Highly Efficient and Diastereoselective Construction of Tricyclic Pyrrolidine‐Fused Benzo[b]thiophene 1,1‐dioxide Derivatives via 1,3‐Dipolar [3 + 2] Cycloaddition

Abstract

A rapid and highly efficient 1,3‐dipolar [3 + 2] cycloaddition of nonstabilized azomethine ylides generated in situ with benzo[b]thiophene 1,1‐dioxides as the dipolarophiles has been developed. The efficient method affords tricyclic pyrrolidine‐fused benzo[b]thiophene 1,1‐dioxide derivatives in high to excellent yields (up to 99%) with excellent diastereoselectivities (up to >25:1 dr) under mild reaction conditions. The structure of a typical product was confirmed by X‐ray crystallography.

Highly Efficient and Diastereoselective Construction of Substituted Pyrrolidines Bearing A Quaternary Carbon Center via 1,3-Dipolar [3 + 2] Cycloaddition

“…Additionally, the effect of the sulfonyl group of cyanosulfone 1q [39][40] and 1r [41][42][43][44][45] was studied to give the corresponding products 3q and 3r in 95% and 95% yields, respectively. It's worth noting that the cycloaddition reaction was also amenable to the present system, and a similar degree of diastereoselectivities was observed when the cyano group or ester group instead of the sulfonyl group (entries [19][20]. However, when the substrate 1u and 1v [46]of the acetyl group or benzoyl group instead of the sulfonyl group and the alkylsulfonyl-substituted cyanosulfone substrate 1w were treated with the [3 + 2] cycloaddition reaction under the standard condition, the reaction was disordered and offered inseparable mixture.…”

Highly efficient and diastereoselective construction of substituted pyrrolidines bearing a quaternary carbon center via 1,3‐dipolar cycloaddition

“…To the best of our knowledge, the [3 + 2] cycloaddition reaction of azomethine ylides with activated alkenes was proved to be one of the most effective and well‐established methods for the chemo‐ and stereoselective construction of polyfunctional pyrrolidines in a single step [10–14]. In particular, azomethine ylides of non‐stabilized type generated in situ from N ‐(methoxymethyl)‐ N ‐(trimethylsilylmethyl)‐alkyl‐amine are highly reactive intermediates [15], which reached with a diverse range of dipolarophiles to afford various nitrogen compounds via [3 + 2] [16–26] or [3 + 3] [27,28] cycloaddition reactions. Moreover, the non‐stabilized azomethine ylides could react with the cyano‐group (Scheme 1A) [29].…”

Dearomative [3 + 2] cycloaddition reaction of nitrobenzothiophenes with nonstabilized azomethine ylides

“…On the other hand, 1,3-dipolar cycloaddition of azomethine ylides with electron decient dipolarophiles that have a wide range of applications in organic synthesis, is a useful and facile synthetic process for ve or six membered heterocyclic rings in one step. 6 Especially, nonstabilized azomethine ylides generated in situ are highly active intermediates, 7 with electron-decient benzoheterocycles, including 2-nitroindoles or 3nitroindoles (Scheme 1a) 8 and benzo[b]thiophene 1,1-dioxides (Scheme 1b) 9 as robust electrophiles to construct various polycyclic heterocyclic skeletons via the dearomative [3 + 2] 1,3dipolar cycloaddition reaction in the simple way. However, 3and 2-nitrobenzothiophenes have been uncovered as electrophiles for the dearomative 1,3-dipolar cycloaddition reactions with nonstabilized azomethine ylides to provide S-containing polyheterocyclic compounds.…”