with a wide array of functional groups, including alcohols, aldehydes, epoxides, indoles, nitroalkanes, and sulfides.
W. Zhao, R. P. Wurz, J. C. Peters, G. C. Fu, J. Am. Chem. Soc., 2017, 139, 12153-12156.

An efficient palladium-catalyzed asymmetric amination of 2,3-allenyl phosphates with nitrogen nucleophiles such as amines, hydroxylamines, and imides can be performed in presence of SEGPHOS or MeOBIPHEP ligand, affording the corresponding optically active 1-aminated derivatives with high enantiomeric excess.
Y. Imada, M. Nishida, K. Kutsuwa, S.-I. Murahashi, T. Naota, Org. Lett., 2005, 7, 5837-5839.

Iridium-catalyzed allylation of potassium trifluoroacetamide or the highly reactive ammonia equivalent lithium di-tert-butyliminodicarboxylate forms a range of conveniently protected, primary, α-branched allylic amines in high yields, high branched-to-linear regioselectivities, and high enantiomeric excess.
M. J. Pouy, A. Leitner, D. J. Weix, S. Ueno, J. F. Hartwig, Org. Lett., 2007, 9, 3949-3952.

Hydroamination of substituted allenes with benzyl carbamate catalyzed by (NHC)AuCl and AgOTf in dioxane led to isolation of allylic carbamates in good yield as single regio- and diastereomers.
R. E. Kinder, Z. Zhang, R. A. Widenhoefer, Org. Lett., 2008, 10, 3157-3159.

A mild, gold(I)-catalyzed hydroamination of 1,3-dienes is reported. Various carbamates and sulfonamides add to conjugated dienes to affort protected allylic amines in good to high yields.
C. Brouwer, C. He, Angew. Chem. Int. Ed., 2006, 45, 1744-1747.

Addition of sulfonamides to alkenes and conjugated dienes can be carried out using a low catalytic amount of (triphenyl phosphite)gold(I) chloride and silver triflate under thermal or microwave conditions and at r.t. in the case of dienes. Terminal alkenes undergo regioselective hydroamination at the internal carbon atom and dienes at the less substituted double bond.
X. Giner, C. Nájera, Org. Lett., 2008, 10, 2919-2922.

Ph₃PAuOTf catalyzes efficient intra- and intermolecular hydroamination of unactivated olefins with sulfonamides.
J. Zhang, C.-G. Yang, C. He, J. Am. Chem. Soc., 2006, 128, 1798-1799.

The copper-catalyzed ring-opening of arylcyclopropanes in the presence of N-fluorobis(arenesulfonyl)imides and (2,2′-bipyridine)Zn(CF₃)₂ affords γ-trifluoromethylated amines in good yields at room temperature.
H. Zhang, H. Xiao, F. Jiang, Y. Fang, L. Zhu, C. Li, Org. Lett., 2021, 23, 2268-2272.

Copper(II) trifluoromethanesulfonate catalyzed a mild amidation of cyclic ethers with iminoiodanes with good yields and selectivity. A subsequent reductive ring-opening of the tosylamidated products gives α,ϖ-amino alcohols.
L. He, J. Yu, J. Zhang, X.-Q. Yu, Org. Lett., 2007, 9, 2277-2280.

An efficient amidation reaction of saturated C-H bonds catalyzed by a unique disilver(I) complex is reported. The reaction is stereospecific and practical for the construction of amine-containing molecules.
Y. Cui, C. He, Angew. Chem. Int. Ed., 2004, 43, 4210-4212.

Y. Cui, C. He, Angew. Chem. Int. Ed., 2004, 43, 4210-4212.

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 highly chemoselective PPh₃-catalyzed three-component reaction of an imine, alkyl vinyl ketone, and phthalimide or succinimide gives various highly functional adducts with high diastereoselectivities via aza-Morita-Baylis-Hillman reactions of aryl-substituted imines and alkyl vinyl ketones followed by Michael additions of imides and then epimerization.
S.-e. Syu, Y.-T. Lee, Y.-J. Jang, W. Lin, J. Org. Chem., 2011, 76, 2888-2891.

A new procedure for aminobromination of olefins gives vicinal bromoamine derivatives in high yields using Cu, Mn, or V catalysts with p-toluenesulfonamide as nitrogen source and N-bromosuccinimide (NBS) as bromine source. Excellent regio- and stereoselectivity is shown for different olefinic substrates as well as transition metal catalysts.
V. V. Thakur, S. K. Talluri, A. Sudalai, Org. Lett., 2003, 5, 861-864.

In a highly regioselective, direct visible-light-mediated aminofluorination of styrenes, a shelf-stable N-Ts-protected 1-aminopyridine salt serves as the nitrogen-radical precursor, and the commercially available hydrogen fluoride-pyridine was used as the nucleophilic fluoride source.
J.-N. Mo, W.-L. Yu, J.-Q. Chen, X.-Q. Hu, P.-F. Xu, Org. Lett., 2018, 20, 4471-4474.

Related:

An efficient dynamic kinetic resolution of amines combines a ruthenium-catalyzed racemization with a lipase-catalyzed resolution. A variety of primary amines were transformed into one enantiomer of the amide in high yield and high enantioselectivity.
J. Paetzold, J. E. Bäckvall, J. Am. Chem. Soc., 2005, 127, 17620-17621.

A practical procedure for an efficient dynamic kinetic resolution of primary amines employs a palladium nanocatalyst as racemization catalyst, a commercial lipase as resolution catalyst, and ethyl acetate or ethyl methoxyacetate as acyl donor. Various amines and one amino acid amide have been resolved with good yields and high enantiomeric excesses.
M.-J. Kim, W.-H. Kim, K. Han, Y. K. Choi, J. Park, Org. Lett., 2007, 9, 1157-1159.

M.-J. Kim, W.-H. Kim, K. Han, Y. K. Choi, J. Park, Org. Lett., 2007, 9, 1157-1159.