Synthesis of benzo(or furo)[5,6]azepino[2,1-a]isoindolone derivatives: π-cyclisations of N-acyliminium ions

Abstract

Benzo(or furo)[5,6]azepino[2,1-a]isoindolone and derivatives were obtained easily in one-pot via N-acyliminium ions by treatment of 2-(2-methoxycarbonylbenzyl(or fur-3-yl))phthalimide with alkylmagnesium iodide followed by an acidic hydrolysis.

Evaluation of N‐Hydroxymethylphthalimide in Alkaline Medium: Novel Entry to the Tricyclic [1,3]Oxazepine Core via an Intramolecular π and O‐Cationic Cyclization.

“…Attempts to extend this reaction to heteroaromatic, alkyl, functionalized alkyl, functionalized aromatic and functionalized heteroaromatic halides was successful and produced only the corresponding N-alkylated products 9b (75%) [18], 9c (49%) [19], 9d (58%) [20], 9e (69%) [21], and 9f (71%) [21], respectively. In light of these results, its seems that the imidate anion D is more stable than the alcoholate one C under basic conditions at these temperatures.…”

Methods for the construction of [1,2]isoindolo-condensed benzazepines, benzazocines, quinolines, and isoquinolines. 1. Isoindolobenzazepines, isoindolobenzazocines. (Review)

“…Information on methods for the construction of and the chemical characteristics of the polycycles 1 and 2 can be gleaned from a limited number of publications [1][2][3][4]. We were only able to find mention of derivatives of isoindolo[2,1-b]benz-2-azepines 3 in nine papers [5][6][7][8][9][10][11][12][13], four of which are patents (10-13).…”

“…The unsaturated isoindolo[2,1-b]benz-2-azepine 98 can be obtained from the corresponding phthalimide 96. In [7] two methods were proposed for this cyclization, i.e., a one-pot method and a two-stage method with the isolation of the hydroxylactam 97. Reaction of the imidic ester 96 with methylmagnesium iodide followed by hydrolysis leads to the formation of the required compound 98 (83%).…”

“…Synthesis of Isoindolo[1,2-b]benz-3-azepines from Ten-membered Lactams.Isoindolo[1,2-b]-benz-3-azepines 70 and 71 can be obtained by[7,5]-transannular cyclization of ten-membered lactams 69a-e. The initial macrolactams 69 are synthesized from o-(trimethylsilylethynyl)benzamides 68a-d[29,63,64] of unsubstituted o-ethynylbenzamide 68e[65] by radical 10-endo-macrocyclization.In the case of the alkynes 68a-d cyclization takes place stereoselectively with the formation of only the Z-isomer, while in the case of compound 68e a mixture of Z-and E-isomers (47:24) of the polycycles 69 is formed.13-Trimethylsilyl-substituted 70 or 13-unsubstituted 71 isoindolo[1,2-b]benz-3-azepines can be obtained from the amides 69a-d, depending on the reaction conditions.…”

Thieno[2′,3′:5,6]azepino[2,1‐a]isoindolones from hydroxylactam‐alcohols via N‐acyliminium ion olefin cyclization

“…This latter could be isolated as pure product by a recrystallization from ethanol. It is interesting to note that the minor product 7b was the single product when the thiophene ring was changed for a furan or a benzene ring [16]. The loss of a proton in 6b gave preferentially an endocyclic double bond (8b) rather than an unsubstituted exocyclic one (7b).…”