Cinchona hydroxyalkylation

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. 

Scheme 35.7 Cinchona alkaloid catalyzed hydroxyalkylation of indoles.

The scope of this F-C hydroxyalkylation of indoles was extended to a range of different carbonyl compounds, giving rise to the desired compounds in high yields (up to 97%) and enantioselechvities (up to 99% ee) in the presence of catalysts 13 and 14 [18]. Catalyst 14 also proved to be highly selective when carrying out the first example of cinchona alkaloid mediated F-C alkylation of phenols with 45 (Scheme 35.8) [58]. Chiral phosphoric acids were also used to mediate F-C alkylation in the presence of ethyl trifluoropyravate [31], trifluoroacetate [59], and trif-luoromethyl ketones [60]. 

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