Primary Aminothiourea-Catalyzed Enantioselective Synthesis of Rauhut–Currier Adducts of 3-Arylcyclohexenone with a Tethered Enone on the Aryl Moiety at the Ortho-Position

Abstract

An enantioselective synthesis of Rauhut-Currier (RC) adducts from 3-aryl cyclohexenone with a tethered enone moiety at the ortho-position on the aryl group is accomplished. This method provides a wide range of valuable synthetic building blocks having a unique [6-5-6] all-carbon-fused tricyclic skeleton. A primary amine-containing thiourea, a bifunctional organocatalyst, was found to be an efficient catalyst for this transformation. The primary amine counterpart of the catalyst possibly activates the aliphatic enone via dienamine formation (HOMO activation), whereas the thiourea counterpart activates the tethered enone (LUMO activation). Considering the difficulty in achieving an RC reaction of β,β-disubstituted (alkyl and aryl) enones, this method would be significantly rewarding.

Progress in catalytic asymmetric α-functionalization of vinylogous nucleophilic species

“…In 2018, Ghorai's group presented a catalyzed enantioselective intramolecular Rauhut–Currier reaction of 3-aryl cyclohexenones 163 that bear a tethered enone moiety at the ortho -position on the aryl group (Scheme 39). 54 The reaction was promoted by primary amine thiourea C21 to provide Rauhut–Currier adducts 164 in 40–85% yields with 58–98% ee via the sequential selective α-addition and isomerization of the double bond. Synthetic elaboration was also conducted in this report.…”

Regiodivergent Organocatalytic Reactions

“…In the past two decades, L -proline and its derivatives have found rapidly growing application in various transformations to yield products with excellent ee and dr [119][120][121][122][123][124][125][126]. Remarkable advances have been made after the seminal work of List [127,128], Córdova [129,130], Barbas [131,132], and many other research groups.…”

Organocatalytic Strategies for the Synthesis of Cyclopenta‐Fused Arenes and Heteroarenes

“…Recently,i n2 018, Ghorai and co-workersp resented ab ifunctional thiourea (18)-catalyzed enantioselective intramolecular Rauhut-Currier (RC) reaction of 3-aryl cyclohexenones with a tethered enone moiety at the ortho-position of the aryl group (16;S cheme 5). [16] This methoda lso represents aR Cr eactiono f b,b-disubstituted enones,w hich otherwise can be difficultt o achieve under traditional nucleophilic catalysis. Dienamine 17 formed between chiral amine 18 and 3-aryl cyclohexenone 16 undergoes aM ichael addition to the enone moiety to give indenes 19 with ac hiral center.…”

“…Recently, in 2018, Ghorai and co‐workers presented a bifunctional thiourea ( 18 )‐catalyzed enantioselective intramolecular Rauhut–Currier (RC) reaction of 3‐aryl cyclohexenones with a tethered enone moiety at the ortho ‐position of the aryl group ( 16 ; Scheme ) . This method also represents a RC reaction of β,β‐disubstituted enones, which otherwise can be difficult to achieve under traditional nucleophilic catalysis.…”