DOI: 10.1002/adsc.200900018 Expanding the Suzuki–Heck-Type Coupling Cascade: A New IndenoACHTUNGTRENNUNG[1,2,3]-Annelation of Polycyclic Aromatic Hydrocarbons Jennifer M. Quimby a and Lawrence T. Scott a, * a Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, MA 02467-3860, USA Fax: (+ 1)-617-552-6454; phone: (+ 1)-617-552-8024; e-mail: lawrence.scott@BC.edu Received: January 12, 2009; Published online: March 17, 2009 Dedicated to Professor Dr. Armin de Meijere on the occasion of his 70th birthday. Supporting information for this article is available on the WWW under http ://dx.doi.org/10.1002/adsc.200900018. Abstract: Fluoranthene derivatives can be con- structed in a single operation by a palladium-cata- lyzed cascade reaction sequence, starting from a peri-dichloronaphthalene derivative and various ar- ylboronic acids. Keywords: aryl halides; C À H activation; cross-cou- pling; microwave heating; palladium; synthetic methods Methods for the synthesis of fully unsaturated 6-mem- bered (benzenoid) carbocycles greatly outnumber those available for the synthesis of fully unsaturated 5-membered carbocycles. [1] To address this imbalance, we introduced two complementary Suzuki–Heck-type coupling cascades several years ago (Scheme 1, top) that provide expedient means for the indenoACHTUNGTRENNUNG[1,2,3]- annelation of polycyclic aromatic hydrocarbons (PAHs). [2] The overall processes build the new 5- membered rings by two distinct aryl-aryl coupling re- actions, both catalyzed by palladium, starting from simple, mono-functional derivatives of the PAH. The first step involves a classical intermolecular Suzuki–Miyaura cross-coupling of an arylboronic acid [Ar À B(OH) 2 ] with an aryl bromide (Ar’ À Br). [3] A second halogen atom, strategically located on one or the other of the two reaction partners, then directs a second palladium insertion, which sets the stage for an intramolecular Heck-type arylation reaction [4] on the peri-position of the PAH (Scheme 1, top). Both of these incarnations of the Suzuki–Heck-type coupling cascade start from a mono-functionalized PAH and an ortho-difunctionalized benzene as the two reaction partners. In principle, however, it should be possible to implement this same strategy starting from a peri-difunctionalized PAH and a singly-func- tionalized benzene derivative (Scheme 1, bottom). Herein we report the successful realization of this latter variation on the indenoACHTUNGTRENNUNG[1,2,3]-annelation cas- cade, starting from a peri-dihalo-PAH (Scheme 1, bottom left). The fourth variation, starting from a peri-halo-arylboronic acid remains unknown at this time (Scheme 1, bottom right). The lack of general methods for accessing peri-di- functionalized PAHs will undoubtedly limit the utility of indeno-annelations that require such substrates as starting materials; however, many peri-dihalo-PAHs are readily available; Chemical Abstracts lists nearly 2000 known peri-dihalo-PAHs (X = Cl, Br, or I, ex- cluding X = F), of which more than 100 can be ob- tained commercially. For our experiments, we chose 5,6-dichloroacenaph- thene (1), which is easily prepared by direct chlorina- tion of acenaphthene. [5] After screening several cata- lysts, ligands, bases, and other reaction conditions, we were pleased to find that 1 can be indeno-annelated with 3,4-dimethoxybenzeneboronic acid (2) to pro- duce the bridged dimethoxyfluoranthene (3) in 89% isolated yield (Scheme 2). The conditions that give this yield employ 20% tris(dibenzylideneacetone)dipalladium(0) as the cata- lyst, 50% tri-tert-butylphosphonium tetrafluoroborate as the ligand source, and 29 equiv. of 1,8-diazabicyclo- ACHTUNGTRENNUNG[5.4.0]undec-7-ene as the base. The reaction is run in anhydrous N,N-dimethylacetamide under a nitrogen atmosphere at 175 8C with microwave heating for 40 min. It should be noted that palladium catalyzes two coupling reactions for each molecule of product formed and that the ratio of phosphine ligand to pal- ladium is 1.25/1.00. Using these same conditions, the substituted fluoranthenes pictured in Scheme 3 were likewise prepared from 1 (isolated yields indicated). Adv. Synth. Catal. 2009, 351, 1009 – 1013  2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 1009 COMMUNICATIONS