In ionic liquids [Bmim][PF6] or [Bmim][BF4], a highly regioselective N-substitution of pyrrole with alkyl halides, sulfonyl chlorides, and benzoyl chloride gave substituted pyrroles in excellent yields. Michael addition of pyrrole with electrophilic olefins was completed in a highly regioselective manner to afford N-alkylpyrroles.
Z.-G. Lea, Z.-C. Chen, Y. Hu, Q.-G. Zheng Synthesis, 2004, 1951-1954.
Reaction of 4-bromo-NH-1,2,3-triazoles with alkyl halides in the presence of K2CO3 in DMF produced the corresponding 2-substituted 4-bromo-1,2,3-triazoles in a regioselective process. Subsequent Suzuki cross-coupling reaction provided an efficient synthesis of 2,4,5-trisubstituted triazoles, whereas hydrogenation furnished an efficient synthesis of 2,4-disubstituted triazoles.
X.-j. Wang, K. Sidhu, L. Zhang, S. Campbell, N. Haddad, D. C. Reeves, D. Krishnamurthy, C. H. Senanayake, Org. Lett., 2009, 11, 5460-5493.
A series of N,N′-asymmetrically substituted imidazolium iodides have been synthesized, starting from N-arylimidazoles and the less expensive, but less reactive, 1-chlorobutane or (3-chloropropyl)trimethoxysilane. The addition of potassium iodide and the use of 1,2-dimethoxyethane as a solvent allowed the synthesis of multigram quantities of these salts.
A. M. Oertel, V. Ritleng, M. J. Chetcuti, Synthesis, 2009, 1647-1650.
N-Methylimidazole is a promising catalyst for aza-Michael reactions. Various N-heterocycles were introduced to α,β-unsaturated carbonyl compounds employing N-methylimidazole in a highly efficient, rapid and high yielding synthesis of N-heterocyclic derivatives.
B. K. Liu, Q. Wu, X. Q. Qian, D. S. Lv, X. F. Lin, Synthesis, 2007, 2653-2659.
Bu4NI catalyzes regioselective N2-alkylations and N2-arylations of tetrazoles using tert-butyl hydroperoxide as a methyl source, alkyl diacyl peroxides as primary alkyl source, alkyl peresters as secondary and tertiary alkyl sources, and aryl diacyl peroxides as arylating source. These reactions proceed without pre-functionalization of the tetrazoles and in the absence of any metal catalysts.
S. Rajamanickam, C. Sah, B. A. Mir, S. Ghosh, G. Sethi, V. Yadav, S. Venkateramani, B. K. Patel, J. Org. Chem., 2020, 85, 2118-2141.
A convenient, efficient, and selective N-Alkylation of N-acidic heterocyclic compounds with alkyl halides is accomplished in ionic liquids in the presence of potassium hydroxide as a base. In this manner, phthalimide, indole, benzimidazole, and succinimide can be successfully alkylated.
Z.-G. Le, Z.-C. Chen, Y. Hu, Q.-G. Zheng, Synthesis, 2004, 208-212.
A consecutive detosylation/alkylation transformation of tosylated indoles and phenols with alkoxides/alcohols as the alkylation reagents features mild reaction conditions, high ipso-selectivity, and good functional group tolerance. A one-pot selective N-alkylation of unprotected indoles with alcohols and TsCl is also realized.
M.-H. Zhu, C.-L. Yu, Y.-L. Feng, M. Usman, D. Zhong, X. Wang, N. Nesnas, W.-B. Liu, Org. Lett., 2019, 21, 7073-7077.
Tetramethylammonium fluoride (TMAF) enables a direct and selective methylation of various amides, indoles, pyrroles, imidazoles, alcohols, and thiols. The method is characterized by operational simplicity, wide scope, and ease of purification.
H.-G. Cheng, M. Pu, G. Kundu, F. Schoenebeck, Org. Lett., 2020, 22, 331-334.
Due to the poor nucleophilicity of the nitrogen atom of indoles and the competing alkylation reaction at the C-3 position, the use of more sterically hindered ketones with a lower electrophilicity as N-alkylation reagents has been a great challenge. A dearomatization-rearomatization strategy enables a reductive cross-coupling of indoles with ketones in water in good yield.
Z. Wang, H. Zeng, C.-J. Li, Org. Lett., 2019, 21, 2302-2306.
A radical-mediated decarboxylative C(sp3)-N cross-coupling of diacyl peroxides with nitrogen nucleophiles, including indazoles, triazoles, indoles, and anilines provides a broad range of alkylated products. The primary and secondary alkyl radicals derived from corresponding diacyl peroxides were generated by copper catalysis or by merging copper catalysis and photoredox catalysis, respectively.
Z. -L. Tang, X.-H. Ouyang, R.-J. Song, J.-H. Li, Org. Lett., 2021, 23, 1000-1004.