Catalytic Atroposelective Electrophilic Amination of Indoles

Abstract

Reported here is the first catalytic atroposelective electrophilic amination of indoles, which delivers functionalized atropochiral N-sulfonyl-3-arylaminoindoles with excellent optical purity. This reaction was furnished by 1,6-nucleophilic addition to p-quinone diimines. Control experiments suggest an ionic mechanism that differs from the radical addition pathway commonly proposed for 1,6-addition to quinones. The origin of 1,6-addition selectivity was investigated through computational studies. Preliminary studies show that the obtained 3-aminoindoles atropisomers exhibit anticancer activities. This method is valuable with respect to enlarging the toolbox for atropochiral amine derivatives.

Tandem imine generation/N-cyclization/C-alkylation sequence to access N-functionalized indoles featuring an aza-quaternary carbon

“…After Kagan et al pioneered the addition of Grignard reagents to α-iminoesters at the N-terminus, 5 a the N-attack reactions of such activated imines have drawn increasing attention because of their potential to synthesize amino acid derivatives and secondary amines. 5 However, despite advances, the exploitation of tandem reactions based on N-attack nucleophilic addition of imines remains underdeveloped. To our knowledge, only three reaction types have been reported, as shown in Fig.…”

Synthesis of isochromanonesvialaccase-mediated oxidative [4 + 2] cyclization of pyrocatechuic acid with styrenes

“…and the relatively low yield hampered its synthetic potential. On the other hand, a number of other bioinspired oxidative cyclization manifolds of phenol substrates were disclosed by using iron salts, 6 biomimetic metal complexes, 7 and other oxidants 8 as surrogates of copper enzymes. However, the reaction partner of these processes was mainly centered on indoles towards the assembly of a benzofuroindole framework.…”

Recent advances in catalytic oxidative reactions of phenols and naphthalenols

“…Moreover, in recent years, quinone diimines have also been exploited as the aza-counterparts in several electrophilicitybased cyclization and conjugated addition reactions, leading to the assembly of N-heterocyclic compounds 108,109 and amine derivatives. 110,111 In the preceding discussion, we have observed the oxidative reactions of phenol by the in situ formation of relevant quinones via chemical oxidation, enzymatic oxidation, and electrochemical oxidation. The in situ creation of chemical intermediates is not only economically advantageous, but it is also advantageous for those intermediates that are highly labile and cannot be isolated.…”

“…Moreover, in recent years, quinone diimines have also been exploited as the aza-counterparts in several electrophilicity-based cyclization and conjugated addition reactions, leading to the assembly of N-heterocyclic compounds 108,109 and amine derivatives. 110,111…”