Letter pubs.acs.org/OrgLett
Dehydrogenative Aromatic Ring Fusion for Carbazole Synthesis via C−C/C−N Bond Formation and Alkyl Migration Saikat Maiti and Prasenjit Mal* School of Chemical Sciences, National Institute of Science Education and Research (NISER) Bhubaneswar, HBNI, P.O. Bhimpur-Padanpur, Via Jatni, Khurda 752050, Odisha, India S Supporting Information *
ABSTRACT: An intermolecular dehydrogenative annulation (IDA) for carbazole synthesis via sequential C−C/C−N bond formation with a selective alkyl group migration is reported. Using the hypervalent iodine(III) reagent PhI(OAc)2 (PIDA), in a one-pot operation, up to five C(sp2)−H bonds, one N(sp3)−H bond functionalization, and one alkyl (Me, Et) group migration could all be achieved from non-prefunctionalized 1,3,5-trialkylbenzenes and anilides under ambient laboratory conditions. Mechanistically, it is shown that PIDA reacts with anilides to generate a nitrenium ion or an equivalent carbenium ion which influences the second aromatic ring to be activated for C−C/C−N bond formation. Strategically, regioselective fusion of arenes to anilides is described.
A
Scheme 1. Dehydrogenative Annulation through Sequential C−C/C−N Bond Formation
nnulation reactions are extremely alluring for the construction of new ring systems from different fragments in a single step.1 However, most transition-metal-catalyzed annulation reactions involve preorganized or prefunctionalized2 substrates.3 Major challenges in annulation reactions involve building new cyclic scaffolds from readily available chemical feedstocks. With this object, cross-dehydrogenative coupling (CDC) reactions4 for the construction of sequential C−C and C−N bonds via direct functionalization of C−H and N−H bonds are more strategic than traditional coupling reactions. Cross-dehydrogenative coupling (CDC) reactions may be considered as waste-minimized synthetic alternatives to usual coupling processes employing prefunctionalized substrates.5 Recently, hypervalent iodine(III) reagents have gained attention in driving both C−H and N−H bond functionalization reactions due to their low toxicity, easy availability, significant reactivity, and environmentally benign nature.6 Remarkably, intermolecular annulation processes using hypervalent iodine reagents for sequential C−C and C−N bond formation are limited in number.7 Literature examples of dehydrogenative ring fusing methods via sequential C−C/C−N bond formation are based mainly on transition-metal catalysis. Coupling reactions between Nmethoxybenzamides and arenes toward the synthesis of phenanthridinones were demonstrated by Cheng’s group using palladium catalysis.8 Additionally, palladium-catalyzed oxidative annulation of diphenylamine and cyclic olefins was developed by Maiti and co-workers for the synthesis of substituted indoles (Scheme 1a).9 In continuation of our research interest in hypervalent iodine(III)-mediated C−H amination,10 herein we disclose our discovery of a method for the one-pot multisubstituted three-ring heterocycle (carbazole)11 synthesis from two unactivated arenes via cascade cross-dehydrogenative coupling reaction under metal-free mild conditions (Scheme © 2017 American Chemical Society
1a). Readily available 1,3,5-trialkylbenzenes were strategically coupled with anilide substrates to provide new aromatic threering heterocycle compounds. Hypervalent iodine(III) reagent PIDA was the preferred oxidant because residual contamination by toxic metals is not a concern with this type of reagent.12 In addition to multiple C−H and N−H bond functionalizations, one of the alkyl (Me, Et) groups of the arene migrated to its adjacent C-position to furnish 1,2,4-trialkyl-substituted carbazole products. In some instances, regioselective incorporation of another 1,3,5-trimethylaryl group into the anilide component was achieved in addition to annulation with an appropriate choice of anilide (Scheme 1b). Received: April 13, 2017 Published: April 21, 2017 2454
DOI: 10.1021/acs.orglett.7b01117 Org. Lett. 2017, 19, 2454−2457
Letter
Organic Letters Initially, the reaction between N-(4-bromophenyl)benzenesulfonamide (1a) and mesitylene (2) at room temperature was evaluated in the presence of 2.5 equiv of PIDA as oxidant. After screening different solvents, we realized that TFE (2,2,2-trifluoroethanol) (0.2 M) was the best, providing 6bromo-1,2,4-trimethyl-9-(phenylsulfonyl)carbazole (3a). However, the use of different hypervalent iodine(III) reagents like PhI(OCOCF3)2, PhI(OPiv)2, or PhI(OCOPh)2 as oxidant did not furnish better results (Table 1, entry 4−6). Dilution of
Scheme 2. Scope of the Dehydrogenative Annulation Reaction
Table 1. Condition Optimizationa
entry 1 2 3 4 5 6 7 8 9 10 11c 12
oxidant (equiv) PIDA (2.5) PIDA (2.5) PIDA (2.5) PIFA (2.5) PhI(OPiv)2 (2.5) PhI(OCOPh)2 (2.5) PIDA (2.5) PIDA (2.5) PIDA (2.5) PIDA (2.0) PIDA (2.5) PIDA (2.5)
additive (2.5 equiv)
solvent DCM CH3CN HFIP HFIP HFIP HFIP
K2CO3 K2CO3
HFIP TFE TFE TFE TFE TFE:DCM (1:1)
yieldb (%) 0 54 76
