The scope and limitations of intramolecular Nicholas and Pauson-Khand reactions for the synthesis of tricyclic oxygen- and nitrogen-containing heterocycles.
We studied the scope and limitations of a tandem intramolecular Nicholas/Pauson-Khand strategy for the synthesis of tricyclic oxygen- and nitrogen-containing heterocycles. This methodology enables conversion of simple acyclic starting materials into a series of previously unknown heterocyclic architectures. For the preparation of cyclic ethers (Z = O), tricyclic [5,6,5]- through [5,9,5]-systems (m = 1, n = 1-4) are available with the [5,7,5]- and [5,8,5]-systems amenable to quick and efficient synthesis. Tricyclic [5,7,5]- and [5,8,5]-amine-containing (Z = NTs) heterocycles can be successfully prepared. Attempts to make larger ring systems (Z = O, m = 2; Z = O, n = 5; or Z = NTs, n = 4-5) or prepare lactones via Nicholas reactions with carboxylic acid nucleophiles (available via oxidation of alcohol nucleophiles, Z = O) result in decomposition or dimerization. The latter process enables formation of 14-, 16-, and 18-membered ring diolides when using carboxylic acid nucleophiles. We also investigated the use of chiral amine promoters in the Pauson-Khand step but found no asymmetric induction.
Department of Chemistry, Smith College, Northampton, Massachusetts 01063, USA.
Kristina D
KD
Closser
Miriam M
MM
Quintal
Kevin M
KM
Shea
D019281:Dimerization; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000737:chemistry; D009584:Nitrogen / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry*; D013237:Stereoisomerism; D013379:Substrate Specificity
D006575:Heterocyclic Compounds, 3-Ring; D009584:Nitrogen; D010100:Oxygen