Diazo Compounds DOI: 10.1002/ange.201107717 Indium-Catalyzed Cycloisomerizations of Cyclopropene-3,3-Dicar- bonyl Compounds: Efficient Access to Benzo-Fused Heteroaromatics and Heterobiaryls** Lien H. Phun, Joel Aponte-Guzman, and Stefan France* Benzo-fused heteroaromatics and heterobiaryls [1] are common structural motifs termed as “privileged” [2] by medic- inal chemists because of their presence in a diverse range of pharmaceutically relevant small molecules and bioactive natural products. Both have been used as probes to explore biochemical pathways and to understand biological function. Because of their interesting photophysical properties, each has found application in materials science as organic light- emitting diodes (OLEDs) and organic photovoltaics (OPVCs). [3] Furthermore, they both serve as ligands for many metal complexes. Given this diverse utility, the devel- opment of efficient methods for the synthesis of benzo-fused heteroaromatics and heterobiaryls has been an important goal for synthetic chemists. Whereas alkynes have been widely used as reactive units to generate benzo-fused substrates, [4] cyclopropenes have received limited attention in this area despite their unique reactivity that results from their substantial ring strain. Cyclopropenes readily participate in an assortment of additions, substitutions, cycloadditions, and metal-promoted transformations. [5] In particular, the metal-catalyzed rear- rangement, or cycloisomerization, of 2-acyl- and 2-iminocy- clopropenes to afford heterocyclic compounds has recently garnered a lot of attention from both a synthetic and mechanistic viewpoint. This method has become a powerful way to prepare furans, [6] indolizines, [7, 8] imidazopyridines, [7] and pyrrolo[2,1-b]oxazoles. [8] In contrast, only few examples of the analogous metal-catalyzed cycloisomerizations to form benzenoid rings have been disclosed. In a seminal report, Shi and co-workers demonstrated that arylvinylcyclopropenes rearrange in the presence of Lewis acids to give functional- ized naphthalenes. [9] While this example (and subsequent publications) [10] has provided invaluable insight into the potential of using cyclopropenes as substrates for benzannu- lation reactions, only carbocyclic products were generated. As part of our ongoing efforts toward the reactions of small strained rings in the presence of Lewis acids, [11] we were keenly interested in utilizing cyclopropene-3,3-dicarbonyl compounds as templates for intramolecular cyclizations. Although this class of cyclopropenes has not been employed as a substrate for cycloisomerizations, it has been shown to undergo ring-opening reactions in the presence of halides [12] or organometallic reagents. [13] These reagents serve as nucleo- philes to promote an S N 2-like ring-opening of the cyclo- propene. However, to the best of our knowledge, ring- opening of cyclopropene-3,3-dicarbonyl compounds pro- moted by Lewis acids have not been disclosed. Herein, we report the first example of a Lewis acid catalyzed cyclo- isomerization of cyclopropene-3,3-dicarbonyl compounds to give a wide array of benzo-fused heteroaromatics and heterobiaryls (Scheme 1). Cyclopropene-3,3-dicarbonyl substrates (3) were readily synthesized by using the general protocol disclosed by Gonzales-Bobes et al. [14] in which the corresponding a- diazo-b-keto esters 2 are added to solutions of alkynes in the presence of Dubois catalyst, [15] [Rh 2 esp 2 ] (dirhodium a,a,a’,a’-tetramethyl-1,3-benzene dipropanoate; Scheme 2). However, while the expected cyclopropenes 3 were observed as the major products in all cases, varying amounts of the cycloisomerization products 4 (for structure see Table 1) were also obtained. [16] Attempts to reverse the product ratio by Scheme 1. In(OTf) 3 -catalyzed cycloisomerizations of 3,3-dicarbonyl cyclopropene substrates. Tf = trifluoromethanesulfonyl. Scheme 2. Rhodium(II)-catalyzed cyclopropenation. [*] L. H. Phun, J. Aponte-Guzman, Prof. S. France School of Chemistry and Biochemistry Georgia Institute of Technology 901 Atlantic Drive, Atlanta, GA 30332 (USA) E-mail: stefan.france@chemistry.gatech.edu Homepage: http://www.chemistry.gatech.edu/faculty/France [**] S.F. gratefully acknowledges financial support from the National Science Foundation (CAREER Award CHE-1056687). L.H.P. thanks the Georgia Tech Center for Drug Design, Development and Delivery (CD4) for a GAANN fellowship. J.A.-G. thanks Georgia Tech for a Presidential Fellowship. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/anie.201107717. . Angewandte Zuschriften 3252  2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Angew. Chem. 2012, 124, 3252 –3256