Application of a CC Bond‐Forming Conjugate Addition Reaction in Asymmetric Dearomatization of β‐Naphthols

Abstract

AC À Cb ond-forming conjugate reaction was successfully applied to the enantioselective dearomatization of b-naphthols.AC(sp2)ÀC(sp3) bond is formed by using propargylic ketones as reactive partners.G ood to excellent Z/ Eratios and ee values were obtained by employinga ni nsitu generated magnesium catalyst. Further transformations of the Z-configured C À Cdouble bond in the products were achieved under mild reaction conditions.M oreover,t he stereocontrolling element of this magnesium-catalyzed dearomatization reaction was explored by computational chemistry.Recently,the catalytic asymmetric dearomatization reactions [1] of phenols have received much attention because the dearomatization product, containing ac yclic ketone framework, could be used for further transformations to provide various molecules and natural products.[2] Catalytic asymmetric dearomatization of phenols under non-oxidative conditions are highly desirable because of their atom economy. However,t here is limited progress in this area compared to the corresponding studies for the oxidative dearomatization of phenols.[3] To date,o nly af ew examples of direct dearomatization of phenols under non-oxidative conditions have been reported, specifically for intermolecular pathways.[4] In 2013, Toste and co-workers reported ad irect catalytic asymmetric fluorination of phenols by employing ap hase-transfer chiral-anion catalyst.[5] Almost simultaneously,t he group of Your eported ap alladium-catalyzed intermolecular asymmetric allylic dearomatization of bnaphthols with good results.[6] Recently,w ed escribed ah ighly enantioselective dearomatization reaction of bnaphthols with meso-aziridines by identifying an ovel in situ generated magnesium catalyst. [7,8] However,s urprisingly,t o date,t here are almost no reports on catalytic asymmetric dearomatization of phenols by using of common conjugate addition reactions.V ery recently,t he breakthrough work utilizing CÀNb ond-forming conjugate additions in direct asymmetric dearomatization of b-naphthols was realized by the groups of Youa nd Luan independently,a lthough they employed different catalytic systems (Figure 1a). [9,10] Nevertheless,t he application of other conjugate addition reactions in direct enantioselective dearomatization of b-naphthols is still unrealized, yet highly desirable.H erein, we report an enantioselective dearomatization reaction of b-naphthols by aC À Cb ond-forming conjugate addition employing propargylic ketones as reactive partners (Figure 1b). [11,12] We began our initial investigations by searching for as uitable in situ generated magnesium catalyst [13] for the conjugate addition reaction of the b-naphthol 1a (Scheme 1). Several representative chiral oxazoline-OH-type ligands were tested, but these ligands did not introduce high levels of enantioselectivity (L1-L4). We therefore evaluated the effects of other oxazoline-OH ligands derived from orthohydroxyphenylacetic acid, which was developed by us recently. [7] Thes creening process showed that moderate ee val...

Chromium‐Catalysed Asymmetric Dearomatization Addition Reactions of Bromomethylnaphthalenes

“…several elegant asymmetric dearomatization of naphthalenes have been reported to construct a variety of benzocyclohexane derivatives which occurs widely as an important structural core in complex natural products and pharmaceuticals agents (Scheme ). Halomethyl naphthalenes are one class of important building blocks leading to alkylated products. Dearomatization‐type reaction of halomethylnaphthalenes have been scarcely investigated in palladium catalysed coupling reactions and Grignard reaction with aldehyde .…”

Enantioselective Dearomatization of Naphthol Derivatives with Allylic Alcohols by Cooperative Iridium and Brønsted Acid Catalysis

“…[1,2] Thus,m uch attention has been paid. To date,aseries of successful examples of enantioselective dearomatizations of phenols and naphthols have been realized by using oxidative [3] and non-oxidative [4][5][6][7][8] strategies.R emarkably,t he non-oxidative dearomatization reactions have been developed for the asymmetric installation of various functionalities adjacent to ac arbonyl group by using different electrophiles such as nitroethylenes, [4] azodicarboxylates, [5] aziridines, [6] halogenation reagents, [7] activated propargylic compounds, [8] etc.D espite these impressive advances,arejuvenation of the CADAreaction by exploring new types of electrophiles,toenrich the application scope of these transformations,isstill challenging and highly desirable.…”

“…Having identified the optimized reaction conditions of the enantioselective allylic dearomatization reaction, we explored the substrate scope of the reaction in the presence of the (R)-L1/Ir I complex and rac-PA7,a ss ummarized in Table 3. Firstly,various allylic alcohols (1)w ere reacted with 2a to afford the linear products with excellent chemo-and enantioselectivities (entries [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. Awide range of aromatic groups bearing electron-rich and electron-deficient substituents on either the ortho-, meta-, or para-position of the allyl alcohols 1 were all tolerated and gave rise to the products in moderate to good yields (51-87 %) with good to excellent enantioselectivities (86-> 99 % ee).…”