Substrate‐Controlled Regioselectivity Switch in a Three‐Component 1,3‐Dipolar Cycloaddition Reaction to Access 3,3′‐Pyrrolidinyl‐Spirooxindoles Derivatives

Abstract

The additive-free 1,3-dipolar cycloaddition reaction of isatin-derived azomethine ylides with αcyano-α,β-unsaturated compounds was developed, which enabled diversity-oriented synthesis of a series of novel and structurally complex 3,3'-pyrrolidinyl-spirooxindoles derivatives containing four contiguous and two quaternary stereogenic centers in high yields (up to 92%) and excellent diastereoselectivities (up to > 25:1 dr). The reaction displays switchable regioselectivity depending on the steric effect of the substrates.

Decarboxylative 1,3-dipolar cycloadditions of l-proline

“…90 L-Proline 1, syn-4-hydroxy-Lproline 151, and L-thioproline 7 as amino acids were In 2022, conjugated arylcyanosulfones 160 were applied by Chen and Wang et al for a 1,3-DC reaction with isatin and Lproline (Scheme 46). 91 Various 3,3 0 -pyrrolidinyl-spiro-oxindole structures were obtained depending on the steric effect between electron-withdrawing groups (EWG) and substituents (R 3 ) of the electrophilic substrates 160 in the formation of the nal product. Therefore, the presence of p-toluenesulfonyl (Ts) as the EWG led to the formation of diastereomer 161 and 162 in the presence of L-proline, or L-thioproline.…”

Engaging Isatins and Amino Acids in Multicomponent One-Pot 1,3-Dipolar Cycloaddition Reactions—Easy Access to Structural Diversity

“…In 2022, a novel and structurally complex series of 3,3′-pyrrolidinyl-spirooxindoles derivatives 3 – 4 containing four contiguous and two quaternary stereogenic centers were synthesized via the additive-free 1,3-dipolar cycloaddition reaction of isatin-derived azomethine ylides with α-cyano-α, β-unsaturated compounds [ 62 ]. The desired products were obtained in high yields (up to 92%) and excellent diastereoselectivities (up to >25:1 dr).…”

Dipolarophile-Controlled Regioselective 1,3-Dipolar Cycloaddition: A Switchable Divergent Access to Functionalized N-Fused Pyrrolidinyl Spirooxindoles

“…In this context, the scaffolds of N -fused pyrrolidinyl spirooxindoles can be regulated and switched via the dipole-controlled or dipolarophile-controlled strategy. To date, several powerful dipole-controlled multicomponent 1,3-dipolar cycloadditions have been explored selectively to access N -fused pyrrolidinyl spirooxindoles by using diverse α -amino acids as precursors to furnish isatin-derived azomethine ylides [ 40 , 56 , 57 , 58 , 59 ] ( Scheme 1 b). Noticeably, 1,4-enedione derivatives [ 60 , 61 , 62 ], such as maleimides [ 63 , 64 ], methylene indolinones [ 65 , 66 , 67 ], 1,4-naphthoquinone [ 68 , 69 , 70 , 71 ], maleic anhydride, etc., can be activated by two carbonyl groups, which can enhance the flexibility and diversity of cyclization in synthetic chemistry.…”