Terminal ynamides: synthesis, coupling reactions, and additions to common electrophiles

Abstract

Ynamides consist of a polarized triple bond that is directly attached to a nitrogen atom carrying a sulfonyl, an alkoxycarbonyl, an acyl or another electron withdrawing group. The triple bond polarization renders ynamides broadly useful building blocks with synthetic opportunities that go far beyond traditional alkyne chemistry. The versatile reactivity of ynamides in cycloadditions, cycloisomerizations, regioselective additions with various nucleophiles or electrophiles, ring-closing metathesis, and many other reactions has been investigated in detail during the past decades. A common feature of these methods is that the triple bond is consumed and either cleaved or transformed to a new functionality. The wealth of reports on these ynamide reactions is in stark contrast to the dearth of carbon-carbon bond formations that leave the triple bond of terminal ynamides intact. The recent introduction of effective synthetic methods for the preparation of terminal ynamides has set the stage to fully explore the synthetic potential of this intriguing class of compounds. This digest letter summarizes the most effective routes to terminal ynamides and the current state of selective nucleophilic addition, substitution and coupling reactions, including the first examples of asymmetric synthesis.

Generation of Oxazolidine‐2,4‐diones Bearing Sulfur‐Substituted Quaternary Carbon Atoms by Oxothiolation/Cyclization of Ynamides

“…Additionally, ynamide 6 x gave a good yield under the same reaction conditions. The activity of terminal ynamide 6 y was also investigated under the optimized reaction conditions . Interestingly, 3‐phenyl‐5,5‐bis( p ‐tolylthio)oxazolidine‐2,4‐dione ( 3 ay ) was obtained in 69 % yield, and its structure was further confirmed by single‐crystal X‐ray diffraction (see the Supporting Information for details).…”

“…Next, we explored the oxidative cyclization betweenv arious benzenesulfenyl chlorides 5 andy namide 1a ( Table 2, entries [12][13][14][15][16][17][18][19][20][21].N otably,d ifferent positions of the aryl ring did not affect the product yields, and various benzenesulfenyl chlorides with am ethyl group on the ortho, meta,a nd para positions of the aryl ring were converted into the corresponding products in 79-87 %y ields ( Table 2, entries [12][13][14][15]. The reaction was compatible with both the electron-donating (tBu and methoxy) and electron-withdrawing (trifluoromethyl) groups substituted on benzenesulfenyl chlorides 5f-5h (Table2,e ntries 16 and 17), but ab enzenesulfenyl chloride with as trong electron-withdrawingg roup afforded al ower yield ( Table 2, entry 18).…”

“…The structure of 3aj was furtherc onfirmed by single-crystal X-ray diffraction (see the Supporting Information for details). Meanwhile, the para effect was not obviousf or methyl, bromo, or chloro groups on the para positiono ft he N-aryl ring in the reaction (Table 4, entries [13][14][15]. Ynamides possessing benzyl, 2-naphthyl, and benzo[d][1,3]-dioxol-5-yl groups on theNatomc ould succeed in producing the desired oxazolidine-2,4-diones in 59-72 %y ields (Table 4, entries [16][17][18].…”

Basenfreie katalytische asymmetrische C‐C‐Kupplung mit terminalen Inamiden als effizienter Zugang zu multifunktionellen Trifluormethylalkoholen

“…[5][6][7][8][9][10][11][12]. Der Wert der b-Hydroxyinamide für Synthesen beruht auf der hohen Dichte an funktionellen Gruppen, die in einem relativ kleinen chiralen Baustein vereint sind.…”

“…[9] Te rminale Inamide sind in der jüngeren Vergangenheit zunehmend als leicht zugängliche Ersatzverbindungen für hochreaktive und weniger praktische Inamine verwendet worden;s ie wurden in einigen Cycloadditionen [10] und in anderen Reaktionen eingesetzt. [11] Dagegen ist der Nutzen der terminalen Inamide in nukleophilen Additionen nur spärlich untersucht worden, [12] und über die Reaktion mit Tr ifluormethylketonen ist bis heute nicht berichtet worden. Wirv ermuteten, dass eine katalytische asymmetrische Methode für die Addition von terminalen Inamiden an Tr ifluoracetophenon und seine Derivate die verbleibenden Nachteile der Reaktion mit Alkinen, insbesondere die Verwendung eines Überschusses an pyrophorem Dimethylzink, ausräumen kçnnte.D ie enantioselektive Synthese von Inamidderivatisierten, CF 3 -substituierten Propargylalkoholen würde gleichzeitig einen neuen Zugang zu einer Vielfalt an hoch funktionalisierten chiralen chemischen Bausteinen çffnen, wenn man die einzigartige Reaktivität der polarisierten Nsubstituierten Dreifachbindung nutzen kçnnte (Schema 1).…”