Catalytic Asymmetric Conjugate Addition/Oxidative Dearomatization Towards Multifunctional Spirocyclic Compounds

Abstract

Naphthol compounds bearing a pendant α,β‐unsaturated ester undergo a copper(I)‐catalyzed asymmetric conjugate addition/copper(II)‐mediated intramolecular oxidative coupling to afford benzofused spirocyclic cyclohexenones (see scheme). This one‐pot strategy results in two new carbon–carbon bonds and three contiguous stereocenters. The products contain a high degree of functionality and molecular complexity.

Iridium‐Catalyzed Intermolecular Asymmetric Dearomatization of β‐Naphthols with Allyl Alcohols or Allyl Ethers

“…[10] We began our study by testing the reaction between 1,3dimethyl-2-naphthol (1a)and cinnamyl alcohol (2a)with the Ir catalyst derived from ac hiral P/olefin ligand (Table 1). Other tested Lewis acids like Zn(OTf) 2 ,Yb(OTf) 3 ,and In(OTf) 3 did not give better results (entries [3][4][5]. [11] To our delight, when Fe(OTf) 2 was utilized as aL ewis acid additive,t he desired dearomatization product 3aa was obtained in 85 %yield and 93 % ee after 17 hours in dichloromethane (DCM) (entry 2).…”

Visible‐Light‐Promoted Intermolecular Oxidative Dearomatization of β‐Naphthols with N‐Hydroxycarbamates

“…[2] Of particular note, oxidative dearomatization reactions have emerged as attractive methods given their atom-economic nature and useful products generated therein. [1d,g,h,m,o,p,r] Accordingly,t remendous efforts have been made on the oxidative dearomatization of phenolsa nd naphthols.I ng eneral, these reported methods are mediated by hypervalent iodine reagents, [3] transition metals [4] and others, [5] and the requirement of strongo xidants or harsh conditions presentsachallenge fors ubstrate scope and practical application.M eanwhile, the past decadeh as witnessed ar enaissance of visible-light-mediated photoredox catalysis since it produces open-shell species under mild conditions to promotev aluable transformations with ag ood tolerance of functional groups. [6] Despite this blooming of photo-chemistry,t he utilization of visible-light-mediated photoredox catalysis in intermoleculard earomatization of naphthols remainsl argely underexplored.…”

Iridium‐Catalyzed Intermolecular Asymmetric Dearomatization of β‐Naphthols with Allyl Alcohols or Allyl Ethers

“…[1] Thec atalytic asymmetric dearomatization (CADA) reactions [2] of phenols have evolved as enabling methods for the synthesis of highly functionalized chiral cyclic enones which frequently appear as basic skeletons in biologically active natural products.T herefore,v arious strategies including oxidation, alkylation, arylation, amination, and halogenation have been developed for the dearomatization reactions of phenols. [3] Despite significant achievements in the transition-metalcatalyzed dearomatization of phenols in recent years, [4] there are limited examples of intermolecular reactions as phenols are well-known oxygen nucleophiles and readily participate transition-metal-catalyzed allylic etherification reactions. [5] Recently,the Hamada group [6] and we [7] reported respectively Pd-and Ir-catalyzed asymmetric allylic dearomatization reactions of phenols,i nw hich an intramolecular design was applied to avoid the O-alkylation pathway.W ealso described an asymmetric intermolecular dearomatization reaction of b-naphthols through aP d-catalyzed asymmetric allylic substitution reaction (Scheme 1).…”

“…[11] To our delight, when Fe(OTf) 2 was utilized as aL ewis acid additive,t he desired dearomatization product 3aa was obtained in 85 %yield and 93 % ee after 17 hours in dichloromethane (DCM) (entry 2). Other tested Lewis acids like Zn(OTf) 2 ,Yb(OTf) 3 ,and In(OTf) 3 did not give better results (entries [3][4][5]. Notably,Brønsted acids could also promote the reaction, albeit with low efficiency( see the Supporting Information for details).…”