SPRIX ligands

In all these enantioselective cyclization reactions, SPRIX ligands were shown to be significantly superior to all other standard bidentate ligands. SPRIX ligands have made additional contributions to the field of palladium oxidation catalysis [25]. 

Later on, Hamed s group explored another desymmetrization method based on a Pd-catalyzed acetoxylation-cyclization of 45 -type alkyne-tethered cyclohexa-2,5-dienones 75, which were generated by a DIB- or BTI-mediated dearomatization of para-substituted phenols 51 in the presence of propargyl alcohol or but-2-yn-l-ol as solvent (Fig. 20). The control of stereoselectivity of the Pd-catalyzed cycUzatiOTi event was brought by the use of the pinene-derived bipyridine ligand 76, but enantiomeric excesses of only up to 62% could be obtained for the formation of the bicycles 77 [68]. An extension of this exploratory work was later reported by Sasai and co-workers, who used their SPRIX ligand 78 under oxidative conditions to generate a-acetoxylated variants of 77 (i.e., 79) with ee values up to 82% (Fig. 20) [69]. 

Isoxazoline rings include two heteroatoms which could serve as Lewis bases. Chiral spiro bis(isoxazoline) ligands, named SPRIXs, bearing a chiral spiro skeleton and two isoxazoline rings, have been reported <19990L1795>. 

In 2011, Sasai and co-workers developed an asymmetric oxidative cyeliza-tion of 4-alkenoic acids in good yields and moderate ees (Scheme 5.16). The utilization of the spiro bis(isoxazoline) ligand (M,5,5)- Pr-SPRIX was crucial for this asymmetric transformation. Preliminary mechanistic investigation showed that a [(n-allyl)Pd] intermediate was involved in the reaction. This represents the first example of enantioselective oxidation of allylic C—H bonds by using only a chiral palladium catalyst. 

An oxidative cyclization of 4-alkenoic acids (37) has been developed. The reaction occurs in the presence of p-benzoquinone as oxidant and is believed to proceed via the TT-allyl Pd intermediate (38), generated by an allylic C—H activation. Moderate to good enantioselectivity was observed when the spiro bis(isoxazoline) ligand (SPRIX) (39) was employed. ... 

Moreover, the unique structural properties of spirocyclic compounds inspired the design of new ligands and catalysts such as spirobisoxazolines (8), SPINOL (9), SPRIX (10), SPINOL-derived phosphoric acids (11), and spirOP (12) with excellent catalytic activities (Figure 10.2) [2]. 

The reactions were performed in the presence of a series of different substituted chiral spiro bis(isoxazoline) ligands (SPRIX), Pd(II), and benzoquinone. The best results (53% ee), obtained under catalytic conditions, employ 30% mol Pd (0C0CF3)2/(M,S,S)-H-SPRIX 72, 4 equiv. of benzoquinone at —20°C under CO (1 atm) in methanol. 

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