Indoles aryl sulfonyl

Two years after the discovery of the first asymmetric Br0nsted acid-catalyzed Friedel-Crafts alkylation, the You group extended this transformation to the use of indoles as heteroaromatic nucleophiles (Scheme 11). iV-Sulfonylated aldimines 28 are activated with the help of catalytic amounts of BINOL phosphate (5)-3k (10 mol%, R = 1-naphthyl) for the reaction with unprotected indoles 29 to provide 3-indolyl amines 30 in good yields (56-94%) together with excellent enantioselec-tivities (58 to >99% ee) [21], Antilla and coworkers demonstrated that A-benzoyl-protected aldimines can be employed as electrophiles for the addition of iV-benzylated indoles with similar efficiencies [22]. Both protocols tolerate several aryl imines and a variety of substituents at the indole moiety. In addition, one example of the use of an aliphatic imine (56%, 58% ee) was presented. 

Some bifunctional 6 -OH Cinchona alkaloid derivatives catalyse the enantioselective hydroxyalkylation of indoles by aldehydes and a-keto esters.44 Indole, for example, can react with ethyl glyoxylate to give mainly (39) in 93% ee. The enan- tioselective reaction of indoles with iV-sulfonyl aldimines [e.g. (40)] is catalysed by the Cu(OTf)2 complex of (S)-benzylbisoxazoline (37b) to form 3-indolylmethanamine derivatives, in up to 96% ee [e.g. (41a)] 45 Some 9-thiourea Cinchona alkaloids have been found to catalyse the formation of 3-indolylmethanamines [e.g. (41b)] from indoles and /V-PhS02-phenyli mines in 90% ee.46 Aryl- and alkyl-imines also give enantioselective reactions. 

Direct cyclisation of ortfto-alkynyl-anilines can be effected simply by treatment with tetra-n-bntylam-monium fluoride, potassium f-butoxide or potassium hydride, or simply with gold(III) chloride. Treatment of l-(2-arylethynyl)-2-nitroarenes with indium and aqneons hydrogen iodide prodnces 2-aryl-indoles, the reagent combination both reduces the nitro to amine and then the acid activates the alkyne for the ring closure. Copper(II) salts or diethylzinc in refluxing toluene can be ntihsed with IV-sulfonyl-ort/fo-alkynyl-anilines. 

The synthesis of highly functionalized cyclohepta[l)]indoles was achieved through an efficient sequence of [4 + 3]-cycloaddition-cydization-elimination. The cycloaddition features nitrogen-stabilized oxyallyl cations derived from epoxidations of N-aryl-N-sulfonyl-substituted allenamides, while the cyclization and elimination employed an intramolecular Grignard addition and a useful one-step Chugaev process, respectively (14OL2180). 

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