Study of the oxidation of 3-hydroxypyrroloindoles to pyrrolobenzoxazine alkaloids

• Published in: Tetrahedron Vol. 67; no. 51; pp. 9899 - 9908
• Main Authors: Commandeur, Claude, Commandeur, Malgorzata, Bathany, Kathell, Kauffmann, Brice, Edmunds, Andrew J.F., Maienfisch, Peter, Ghosez, Léon
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 23.12.2011; Elsevier
• Subjects: Alkaloids; Boc protection; Chemistry; Chemistry, Organic; Derivatives; Ethyl esters; Formations; Meisenheimer rearrangement; Neighbouring; Nitrogen atoms; Parents; Physical Sciences; Pyrrolobenzoxazines; Pyrroloindoles N-oxides; Science & Technology; Tetrahedrons; Pyrrolobenzoxazines; Meisenheimer rearrangement; Boc protection; Pyrroloindoles N-oxides; TERTIARY AMINE OXIDES; PHOTOSENSITIZED OXYGENATION; N-OXIDES; RAY CRYSTAL-STRUCTURE; THERMAL REARRANGEMENT; METHYL-ESTER; HETEROCYCLIC SYNTHESIS; GENESERINE; DERIVATIVES
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2011.09.112

This report describes a detailed study of the oxidation-Meisenheimer rearrangement of N-methyl-3-hydroxy-7-chloropyrroloindoline ethyl ester and the corresponding O-Boc and N-Boc derivatives. Experimental conditions were found, which allowed the selective Boc protection of either the tertiary alcohol substituent or the NH group of the aminal function. It was shown that both the parent compound and its O-Boc derivative yielded a mixture of oxazines and, in some cases, N-oxides upon treatment with m-CPBA. MS fragmentation (APCI) clearly differentiates formation of N-oxides and oxazines. The N-Boc derivatives exclusively yielded the N-oxides showing that the Meisenheimer rearrangement requires the presence of a high energy lone pair on the neighbouring nitrogen atom. Both the parent compound and the O-Boc derivative gave a mixture of rearranged products and N-oxide depending on the reaction conditions. [Display omitted]