P-Indolyl alcohol

In 2004, Umani-Ronchi et al. discovered that chiral (RJi)-[Cr(salen)]Y complexes (Jacobsen catalysts 70/71) could effectively undergo asymmetric F-C alkylation via kinetic resolution of racemic disubstituted epoxides. Treatment of 2-methylindole 74 with 3 equiv trans-1,2-disubstituted epoxides (72a-d) and 3.5 mol % of (/ ,/ )-[Cr(salen)]SbF6 catalyst (71) provided excellent yields (82-99%) of the corresponding chiral P-indolyl alcohols (73a-d) with good optical purity (72-91% ee). With this catalyst, only the (5 iS)-isomer of 72a-d reacts to form the (J ,S)-isomer of 73a-d, respectively. 

The (/ ,/2)-[Cr(salen)]X catalyzed addition of indoles of type 75 was also applied by Umani-Ronchi (2004) to the asymmetric ring opening of mejo-stilbene oxide (76). Treatment of indoles 75a-c (1.5 equiv) and meso-stilbene oxide (1.0 equiv 76) in TBME with 5 mol% of (if )-[Cr(salen)]Cl afforded the corresponding chiral (S,./ )-P-indolyl alcohols (77a-c) in superb yield (95-98%) and enantiomeric purity (90-98% ee). Incorporation of a 2-Me moiety or a 5-MeO moiety into the framework of the indole nucleus in place of H improves or reduces the optical purity of the alkylated product [compare 77c (98% ee) and 77b (90% ee) versus 77a (93% ee), respectively]. 

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