Microwave acceleration in DABAL-Me3-mediated amide formation

On DABAL-Me3 promoted formation of amides

“…[4] In previous reports, we had recommended the use of 0.8 equivalents of DABAL-Me 3 per equivalent of a 1:1 methyl ester:amine mixture at 0.25 M in THF. [4] However, when model couplings of methyl benzoate and pyrrolidine were compared applying the varying reaction conditions detailed in Table 2 (1 mmol scales in PhCO 2 Me) it was observed that with DABAL-Me 3 loadings at or below 0.8 equivalents (with 0.25 M [substrate]) conversion efficiency could become poor or erratic. This was attributed the presence of minor variations in THF solvent quality (which result if it has not been rigorously dried).…”

“…Over 300 such 'coupling agents' are described in key reviews covering this area [2] and some of the more commonly used species are shown in Scheme 1. In 2006 [3] and 2008 [4] we provided preliminary details of the use of DABCO·(AlMe 3 ) 2 (which we call DABAL-Me 3 ) in such rolesbased on the seminal direct coupling of RCO 2 Me and amines using AlMe 3 by Weinreb. [5] Recently, related AlMe 3 alone couplings of free carboxylic acids and amines have also appeared.…”

“…In this regard it is insightful to initially compare the reagents of Scheme 1 in a hypothetical R (Table 1). It might be suggested, based on Table 1, that AlMe 3 -based 'coupling agents' [3][4]6] are: mid-cost, rather too active for peptide coupling, uniquely able to use both free carboxylic acids and their esters (see later), but of significant utility for formation of tert-amides. This present paper attempts to provide comprehensive answers to the questions (i)-(v) posed above and thus more fully define the scope and limitations of these DABAL-Me 3 promoted couplings.…”

DABAL-Me3: A Versatile Methylating Agent

“…6 Woodward and co-workers later utilized microwave irradiation in DABAL-Me 3 -mediated amide bond formation in order to carry out the reaction in a shorter span of time. 7 …”

Microwave‐Assisted Conversion of 4‐Nitrophenyl Esters into O‐Protected Hydroxamic Acids

“…[9] Recently, Woodward reported the microwave-assisted, DABAL-Me 3 -catalyzed preparation of Weinreb amides starting from N,O-dimethyl hydroxylamine hydrochloride, sodium hydride and aliphatic esters. [10] Due to their diprotic nature, the hydroxamate functionality is often introduced into a molecule in an O-protected form during a synthetic sequence. [1,8] Commonly O-protected hydroxamic acids are prepared by reacting O-protected hydroxylamines with reactive carboxylic acid derivatives (e.g.…”