Letter pubs.acs.org/OrgLett
Rh(III)-Catalyzed C−H Cyclization of Arylnitrones with Diazo Compounds: Access to N‑Hydroxyindolines Ramesh B. Dateer†,‡ and Sukbok Chang*,†,‡ †
Center for Catalytic Hydrocarbon Functionalizations, Institute for Basic Science (IBS), Daejeon 305-701, Korea Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 305-701, Korea
‡
S Supporting Information *
ABSTRACT: We have developed the Cp*Rh(III)-catalyzed cyclization reaction of arylnitrones with diazo compounds to obtain N-hydroxyindoline products under mild conditions. The substrate scope and functional group compatibility were examined with the demonstration of synthetic utility.
I
diazoacetates to give functionalized 3-hydroxypyrroles (Scheme 1b).8 Metal-mediated transformations of nitrone compounds can lead to the development of facile synthetic methods.9 The fact that we can take advantage of the nitrone moiety as a reacting site as well as a directing group may allow an additional opportunity to form heterocyclic products of structural diversity.6 Indeed, in continuation of our efforts on C−H functionalizations,10 we recently reported an efficient Rh(III)catalyzed redox-neutral cyclization reaction of arylnitrones to afford indolines via C−H bond activation and a subsequent oxygen atom transfer pathway.11 This development was inspired by the recent advances in Rh-carbene chemistry12 contributed by Rovis,13 Glorius,14 Yu,15 and others.16 Along this line, we herein report the Rh(III)-catalyzed C−H cyclization of nitrones in reaction with diazo compounds leading to N-hydroxyindoline products under mild conditions (Scheme 1c). It should be mentioned that, during the preparation of this manuscript, Zhou et al. reported an analogous transformation using a similar catalytic system.7b We commenced our studies by examining the reaction parameters in a reaction of a nitrone species 1a with dimethyl 2-diazomalonate 2a (Table 1). The well-established combination of [RhCp*Cl2]2 (3 mol %) and AgSbF6 (12 mol %) in 1,4dioxane resulted in the poor yield of the desired indoline product 3a (entry 1). Decomposition of the diazo reactant 2a was observed to occur slowly over time under these conditions. The cyclization efficiency was significantly improved by the addition of acid additives.17 Among those acids screened, pivalic acid (2.0 equiv) was especially effective and the indoline product could be isolated in 89% yield (entry 2). The structure of indoline 3a was unambiguously confirmed by X-ray crystallographic analysis. A satisfactory product yield was obtained still with a lower catalyst loading (73% with 1 mol % of Cp*Rh catalyst, entry 3). While a lower loading of pivalic
ndolines are an important structural motif present in numerous alkaloid compounds1 displaying interesting biological and pharmaceutical properties.2 Their facile preparation, as a result, has drawn much attention, thus leading to the development of indolines and various derivatives bearing synthetically valuable functional groups. Especially noteworthy among those are a CuH-catalyzed route to 2,3-disubstituted indolines3 and a Pd-catalyzed C−C coupling procedure involving unactivated methylenes.4,5 A more direct approach using redox-neutral C−H functionalization has been demonstrated to be fruitful for the synthesis of broad types of heterocycles.6 For example, Zhou et al. reported a Rh(III)catalyzed C−H functionalization of arylamine N-oxides in reaction with diazo compounds.7a While this annulation works efficiently with polyaromatic amine N-oxides to give 1Hbenzo[g]indolines (Scheme 1a, right side), aniline N-oxides afford acyclic aminomandelic acids via an O atom transfer pathway (Scheme 1a, left side). Doyle et al. reported a cooperative catalytic reaction of nitrones with substituted vinyl Scheme 1
Received: November 13, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b03273 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters Table 1. Optimization of Reaction Conditionsa
Scheme 2. Substrate Scope of Arylnitronesa
entry
catalyst/[Ag] salt
additive (equiv)
t (h)
yield (%)b
1 2 3d 4 5 6 7 8 9 10 11 12 13e 14f
[RhCp*Cl2]2/AgSbF6 [RhCp*Cl2]2/AgSbF6 [RhCp*Cl2]2/AgSbF6 [RhCp*Cl2]2/AgSbF6 [RhCp*Cl2]2/AgSbF6 [RhCp*Cl2]2/AgSbF6 [RhCp*Cl2]2/AgSbF6 [RhCp*Cl2]2/AgSbF6 [RhCptCl2]2/AgSbF6 [IrCp*Cl2]2/AgSbF6 [Ru(p-cymene)Cl2]2/AgSbF6 [RhCp*Cl2]2/AgNTf2 [RhCp*Cl2]2/AgSbF6 [RhCp*Cl2]2/AgSbF6
none PivOH (2) PivOH (2) PivOH (0.5) AcOH (2) PhCO2H (2) CF3CO2H (2) p-TsOH (2) PivOH (2) PivOH (2) PivOH (2) PivOH (2) PivOH (2) PivOH (2)
24 12 24 12 12 15 12 15 12 12 10 10 24 24
13 93 (89)c 73 67 68 61 36 29 78
Rh(III)-Catalyzed C−H Cyclization of Arylnitrones with Diazo Compounds: Access to N‑Hydroxyindolines Ramesh B. Dateer†,‡ and Sukbok Chang*,†,‡ †
Center for Catalytic Hydrocarbon Functionalizations, Institute for Basic Science (IBS), Daejeon 305-701, Korea Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 305-701, Korea
‡
S Supporting Information *
ABSTRACT: We have developed the Cp*Rh(III)-catalyzed cyclization reaction of arylnitrones with diazo compounds to obtain N-hydroxyindoline products under mild conditions. The substrate scope and functional group compatibility were examined with the demonstration of synthetic utility.
