Asymmetric [3+2] Annulations of Thioaurone and Aurone Derivatives for the Construction of Spiroheterocycles

Abstract

Aurones and their analogues are convenient twoatom units for the rapid construction of valuable spiroheterocycles. Here, we demonstrate that the Morita-Baylis-Hillman carbonates of isatins can be efficiently assembled with thioaurones, aurones, or even methyleneindolinones in a highly asymmetric [3 + 2] annulation manner, affording a broad spectrum of densely functionalized spiro-benzothiophene, -benzofuran and bisspirooxindole frameworks in high yields with good to excellent stereoselectivity.

A concise update on the synthetic transformation of aurones via asymmetric cycloaddition, annulation, and Michael/Mannich reactions

“…In 2021, Ying-Chun Chen and co-workers 58 introduced a novel method for the asymmetric α-regioselective [3 + 2] annulation reactions of aurone derivatives 1 with isatin-derived Morita–Baylis–Hillman (MBH) carbonates 59 ( Scheme 21 ). This reaction was carried out under the catalysis of a chiral DMAP-type catalyst 58, resulting in the efficient synthesis of a diverse range of spiro-benzofuran 64 frameworks with remarkable levels of diastereo- and enantioselectivity.…”

“…This approach holds great potential for further applications in the fields of synthetic chemistry and medicinal chemistry. 58 …”

“…This approach holds great potential for further applications in the elds of synthetic chemistry and medicinal chemistry. 58 In 2022, Jie Huang et al, developed an efficient method for synthesizing poly-substituted pyrazoles 68 using tosyldiazomethane (TsDAM) 65 and (Z)-aurones 1 as starting materials (Scheme 23). This protocol involved the use of Cs This method was successful in synthesizing novel and interesting pyrazoles 68.…”

DMAP-Catalyzed [4+3] Spiroannulation of Pyrazolone-Derived Morita–Baylis–Hillman Carbonates with N-(o-Chloromethyl)aryl Amides to Forge Spiro[pyrazolone-azepine] Scaffolds

“…Morita–Baylis–Hillman (MBH) carbonates, as vital one-carbon or three-carbon synthons, have recently been shown to possess enormous synthetic potential to participate in various annulation processes, including [2+1], [4+1], [3+2], [3+3], and [4+3] cycloaddition reactions, thereby providing the corresponding carbocycle and heterocycle products. With respect to azepine formation, Chen’s group in 2015 developed an effective [4+3] cycloaddition reaction by combining bromo-substituted MBH adducts of isatins and in situ generated aza-orthoquinone methides (aza-oQMs) to construct aza-spirocycloheptane oxindole analogues .…”