Oxidative Rearrangement of 1‐Alkylidene‐1,2,3,4‐tetrahydro‐2‐(trichloroacetyl)isoquinolines to 1,5,6,10b‐Tetrahydro‐10b‐(trichloromethyl)‐3H‐oxazolo [4,3‐a]isoquinolin‐3‐ones.

Abstract

On treatment with lead tetraacetate (Pb(OAc) 4 ), the 1-(alkylidene)-1,2,3,4-tetrahydro-N-(trichloroacetyl)-isoquinolines 2a ± 2c as well as the tribromoacetyl derivative 4 undergo an oxidative cyclization with concomitant migration of the trihalogenomethyl group to afford the 1,5,6,10b-tetrahydro-10b-(trichloromethyl)-3H-oxazolo[4,3-a]isoquinolin-3-ones 3a ± 3c or the tribromomethyl derivative 6, respectively. These tricycles are also accessible via esterification of 3,4-dihydro-1-(1-hydroxy-1-methylethyl)isoquinoline 8 with either trichloroacetyl chloride or tribromoacetyl bromide, respectively. A plausible mechanistic description for these reactions involves an ± unprecedented ± −intramolecular iminoÀhaloform× rearrangement.Introduction. ± The oxidative ring expansion of −isoquinoline enamides× to tetrahydro-3-benzazepin-2-ones (i.e., I 3 II) occurs readily for different N-acyl functionalities when a) the isoquinoline ring contains electron-releasing, e.g., MeO substituents and b) the exocyclic CC bond is either unsubstituted or monoalkylsubstituted [1]. For compounds in which the exocyclic CC bond is dialkyl-substituted, the oxidation with Pb(OAc) 4 (LTA) occurs readily, but does not lead to ring expansion. Instead, phenyl tetrahydroisoquinoline-2-carboxylates cyclize to oxazoloisoquinolines (i.e., III 3 IV), while N-benzoyl or N-(trifluoroacetyl) derivatives undergo a formal oxidative rearrangement (i.e., V 3 VI) to afford the corresponding carboxylates [2] [3] (Scheme 1).In recent studies on effective routes to isoquinoline alkaloids, oxazoloisoquinolines of type IV bearing an alkyl group instead of the oxy function at C(10b) have been synthesized by intramolecular amidoalkylation of 4-hydroxyoxazolidin-2-ones [4] [5]. Here, we report on the synthesis of such compounds by LTA oxidation of appropriately substituted −isoquinoline enamides× by interconnecting the latter two reaction types in Scheme 1 accordingly.