General Synthesis of 8-Aryl-2-tetralones

Abstract

Two alternative routes are described for the synthesis of 8-aryl-2-tetralones (1). Route A starts from alpha-tetralone 3 and involves 3 or 4 steps, with the selective Na-EtOH reduction of 1-aryl-7-methoxynaphthalenes 2 being the key step. The exclusive reduction of the A ring of naphthalenes 2 occurs when the aryl group at C-1 has no substituent at the ortho positions, affording tetrahydronaphthalenes 11. Reduction of the B ring of 2 becomes the major process when the aryl fragment has two substituents at the ortho positions, affording 8-aryl-2-tetralones 1 as the major component. Route B involves 5 steps starting from 2-tetralone 5, with the key step being the Suzuki coupling with triflate 4. This approach allows the synthesis of 8-aryl-2-tetralones 1 with no substituent at the ortho positions of the aryl fragment and with naphthalene and anthracene rings at C-8.

Atom‐Efficient Vinylic Arylations with Triarylbismuths as Substoichiometric Multicoupling Reagents under Palladium Catalysis

“…The functionalized 4‐aryl‐1,2‐dihydronaphthalene products that are obtained in this coupling reaction are useful precursors for the synthesis of substituted naphthalenes and also other derivatives 14. Earlier, these compounds were synthesized either through Suzuki‐type cross‐coupling reactions involving the corresponding vinylic triflate or the Grignard addition reaction to α‐tetralone followed by acid‐mediated elimination 14a,14b. The present method of obtaining 4‐aryl‐1,2‐dihydronaphthalenes through the coupling reaction of triarylbismuths with 4‐iodo‐1,2‐dihydronaphthalene has a definitive advantage in terms of atom‐efficient coupling ability of triarylbismuths and also short reaction times.…”

Discovery of 6-(2,4-Dichlorophenyl)-5-[4-[(3S)-1-(3-fluoropropyl)pyrrolidin-3-yl]oxyphenyl]-8,9-dihydro-7H-benzo[7]annulene-2-carboxylic acid (SAR439859), a Potent and Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen-Receptor-Positive Breast Cancer

“…The carbonyl group of the substituted tetralone 11 was transformed into the enol triflate 12 by reacting the enolate (formed under basic conditions) with phenyltriflimide. 21 The triflate derivative 12 was sequentially engaged in a Suzuki coupling reaction with p-phenol boronic acid to afford compound 13. The double bond was then brominated with pyridinium tribromide 22 to give bromo derivative 14, which was immediately submitted to a second Suzuki coupling reaction with p-methoxyphenyl boronic acid, thus introducing the second substituted distal aryl group to give 15.…”

“…To a solution of tert-butyl 3-[4-(2-bromo-7-methoxy-3,4-dihydronaphthalen-1-yl)phenoxy]azetidine-1-carboxylate (19) (7.1 g, 14.60 mmol) in methanol (40 mL) was added hydrochloric acid in 4 N dioxane (29 mL, 116 mmol). The reaction mixture was stirred for 1 h at room temperature, then concentrated under reduced pressure, and the residue obtained was triturated with dichloromethane and filtered to give 5.10 g (81%) of 3-[4-(2-bromo-7-methoxy-3,4-dihydronaphthalen-1-yl)phenoxy]- (21). Obtained from 20 in 64% yield by an analogous method to 17a.…”

Versatile Synthesis of 4‐Aryl Chroman and 1‐Aryl Tetralins Through Metal‐Free Reductive Arylations

“…Hajra et al demonstrated that rationally tethered alkenes can be used to develop these architectures through Lewis acid promoted halo‐arylations ( b , Scheme ). Urbano et al in an effort to synthesize 8‐aryl‐2‐tetralones, demonstrated the synthesis of 1‐aryl tetralins by selective Birch reduction of 1‐aryl‐7‐methoxynaphthalenes. In a pioneering report,[17a] K. A. Jorgenson developed diphenyl prolinol ether catalysed Friedel‐Crafts cyclization cascade between α,β‐unsaturated aldehydes and phenols to access the 4‐aryl chromans.…”