Chemoselective Nitrosylation of Anilines and Alkynes via Fragmentary or Complete NO Incorporation

Abstract

The cycloaddition reactions have been explored extensively and provided an efficient strategy for the synthesis of cyclic compounds. Traditionally, the reaction partners were in extenso incorporated into the cyclic products without fragmentation. From a different perspective, if certain fragmentations via chemical-bond cleavage are involved in this cycloaddition reaction, it would change the assembly sequence and enable more product diversity. Here, we report a chemoselective nitrosylation of anilines and alkynes through fragmentary or complete NO radical incorporation. The formation of multiple C-N bonds, an unexpected C-N bond, and N=O bond cleavage make this fragmentary cycloaddition reaction an efficient approach to 2,5-dihydrooxazoles, 1H-1,2,3-triazole 2-oxides or quinoxaline N-oxides. Facile operation in open-air, metal-free, and mild conditions renders this protocol particularly practical and attractive. A series of mechanistic studies and density functional theory calculations were also conducted, which help to explain the fragmentary or complete NO incorporation processes, broadening the field of new reaction discovery.

Metal‐Free Oxidative [5+1] Cyclization of 1,5‐Enynes for the Synthesis of Pyrazine 1‐Oxide

“…The product 2 a could be easily deoxidized into multi‐substituted pyrazine derivative 4 under the reductive conditions in high yield (Scheme ‐b) . An interesting hydrolysis and debenzoylation product 5 was obtained in high yield under the basic and refluxing conditions, and the corresponding product could be isolated through direct filtration without further purification (Scheme ‐c) . In addition, pyrazine derivative 4 could also be easily transformed into product 6 under the same basic reaction conditions in 83% yield (Scheme ‐d).…”

“…On the basis of the above results and previous reports, a tentative mechanism is depicted in Scheme . The first step of this transformation is the formation of the tert ‐butoxy radical and NO radical generated by homolysis of TBN .…”

“…Recently, tert ‐butyl nitrite (TBN) has been shown to be a very useful building block as the source of NO and NO 2 for the construction of corresponding N‐containing compounds under mild conditions . For instance, Jiao group recently reported an efficient approach for the synthesis of quinoxaline N‐oxides via [5+1] radical cyclization (Scheme ‐b) . However, the direct construction of six membered N‐containing compounds from 1,5‐enynes by [5+1] radical cycloaddition reaction is still a challenging task due to the manifold cyclization modes .…”

Direct Synthesis of Structurally Divergent Indole Alkaloids from Simple Chemicals

“…Unfortunately, some common N-sources, such as NaNO 2 , AgNO 2 , TMSN 3 , TsN 3 , and BocNHOH did not provide the desired tryptamine derivative products (see SI). Interestingly, in the presence of tBuONO, which is widely employed in nitration reactions, [8] the trypthamine-related oxime product 3a was obtained in 90% yield (see SI). To our delight, by using a simple tandem reaction with zinc dust reduction, tryptamine derivatives 4a could be obtained in 72% yield (4a).…”

“…The generated cyclobutane intermediate A [16] is unstable and easily undergoes C-C bond homolytic cleavage to form a di-radical intermediate B. Subsequently, the formed NO radical and tBuO radical from TBN synergisticly react with the Scheme 7 Further application of this protocol in the total synthesis of natural products Reagents and conditions: 1a was prepared from 2-aminophenethanol (8) with KOH by distillation in 88% yield (19.2 g) (see SI). a, 1a, 2a…”