A general synthesis of N-hydroxyindoles.
A general method for the formation of N-hydroxyindoles is demonstrated through a lead-promoted intramolecular reductive cyclization of o-nitrobenzyl ketones and aldehydes under transfer hydrogenation conditions. The N-hydroxyindoles are isolated in high purity and excellent yield (>90%) in an operationally simple procedure. This new method is exemplified by a two-step synthesis of the naturally occurring 1-methoxyindole-3-carboxaldehyde, which is pivotal in many alkaloid total syntheses.
Wong
Audrey
A
Department of Process Research, Merck & Co., Inc., P.O. Box 2000, Rahway, New Jersey 07065, USA. audrey_wong@merck.com
Kuethe
Jeffrey T
JT
Davies
Ian W
IW
D000447:Aldehydes / Q000737:chemistry; D003500:Cyclization; D006865:Hydrogenation; D006900:Hydroxylation; D007211:Indoles / Q000138:chemical synthesis*; D007659:Ketones / Q000737:chemistry; D007854:Lead / Q000737:chemistry; D009578:Nitrobenzenes / Q000737:chemistry
D000447:Aldehydes; D007211:Indoles; D007659:Ketones; D009578:Nitrobenzenes; D007854:Lead