Access to Spirocyclic Benzothiophenones with Multiple Stereocenters via an Organocatalytic Cascade Reaction

Abstract

The present report describes an organocatalytic cascade reaction between 2-alkylidene benzo[b]thiophenone derivatives and enones in the presence of the Cinchona alkaloid amine. Spirobenzothiophenonic cyclohexane derivatives containing three stereocenters were prepared via one-step synthesis in yields ranging from 88 to 96% and in enantioselectivities (enantiomeric excess (ee)) ranging from 85 to 97%, with diastereoselectivities of approximately 14/2/1. Therefore, this method provides an efficient route for the synthesis of a new class of optically active 2-spirobenzothiophenones.

Catalytic Stereoselective Multicomponent Reactions for the Synthesis of Spiro Derivatives: Recent Progress

“…Synthesis of spirocyclic benzothiophenone by Veselý and coworkers. [109] Scheme 18. Synthesis of spirocyclohexanebenzofuranone and bispiro-carbocyclic pyrazolone reported by Liu, Zhou, and co-workers.…”

“…Veselý and co-workers developed spirocyclic benzothiophenones (21) ). [109] Liu and Zhou reported an enantioselective reaction of spirocyclohexanebenzofuranones (22) and bispirocarbocyclic pyrazolones (23) using a bifunctional pyrazolone-chromone synthon and functionalized methyleneoxindole or methylene benzofuranone. The title reaction proceeds smoothly using a quinine-based thiourea catalyst (Cat.14) in diethyl ether at room temperature, providing a reaction yield up to 87 %, and showing good control of stereoselectivity (dr > 20 : 1 and ee > 99 %).…”

“…To give readers a clear idea, this review is primarily organized by spiro derivatives through stereoselective Michael cascade cyclization reactions. [94][95][96][97][98][99][100][101][102][103][104][105][106][107][108][109][110][111][112][113] This first section is organized by the type of Michael cascade cyclization reactions, i. e., Michael spiro-cyclization, [94][95][96][97][98] Michael/N-hemiketalization or alkylation reaction, [99][100][101][102][103] Michael-Michael aldol reaction, [104][105][106][107] double Michael addition cyclization reaction, [108][109][110] and oxa/aza Michael cascade reaction. [111][112][113] The second part of this review is devoted to stereoselective multicomponent cycloaddition reactions, [114][115][116][117][118]…”

Recent Advances in the Cycloaddition Reactions of 2‐Benzylidene‐1‐benzofuran‐3‐ones, and Their Sulfur, Nitrogen and Methylene Analogues

“…[35] In 2020, Veselý's group described an organocatalytic cascade reaction between (Z)-2-(arylmethylidene)-1-benzothiophen-3(2H)-ones 15 and enones 49 in the presence of the cinchona alkaloid amines Cat-13 (Scheme 8b). [36] A series of spirobenzothiophenonic cyclohexane derivatives containing three stereocenters were obtained using the double Michael addition domino process.…”

Enantioselective Construction of Chiral Bispiro[Oxindole-Pyrrolidine-Pyrazolone] Derivatives via Sequential and One-Pot Mannich/Hydroamination Reaction

“…Recently, in 2018, Liu, Fan, and Li developed another sequential process to construct chiral trispirocyclic oxindoles with high efficiency merging squaramide and gold-catalysis (Scheme ). Considering the above, and in light of our ongoing interest in the enantioselective synthesis of spirocyclic compounds, we turned our attention to the construction of novel bispirocyclic [oxindole-pyrrolidine-pyrazolones] based on the one-pot sequential Mannich/hydroamination reaction of ketimines with alkyne tethered pyrazolones.…”