Of ynamines and derivatives thereof differs significantly from that of enamines
Of ynamines and derivatives thereof differs considerably from that of enamines and alkynes because the reactivity with the electronrich triple bond is dominated by the adjacent, strongly polarizing amine moiety. Because ynamines are very reactive and as a result of restricted sensible use, ynamides that may be isolated and stored have turn out to be far more preferred in recent years. The escalating availability of terminal ynamides, ynesulfonamides, and ynecarbamates depending on practical procedures developed by Witulski,2 Bruckner,3 Saa,4 and other people has additional extended the basic utility of ynamine chemistry, Figure 1.five Amongst by far the most noteworthy reactionsTFigure 1. Structures of terminal ynamines and significantly less reactive ynamide and ynesulfonamide analogues.are cycloadditions,6 cycloisomerizations,7 homo- and crosscouplings,8 ring-closing metathesis,9 radical additions,10 and titanium-mediated carbon-carbon bond formations.11 Surprisingly, few examples of nucleophilic additions of terminal ynamides, ynesulfonamides, and ynecarbamates to aldehydes, ketones, along with other electrophiles, all requiring strongly standard situations, could be found in the literature.12 The2014 American Chemical Societyabsence of a catalytic procedure that allows mild carbon- carbon bond formation with acyl chlorides and N-heterocycles is in stark contrast to the wealth of reports on this reaction with terminal alkynes. Encouraged by our prior obtaining that indole-derived ynamines undergo zinc-catalyzed additions with aldehydes toward N-substituted propargylic alcohols, we decided to look for a catalytic variant that’s applicable to other electrophiles.13 We now wish to report the coppercatalyzed nucleophilic addition of a readily readily available terminal ynesulfonamide to acyl chlorides and activated pyridines and quinolines furnishing 3-aminoynones and also the corresponding 1,2-dihydro-2-(3-aminoethynyl) N-heterocycles. Propargylic ketones are crucial intermediates for the preparation of organic goods and heterocyclic compounds and most conveniently ready through catalytic alkynylation of acyl chlorides14 or by means of carbonylative Sonogashira coupling.15 Many procedures demand heating and long reaction times and are not applicable to ynamides, which lack the thermal stability of alkynes.16 We as a result investigated the possibility of carbon-carbon bond formation using the readily out there N-ethynyl-N-phenyl-4-tolylsulfonamide, 1, under mild reaction situations. Following a literature process, we synthesized gram amounts of 1 from N-tosyl aniline, Scheme 1.three Initial evaluation of the reaction in between ynesulfonamide 1 and benzoyl chloride showed that copper(I) salts have been superior more than each zinc and palladium complexes commonly used in alkynylation reactions. Employing ten mol of cuprous iodide and 2 equiv of diisopropylethylamine in THF, we obtained the preferred N-(3-phenyl-3-oxoprop-1-ynyl)-N-phenyl-4-tolylsulfoReceived: February 14, 2014 Published: April 11,dx.doi.org/10.1021/jo500365h | J. Org. Chem. 2014, 79, 4167-The Journal of Organic Chemistry Scheme 1. Synthesis of Ynesulfonamide 1 (Top rated) and Targeted Catalytic 1,H1 Receptor Antagonist Species 2-Additions (Bottom)Notenamide, two, in 50 yield immediately after 20 h. The screening of different copper(I) salts, organic solvents, base, and temperature revealed that two might be isolated in 90 yield when the reaction is performed within the presence of ten mol of Dopamine Receptor Antagonist Purity & Documentation copper iodide in chloroform at 30 ; see entry 1 in Table 1. To the Table 1. Copper(I)-Catalyzed Addition to Acyl Chloridesexamples with aliphatic.