Cesium Carbonate Catalyzed Esterification of N-Benzyl-N-Boc-amides under Ambient Conditions

Abstract

We report a general activated amide to ester transformation catalyzed by Cs2CO3. Using this approach, esterification proceeds under relatively mild conditions and without the need for a transition metal catalyst. This method exhibits broad substrate scope and represents a practical alternative to existing esterification strategies. The synthetic utility of this protocol is demonstrated via the facile synthesis of crown ether derivatives and the late-stage modification of a representative natural product and several sugars in reasonable yields.

Transamidation of N-Benzyl-N-Boc-amides under Transition Metal-Free and Base-Free Conditions

“…We started our investigations by optimizing the transamidation between N-benzyl-N-Boc-amide 1a and pyrrolidine 2a (Table 1). Following our previous studies involving the Cs 2 CO 3 -catalyzed esterification of N-activated amides, [17] Cs 2 CO 3 was initially selected as the putative catalyst and DMF as the solvent. To our surprise, the yield increased as the loading of Cs 2 CO 3 decreased.…”

“…Generally, aliphatic amines are better nucleophiles than alcohols. Inspired by the success of our recent esterification of N-benzyl-N-Boc-amides promoted by catalytical quantities of Cs 2 CO 3 , [17] we envisioned that the transamidation of N-benzyl-N-Boc-amides with aliphatic amines might be feasible. Realization of this transformation would complement the existing transamidation protocols, and might expand the synthetic utility of N-benzyl-N-Boc-amides as a bench-stable, readily available acyl-transfer reagents in organic synthesis.…”

Transition‐Metal‐Free Activation of Amides by N−C Bond Cleavage

“…[42] The Lei group discovered a Cs2CO3-catalyzed esterification of Nactivated amides under mild conditions and applied this method to the synthesis of crown ethers (Scheme 14C). [43] The Dash group developed KOt-Bu-mediated transamidation of DMF, DMAC and DMBA at room temperature (Scheme 14D). [44] A further important study was reported by the Maes group through Zn(OAc)2-catalyzed direct esterification of secondary amides in a biomimetic pathway, [45] relying on electronic destabilization of the amide bond through nN→Ar delocalization [46] (Scheme 15).…”

Transition‐Metal‐Free DMAP‐Mediated Aromatic Esterification of Amides with Organoboronic Acids

“…For instance, the groups of Garg [6] and Danoun [7] reported the amide to ester interconversion using transition‐metal‐catalyzed activation of the amide C−N bond via a versatile acyl‐metal intermediate (Scheme 1A, left). Later, Szostak [8] and Lei [9] developed a remarkable esterification of amide under transition‐metal free condition using excess base, which widely expand the scope of amide substrates (Scheme 1A, right). Very recently, a general transition‐metal‐free hydrogen bond assisted base‐catalyzed esterification of diverse amides has also been realized by Tu and co‐workers (Scheme 1A, right) [10] .…”