Development of P-stereogenic 2-phenyl-1,3,2-oxazaphosphorine ligands and their unexpected sensitivity to oxidation

P-Stereogenic oxazaphosphorine compounds of the form 4 have not previously been reported as asymmetric ligands for metal-catalyzed reactions. In an effort to explore the behavior of such oxazaphosphorine ligands, monomeric oxazaphosphorine borane 9 and dimeric oxazaphosphorine boranes 25 and 26 were synthesized as catalyst precursors. The absolute configuration of the phosphorus center contained in the oxazaphosphorines was determined by X-ray crystallography. Rhodium-catalyzed hydrogenation of methyl 2-acetamidoacrylate using a dimerized spiro oxazaphosphorine ligand was performed with up to 15% ee. The extreme sensitivity of the oxazaphosphorine ligands toward oxidation prevented further optimization of the enantioselectivity.

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(1R,5R,6R)-6-Methylamino-spiro[4.4]nonan-1-olC10H19NOEe = >98%[α]D20=-9.6 (c 0.4, CHCl3)Source of chirality: derivative of (1R,5R,6R)-aminospiro[4.4]nonan-1-olAbsolute configuration: (1R,5R,6R)

(Sp)-(3aR,6aR,9aR)-6-Methyl-5-phenyl-1,2,3,3a,5,6,6a,7,8,9-decahydro-4-oxa-6-aza-5-phosphacyclopenta-[d]indene boraneC16H25BNOPEe = >98%[α]D23=+27.1 (c 7.0, CHCl3)Source of chirality: derivative of (1R,5R,6R)-aminospiro[4.4]nonan-1-olAbsolute configuration: (Sp)-(3aR,6aR,9aR)(Sp)-confirmed by X-ray crystal structure

(Sp)-(3aR,6aR,9aR)-5-Phenyl-1,2,3,3a,5,6,6a,7,8,9-decahydro-4-oxa-6-aza-5-phosphacyclopenta[d]-indene boraneC15H23BNOPEe = >98%[α]D20=+11.75 (c 0.4, CHCl3)Source of chirality: derivative of (1R,5R,6R)-aminospiro[4.4]nonan-1-olAbsolute configuration: (Sp)-(3aR,6aR,9aR)

Rp-(3aR,6aR,9aR)-5-Phenyl-1,2,3,3a,5,6,6a,7,8,9-decahydro-4-oxa-6-aza-5-phosphacyclopenta-[d]indene boraneC15H23BNOPEe = >98%[α]D20=-2.6 (c 0.4, CHCl3)Source of chirality: derivative of 1R,5R,6R-aminospiro[4.4]nonan-1-olAbsolute configuration: (Rp)-(3aR,6aR,9aR)

(Sp)-Bis[(3aR,6aR,9aR)-6-methyl-5-phenyl-1,2,3,3a,5,6,6a,7,8,9-decahydro-4-oxa-6-aza-5-phospha-cyclopenta[d]indene borane] methaneC31H46B2N2O2P2Ee = >98%[α]D20=-54.5 (c 0.5, CHCl3)Source of chirality: derivative of (1R,5R,6R)-aminospiro[4.4]nonan-1-olAbsolute configuration: (Sp)-(3aR,6aR,9aR)(Sp)-confirmed by X-ray crystal structure

(Rp)-Bis[(3aR,6aR,9aR)-6-methyl-5-phenyl-1,2,3,3a,5,6,6a,7,8,9-decahydro-4-oxa-6-aza-5-phospha-cyclopenta[d]indene borane] methaneC31H46B2N2O2P2Ee = >98%[α]D20=-19.1 (c 1.1, CHCl3)Source of chirality: derivative of (1R,5R,6R)-aminospiro[4.4]nonan-1-olAbsolute configuration: (Rp)-(3aR,6aR,9aR) confirmed by X-ray crystal structure