Biomaterial Database

A general synthesis of N-hydroxyindoles. 2003

Audrey Wong, and Jeffrey T Kuethe, and Ian W Davies

Department of Process Research, Merck & Co., Inc., P.O. Box 2000, Rahway, New Jersey 07065, USA. audrey_wong@merck.com

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.

UI	MeSH Term	Description	Entries
D007211	Indoles	Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D007659	Ketones	Organic compounds containing a carbonyl group	Ketone
D007854	Lead	A soft, grayish metal with poisonous salts; atomic number 82, atomic weight 207.2, symbol Pb.
D009578	Nitrobenzenes	BENZENE derivatives carrying nitro group substituents.
D003500	Cyclization	Changing an open-chain hydrocarbon to a closed ring. (McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)	Cyclizations
D006865	Hydrogenation	Addition of hydrogen to a compound, especially to an unsaturated fat or fatty acid. (From Stedman, 26th ed)	Hydrogenations
D006900	Hydroxylation	Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed)	Hydroxylations
D000447	Aldehydes	Organic compounds containing a carbonyl group in the form -CHO.	Aldehyde