Ring Selectivity in the Na/EtOH Reduction of 1-Aryl-7-methoxynaphthalenes

Abstract

Na/EtOH reduction of 1-aryl-7-methoxynaphthalenes occurred preferentially at the A-ring when no substituents were present at the ortho-positions of the aryl group (up to 100% selectivity), to afford 1-aryl-7-methoxy-1,2,3,4-tetrahydronaphthalenes. Ortho-substitution of the 1-aryl moiety favored B-ring reduction (up to 85:15 selectivity) giving rise, after acidic hydrolysis of the vinyl ether intermediate, to the corresponding 8-aryl-2-tetralones.Selective reduction of polyaromatic compounds has received little attention despite the fact there is much interest in a controlled access to differently substituted hydroaromatic derivatives. The few studies published so far deal with metal/ammonia reduction of terphenyls 1 and naphthyl or dinaphthylbenzenes. 2 These studies revealed that the ratio of central to outer ring reduction products depended on the particular metal used in the case of p-terphenyls, whereas m-and o-terphenyls gave only central ring reduction. Moreover, reduction of 1-and 2-phenylnaphthalene never occurred at the phenyl ring. 2a The controlled reduction of substituted 2-methoxy naphthalene derivatives is of great interest since the resulting vinyl ether can be easily hydrolyzed to 2-tetralones. Such compounds have been frequently used in organic synthesis due to their high versatility and suitability as precursors of a wide range of synthetic and natural products and their derivatives, 3 heterocycles, 4 and pharmaceuticals 5 showing biological activities and other useful properties. However, unlike their congeners the 1-tetralones, which are inexpensive, easily prepared, and commercially available substances, 2-tetralones are often very expensive and much more difficult to synthesize.The most common methods for the preparation of 2-tetralones 6 involves 1,2-transposition of the carbonyl group of 1-tetralones, 7 reduction of substituted 2-methoxy-naphthalenes followed by hydrolysis, 8 cyclization of diazoketones, 9 and the Friedel-Crafts reaction of aromatic acyl chlorides with olefins. 10In connection with a program devoted to the synthesis of polyaromatic compounds such as helicenes, 11 we required several 8-aryl-2-tetralones (1; Scheme 1) bearing different substituents at the aryl moiety. To the best of our knowledge, the synthesis of 8-aryl-2-tetralones has been addressed only using the carbanion-induced condensation of differently substituted 2H-pyran-2-ones with a 1,4-cyclohexanedione monoketal, 12 however, the synthesis of these starting materials is not easy.Scheme 1 Retrosynthesis to 8-aryl-2-tetralones 1.Among the known synthetic approaches to 2-tetralones, we decided to use the Na/EtOH reduction of 2-methoxynaphthalenes, 13 initially described by Cornforth et al., 14 which had been successfully applied by us for the synthesis of differently substituted 8-alkyl-2-tetralones. 15 Birch reductions 16 of naphthalenes bearing electron-releasing substituents at the C-1 are known to occur at the unsubstituted aromatic ring, whereas electron-withdrawing groups at C-1 direct the reduction to the s...

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.…”

General Synthesis of 8-Aryl-2-tetralones

“…The presence of different aromatic rings at the C-1 position of the starting naphthalenes 2 , required to know the ring selectivity of the process (Scheme ). The study of the Na/EtOH reduction of compounds 2 bearing differently substituted phenyl groups at C-1 allowed us to synthesize a few 8-aryl-2-tetralones with one or two susbtituents at the ortho position of the 8-aryl group with yields ranging from 29 to 60% . Looking for an improved and more general access to these targets, we thought of a different strategy starting from 2-tetralones bearing at the C-8 position a substituent that enabled the introduction of the 8-aryl moiety at the final steps.…”