Syntheses and resolutions of heterobifunctionalized p-stereogenic phosphines: applications as substrate-bound chiral auxiliaries and ligands in asymmetric reactions
Creators: name: Benoit, Wendy L.
Publisher: name: University of Calgary
Year: 2007

description: Bibliography: p. 252-268
description: Some pages are in colour.
description: P-stereogenic phosphine ligands play an important role m the development of new and effective asymmetric catalysts. A review of the recent literature revealed that P­stereogenic phosphines are challenging synthetic targets, as they do not occur naturally and must therefore be made through asymmetric synthesis. Plans were then devised to test a camphor-derived chiral auxiliary and a spiro-1 ,3-arnino alcohol auxiliary for the asymmetric synthesis of P-stereogenic phosphines for use as ligands in asymmetric catalysis Camphor-derived organoazide [2-(tert-butyl-dirnethyl-si lanyloxy )-7, 7-di??ethyl­bicyclo[2.2. l ]hept- l-yl]-methanesulfony l azide was attached to a heterobifunctionalized racemic P-stereogenic oxazaphospholidine to give a 1: 1 mixture of diastereomeric phosphinimines that were separated by chromatographic methods. The absolute configuration of each phosphorus center was determined by X-ray crystallography. Efforts to remove the chiral auxiliary were unsuccessful. Thus, the introduction of different functional groups at phosphorus were carried out with the auxiliary attached with up to 77% yield of ring-opened product. However, the tedious chromatography and troublesome later steps forced abandonment of the approach in pursuit of more practical methods. A derivative of spiro 1,3-amino alcohol ( 5R,6R)-6-amino-spiro[ 4.4 ]nonan-1-ol was used as a chiral auxiliary to form a heterobifunctionalized P-stereogenic oxazaphosphorinane in a 2.5: 1 mixture of diastereomers. The major diastereomer was isolated from the mixture via recrystallization in a 36% yield and its absolute stereochemistry was found to be Rp by X-ray crystallography. (SR, 6aR, 9aR)-6-Methyl-5-phenyl-decahydro-4-oxa-6-aza-5-phospha-cyclopenta[ d]indene borane was then reacted with various nucleophiles in efforts to develop a general route to P-stereogenic phosphines. The nucleophilic oxazaphosphorinane ring openings were perfom1ed in up to 77% yield, but unfortunately gave a 50:50 mixture of diastereomeric products. The lack of stereoselectivity prompted efforts to be directed toward using deprotected (SR, 6aR, 9aR)-6-methyl-5-phenyl-decahydro-4-oxa-6-aza-5-phospha-cyclopenta[ d]indene borane as a P-stereogenic catalyst precursor. After failed attempts at using (SR, 6aR, 9aR)-6-methyl-5-phenyl-decahydro-4- oxa-6-aza-5-phospha-cyclopenta[ d]indene borane as a P-stereogenic organocatalyst, conditions were developed to remove the borane protecting group and use (SR, 6aR, 9aR)-6-methyl-5-phenyl-decahydro-4-oxa-6-aza-5-phospha-cyclopenta[ d]indene as a P­stereogenic ligand for transition metal catalysis. Poor results from this led to the synthesis of a chelating spiro oxazaphosphorinane derivative. Rhodium-catalyzed hydrogenation of methyl 2-acetamidoacrylate usmg the dimerized sp1ro oxazaphosphinane ligand was performed with up to 15% ee. Extreme sensitivity of the oxazaphosphinane ligands toward oxidation prevented further optimization of the enantioselectivity.