Stereochemistry and mechanistic insights in the [2^t + 2ⁱ + 2ⁱ] annulations of thioketenes and imines

Abstract

Stereochemical models and mechanistic insights are proposed for [2 + 2 + 2] annulations of thioketenes and imines on the basis of experimental and computational investigations. In the [2 + 2 + 2] annulations involving cyclic imines, the zwitterionic intermediates generated from monosubstituted thioketenes and the cyclic imines undergo a stepwise nucleophilic endo-addition/Si-face attack pathway with a second imines molecule, giving initially (2,4)-cis-(4,5)-cis-[2 + 2 + 2] annuladducts, which completely epimerize into the corresponding (2,4)-cis-(4,5)-trans-annuladducts under basic reaction conditions. The annuloselectivity of thio-Staudinger cycloadditions is dependent on the substituents of both thioketenes and imines. The reactivities and annuloselectivities of Staudinger, thio-Staudinger, and sulfa-Staudinger intermediates are compared.

Annulation of Diaryl(aryl)phosphenes and Cyclic Imines to Access Benzo-δ-phospholactams

“…The reaction is well-known as the Staudinger cycloaddition . However, in some cases, different six-membered heterocyclic annulated products are generated from two ketenes and one imine or one ketene and two imines, respectively, showing diverse annuloselectivities (Scheme a) …”

Chemoselectivity in the Transannulaction of 1,2,3‐Thiadiazoles and Alk‐2‐enenitriles: Specific Synthesis of 3‐(Alk‐1‐enyl)isothiazoles

“…In 2017, our research group used 1,2,3‐thiadiazoles as the thioketene precursors by the treatment with base. We investigated the diastereoselective control in the (2+2) transannulation of 1,2,3‐thiadiazoles and imines [7] and annuloselectivity in the transannulation of 1,2,3‐thiadiazoles and imines [8] . Recently, we developed formal (3+3) transannulations of ethyl 1,2,3‐thiadiazole‐4‐carboxylates with conjugated alk‐2‐ynals and alk‐2‐enals, accessing six‐membered thiaheterocycles, 4 H ‐thiopyran‐4‐one and 2,3‐dihydro‐4 H ‐thiopyran‐4‐one derivatives, [9] respectively (Scheme 1b).…”

Synthesis of Benzoindolizines through 1,5-Electrocyclization/Oxidation Cascades

“…Cyclizations based on the formation of 1, n -dipoles ( n > 3) and conjugated 1,3-dipoles have been enabling the facile synthesis of highly functionalized and diversified azacycles in recent years. − Fruitful achievements in the construction of interesting nitrogen-containing molecules have been realized through this strategy. In our previous work, we have developed a catalyst-free [2 + 2 + 2] cyclization of dihydro-β-carboline and ynone, allowing access to novel complex dimeric β-carboline derivatives in a single step. , The in situ-generated 1,6-dipole was proposed as the key intermediate in this process. On the basis of the same 1, n -dipole cyclization strategy, we have subsequently disclosed the formal [3 + 2] cyclizations of dihydroisoquinoline with Morita–Baylis–Hillman (MBH) carbonates. , Electrocyclizations of in situ-formed conjugated azomethine ylides successfully provided a range of interesting tetrahydropyrrolo­[2,1- a ]­isoquinolines and tetrahydroisoquinoline-fused spirooxindoles.…”

“…In our previous work, we have developed a catalyst-free [2 + 2 + 2] cyclization of dihydro-β-carboline and ynone, allowing access to novel complex dimeric β-carboline derivatives in a single step. 15,16 The in situ-generated 1,6-dipole was proposed as the key intermediate in this process. On the basis of the same 1,n-dipole cyclization strategy, we have subsequently disclosed the formal [3 + 2] cyclizations of dihydroisoquinoline with Morita− Baylis−Hillman (MBH) carbonates.…”