Iridium‐Catalyzed Intramolecular Asymmetric Allylic Dearomatization of Phenols

Abstract

Dearomatization reactions provide the most direct synthesis of ring systems starting from readily available aromatic compounds.[1] The combination of a dearomatization reaction with asymmetric synthesis would lead to the enantioselective construction of carbocyclic and heterocyclic derivatives. [2] Despite progress in this area, the reported methods have so far focused on a stepwise protocol, which involves the dearomatization process and a subsequent asymmetric reaction.[3] The direct asymmetric dearomatization reaction where the dearomatization and asymmetric catalysis occur in one step is highly desirable but very challenging. [4] As part of our recent studies on iridium-catalyzed allylic substitution reactions, [5][6][7] we found that iridium-catalyzed intramolecular asymmetric allylic alkylation of indole provided enantioenriched spiroindolenine compounds. [8] Phenols are cheap and abundant chemicals widely used in organic synthesis. Transition-metal-catalyzed allylic alkylation reactions of phenols generally proceeds as O allylation [9] with limited examples of C allylation. [9c, 10] Despite the challenges of chemo-, regio-, and enantio-selectivity, we recently envisaged that phenols might function as carbon nucleophiles in the iridium-catalyzed intramolecular allylic dearomatization reactions (Scheme 1). This protocol would provide a direct access to enantiopure spirocyclohexadienones, which serve as a popular structural core in numerous biologically interesting natural products and pharmaceuticals. Scheme 1. Iridium-catalyzed asymmetric allylic dearomatization of phenols. cod = cycloocta-l,5-diene. ,8-diazabicyclo[5.4.0]undec-7-ene, DIEA = N,N-diisopropylethylamine, DMAP = 4-dimethylaminopyridine, DME = 1,2-dimethoxyethane, HMDS

Diversity in Reduction with Short‐Chain Dehydrogenases: Tetrahydroxynaphthalene Reductase, Trihydroxynaphthalene Reductase, and Glucose Dehydrogenase

“…Nonenzymatic dearomatization reactions such as the Birch reduction are well established in chemistry but are still challenging owing to the lack of chemo‐, regio‐, and stereoselective methods . Biocatalytic dearomatization reactions are frequently found in the biosynthesis of secondary metabolites as a tool to deoxygenate phenolic compounds in a highly chemo‐ and regioselective fashion.…”

“…Nonenzymatic dearomatization reactions such as the Birch reduction are well established in chemistry but are still challenging owing to the lacko fc hemo-, regio-, and stereoselective methods. [1,2] Biocatalytic dearomatization reactions are frequentlyf ound in the biosynthesis of secondary metabolites as at ool to deoxygenate phenolic compounds in ah ighly chemo-a nd regioselective fashion.T his often goes with ah ighly stereoselective reduction of polyketide-based polyhydroxy compounds, as shown in the reduction of emodin hydroquinone duringt he biosynthesis of prenyl xanthones in Aspergillus nidulans. [3][4][5][6] In another example, 1,8-dihydroxynaphthalene( DHN, 1)i sp roduced followingt wo deoxygenation reactions during the biosynthesis of fungal melanin (Scheme 1).…”

Spectral assignment of new adamantane derivatives of 1,3‐; 1,5‐dihydroxy‐ and 1,5‐dimethylnaphthalenes

“…Also it should be noted that aromatic compounds with an adamantane at the ortho ‐position to the hydroxyl groups are the key skeletons of synthetic retinoid analogues and supporting ligands of many homogeneous transition‐metal catalysts . Moreover, recently much attention has been heeded to dearomatization reactions of aromatic and heteroaromatic compounds due to the highly reactive intermediates opportunities …”

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. [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). [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).…”