Tetralone, regioselective synthesis

This regioselective synthesis of benzannelated rings, which, unlike its Friedel Crafts equivalent, is not perturbed by the nature of other directing groups carried by the ring, has been used in several syntheses. Indanone 76 from cyclisation of 75 is an intermediate in a synthesis of nanaomycin A,44 and tetralone 77 is an intermediate in a synthetic study towards daunomycin 45... 

Vasil tsov, A.M., A.V. Ivanov, A.I. Mikhaleva, and B.A. Trofimov. 2010. A three-component domino reaction of 2-tetralone, hydroxylamine and acetylene A one-pot highly regioselective synthesis of 4,5-dihydrobenz[e]indoles. Tetrahedron Lett 51 (13) 1690-1692. 

The substitution pattern in the benzene ring of 1 controls the regioselectivity of this 3-tetralone synthesis. 7-Substituted-2-tetralones arc obtained from precursors substituted in the p-position (CH, OCH, OAc). An -methyl substituent in 1 results in 5-methyl-2-tetralone (86%), whereas a j-methoxyl substituent in 1 results in a one-step direct conversion to 6-methoxy-2-tetralone (86%). 

A cunning way to get unusual regioselectivity is to make the reaction intramolecular. The synthesis from benzene of the cyclic ketone known as tetralone may look difficult as we must get an ortho relationship on the benzene ring. But if we make the final bond in the ring by a Frledel-Crafts acylation there is no problem. The alkyl group is ortho,para-diiecting and the acid cannot reach the para position. 

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