Enantioselective Synthesis of Spirocyclohexadienones by NHC‐Catalyzed Formal [3+3] Annulation Reaction of Enals

Abstract

The enantioselective synthesis of pyrazolone-fused spirocyclohexadienones was demonstrated by the reaction of α,β-unsaturated aldehydes with α-arylidene pyrazolinones under oxidative N-heterocyclic carbene (NHC)catalysis. This atom-economic and formal [3+3] annulation reaction proceeds through a vinylogous Michael addition/spiroannulation/dehydrogenation cascade to afford spirocyclic compounds with an all-carbon quaternary stereocenter in moderate to good yields and excellent ee values. Key to the success of the reaction is the cooperative NHC-catalyzed generation of chiral α,β-unsaturated acyl azoliums from enals, and base-mediated tandem generation of dienolate/enolate intermediates from pyrazolinones.

N-Heterocyclic carbene-catalyzed oxidative [3 + 2] annulation of dioxindoles and enals: cross coupling of homoenolate and enolate

“…4 In 2004, Bode et al and Glorius et al reported the elegant NHC-catalyzed reaction of enals involving homoenolate as the key intermediate (Scheme 1, reaction a). 5 The homoenolate intermediate could be oxidized to give α,β-unsaturated acyl azolium, which worked as a versatile 1,3-biselectrophile (Scheme 1, reaction b). 6 Single electron oxidation could open new ways for organic reactions.…”

Mechanism and Selectivity of RuII‐ and RhIII‐Catalyzed Oxidative Spiroannulation of Naphthols and Phenols with Alkynes through a C−H Activation/Dearomatization Strategy

“…The spirocyclic framework is commonly observedi nm any biologicallya ctive naturalp roducts, pharmaceutical molecules, and optoelectronic materials. [1] Although aw ide variety of synthetic strategies have been witnessed over the past two decades, [2] the development of more efficient syntheticm ethods for the construction of spirocyclic compounds remains highly desired. In this context, transition-metal-catalyzed oxidative spiroannulation reactionsh ave recently gained tremendousr esearch interest, providing af acile route for the synthesis of spirocyclic compounds.…”

Catalytic Asymmetric Synthesis of Spiropyrazolones and their Application in Medicinal Chemistry

“…In 2016, Biju and co‐workers demonstrated an NHC‐catalyzed [3+3] annulation between α‐arylidene pyrazolinones 82 and α,β‐unsaturated aldehydes 9 , thereby providing access to optically pure pyrazolone‐fused spiro‐1,3‐cyclohexadienones 84 (Scheme a) . This vinylogous Michael addition‐spiroannulation‐dehydrogenation cascade proceeded with optimal yield and enantioselectivity by using chiral triazolium salt‐derived carbene Cat.…”