Arylation using diaryliodonium salts generates one equivalent of an iodoarene as a side-product, a significant waste of atom economy. Here, we show that diaryliodoniums can undergo Cu-catalyzed tandem C-H/N-H arylation, producing novel indoles that incorporate both aryl groups from the reagent.
Gold-catalyzed carbocyclization and heteroannulation strategies have recently attracted much attention owing to the selective and efficient activation of the CC bond towards a wide range of nucleophiles that these methods provide.[1] Domino approaches involving gold-catalysis lead to complex heterocyclic compounds under exceedingly mild reaction conditions.[2] Although gold-catalyzed approaches are rising to prominence, they suffer in terms of diversity and procedural length. Multistep sequences are usually required for assembling the starting material for cyclization. We have recently reported a concise route to indoloazocines by a sequential Ugi/gold-catalyzed intramolecular hydroarylation approach.[3] Inspired by these findings and as a result of our continued synthetic interest in the indole core, [4] multicomponent reactions [5] and transition metal-catalysis, [6] we have developed a post-Ugi gold-catalyzed domino cyclization method to generate spiroindolines.The Ugi four-component reaction (4-CR) [7] of indole-3-carboxaldehyde (1 a) with p-methoxybenzyl amine (2 a), 2-butynoic acid (3 a) and tert-butyl isonitrile (4 a) in methanol at 50 8C gave Ugi-adduct 5 a in 71 % yield. When this was treated with 5 mol % of Au[PPh 3 ]OTf (OTf = trifluoromethanesulfonate) in CDCl 3 at RT, the expected outcome of the reaction was indoloazepinone 6 a' through an endo-dig cyclization [1m,n, 3] followed by rearrangement (Scheme 1). Surprisingly, an exo-dig cyclization followed by intramolecular trapping of the spiro intermediate occurred instead, resulting in the diastereoselective formation of tetracyclic spiroindoline 6 a in 61 % yield (Scheme 1).This observation was remarkable, as the attack on the a-position of an alkyne conjugated with an amide is rare, and trapping of the spiro intermediate by a sterically hindered tert-butyl amide is rather unexpected, as was the diastereoselectivity observed. Spiroindolines [8] are prominent molecular motifs that are frequently encountered among the large family of alkaloids; for example, it is present in communesines [8,9] and perophoramidines [8,10] (Figure 1), which display distinct pharmacological properties. [8][9][10] These fused polycyclic systems, which feature quaternary stereocenters, present a nontrivial challenge for organic chemists to develop synthetic approaches.
Transition metal-catalyzed C-C bond formations have been well studied over the last four decades. An improved mechanistic understanding of such reactions has helped chemists to develop further improvements, modifications and even new reactions. In the area of transition metal-catalyzed cross-coupling reactions the C-S bond cleaving reactions have attracted a lot of attention in the last decade as they provide a good alternative to the use of organo-halide reagents in traditional cross-coupling reactions. The availability of a wide range of organo-sulfur species provides the opportunity for developing different transformations for the synthesis of interesting organic compounds. This tutorial review focuses on recent examples of the transition metal-catalyzed C-C bond forming reactions using organo-sulfur species.
Both aryl components of diaryliodonium salts can be used in a domino one-pot reaction via in situ generation of a directing group. A number of heterocycles undergo N-arylation which is followed by ruthenium-catalyzed C-arylation. Notably the reaction extends well to unsymmetrical diaryliodonium salts with a number of highly selective examples shown.
A diversity oriented approach for the synthesis of indoloazocines is reported employing an Ugi reaction followed by a gold-catalyzed intramolecular hydroarylation.
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