Synthesis of N‐Cbz Amides and Their Applications in the Transamidation Reactions at Room Temperature

Abstract

A wide range of aryl and alkyl N-Cbz amides were prepared from secondary amides and benzyl chloroformate in the presence of LiHMDS. Application of N-Cbz amides in transamidation was demonstrated with different amines at room temperature in the presence of DBU. The reactivity of N-Cbz amides is comparable with N-Boc and N-Ts amides in transamidation and transesterification reactions. The optimized condition was well-suited for the transesterification reactions with thiols and alcohols. Broad substrate scope and excellent yields are the merits of the developed methodology.

Amidic resonance not a barrier for transamidation of N-pivaloyl activated amides: catalyst, base and additive free conditions

“…3 In the endeavour to achieve transamidation with a broad substrate scope, activation of amides prior to transamidation has been recognized as the most effective and successful method, 1,[3][4][5] in which the amides are activated by coupling an electron-withdrawing group to the amide nitrogen. [6][7][8][9][10][11][12][13][14][15][16][17][18][19] In recent years, transamidation of N-activated acyclic twisted amides has gained wide attention. Among them, the most notable ones are the transition-metal-free transamidations using LiHMDS, 1 Et 3 N, 9,19 DBU, 9,17 TBHP, 20 CsF, 21,22 and CsCO 3 23 and under catalyst-free conditions.…”

“…[6][7][8][9][10][11][12][13][14][15][16][17][18][19] In recent years, transamidation of N-activated acyclic twisted amides has gained wide attention. Among them, the most notable ones are the transition-metal-free transamidations using LiHMDS, 1 Et 3 N, 9,19 DBU, 9,17 TBHP, 20 CsF, 21,22 and CsCO 3 23 and under catalyst-free conditions. 5,10,14,[23][24][25][26][27] To date, transamidation has been primarily achieved with N-activated amides endowed with significant amide bond twists.…”

Synthesis of Glycouronamides by Transamidation Approach at Room Temperature

“…In the last few years, our group has focused on amide activation and transamidation reactions [8] . Towards this end, we demonstrated the transamidation of secondary amides via N ‐nitroso and N ‐Cbz amide intermediates, [8b,d] synthesis of aryl and alkyl α‐ketoamides via transamidation reactions, [8c,f] transformation of N ‐Boc‐amides into aryl ketones, [8a] and controlled reduction of N ‐Boc and N ‐Ts amides into aldehydes [8e] . On the other hand, our group also focused on the synthetic carbohydrate chemistry [9] and have explored the synthesis and applications of uronic acids, [9h] uronic esters [9f] and photolabile groups protected uronic acid building blocks, [9g] etc.…”

Synthesis of 1,3‐Dicarbonyl Compounds usingN‐Cbz Amides as an Acyl Source under Transition‐metal‐free Conditions at Room Temperature

“…We have demonstrated a metal‐free transamidation of secondary amides and α‐ketoamides, the transformation of N ‐Boc‐amides into aryl ketones with Grignard reagents, and conversion of activated amides into aldehydes. Recently, we have also demonstared the synthesis of N ‐Cbz amides and their applications in transamidation and esterification reactions [18d] . The N ‐Cbz amides are stable and easy to prepare in good yields compared with N ‐Boc and N ‐Ts amides.…”