Oxidative Radical Cyclization of (.omega.-Iodoalkyl)indoles and Pyrroles. Synthesis of (-)-Monomorine and Three Diastereomers

Abstract

Addition of excess hydrogen peroxide (10 equiv) to a sonicated solution of FeS04:7Hz0 ( 1 equiv) in DMSO containing the N-(o4odoalkyl)indoles 4,5, 11, and 13 effected oxidative radical cyclization to 6,7,14, and 15, respectively. The (o4odoalkyl)pyrroles 21,22,27,38, and 49 underwent analogous cyclization reactions to 23, 24, 28, 39, and 50, respectively. The regiochemistry of these radical cyclization reactions was correctly predicted by FMO calculations in all cases but one. For compound 38, FMO calculations indicated that radical attack should take place at both C-3 and C-5. Only the product of cyclization at C-5, i.e., 39, was observed. The enantiomerically pure bicyclic ketone 42, prepared by the above technique from the iodide 53, was converted into 56 which, on catalytic reductio; (HdRh-Al203), gave a mixture of (-)-monomorine (40) and three of ita diastereomers 56-58 (see, however, Note Added in Proof).The intramolecular addition of a radical to an aromatic nucleus followed by oxidation of the new resonancestabilized radical thus produced back to the aromatic system (oxidative radical cyclization) is a process which has considerable synthetic utility, and several methods have recently been devised to effect such cyclizations. For example, oxidative intramolecular additions to aromatic systems mediated by Mn(III),1*2 Fe(II1),2 Cu(II),3 Ce(IV),2p3 and tri-n-butyltin hydride4ts which proceed with varying degrees of efficiency have been reported. As a long-term goal, we have been interested in devising efficient and inexpensive methods of effecting oxidative radical cyclization to aromatic systems. In addition, we have been investigating the use of simple computational methods as a possible means of predicting the regioselectivity of such reactions (Artis et al., ref 1). This publication describes some of our recent results in the indole and pyrrole areas.Dixon et al.6 showed by EPR spectroscopy that methyl radicals were produced in the reaction of hydroxyl radicals (generated from Ti(II1) and hydrogen peroxide) with DMSO. This reaction (eq 1) proceeds in >90 % yield based on hydroxyl radicals produced and also can be applied to sulfoxides other than DMSO.' Torsell and co-workers* + Contribution no. 881 from the

Short, Enantiospecific Syntheses of Indolizidines 209B and 209D, and Piclavine A from Diethyl‐L‐Glutamate

“…The foregoing result contrasted with those recently reported for certain 3,5-dialkyl-5,6,7,8-tetrahydroindolizines [21] [22]. These non-ketonic derivatives were found to decompose on attempted catalytic hydrogenation in 6~ HCl/AcOH solution.…”

2-[2-(Aziridin-1-yl)ethyl]-5,5-dimethyl-2,5-dihydro-4H-benzo [e]isoindol-4-one (Cytotoxic Oxonaphthalene-Pyrroles, Part IV)

“…The following deprotection with tetrabutylammonium fluoride [19] furnished the alcohol which was treated with methansulfonic chloride [20]. The resulting mesylate was…”

Five‐Membered Heterocycles: Pyrrole and Related Systems

“…Similar intramolecular processes provide routes to fused pyrroles, as illustrated by the manganese(III) acetate generated in situ induced conversion of the 2-aroylpyrrole 284 into the fused system 285 (Scheme 4.81), a useful precursor to the analgesic molecule ketorolac (10) [427]. In addition, [1,2-a]-fused pyrroles are also available via intramolecular radical cyclization of 1-(bromoalkyl)pyrroles induced by Bu 3 SnH in the presence of AIBN [428,429], annulation of 1-(iodoalkyl)pyrroles with the H 2 O 2 /Fe(II) system (vide supra) [430], or employing electroreduction with a Ni(II) complex as the electron-transfer catalyst [431]. Intramolecular cyclization of acyl radicals onto pyrroles leading to [1,2-a]-fused pyrrole derivatives in modest yields has also been reported [432].…”