Organocatalytic Asymmetric Michael/Dieckmann Cyclization Reaction of Alkynones To Construct Spirocyclopentene Oxindoles

Abstract

A highly enantioselective conjugate addition/ Dieckmann cyclization of 3-carboxymethyl substituted oxindoles with electron-deficient internal alkynes was achieved under the catalysis of a chiral guanidine catalyst and NaH. This protocol provides access to a wide range of synthetically useful optically active spirocyclopentenone oxindoles and their derivatives under mild reaction conditions.

Asymmetric Organocatalysis of Activated Alkynes and Enynes

“…In 2019, Liu and co‐workers developed a strategy to give optically active spirocyclopentenone oxindoles 69 through a highly enantioselective conjugate addition/Dieckman cyclisation of 3‐carboxymethyl oxindoles 60 with electron‐deficient ynones 21 through chiral guanidine 68 catalysis (Scheme 21). [41] The enantioenriched spirocyclopentenone oxindoles 69 were obtained in excellent yields and enantioselectivity (70–99% yield and 86–99% ee). The bifunctional guanidine catalyst promotes enolate formation in 3‐substituted oxindole and activates alkynone electrophile through hydrogen bonding activation.…”

Advances in the Synthesis of Benzo‐Fused Spiro Nitrogen Heterocycles: New Approaches and Modification of Old Strategies

“…A noticeable decrease in the enantiomeric enrichment of the reaction product 229 (to 88 % ee), according to the tables of the authors in the article, is observed in two cases: when R 1 = Ph, R 2 = Pentyl, R 3 = H (70 % yield) and R 1 = R 2 = Ph, R 3 = I (93 % yield; Scheme 60). [252] The organocatalyzed asymmetric Mannich-type spirocyclization was employed to access the spiro[pyrrolidin-3,3'-oxindoles] 230 from 2-oxo-tryptophan methyl ester 231 and halogen-, methyl-or methoxybenzaldehydes 232. The nature of the organocatalysts and solvents used in carrying out these reactions strongly influence the stereoselectivity of cyclization.…”

“…A noticeable decrease in the enantiomeric enrichment of the reaction product 229 (to 88 % ee ), according to the tables of the authors in the article, is observed in two cases: when R 1 =Ph, R 2 =Pentyl, R 3 =H (70 % yield) and R 1 =R 2 =Ph, R 3 =I (93 % yield; Scheme 60). [252] …”

Formal (3 + 1 + 1) Carboannulation of Morita–Baylis–Hillman Carbonates with Pyridinium Ylides: Access to Spiro-Cyclopentadiene Oxindoles

“…Spiro-cyclopentadienes 3 could be easily transformed to spirocyclopenta [c]furan oxindoles 7 through a cascade reduction/ Paal−Knorr process (Scheme 3b). 12 To understand the mechanism of the (3 + 1 + 1) annulation, we tried to isolate and identify the reaction intermediate. The model reaction of 1a with 2a afforded diene (E,E)-8a and (Z,E)-8a in 66% total yield by quenching the reaction after 10 min (Scheme 4a).…”

“…To verify the synthetic potential of our method, we explored the derivatization of products 3 . Spiro-cyclopentadienes 3 could be easily transformed to spiro-cyclopenta­[ c ]­furan oxindoles 7 through a cascade reduction/Paal–Knorr process (Scheme b) …”