Item – Theses Canada

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OCLC number
63704554
Link(s) to full text
LAC copy
LAC copy
Author
Lait, Susan M.(Susan Margaret),1976-
Title
Synthesis of cis, cis-6-aminospiro(4.4)nonan-1-ol and application of its derivatives as chiral ligands and auxiliaries.
Degree
Ph. D. -- University of Calgary, 2004
Publisher
Ottawa : Library and Archives Canada = Bibliothèque et Archives Canada, [2005]
Description
3 microfiches.
Notes
Includes bibliographical references.
Abstract
A review showed that 1,3-amino-alcohos and their derivatives had proven useful as sources of chiral induction in organic synthesis and that there was much room for research in this area. Of particular interest was a ' cis,cis'-spiro-1,3-amino-alcohol in which two spirocyclic pentacycles offered structural rigidity and the 'cis,cis' geometry of the molecule held the amino and hydroxy moieties in close proximity. A synthesis of (1'RS',5'RS',6'RS ')-6-aminospiro[4.4]nonan-1-ol is reported in which only one diastereomer was produced in 22% yield over 6 steps. The structure of this amino-alcohol was confirmed by X-ray crystallography of the pivalamido-'p'-bromobenzoate derivative. Resolution of this amino-alcohol was achieved by co-crystallization with 0.5 equiv. mandelic acid in acetonitrile to give material that which appeared enantiopure by chiral GC. Conversion of (1'R',5'R',6'R')-6-aminospiro[4.4]nonan-1-ol to (1'R',5'R',6'R')-' N'-(6-hydroxyspiro[4.4]non-1-yl)-2,2-dimethylpropionamide was accomplished in 1 step with 97% yield, and this amido-alcohol was used as a chiral auxiliary in BCl3-catalyzed Diels Alder reactions. Dienophiles were prepared in 1 step, in 74-77% yield, from (1'R',5'R',6' R')-'N'-(6-hydroxyspiro[4.4]non-1-yl)-2,2-dimethylpropionamide, and reaction of these dienophiles with a variety of dienes in the presence of 2 equiv. BCl3 at -78°C gave Diels-Alder adducts with 77 to >98% de. The amido-alcohol auxiliary was readily cleaved from the Diels-Alder adducts by saponification and could be recovered in sufficient quantity and purity to warrant recycling. (1'S',5'S',6'S')-6-Aminospiro[4.4]nonan-1-ol was converted to phosphino-oxazine ligand (3a'S',6a' S',9a'S')-5-(2-diphenylphosphanylphenyl)-1,2,3,3a,6a,7,8,9-octahydro-4-oxa-6-azacyclopenta[d]indene in 90% yield over 2 steps. Its structure was confirmed by X-ray crystallography of the ZnCl2 complex. The phosphino-oxazine was used as a ligand for asymmetric Pd-catalyzed alkylation of dimethyl malonate with 1,3-diphenyl acetate to give product with up to 91% 'ee'.
ISBN
0612977501
9780612977501