Diastereoselective Synthesis of Nine‐Membered Heterocycles via the Cycloaddition and Sequential Rearrangement of N‐Vinyl Nitrones with Isocyanates

Abstract

A metal-free construction of highly diastereoselective nine-membered heterocycles is described via the cycloaddition and rearrangement of N-vinyl-a,b-unsaturated ketonitrones and isocyanates. Notably, the prepared nine-membered heterocycles afforded 2,3-dihydropyrrolizines under heating conditions. Mechanistic studies showed that the nine-membered rings might undergo decarboxylation, isomerization, aza-Michael addition, and aromatization to afford 2,3-dihydropyrrolizines in a one-pot reaction.

Copper‐Catalyzed [3+2] Cycloaddition and Interrupted Fischer Indolization to Prepare Polycyclic Furo[2,3‐b]indolines from N‐Aryl Isatin Nitrones and Methylenecyclopropanes

“…The yield of 3 aa decreased when using other copper salts, while the dr of 3 aa was increased to 20:1 using Cu(II), and decreased to 3:1 using Cu(I) ( Table 1, entries [10][11][12]. Other Lewis acids, such as Pd(OAc) 2 , Fe(OTf) 3 , Sc(OTf) 3 , and Yb(OTf) 3 , did not greatly improve the yield and dr of 3 aa (Table 1, entries [13][14][15][16]. Increasing the temperature to 60 8C decreased the yield of 3 aa to 69% with a 4:1 dr (Table 1, entry 17).…”

“…[10] Furthermore, the Brandi-Guarna rearrangement, namely, the NÀO bond cleavage of 5-spirocyclopropane-isoxazoline cycloadducts produced by the cycloaddition of nitrones and methylenecyclopropanes, which can then undergo rearrangement to afford piperidin-4-ones owing to the highly strained spirocyclopropane ring, has been successfully applied to natural product synthesis. [11] During our studies on the preparation and cycloaddition of isatin nitrones, [12,13] we surmised that the carbonyl group in isatin nitrones could act as a directing group and coordinate with a catalyst to control diastereoselectivity in the cycloaddition of isatin nitrones and methylenecyclopropanes. [14] Sequential reduction of the cycloadducts would provide furo [2,3-b]indolines through interrupted Fischer indolization.…”

“…The dr was determined by 1 H NMR analysis of the crude mixture. Other Lewis acids, such as Pd(OAc) 2 , Fe(OTf) 3 , Sc(OTf) 3 , and Yb(OTf) 3 , did not greatly improve the yield and dr of 3 aa (Table 1, entries [13][14][15][16]. Pleasingly, the yield of 3 aa was dramatically improved to 81% and the diastereomeric ratio was increased to 15:1 when the reaction was performed in MeOH ( Table 1, entry 8).…”

Advances on the Synthesis and Application of α,β-Unsaturated Nitrones

“…2017 年, 莫冬亮课题组 [37] 报道了无金属参与条件 下, N-烯基-α,β-不饱和硝酮和异腈酸酯发生[3＋2]环加 有机化学 综述与进展 成和 [3,3]-重排串联反应, 高非对映选择性地合成了氮 杂九元环化合物 56 (Scheme 22). 该反应原料易得, 条 件温和, 操作简单, 底物范围广, 官能团兼容性好.…”

DBU‐Promoted 6π‐Azaelectrocyclization and Hydrogen‐Migration to Prepare 6‐Alkyl Pyridine N‐Oxides from N‐Vinyl‐α,β‐Unsaturated Nitrones

“…Initially, N-vinyl-α,β-unsaturated nitrone (1 a) easily prepared from the copper(II)-mediated cross-coupling reaction of α,β-unsaturated oximes and vinylboronic acids [14,15] was selected as a model substrate to test the 6π-azaelectrocyclization. As shown in Table 1, nitrone 1 a was conducted in toluene without any base at 120 °C for 8 h affording 6-vinylpyridine N-oxide 3 a in only 12% yield and 6-alkyl pyridine N-oxide 2 a was not observed (Table 1, entry 1).…”