(4+3) Annulation of Donor‐Acceptor Cyclopropanes and Azadienes: Highly Stereoselective Synthesis of Azepanones

Abstract

Azepanes are important seven-membered heterocycles, which are present in numerous natural and synthetic compounds. However, the development of convergent synthetic methods to access them remains challenging. Herein, we report the Lewis acid catalyzed (4+3) annulative addition of aryl and amino donoracceptor cyclopropanes with 2-aza-1,3-dienes. Densely substituted azepane derivatives were obtained in good to excellent yields and with high diastereoselectivity. The reaction occurred under mild conditions with ytterbium triflate as the catalyst. The use of copper triflate with a trisoxazoline (Tox) ligand led to an enantioselective transformation. The obtained cycloadducts were convenient substrates for a series of further modifications, showing the synthetic utility of these compounds.

SnCl4-mediated one-pot synthesis of 2,4,5-trisubstituted thiazoles from nitro-substituted donor–acceptor cyclopropanes and thioamides

“…The popularity of donor–acceptor cyclopropanes (DACs) as building blocks in organic synthesis has increased dramatically in the past two decades. 1 Their signature reactions such as annulation, 2 ring-opening 3 and rearrangement 4 reactions have provided access to numerous carbocyclic and heterocyclic compounds. The advantages of synthetic methodologies developed from DACs include easy accessibility of the starting materials, operational simplicity of the reactions and formation of the products with high yield and selectivity.…”

Tandem Dearomative/Rearomative (3 + 2) Annulation of Aroyl-Substituted Donor–Acceptor Cyclopropanes with Benzothiazoles

“…Among various reactions of DACs, their (3 + n ) ( n = 2, 3, 4, etc.) annulations are regarded as potential tools for accessing various carbo- and heterocycles . The merits of the methods include simplicity, high atom economy, and excellent regio- and stereoselectivity.…”

Asymmetric ring-opening reactions of donor–acceptor cyclopropanes with 1,3-cyclodiones

“…1 The nucleophilic ring-opening reactions of D–A cyclopropanes have been recognized as useful strategies to access 1,3-bifunctionalized scaffolds. 1–3 Asymmetric ring-opening reactions of D–A cyclopropanes 3 with heteroatom containing nucleophiles have been well established. 3 a – g For example, Tang and co-workers reported chiral Ni/bisoxazoline (BOX)-catalyzed asymmetric ring-opening reactions of D–A cyclopropanes with secondary aliphatic amines for the synthesis of γ-aminobutyric acid derivatives.…”

“…1–3 Asymmetric ring-opening reactions of D–A cyclopropanes 3 with heteroatom containing nucleophiles have been well established. 3 a – g For example, Tang and co-workers reported chiral Ni/bisoxazoline (BOX)-catalyzed asymmetric ring-opening reactions of D–A cyclopropanes with secondary aliphatic amines for the synthesis of γ-aminobutyric acid derivatives. 3 a , b In addition, related asymmetric ring-opening processes using aromatic amines as nucleophiles were also reported by Feng, Wang and Cai.…”

“…3 a , b In addition, related asymmetric ring-opening processes using aromatic amines as nucleophiles were also reported by Feng, Wang and Cai. 3 c – e Using thiols as the nucleophiles, Feng and co-workers disclosed highly enantioselective ring-opening of D–A cyclopropanes in the presence of the chiral Sc/ N , N ′-dioxide catalyst to afford γ-thiobutyric acid derivatives. 3 f Furthermore, Tang's group developed a method to access enantioenriched γ-hydroxybutyric acid derivatives by Cu/trisoxazoline (TOX)-catalyzed ring-opening of D–A cyclopropanes with water and alcohols.…”