Sterically controlled diastereoselectivity in thio-Staudinger cycloadditions of alkyl/alkenyl/aryl-substituted thioketenes

Abstract

The [2 + 2] cycloadditions of thioketenes and imines are named as thio-Staudinger cycloadditions. The diastereoselectivity in thio-Staudinger cycloaddtions of alkyl/alkenyl/aryl-substituted thioketenes is rationalized. The steric effects of the thioketenes play an extremely important role in deciding the diastereoselectivity (cis/trans selectivity) through controlling exo- and endo-attack and subsequent ring closure. The conclusion is further supported by our additional experimental and calculational results. The isomerization of the iminium moiety in zwitterionic intermediates generated from the thioketenes and linear imines also affects the diastereoselectivity. The electronic effect of imine substituents slightly impacts the diastereoselectivity, while epimerization of cis-β-thiolactams to trans-diastereomers is a significant factor in the thio-Staudinger cycloadditions of mono-substituted thioketenes under basic conditions.

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).…”

Asymmetric Rh(II)/Pd(0) Relay Catalysis: Synthesis of α-Quaternary Chiral β-Lactams through Enantioselective C–H Insertion/Diastereoselective Allylation of Diazoamides

“…Among the Rh(II) catalysts investigated, the Rh 2 [(S)-tert-PTTL] 4 exhibited best result, affording product 3aa in almost quantitative yield with 91:9 diastereomeric ratio and 96 %ee (entry 12, Table 1). The structure of 3aa could be determined unambiguously by X-ray structure analysis, 13 in which the allyl and phenyl groups were installed in a trans position, implying a sterically controlled allylation event of the enolate. However, the reaction efficiency was not improved by utilizing other Rh(II) catalysts such as Rh 2 [(S)-PTTL] 4 , Rh 2 [(S)-PTPA] 4 , Rh 2 [(S)-NTTL] 4 , Rh 2 [(S)-DOSP] 4 , and Rh 2 [(S)-BTPCP] 4 (entries 13−17, Table 1).…”

Rhodium-Catalyzed 1,1-Hydroacylation of Thioacyl Carbenes with Alkynyl Aldehydes and Subsequent Cyclization

“…17 Our 1,1-hydroacylation/cyclization sequence is useful in the structural modifications of natural products (Scheme 6). 18 For example, submission of estrone (10) to a sequence of triflation, Sonogashira coupling, and deketalization afforded alkynal (12), which was transformed to 4H-thiopyran-4-one (13) in 62% yield by the rhodium-catalyzed formal (3 + 3) transannulation with thiodiazole 2a. O-Methylation of estrone, followed by Horner−Wadsworth−Emmons olefination with phosphonate ( 14) and reduction with DIBAL-H, delivered enal (15).…”

“…Thus, aldehydes and carbene precursors must be well-defined. Gratifyingly, after numerous trials (see Supporting Information), the 1,1-hydroacylation of thioacyl carbenes derived from 1,2,3-thiodiazoles (2) 11,12 with alkynyl aldehydes (1) occurred to deliver thioketones (3), which undergo 6-endo-dig cyclization to give formal (3 + 3) transannulation products 4H-thiopyran-4-ones (4) as important structural subunits in a number of useful compounds. 13 Similar reactions of alkenyl aldehydes also occur to deliver useful products.…”