Optically Active Thiophenes via an Organocatalytic One-Pot Methodology

Abstract

A general methodology for the synthesis of trisubstituted, optically active thiophenes by an organocatalytic one-pot reaction cascade is presented. The target products are synthesized in good yields (up to 92%) and with excellent enantioselectivities (up to 98% ee). Importantly, based on practical and easily available starting materials, the presented methodology can be conducted under mild reaction conditions. To further elucidate the generality, the synthesis of optically active thienoindoles, as well as selenophenes, is also demonstrated.

α,β‐Unsaturated Aldehydes in the Synthesis of Five‐Membered Heterocyclic Compounds with One Heteroatom: Recent Advances from Developments in Metal‐ and Organocatalysis

“…A general methodology for the organocatalytic synthesis of trisubstituted optically active furans, thiophenes, and selenophenes 117 containing α‐hydroxyalkyl‐ or α‐aminoalkyl‐substituents has been developed by Jørgensen and co‐workers in 2010–2012 . The methodology is based on the combination of the enantioselective organocatalytic epoxidation or aziridination of 2‐alkenals 115 followed by an annulation reaction using 1,3‐dinucleophilic reagents 116 .…”

One‐Pot Synthesis of 2,3,5‐Trisubstituted Thiophenes through Three‐Component Assembly of Arylacetaldehydes, Elemental Sulfur, and 1,3‐Dicarbonyls

“…Recently, the transition‐metal‐catalyzed direct C−H arylation of thiophenes has found to be an efficient tool for the thiophene diversification ,. With respect to annulation reactions, non‐readily available starting materials such as functional mercaptans,thioamides,, dialkynes,– and 1,2,3‐thiadiazoles, were frequently employed to generate substituted thiophenes through intermolecular or intramolecular cyclization. Also, few examples of multicomponent reactions led to the construction of thiophene rings from readily available chemicals ,.…”

Reversible oligomerization of 3-aryl-2-cyanothioacrylamides via [2s + 4s] cycloaddition to substituted 3,4-dihydro-2H-thiopyrans

“…Thus, the influence of the substituents could be monitored. Compounds 1b and 1c were synthesized via etherification of p-and m-hydroxybenzaldehyde according to Piñol et al [27] and compound 2a via thionation of the corresponding aldehyde according to Ransborg et al [28] The other educts are commercially available. The resulting 3-aryl-2-cyanothioacrylamides (3a and 3b) are potentially able to dimerize via HDA reaction to form 5,6-dihydro-2H-thiopyrans (4a and 4b).…”