Ynamide Preactivation Allows a Regio‐ and Stereoselective Synthesis of α,β‐Disubstituted Enamides

Abstract

A novel ynamide preactivation strategy enables the use of otherwise incompatible reagents and allows preparation of α,β-disubstituted enamides with high regio- and stereoselectivity. Mechanistic analysis reveals the intermediacy of a triflate-bound intermediate as a solution-stable, effective keteniminium reservoir, whilst still allowing subsequent addition of organometallic reagents.

Hydrative Aminoxylation of Ynamides: One Reaction, Two Mechanisms

“…As shown previously, the treatment of ynamide 1 a with TfOH leads to the transient formation of an E / Z ‐mixture of the triflated species A‐OTf , which exists in equilibrium with the keteniminium ion A . For this reason, calculations of the reaction mechanism for the formation of products 2 a were performed starting from A (Scheme ).…”

On the formation of seven-membered rings by arene-ynamide cyclization

“…As part of our research, we have made extensive use of ynamides as versatile reagents for a range of electrophile-triggered transformations [ 7 – 18 ]. Recently, we developed an efficient approach to prepare α,β-disubstituted enamides via the addition of dialkylzinc reagents to a Bronsted acid-activated ynamide (in the form of a keteniminium/enamide triflate intermediate) [ 18 ]. During this study, we found that ynamide 1a , carrying a phenyl substituent at the end of a three-carbon chain, did not afford the desired product 3 (Fig.…”

Ligand-dependent stereoselective Suzuki–Miyaura cross-coupling reactions of β-enamido triflates

“…First, the influence of the catalyst on the stereoselective outcome of the reaction was studied (Table 1). The use of Pd(PPh 3 ) 4 resulted in Scheme 2: Substrate scope of the Suzuki coupling leading to enamides 2 and 3. a Ratio determined by 19 F NMR; b yield determined by 19 F NMR using PhCF 3 as an internal standard; c isolated yield; d isolated as a mixture of isomers E/Z = 64:36.…”

“…They are also important pharmacophores, which display a range of cytotoxic, antifungal, or antibiotic properties [10][11][12]. Modern stereoselective syntheses leading to highly substituted enamides include cross-coupling of vinyl (pseudo)halides or organoboron compounds [13], hydroamidation of alkynes [14][15][16], ynamide functionalization [17][18][19], or isomerization of N-allyl amides [20], but still possess drawbacks, especially for stereoselective synthesis of tri-and tetrasubstituted enamides.…”