Access to Spiropyrazolone-butenolides through NHC-Catalyzed [3 + 2]-Asymmetric Annulation of 3-Bromoenals and 1H-Pyrazol-4,5-diones

Abstract

The stereoselective synthesis of spirocyclic pyrazolin-5-ones by N-heterocyclic carbene (NHC) organocatalysis has been less studied so far. For this reason and considering the interest of this class of compounds, here, we present the NHC-catalyzed [3 + 2]-asymmetric annulation of β-bromoenals and 1H-pyrazol-4,5-diones that achieves to produce chiral spiropyrazolone-butenolides. The synthesis is general for aryl and heteroaryl β-bromo-α,β-unsaturated aldehydes and 1,3-disubstituted pyrazolones. The spirobutenolides have been obtained in good yields (up to 88%) and enantioselectivities (up to 97:3 er). This constitutes the first described example using pyrazoldiones as the starting materials for this class of spiro compounds.

NHC-Catalyzed Reaction of Aldehydes for C(sp2)–O Bond Formation

“…For oxidant-free redox [3 + 2] annulation, the reducible aldehydes are employed [170][171][172][173][174][175][176][177][178][179][180]. The NHC-linked homoenolate derivatives act as a C3 synthon for [3 + 2] annulation [170][171][172][173][174][175][176][177][178].…”

“…For oxidant-free redox [3 + 2] annulation, the reducible aldehydes are employed [170][171][172][173][174][175][176][177][178][179][180]. The NHC-linked homoenolate derivatives act as a C3 synthon for [3 + 2] annulation [170][171][172][173][174][175][176][177][178]. The NHC-linked homoenolate, generated from α,β-unsaturated aldehyde 44 and NHC catalyst, reacts as a C3 synthon (Scheme 26) [170].…”

Multi-Component Syntheses of Spiro[furan-2,3′-indoline]-3-carboxylate Derivatives Using Ionic Liquid Catalysts

“…The furan-2(5 H )-one cores, generally named butenolides, have been known for their interesting chemical, biological, and medical properties ( Scheme 1 ) [ 9 , 10 , 11 ]. In particular, spirocyclic butanolide derivatives have recently come into the focus of interest [ 12 , 13 , 14 , 15 , 16 ]. Thus, the development of synthetic methods for butenolides is of great importance.…”

“…Thus, the development of synthetic methods for butenolides is of great importance. Amongst them are formylation at the ortho position of aromatic carboxylic acids and its derivatives [ 17 , 18 ], [3+2] annulation reactions between electrophilic carbonyls and homoenolate nucleophiles [ 12 , 13 , 14 , 15 , 16 ], ring-opening [3+2] annulation reactions of cyclopropenones with amides [ 19 ], Ph 3 P catalyzed ring-opening of functionalized cyclopropenones [ 20 ], base-controlled azirine ring expansion [ 21 ], Baeyer–Villiger oxidation of 3-arylcyclobutanones [ 9 , 22 ], and Passerini-like three-component condensation reactions [ 23 ]. Further routes include Aldol reactions, asymmetric Aldol reaction of silyloxyfurans, asymmetric Mannich reaction, asymmetric Mukaiyama–Michael reaction of silyloxyfurans, and enantioselective radical oxyfunctionalizations [ 9 , 24 , 25 ].…”