Synthesis of 5H-dibenzo[a,d]cycloheptene-5-carboxylic acid and related compounds. 1,5-Hydride transfer to inductively destabilized carbonium ions

Abstract

The synthesis of 10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-carboxylic acid (2) and several derivatives of 5H-dibenzo[a,d]cycloheptene-5-carboxylic acid (1; a-c) from 5-hydroxy-l0,ll-dihydro-5H-dibenzo[a,d]cycloheptene-5-carboxylic acid and derivatives thereof (3; a-c) is described.The p-toluenesulfonic acid-catalyzed elimination of water (at 110.6" in toluene) from the deuterated hydroxy ester (3b; C-10, 11 d2) resulted in the incorporation of deuterium at C-5 of the olefinic ester l b with a KH/KD of 2.76. The large magnitude of this isotope effect indicated that the reaction proceeded via a rate-determining transannular 1,Shydride transfer from one of the benzylic positions of 36 t o the carbonium ion generated alpha to the methoxy-carbonyl group.

Electronegatively substituted carbocations

“…An early example of such a reaction is the acid-catalyzed dehydration of the a-hydroxy ester 431 which gives the ester 432. 119 This reaction is proposed to involve formation of the a-carbomethoxy cation 433 which undergoes 1,5-transannular hydride migration. The corresponding a-hydroxy acid gives an analogous transformation.…”

Novel tricyclic systems. Oxazole, thiazole, and imidazole analogs of the amitriptyline type

“…Isomerization of Oxazole Ketones and Hydrolysis of Types 5. 2-Methyl-5,6-dihydro-4H-benzo [3,4]cyclohepta[l,2d]oxazol-4-one (8). The crude mixture of 4 and 5 (120 g) obtained as shown above was dissolved in 250 ml of concentrated H2SO4.…”

The Dibenzosuberenone Scaffold as a Privileged Substructure: From Synthesis to Application

“…174 Hydrocarbons 273-275 are potential intermediates for pharmacologically important compounds (Scheme 45). 175 Dehydration of the C10-C11 deuterated hydroxy ester 275b in acetic acid containing p-toluenesulfonic acid resulted in the incorporation of deuterium at C5 of 273b with a k H /k D of 2.76. The large magnitude of this isotope effect indicated that the reaction proceeded via 1,5-hydride transfer to the inductively destabilized carbenium ion at C5 in 278.…”