(1a; (S,S), R = H); [203399-79-5] · C31H32NO3P · (MW 497.56)
(2a; (S,S), R = Me); [284019-78-9] · C33H36NO3P · (MW 525.62)
(3a; (S,S), R = Ph); [284019-79-0] · C43H40NO3P · (MW 649.76)
(4a; (S,S), R = p-Ph-C6H4); [284019-80-3] · C55H48NO3P · (MW 801.95)
(5a; (S,S), R = 2,4,6-Me3C6H2); [284019-81-4] · C49H52NO3P · (MW 733.92)
(6a; (S,S), R = 3,5-tBu2C6H3); [284019-82-5] · C58H70NO4P · (MW 876.15)
(1b; (R,S), R = H); [203312-03-2] · C31H32NO3P · (MW 497.56)
(2b; (R,S), R = Me); [203312-04-3] · C33H36NO3P · (MW 525.62)
(3b; (R,S), R = Ph); [284019-32-5] · C43H40NO3P · (MW 649.76)
(4b; (R,S), R = p-Ph-C6H4); [284019-33-6] · C55H48NO3P · (MW 801.95)
(5b; (R,S), R = 2,4,6-Me3C6H2); [284019-35-8] · C49H52NO3P · (MW 733.92)
Physical Data: (1a) colorless solid, mp 94 °C, [a]D25 +269 (c 3.10, CHCl3); (1b) colorless solid, [a]D25 -360 (c 0.49, CHCl3); (2a) colorless solid, [a]D25 +339 (c 0.45, CHCl3); (2b) colorless solid, [a]D25 -379 (c 0.92, CHCl3); (3a) colorless solid, mp 121 °C, [a]D20 +312 (c 0.46, CHCl3); (3b) colorless solid, mp 106 °C, [a]D25 -366 (c 0.94, CHCl3); (4a) colorless solid, mp 121 °C, [a]D25 +253 (c 1.19, CHCl3); (4b) colorless solid, mp 125 °C, [a]D25 -301 (c 0.89, CHCl3); (5a) colorless solid, mp 130 °C, [a]D23 +74 (c 1.08, CHCl3); (5b) colorless solid, mp 223 °C, [a]D23 -126 (c 0.52, CHCl3); (6a) colorless solid, mp 113 °C, [a]D23 +164 (c 0.41, CHCl3).
Purification: column chromatography on aluminum oxide (basic). Silica gel can also be used, however, with highly active silica gel, partial hydrolysis of the phosphite was observed.
Solubility: insoluble in H2O; soluble in most organic solvents.
Handling, Storage, and Precautions: phosphite oxazolines of this type are sufficiently stable to be handled in air. For longer periods of time, they should be stored at -20 °C under nitrogen or argon.
Preparative Methods: Preparation of the phosphite-oxazoline ligands and metal complexes: the phosphite-oxazoline ligands are readily prepared in enantiomerically pure form from the BINOL derivative 7 and the oxazoline 8 (
Although a wide range of efficient catalysts are available for enantioselective allylic substitution reactions of substrates such as 9, monosubstituted allylic substrates 10 and 11 generally react predominantly at the unsubstituted allyl terminus with these catalysts, producing achiral products (13) (
Reaction of the palladium complex of ligand 1a with 10a in the presence of N,O-bis(trimethylsilyl)acetamide (BSA), catalytic KOAc as the base, and dimethyl malonate results in good yield and high selectivities for 12a (
Even better regio- and enantioselectivities were observed when 1-naphthyl-substituted allylic acetates (10b and 11b) were used. The regio- and enantioselectivities were essentially the same using either the achiral substrates (10) or the racemic isomers (11) (
There have been several other reports of allylic substitution reactions that proceed with high selectivity for the chiral product 12. Tungsten-phosphinooxazoline complexes give enantioselectivities of up to 96% ee and branched-to-linear ratios of up to 96:4 with aryl-allyl substrates.2 Molybdenum-catalyzed allylic substitution reactions have been reported by Trost and by Pfaltz. Molybdenum complexes with a tetradentate nitrogen ligand (derived from trans-1,2-diaminocyclohexane) gave excellent branched to linear ratios (up to 99:1, generally >20:1) and high enantiomeric excesses (up to 99%) also for aryl-allyl substrates.8 The related bisoxazolines with a trans-1,2-diaminocyclohexane backbone gave branched to linear ratios of 2:1 to 49:1 for a range of aryl- and alkyl-allyl substrates with enantiomeric excesses generally >90%.9 Iridium complexes with phosphoramidite ligands developed by Helmchen are also efficient catalysts, giving branched to linear ratios of up to 99:1 with ees of up to 91%.10
Phosphite-oxazoline copper complexes are highly efficient catalysts for the 1,4-addition of organozinc reagents to 5-, 6- and 7-membered cyclic enones.3,4 Both the chiral oxazoline and the chiral phosphite unit have a significant influence on the enantioselectivity.
The chiral ligands are used in a ligand to copper ratio of 1.2:1 along with 2-3 mol% of Cu(OTf)2 and 1.3 equiv of diethylzinc in toluene, usually for 15 h. All ligands formed catalysts which were highly reactive in the reaction with cycloheptenone (14, n = 3) with enantiomeric excess reaching >80% (
Acyclic substrates were also investigated and promising results were obtained with trans-4-phenylbut-3-en-2-one (
Several other phosphorus ligands produce high enantioselectivities in the 1,4-addition of organozinc reagents. A range of chiral phosphites has been investigated by Alexakis et al. with enantioselectivities of up to 96% for the addition of diethylzinc to cyclohenenone.12 Yan and Chan have used chiral diphosphites and achieved enantiomeric excesses of 89-90% in the addition of diethylzinc to cyclohexenone and cyclopentenone.13 Feringa has developed a range of phosphoramidites for the 1,4-diethylzinc additions.14,15 Enantioselectivities of >98% have been reported for the addition to cyclohexenone and up to 82% for acyclic substrates. Hu et al. have used P,N-ligands derived from binaphthyl, recording enantiomeric excesses of 90% for the addition of diethylzinc to cyclohenanone and 98% for arylsubstituted acyclic enones.16 The best reported method for the addition of a range of dialkylzincs to several different cyclopentenones has been reported by Degrado et al. using peptide-based P,N-ligands.17 Isolated yields were 55-92% with enantioselectivities as high as >98%. The same ligands also gave excellent results (>95% ee) for the addition of dialkylzincs to cylohexenones and cycloheptenones.
Phosphinoxazolines (PHOX ligands),
University of Basel, Basel, Switzerland