Rophiles usually creating ynones in only moderate yields have already been reported.14a,e This could most likely be attributed to quick ketene formation and subsequent side reactions when acyl chlorides exhibiting hydrogens are employed inside the presence of base. Even though the reaction with pivaloyl chloride gave the corresponding propargylic ketone 8 in high yield as anticipated, we were really pleased to discover that the ynone formation with 2methylpropanoyl chloride proceeds smoothly at 15 offering 9 in 70 yield, entries 7 and 8. As discussed above, the properties and reactivity of ynamines and ynamides are influenced by the amine moiety, which strongly GABA Receptor Biological Activity polarizes the triple bond. We hence decided to investigate in the event the sulfonamide unit includes a similar impact around the ynone unit. A single crystal of two was obtained by slow evaporation of a answer in CDCl3. Crystallographic evaluation of this compound plus a survey of representative C-substituted propargylic ketones in the Cambridge Structural Database showed that the bond lengths of your carbonyl group, the adjacent C(sp2)-C(sp) bond, and the triple bond inside the ,unsaturated ketone functionalities are nearly identical, Figure two. Similarly, IR analysis of 2 shows the alkyne and theFigure 2. Crystal structure of two. Selected crystallographic separations [ : N1 3, 1.345; C3 two, 1.197; C2 1, 1.448; C1 1, 1.224.aIsolated yields. b20 . c15 .best of our understanding, this is the first catalytic addition of an ynamide to an acyl chloride. It can be noteworthy that the order of addition on the reagents is important for this reaction. The most effective yields have been obtained when the catalyst, base, plus the ynamide had been stirred for 30 min before addition with the acyl chloride. The reaction also proceeds with higher yields when other aromatic substrates are employed, and we obtained ynones 3-7 in 79-99 yield, entries 2-6. In contrast to the impressive number of high-yielding catalytic cross-couplings of aromatic acyl chlorides with terminal alkynes, pretty fewcarbonyl stretchings at 2202 and 1637 cm-1, respectively, which mGluR3 manufacturer suggests that push-pull conjugation plays a minor part in this 3-aminoynone.17 In contrast to the final results obtained with acyl chlorides, we did not observe any reaction when we applied methyl or ethyl chloroformate in our copper-catalyzed ynamide addition procedure. This led us to investigate the possibility of a catalytic ynamide addition to pyridines by a one-pot process in which the heterocycle is activated toward a nucleophilic attack by means of formation of an N-acylpyridinium intermediate. Substituted 1,2-dihydropyridines along with the corresponding 1,2-dihydroquinolines are significant N-heterocycles that serve as key intermediates in organic synthesis and are ubiquitous units in a lot of biologically active compounds. The direct incorporation of versatile functionalities into readily offered, economical pyridine and quinoline compounds has hence received rising interest in current years. While numerous reports on regioselective 1,2-additions of organometallic species to pyridine and its analogues exist, the nucleophilic attachment of an ynamide moiety has not been achieved to date.dx.doi.org/10.1021/jo500365h | J. Org. Chem. 2014, 79, 4167-The Journal of Organic Chemistry With all the mild protocol for the ynamide addition to acyl chlorides in hand, the optimization in the reaction between 1 and pyridine toward N-ethoxycarbonyl-1,2-dihydro-2-(N-phenyl-N-tosylaminoethynyl)pyridine, 10, was straightforward. We systemat.
