N-Tfa- and N-Fmoc-(α-aminoacyl)benzotriazoles as Chiral C-Acylating Reagents under Friedel−Crafts Reaction Conditions

Abstract

Chiral N-Tfa- and N-Fmoc-protected (alpha-aminoacyl)benzotriazoles 1a-j undergo Friedel-Crafts-type reactions with indole, N-methylindole, pyrrole, N-methylpyrrole, and benzene in the presence of AlCl(3) in efficient two-step sequences leading to enantiomerically pure alpha-amino N-heterocyclic ketones 2, 3, 5, 6, and 7 or diketone 4. In the absence of a reactive partner, Phe- and Trp-derivatives 1a, 1d undergo intramolecular cyclization to afford 12 and 13, again with retention of chirality.

Synthesis of Chiral TFA-Protected α-Amino Aryl-Ketone Derivatives with Friedel–Crafts Acylation of α-Amino Acid N-Hydroxysuccinimide Ester

“…Moreover, l -/ d - 1b and l -/ d - 2b can dissolve well in benzene and thus, no solvent is needed for the reaction system. In comparison, the reported N -protected N -(α-aminoacyl)benzotriazole, which was previously used as an acyl donor for the Friedel–Crafts reaction, showed low solubility for the selected acyl acceptor and utilized CH 2 Cl 2 as the solvent [ 12 ]. However, when isoleucine derivative and its diastereomer allo -isoleucine derivative are utilized for checking the chiral center by 1 H-NMR, it can offer a simple analysis that is able to comprehensively examine all the processes of TFA-protected α-amino acid-OSu synthesis as the acyl donor of Friedel–Crafts acylation.…”

“…Since α-amino acid anhydride consists of two possible α-amino acids, one of the unacylated molecules will be wasted during the reaction. Recently, N -protected N -(α-aminoacyl)benzotriazole has been reported to acylate benzene by using Lewis acid [ 12 ]. Despite this N -acylbenzotriazole being more convenient to handle compared to α-amino acid chloride, only a moderate yield of α-aminoacyl phenyl-ketone can be synthesized.…”

“…Despite this N -acylbenzotriazole being more convenient to handle compared to α-amino acid chloride, only a moderate yield of α-aminoacyl phenyl-ketone can be synthesized. However, the preparation of N -protected N -(α-aminoacyl)benzotriazole [ 12 , 13 , 14 ] was conducted under in situ conditions, which indicated that its isolation takes more effort.…”

Palladium and half sandwich ruthenium(II) complexes of selenated and tellurated benzotriazoles: Synthesis, structural aspects and catalytic applications

“…In the recent past derivatives of benzotriazole have been reported as chiral C-acylating reagents [1]. They show biological activities [2,3].…”

AlMe3‐Mediated Regio‐ and Chemoselective Reactions of Indole with Carbamoyl Electrophiles

“…The most frequent methods employed for the preparation of indole‐3‐carboxamide include (see Scheme ): (i) the conversion of indole‐3‐carbaldehyde to its carboxylic acid/ester followed by a coupling reaction with an amine;5 (ii) the reaction of indole with a Grignard reagent followed by treatment with ethyl chloroformate to give a mixture of C‐3‐ and N ‐ethoxycarbonyl products;6 (iii) the reaction of indole with Viehe's reagent,7a chlorosulfonyl isocyanate,7b–7d or isocyanatophosphoryl dichloride7e followed by basic hydrolysis; (iv) the treatment of indole with chloroformates6b or toxic triphosgene followed by coupling with amines;8 (v) a Pd‐catalyzed carboxamidation of indole by using isocyanide, which was recently reported by Zhu et al;9 and (vi) a Friedel–Crafts acylation of indole that was explored in detail by Katritzky et al by using carbonylbenzotriazole 10a. However, a Friedel–Crafts carbamoylation with carbamoylazole has not been studied so far.…”