I
diazoacetates to give functionalized 3-hydroxypyrroles (Scheme 1b).8 Metal-mediated transformations of nitrone compounds can lead to the development of facile synthetic methods.9 The fact that we can take advantage of the nitrone moiety as a reacting site as well as a directing group may allow an additional opportunity to form heterocyclic products of structural diversity.6 Indeed, in continuation of our efforts on C−H functionalizations,10 we recently reported an efficient Rh(III)catalyzed redox-neutral cyclization reaction of arylnitrones to afford indolines via C−H bond activation and a subsequent oxygen atom transfer pathway.11 This development was inspired by the recent advances in Rh-carbene chemistry12 contributed by Rovis,13 Glorius,14 Yu,15 and others.16 Along this line, we herein report the Rh(III)-catalyzed C−H cyclization of nitrones in reaction with diazo compounds leading to N-hydroxyindoline products under mild conditions (Scheme 1c). It should be mentioned that, during the preparation of this manuscript, Zhou et al. reported an analogous transformation using a similar catalytic system.7b We commenced our studies by examining the reaction parameters in a reaction of a nitrone species 1a with dimethyl 2-diazomalonate 2a (Table 1). The well-established combination of [RhCp*Cl2]2 (3 mol %) and AgSbF6 (12 mol %) in 1,4dioxane resulted in the poor yield of the desired indoline product 3a (entry 1). Decomposition of the diazo reactant 2a was observed to occur slowly over time under these conditions. The cyclization efficiency was significantly improved by the addition of acid additives.17 Among those acids screened, pivalic acid (2.0 equiv) was especially effective and the indoline product could be isolated in 89% yield (entry 2). The structure of indoline 3a was unambiguously confirmed by X-ray crystallographic analysis. A satisfactory product yield was obtained still with a lower catalyst loading (73% with 1 mol % of Cp*Rh catalyst, entry 3). While a lower loading of pivalic
ndolines are an important structural motif present in numerous alkaloid compounds1 displaying interesting biological and pharmaceutical properties.2 Their facile preparation, as a result, has drawn much attention, thus leading to the development of indolines and various derivatives bearing synthetically valuable functional groups. Especially noteworthy among those are a CuH-catalyzed route to 2,3-disubstituted indolines3 and a Pd-catalyzed C−C coupling procedure involving unactivated methylenes.4,5 A more direct approach using redox-neutral C−H functionalization has been demonstrated to be fruitful for the synthesis of broad types of heterocycles.6 For example, Zhou et al. reported a Rh(III)catalyzed C−H functionalization of arylamine N-oxides in reaction with diazo compounds.7a While this annulation works efficiently with polyaromatic amine N-oxides to give 1Hbenzo[g]indolines (Scheme 1a, right side), aniline N-oxides afford acyclic aminomandelic acids via an O atom transfer pathway (Scheme 1a, left side). Doyle et al. reported a cooperative catalytic reaction of nitrones with substituted vinyl Scheme 1
Received: November 13, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b03273 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters Table 1. Optimization of Reaction Conditionsa
Scheme 2. Substrate Scope of Arylnitronesa
entry
catalyst/[Ag] salt
additive (equiv)
t (h)
yield (%)b
1 2 3d 4 5 6 7 8 9 10 11 12 13e 14f
[RhCp*Cl2]2/AgSbF6 [RhCp*Cl2]2/AgSbF6 [RhCp*Cl2]2/AgSbF6 [RhCp*Cl2]2/AgSbF6 [RhCp*Cl2]2/AgSbF6 [RhCp*Cl2]2/AgSbF6 [RhCp*Cl2]2/AgSbF6 [RhCp*Cl2]2/AgSbF6 [RhCptCl2]2/AgSbF6 [IrCp*Cl2]2/AgSbF6 [Ru(p-cymene)Cl2]2/AgSbF6 [RhCp*Cl2]2/AgNTf2 [RhCp*Cl2]2/AgSbF6 [RhCp*Cl2]2/AgSbF6
none PivOH (2) PivOH (2) PivOH (0.5) AcOH (2) PhCO2H (2) CF3CO2H (2) p-TsOH (2) PivOH (2) PivOH (2) PivOH (2) PivOH (2) PivOH (2) PivOH (2)
24 12 24 12 12 15 12 15 12 12 10 10 24 24
13 93 (89)c 73 67 68 61 36 29 78
