The Pd-catalyzed condensation of 2-bromostyrene and 2-chloroaniline derivatives yields stable diphenylamine intermediates, which are selectively converted to either 5-, 6-, or 7-membered heteroaromatics (indoles, carbazoles, acridines and dibenzazepines). The selectivity of these intramolecular transformations is uniquely ligand-controlled, and offers efficient routes to four important classes of heterocycles from a common precursor.The biological activity manifested by tricyclic, nitrogen-containing heterocyclic compounds make them attractive targets for synthetic chemists.1 The 7-membered ring 5H-Dibenz[b,f]azepine nucleus (1) is a pharmaceutically important structure and constitutes the key subunit in tricyclic antidepressant drug substances as Carbamazepine (2) and Oxcarbazepine (3).2 These anticonvulsant and mood stabilizing drugs are primarily used for the treatment of epilepsy, bipolar disorder,3 trigeminal neuralgia4 and other neurological disorders.5 Currently, the most widely employed method for the construction of dibenzazepine analogs involves a gas-phase dehydrogenation of iminobibenzyls at high temperatures.6 , 7 The crude product in these processes is usually contaminated with 9-methylacridine.8 Thus, a general and efficient means for the synthesis of substituted dibenzazepines remains a challenging problem. In addition, the closely related acridine and carbazole tricyclic nuclei also feature prominently amongst natural products and drug substances.9 Various methods utilizing a number of synthetic platforms and starting materials are used for the construction of such heteroaromatic systems.1b , 10 While there are many strategies available for the synthesis of carbazoles,2b , 11 methods for the preparation of acridines12c , 13 are limited and typically require harsh, functional group-intolerant conditions. * sbuchwal@mit.edu . Supporting information:Experimental details for the synthesis of all new compounds and spectral data. This information is available free via the Internet at http://pubs.acs.org. NIH Public AccessAuthor Manuscript J Am Chem Soc. Author manuscript; available in PMC 2011 October 13. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptAn examination of a series of tricyclic heteroaromatic compounds led us to the realization that 5H-dibenzazepines (4), 9-methylacridines (5) and vinylcarbazoles (6) might be derived from a common precursor via controlled intramolecular cyclizations . The key precursor (7) was prepared in 91% yield via a C-N coupling reaction14 , 15 of commercially available 2-bromostyrene and 2-chloroaniline, as shown in Scheme 1.We reasoned that four major factors would control the regioselectivity of the Pd(0)-catalyzed transformation of 7: ligand, base, solvent and temperature. Further examination of these variables led us to discover that the mode of heterocyclization is almost exclusively controlled by the ligand employed. We examined a variety of phosphines (L1-L11)14a and found that DavePhos (L2) was highly effective ligand for t...

A general and highly efficient protocol for the synthesis of dibenzodiazepines and their structural analogs is reported. In the presence of catalytic quantities of palladium, readily accessible precursors are cross-coupled with ammonia and then spontaneously undergo an intramolecular condensation to form the corresponding dibenzodiazepines in one step. This new strategy is applicable to the construction of a wide variety of dibenzooxazepines and other structurally related heterocycles.

An unprecedented Pd-catalyzed cascade Wacker-Heck lactonization-cyclization sequence is reported. The process provides a facile approach to bi- and tricyclic spiranoid lactones in good yields. The reaction shows general substrate scope and a broad functional group tolerability. In addition, a rare 4-exo trig Heck-type cyclization is demonstrated.

Heck, Stille, Suzuki and three‐component coupling reactions with hydrophobic substrates have been carried out in water. The substrates are initially transformed by a general procedure into a microemulsion, which consists of nearly 90 % water with the aid of sodium dodecyl sulfate and either PrOH or BuOH. The surfactant carries the molecules of the substrates to Pd(OAc)2 entrapped within a hydrophobicitized silica sol–gel matrix where the coupling between the substrates is assumed to take place. The products are then returned by the surfactant into the microemulsion from which it can be released. The immobilized palladium catalyst is leach proof and recyclable. It can be used in various coupling processes at least six times without loss of activity. Experiments with D2O have revealed that the water does not take part in the coupling process, but it has an effect on the pore size of the sol–gel matrix, which hosts the palladium catalyst. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)