Organocatalyzed Asymmetric Dearomative [3+2] Annulation of Electron‐Deficient 2‐Nitrobenzo Heteroarenes with 3‐Isothiocyanato Oxindoles

Abstract

An organocatalyzed asymmetric dearomative [3+2] annulation reaction of electron‐deficient 2‐nitrobenzo heteroarenes including 2‐nitrobenzofurans, 2‐nitrobenzothiophenes and 2‐nitroindoles with 3‐isothiocyanato oxindoles was developed. With a multiple hydrogen‐bonding bifunctional thiourea as the catalyst, the reaction displays broad substrate scope and provides an access to structurally diverse polycyclic spirooxindoles containing three contiguous stereogenic centers in high yields with good diastereo‐ and enantioselectivities (up to 99% yield, 94:6 dr, and 97% ee). This organocatalysis protocol is able to afford the products with complementarily diastereoselectivity versus the previous work with transition metal catalysis.

Asymmetric Formal [3+2] Cycloaddition Reactions of 3-Isothio­cyanato Oxindoles: an Update

“…In 2021, Yuan and co-workers explored an asymmetric dearomative [3+2] annulation and subsequent methylthiolation reaction of 3isothiocyanato oxindoles 1 with electron-deficient 2-nitrobenzo heteroarenes including 2-nitrobenzofurans 38, 2-nitrobenzothiophenes 39, and 2-nitroindoles 40 (Scheme 14). 25 The reaction exhibits wide substrate scope and provides a complementary access to structurally diverse polycyclic spirooxindoles 43-45 in excellent yields with moderate to good diastereo-and enantioselectivities (up to 99% yield, 97% ee, and 94:6 dr) under the catalysis of cinchonidine-derived multihydrogen-bonding bifunctional thiourea 41 and squaramide 42.…”

“…The absolute configuration of 65a (R 1 = Me, R 2 , R 3 = H, R 4 = Ts) was determined to be (6S, 7S, 8S) by X-ray analysis, which was different from that of the configuration (R, R, R) catalyzed by organocatalyst 42. 25 Scheme 23 Zn(OTf)2/bis(oxazoline)-catalyzed asymmetric dearomative [3+2] cycloaddition of 3-isothiocyanato oxindoles with 2-nitroindoles and 2-nitrobenzothiophenes…”

Dearomatization of Nitro(hetero)arenes through Annulation

“…More recently, the same group utilized multiple hydrogen‐bonding bifunctional catalysts derived from cinchonine in asymmetric dearomative [3+2] annulation reaction of 2‐nitroheteroarenes with 3‐isothiocyanato oxindoles to access optically enriched structurally diverse polycyclic spirooxindoles (Scheme 42B and (Scheme 42C) [62] . Comparing to the previous Zn(OTf) 2 ‐catalyzed conditions, this organocatalyzed protocol gave access to the structurally diverse polycyclic spirooxindole products with opposite configurations ( R,R,R ) as enantiomers in the reaction of 2‐nitroindoles, and with complementarily configurations ( R,R,S ) as diastereomers in the reaction of 2‐nitrobenzofurans and 2‐nitrobenzothiophenes.…”

Recent Progress of Electron‐Withdrawing‐Group‐Tethered Arenes Involved Asymmetric Nucleophilic Aromatic Functionalizations

“…Chiral bifucntional Brønsted bases have proven to be effective in the deprotonation of nucleophiles, which bear a potential acidic site, generating chiral counterions and then enabling the enantioselective nucleophilic addition with electrophiles. Based on this principle, Yuan and co‐workers adopted the bifunctional catalyst C17 (derived from C2 , Scheme 13) to activate 3‐isothiocyanato oxindole 19 to react with 2‐nitrobenzofurans 45O and 2‐nitrobenzothiophenes 45S , allowing dearomative [3+2] cycloadditions in remarkable yields with good stereoselectivities [41] . Furthermore, the reaction of 2‐nitroindoles 45 N with 3‐isothiocyanato oxindole were investigated under the catalysis of squaramide contained bifunctional catalyst C18 , proving cycloadducts 63 in good yields but with slightly poor stereocontrol (Scheme 24).…”