Divergent Diazo Approach toward Alkyl 5/4-Hydroxy-3H-benzo[e]indole-4/5-carboxylates

Abstract

A divergent diazo approach toward alkyl 5/4hydroxy-3H-benzo[e]indole-4/5-carboxylates has been developed. The reaction of 1,3-diketones with alkyl 2-diazo-3-oxo-3-(2Hazirin-2-yl)propanoates catalyzed by Co(acac) 3 or Ni(acac) 2 gives various alkyl 3-(1H-pyrrol-2-yl)-2-diazo-3-oxopropanoate in good yields. The latter undergo Wolff rearrangement followed by the 6πcyclization of transient ketene to form alkyl 5-hydroxy-3Hbenzo[e]indole-4-carboxylates bearing various substituents in positions 1, 2, 7, and 8, as well as derivatives of methyl 4hydroxy-6H-thieno[2,3-e]indole-5-carboxylates and methyl 5-hydroxy-7H-benzo[c]carbazole-6-carboxylate under thermolysis or Rh 2 (OAc) 4 catalysis. Isomeric benzoindoles, alkyl 4-hydroxy-3Hbenzo[e]indole-5-carboxylates, have been prepared by Boc-protection of the pyrrole nitrogen of alkyl 3-(1H-pyrrol-2-yl)-2-diazo-3oxopropanoates followed by an intramolecular formal carbene insertion into the aromatic C−H bond catalyzed by Cu(OTf) 2 . The hydroxyl group of alkyl 5/4-hydroxy-3H-benzo[e]indole-4/5-carboxylates, through the formation of the corresponding triflates, allows the introduction of various substituents into the 5/4 position of benzo[e]indoles using the cross-coupling reaction and even form a new heterocyclic backbone, benzo[k]pyrrolo[2,3-i]phenanthridine, via a tandem Suzuki reaction/nucleophilic acyl substitution.

Cyclocondensation of 2-(α-Diazoacyl)-2H-azirines with Amidines in Diazo Synthesis of Functionalized Naphtho[1,2-d]imidazoles

“…All solvents were distilled and dried prior to use. Physical and spectral data of methyl 2-diazo-3-oxo-3-(2 H -azirin-2-yl)­propanoates 10a , 10j , and methyl 2-diazo-3-oxo-3-(2 H -azirin-2-yl)­propanoates 10b – i prepared according to the published procedures were in agreement with previously reported values. Amidine hydrochloride 11a-HCl was commercial.…”

“…It was previously established that Boc protection of the pyrrole nitrogen of methyl 3-(3-aryl-1 H -pyrrol-2-yl)-2-diazo-3-oxopropanoates changes the direction of reactions of carbene intermediates, formed during the decomposition of these diazo compounds, from the Wolff rearrangement/6π-cyclization to formal aromatic CH-insertion. This is likely due to a change in the conformation of the diazo compound, which affects complexation with the catalyst . In search of the possibility of implementing a formal aromatic CH-introduction for diazo compounds 1 , which would allow the preparation of naphthoimidazoles 5 , compound 1s with Boc-protected nitrogen was synthesized by treating compound 1a with di- tert -butyl dicarbonate and DMAP (Scheme ).…”

“…The reaction provides good product yields and tolerates differently substituted aryl groups and a 2-thienyl group at C3 of an azirine substrate, but it is impossible to obtain imidazoles 1 with an aryl group containing strong acceptor substituents at C2 in synthetically useful yields, due to the extremely low yields of the starting azirines 10 with such substituents. , It is important that the substituents on the aryl group at C5, which are then transferred to the terminal benzene ring of the target naphtho­[1,2- d ]­imidazoles, can vary widely, including highly electron-withdrawing ones like CF 3 . Ortho -, meta -, and para -substituted arylamidines 11 can be used as starting materials in the reaction.…”

“…Two options for intramolecular cyclization of α-diazo-β-carbonyl compounds containing an aryl or hetaryl substituent in the δ-position with formation of a six-membered ring are possible: 1) Wolff rearrangement of α-diazo-β-carbonyl compounds into ketene and 6π-cyclization of the latter at an unsaturated substituent in the δ-position and (2) formation of a metal carbene complex followed by a formal C–H insertion into an unsaturated substituent (for example, Scheme , (2)). For the implementation of the second option, catalysts based on Rh­(II) − or Cu­(II) compounds can be used, whereas Wolff rearrangement of α-diazo-β-carbonyl compounds into ketene followed by 6π-cyclization at an unsaturated substituent in the δ-position was observed under Rh­(II)-catalytic or thermal conditions . Therefore, we tried denitrogenation of diazo compound 1a in catalytic, photolytic, and thermal conditions (Table S15).…”

“…This paper describes a new reaction of 2-acyl-3-aryl-2 H -azirines with arylamidines, proceeding in an unusual way through the cleavage of the C–C bond of the azirine at rt, allowing the transfer of the aryl substituent from the arylamidine to the appropriate position of the imidazole ring. Using methyl-2-diazomalonyl-substituted azirines 10 , as starting compounds, this method was applied to the preparation of diazocarbonyl-substituted imidazoles 1 , convenient precursors of naphtho­[1,2- d ]­imidazole-4-carboxylates 3 with various substituents at positions 2, 3, 5, 7, 8, and 9 (Scheme , (4)).…”