Coupling Reaction of Cu-Based Carbene and Nitroso Radical: A Tandem Reaction To Construct Isoxazolines

Abstract

In this letter, an unprecedented cross-coupling reaction between copper carbene and nitroso radical has been developed. This radical-carbene coupling reaction (RCC reaction) offers a novel approach for the preparation of various isoxazolines, which features the construction of C-C, C-O, and C═N bonds in a one-pot process. The synthetic utility of our method is further enhanced by its mild reaction conditions, wide substrate scope, and simple procedures.

tert‐Butyl Nitrite (TBN), a Multitasking Reagent in Organic Synthesis

“…In this regard, Sun and Wan group reported an efficient method for the preparation of isoxazolines ( 50 ) via cross‐coupling of metal‐based carbene and NO radical generated from TBN. In this reaction, TBN serves both as an oxidant as well as the NO source (Scheme ) …”

“…In this reaction, TBN serves both as an oxidant as well as the NO source (Scheme 36). [63] Based on control experiments, they proposed ap lausible mechanism for this transformation, which involves the initial cleavage of TBN. Simultaneously,C u-based carbene intermediate (I)i sg enerated by the interaction of the diazo compound and copper catalystw hich is immediately converted to intermediate (II)b yi nteracting with the NO radical.…”

Rapid Interception of CnF2n+1(O)SO. Radical with Copper‐Based Carbene: A Novel Access to Perfluoroalkanesulfinate Ester

“…Recently, we reported the direct coupling of α‐aminoalkyl radicals and metal carbenes to generate β‐ester‐γ‐amino ketones, and indoles . We also developed a RCC method that allowed the efficient preparation of isoxazolines from Cu‐based carbenes and nitroso radicals under mild conditions . These results prompt us to speculate, as illustrated in Scheme b, that the CF 3 (O)SO .…”

tert‐Butyl Nitrite Mediated Nitro‐Nitratosation of Internal Alkenes

“…[3] Styrenes undergo cross-coupling in the presence of metal-based carbene and NO radical (generated in situ from TBN) providing isooxazolines. [4] In this process, styrene serve as a dienophile and undergo [3+2]cycoaddition in situ generated nitrile oxide intermediate. Following the analogous [3+2] cycloaddition strategy our group obtained symmetrical isoxazolines from styrenes in the presence of TBN, Sc(OTf ) 3 and quinoline.…”

“…Under a similar condition α, -unsaturated carboxylic acids and cyclic internal alkene afforded nitroalkenes. [11] During the formation of isoxazoline, [4,5] imidazo [1,2-a]quinolines, [6] and 1,2,4-oxadiazole-5(4H)-ones [7] from styrenes and TBN, the in situ generated NO 2 radical attacks at the -carbon while the NO radical attacks at the α-carbon even though both the radicals coexist in the medium. From the computational calculation, it was found that the attack of NO 2 radical at the terminal carbon that is at the -carbon is stabilised by around 6 kcal/mole less than the attack by NO radical at the same site.…”