Linked Life Data

19453193

Source:http://linkedlifedata.com/resource/pubmed/id/19453193

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2009-5-20
pubmed:abstractText
Two different catalytic enantioselective approaches to 3-aryl- and 3-alkenyl-3-hydroxy-2-oxindoles have been developed. First, enantioselective arylation and alkenylation reactions of isatins using aryltrimethoxysilanes and alkenyltrimethoxysilanes as nucleophiles can be catalyzed by a complex of CuF with structurally tuned Taniaphos (6) in the presence of a catalytic amount of ZnF(2). Despite the wide substrate scope, this intermolecular reaction was not applicable to a catalytic enantioselective synthesis of SM-130686 (1), a highly potent, orally active growth hormone secretagogue containing a sterically congested chiral tetrasubstituted carbon. Therefore, we developed an intramolecular catalytic enantioselective arylation of alpha-keto amides, taking advantage of the robustness of arylboronate reagents under multiple synthetic conversions and silica gel column chromatography purification. A complex of CuF with Ph-BPE (12) catalyzed the enantioselective arylation of alpha-keto amide 19, affording product 20 in 85% ee. The addition of ZnF(2) to this intramolecular reaction was not necessary. The first enantioselective synthesis of SM-130686 was achieved using this catalytic methodology. Because 2-oxyindoles are a versatile motif for biologically active compounds, the two types of Cu-catalyzed asymmetric reactions developed here will be useful for the synthesis of other natural products and pharmaceutical leads.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1520-5126
pubmed:author
pubmed:issnType
Electronic
pubmed:day
27
pubmed:volume
131
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6946-8
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Enantioselective synthesis of SM-130686 based on the development of asymmetric Cu(I)F catalysis to access 2-oxindoles containing a tetrasubstituted carbon.
pubmed:affiliation
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't