Catalytic Asymmetric Hydroacyloxylation/Ring-Opening Reaction of Ynamides, Acids, and Aziridines

Abstract

A highly enantioselective three-component reaction of ynamides with carboxylic acids and 2,2′-diester aziridines has been realized by using a chiral N,N′-dioxide/Ho­(OTf)3 complex as a Lewis acid catalyst. The process includes the formation of an α-acyloxyenamide intermediate through the addition of carboxylic acids to ynamides and the following enantioselective nucleophilic addition to in-situ-generated azomethine ylides induced by the chiral catalyst. A range of amino acyloxyenamides are delivered in moderate to good yields with good ee values. In addition, a possible catalytic cycle with a transition model is proposed to elucidate the reaction mechanism.

Ynamides in Radical Reactions: A Route to Original Persubstituted 2-Aminofurans

“…Control experiments demonstrated that the use of Mn­(OAc) 3 and, in addition, a degassed solvent was mandatory for the reaction to proceed. The use of 2.2 equiv of Mn­(III) in acetic acid at 40 °C led after 24 h to a mixture of furan 3aa and enamide 4a , resulting from the addition of acetic acid to ynamide, in a 1:1 ratio determined from the 1 H NMR spectrum of the crude reaction mixture (entry 1). Moving from acetic acid to dichloromethane (CH 2 Cl 2 ) aprotic medium prevented the formation of 4a , but a significant amount of ynamide 1a was recovered even after reaction for 48 h (entry 2).…”

From A3/KA2to AYA/KYA multicomponent coupling reactions with terminal ynamides as alkyne surrogates – a direct, green route to γ-amino-ynamides

“…Li and coworkers, 8 which combine aldehyde/ketone, terminal alkyne and amine into propargylamine in a one-pot transition metal-catalysed coupling (Scheme 1, top). 9,10 Replacing the alkyne component by a terminal ynamide 11,12 could lead to a one-pot synthesis of γ-amino-ynamides (Scheme 1, bottom). This approach was driven by the following reasoning: (i) despite its interest, 13 accesses to the latter scaffold are so far limited and based on multi-step sequences, 14 a simpler way would thus be beneficial and probably open up new perspectives; (ii) since ynamides are more nucleophilic than alkynes (see N parameters), 15,16 they should be more reactive in A 3 /KA 2 -type reactions; (iii) although green by essence (see above), 8 A 3 /KA 2 reactions could be made greener by avoiding solvent and/or by using recyclable catalyst.…”