Phosphaferrocene- oxazoline

Bidentate phosphaferrocene-oxazoline 7, generated by acylation with the corresponding phos-phaferrocene trifluoroacetate followed by oxazoline formation, has proved to be a highly efficient ligand for asymmetric induction in the copper-catalyzed conjugate addition of diethylzinc to a, (3-... 

A new class of phosphaferrocene-oxazoline ligands has been disclosed by Fu and co-workers30 and applied to the copper-catalyzed asymmetric conjugate addition of diethylzinc to acyclic enones with good enantioselectivity. The substitution pattern on the phosphoryl ring as well as on the oxazoline was shown to have an enormous impact on the selectivity. Ligands 26 and 27, which share the same absolute configuration in the oxazoline, provide the (5)-l,4-adduct preferentially. This observation led to the conclusion that the stereochemistry at the oxazoline, and not the planar... 

On account of their very important biological activity, /9-lactams are important synthetic targets [4-9]. Fused polycyclic -lactam subunits appear in many natural products such as penicillins [4-6] and trinems/tribac-tams [10-13]. Fu et al. reported that such frameworks can be prepared with high levels of enantioselectivity via the intramolecular Kinugasa reaction [ 14, 15] of alkyne-nitrone in the presence of a planar chiral Cu/phosphaferrocene-oxazoline catalyst [16]. For instance, compound 1 was transformed into tricyclic /9-lactam 3 in good stereoselectivity and yielded (88% ee and 74% yield) using 5 mol % of CuBr and 5.5 mol % of complex 2 (Scheme 1). 

Planar chiral phosphaferrocene-oxazolines (379) constitute another family of complexes that are usefiil as ligands in asymmetric catalysis. Preparation of these takes advantage of a modified Friedel-Crafts acylation of (373) and an unusual conversion of the resulting trifluoromethyl ketone into an amide that is then cyclized to an oxazoline. The diastereomeric complexes thus formed are chromatographically separable and are used in a palladium-catalyzed asymmetric allylic substitution. Modification of this complex by using the anion derived from 3,4-dimethyl-2-phenylphosphole gives more... 

Subsequently, better ligands than 44 have been designed for the asymmetric palladium-catalyzed reaction of 1,3-diphenylallyl acetate with sodium mal-onate. Both the bis-(phosphaferrocene) 48 synthesized as shown in Eq. (32) [77] and the phosphaferrocene-oxazolines 49 [78] perform this condensation with much higher ees (79% in the first case and up to 82% in the second case). In the second case, the stereochemical outcome of the reaction is determined by the planar chirality at the phosphaferrocene, rather than the chirality of the oxazo-line [78] ... 

Another type of reaction that has been developed in order to resolve nitrogen-containing compounds is the Diels-Alder cycloaddition. As a rare example, Sibi et al. [235] have recently reported the KR of pyrazohdinones that could not be obtained in high enantioselectivities from direct methods on the basis of a Diels-Alder cycloaddition with cyclopentadiene catalysed by a combination of Cu(OTf)2 with a chiral aminoindanol-derived bisoxazohne hgand. The recovered almost enantiopure (98% ee) substrate was isolated with a selectivity factor of 34. Excellent results were also reported by Fu et al. [236] for the KR of azomethine imines via copper-catalysed [3-1-2] cycloadditions with aUcynes performed in the presence of a chiral phosphaferrocene-oxazoline ligand, which furnished the chiral recovered substrates with high selectivity factors of up to 76, as shown in Scheme 3.15. 

This methodology has been extended to kinetic resolution of azomethine imines (364) bearing a chiral center at the 5-position of the pyrazolidinone ring (Scheme 17.81) [111]. Modification of the chiral ligand to phosphaferrocene-oxazoline (366) proved optimal for kinetic resolution and allowed the catalyst loading to be lowered to 1 mol%. A number of aldehydes used to prepare azomethine imines are well tolerated, and azomethine imines with aryl, heteroaryl, and branched aliphatic substituents in the 5-position are resolved with high enantioselectivity. Unfortunately, kinetic resolution of C4-substituted azomethine imines is not efficient (s < 2). 

Phosphaferrocenes find increasing use as ligands both chiral and achiral for example, a number of new P,N-chelate ligands based on pyridyl-substituted phosphaferrocenes have been prepared—the synthesis uses 2-formyl-3,4-dimethylphosphaferrocene as a precursor. A typical complex is shown as 57. A range of 2-(2 -pyridyl)phosphafer-rocenes have also been prepared and used as ligands an example of which is shown as 58. A number of chiral ligands such as phosphaferrocene-oxazoline ligands have also been prepared and are used in asymmetric catalysis, for example, 59. ... 

---