NaBAr^F₄‐Catalyzed Oxidative Cyclization of 1,5‐ and 1,6‐Diynes: Efficient and Divergent Synthesis of Functionalized γ‐ and δ‐Lactams

Abstract

of main observation and conclusion An efficient NaBAr F 4 -catalyzed oxidative cyclization of readily available 1,5-and 1,6-diynes has been developed. Importantly, this transition metal-free oxidative catalysis proceeds via a presumable Lewis acid-catalyzed S N 2' pathway, which is distinct from the relevant oxidative rhodium and gold catalysis. This method leads to the facile and practical construction of a diverse range of synthetically useful γand δ-lactams in mostly good to excellent yields with broad substrate scope. Scheme 1 Known knowledge and conceptual advance of this contribution Results and DiscussionWe set out to screen different conditions for this reaction by Chin.

Efficient and Divergent Synthesis of Medium‐Sized Lactams through Zinc‐Catalyzed Oxidative Cyclization of Indoly Ynamides†

“…Instead, low efficiency was observed in case of methyl‐ or benzyl‐substituted indolyl ynamides, which is distinctively different from our previous proctol. [ 6d ] The molecular structure of 2a was further confirmed by X‐ray diffraction (Figure ) . Of note, our attempts to extend the reaction to the styryl‐ and alkyl‐substituted ynamides 1z — 1aa and terminal ynamide 1ab only gave a complex mixture of products…”

“…According to the above experimental observations and previous studies, a plausible reaction pathway to rationalize the formation of eight‐membered lactam 2a is presented in Scheme . First, nucleophilic attack of N ‐oxide 3e occurs on the Zn‐activated ynamide 1a to afford the vinyl zinc alkene intermediate B .…”

“…NaBAr F 4 here may enhance the acidity and/or solubility of the zinc complex, thus leading to the improved reactivity. [ 6b ] Somewhat surprisingly, the use of 20 mol% of NaBAr F 4 as sole catalyst also led to the desired product in 76% yield (Table , entry 10). [ 6a , 6b ] Of note, Brønsted acids such as MsOH and Tf 2 NH failed to further improve the reaction (Table , entries 11—12) and the reaction at 60 o C gave a slightly decreased yield (Table , entry 13).…”

“…And importantly, the unwanted overoxidation could be completely suppressed in this type of non‐noble metal catalysis. As a result, this strategy has been widely utilized into the synthesis of a variety of five‐ and six‐membered lactams and α‐functionalized amides (Scheme 1a). …”

Photoinduced ynamide structural reshuffling and functionalization

“…However, we did not observe cleavage of the C( sp )–N bond of ynamide because propargylamide alkyne is more reactive than ynamide 29 , 30 . The reaction of homopropargyl tethered ynamide ( 1ab ) in thin layer chromatography (TLC) showed multiple spots, probably due to the lower stability of starting material 1ab (spontaneous decomposition in the presence of water (trace amount) within 2–3 days yielded hydration products with ynamide alkynes), and the formed product can easily isomerize into various products 66 . In accordance with these reactions, the aromatic ring between the alkyne and ynamide in compound 1 is necessary for stability via electron delocalization.…”