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Mild, Metal‐Free and Protection‐Free Transamidation of N‐Acyl‐2‐piperidones to Amino Acids, Amino Alcohols and Aliphatic Amines and Esterification of N‐Acyl‐2‐piperidones
Author(s) -
Subramani Muthuraman,
Rajendran Saravana Kumar
Publication year - 2019
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201900517
Subject(s) - chemistry , amide , nucleophilic acyl substitution , amine gas treating , organic chemistry , aryl , nucleophile , reactivity (psychology) , peptide bond , amino acid , acylation , alkyl , catalysis , enzyme , medicine , biochemistry , alternative medicine , pathology
Amides are indispensable building blocks of biological systems, pharmaceuticals, and materials. We report a highly selective method for the synthesis of amides via transamidation process. Transamidation of N ‐acyl‐2‐piperidones with a broad range of amines is demonstrated under exceedingly mild and metal‐free reaction condition that relies on the amide bond twist to weaken the amidic resonance. Transamidation proceeds under the neat condition at room temperature, in short reaction times (30–90 min) with good yields. Considerable variation is tolerated with both amine and imide substrates. Of note, amines bearing carboxylic acids (glycine and serine) and hydroxyl groups (dopamine, tyramine, etc.) are well tolerated which are otherwise problematic under the metal‐catalyzed protocol. Our current method is applicable for transamidation of both alkyl and aryl‐ N ‐acyl‐2‐piperidones. The practical value of the method is highlighted by the synthesis of four natural product amide alkaloids in high yields under mild reaction conditions. In the absence of nucleophilic amines, N ‐acyl‐2‐piperidones undergoes esterification with EtOH at elevated temperature. Single crystal X‐ray analysis of an N ‐acyl‐2‐piperidone shows amide bond twist, τ = –20.39° and pyramidalization, χ N = –11.73°. This weakens the amidic conjugation and might be the factor controlling the reactivity and selectivity of these imides. We envision that the N ‐acyl‐2‐piperidone scaffold would be useful in the synthesis of pharmaceuticals and materials.