Gold-Catalyzed Cascade Reactions of 4HFuro[3,2b]indoles with Allenamides: Synthesis of Indolin-3-one Derivatives [component]

unpublished
Merging the ability of cationic gold(I) catalysts to activate unsaturated π-systems with the electrophiles driven ring-opening reactions of furans, we describe a new approach to 2-spiroindolin-3-ones from 4H-furo [3,2-b]indoles. The reaction occurs through a cascade sequence involving addition of a gold-activated allene to the furan moiety of the starting furoindole followed by a ringopening/ring-closing event affording 2-spirocyclopentane-1,2-dihydro-3H-indolin-3-ones in moderate to good
more » ... . KEY WORDS Gold catalysis, furoindoles, allenes, cascade reaction, 2-spiroindolin-3-ones. 4 respectively. Taking into account these premises and our expertise in gold catalyzed reactions of 2vinyl-indoles 14 and in gold catalyzed cascade reactions for the functionalization of the indole nucleus, 15 we planned to test the reactivity of 4H-furo [3,2-b]indoles in the presence of electrophilic gold(I) activate π-systems (allenamides) with the aim to develop a new cascade process encompassing functionalization at the furan moiety, possibly followed by a ring-opening/ring-closing event (Scheme 2). Gold(I) activated C3 unsubstituted allenamides react with nucleophilic partners (electron-rich arenes and heteroarenes) at the terminal carbon giving rise regioselectively to hydroarylated (enamide) derivatives. 16 In this paper we report a full account of the obtained results. Scheme 2. Aim of our work RESULTS AND DISCUSSION There are only few reports on the synthesis of 4H-furo[3,2-b]indoles and, moreover, their reactivity is limited to simple Nor C2-functionalization reactions. 17 Therefore, we started our investigations with the synthesis of a small set of 4H-furo[3,2-b]indole-4-carboxylates (1a-k, Scheme 3). Compounds 1a-j, bearing a hydrogen or a methyl group at C2, were synthesized in a four steps procedure by adaptation of reported methodologies (Scheme 3). 17 In the last step, N-4 was protected as carbamate in order to avoid the formation of undesired hydroamination side products in the reaction with activated allenamides. 16b,d C2-Ph derivative 1k was prepared from 1a via bromination followed by Suzuki-Miyaura coupling with phenyl boronic acid. N-allenamides 2a-g, employed in this work, are known compounds and were prepared according to literature procedures. 18 5 Scheme 3. Synthesis of starting 4H-furo[3,2-b]indole-4-carboxylates 1a-k At the outset, furoindoles 1a and 1b were chosen as model compounds for the reactions with allenamide 2a in the presence of preformed cationic complex [Au(JohnPhos)NTf2] (Scheme 4). The reactions resulted in the isolation, in low yields, of simple hydroarylation product 3a with furoindole 1a and of 2-spirocyclopentane-indolin-3-one 4a with furoindole 1b. 6 Scheme 4. Gold-catalyzed reactions of furoindoles 1a-b with allene 2a: initial findings Formation of compound 3a was quite disappointing, although predictable. Instead, the formation of the spiro compound 4a was remarkable as it involves the formation in a single step of a highly substituted 2-spiroindolin-3-one. The structures and the geometries around the double bonds of compounds 3a and 4a were assigned based on analytical and spectroscopic data and unambiguously confirmed by X-ray diffraction analysis of a single crystal (Figure 2). Figure 2. Left: ORTEPIII plot of compound 3a showing the numbering schemes for all non-hydrogen atoms. Ellipsoids drawn at 50% probability. Right: ORTEPIII plot of compound 4a showing the numbering schemes for all non-hydrogen atoms. Ellipsoids drawn at 50% probability. Only one of the two crystallographically independent, but conformationally equivalent molecules, is shown.
doi:10.1021/acs.joc.9b00143.s002 fatcat:w5qr6trstzdcnfyxnvzpbfy23u