Oxazoline Wacker

In 1997, Uozumi and Hayashi found high enantioselective Wacker-type cycUza-tion of o-allylphenols or o-homoaUylphenols by using Pd(II) catalysts coordinated with chiral bis(oxazoline) ligands based on the 1,1 -binaphthyl backbone (Eq. 6.36)... 

Wacker cyclization has proved to be one of the most versatile methods for functionalization of olefins.58,59 However, asymmetric oxidative reaction with palladium(II) species has received only scant attention. Using chiral ligand 1,1 -binaphthyl-2,2 -bis(oxazoline)-coordinated Pd(II) as the catalyst, high enantioselectivity (up to 97% ee) has been attained in the Wacker-type cyclization of o-alkylphenols (66a-f) (Scheme 8-24). 

Bis(oxazoline) ligands have also been used in Wacker-type cycUzations. " For example, the phenolic derivative 238 was cyclized in the presence of ligand 13b complexed with palladium(ll) to yield the 2,3-dihydrobenzofuran 239 in 86% yield with an ee of 94% (Fig. 9.70). 

A Pd-catalyzed oxidative cyclization of phenols with oxygen as stoichiometric oxidant in the noncoordinating solvent toluene has been developed for the synthesis of dihydrobenzo[ ]furans (Equation 136). Asymmetric variants of this Wacker-type cyclization have been reported by Hayashi and co-workers employing cationic palladium/2,2 -bis(oxazolin-2-yl)-l,l -binaphthyl (boxax) complexes <1998JOC5071>. Stoltz and co-workers have reported ee s of up to 90% when (—)-sparteine is used as a chiral base instead of pyridine <2003AGE2892, 2005JA17778>. Attempts to effect such a heteroatom cyclization with primary alcohols as substrates, on the other hand, led to product mixtures contaminated with aldehydes and alkene isomers, which is in contrast to the reactions with the Pd(ii)/02 system in DMSO <1995TL7749>. 

Uozumi developed polymer-supported 2,2 -bis(oxazolin-2-yl)-l,l -binaphthyls 252 as chiral ligands for the asymmetric Wacker-type cyclization reaction (Scheme 3.81) [152]. In the presence ofthe polymeric catalyst derived from [Pd(MeCN)4](BF4)2] and 252 o-allylphenol, 253 was asymmetrically cychzed to give 254 in 46% yield with 95% ee. 

One of the exciting developments of the Wacker-type oxidation is the asymmetric synthesis of the reaction. For instance, using a new chiral bis(oxazoline) ligand L = 3,3 -Disubstituted 2,2 -bis(oxazolyl)-l,r-binaphthyls (boxax), a catalytic asymmetric Wacker -type cyclization converted allyl-phenol 55 to dihydrofuran 74 with 67% ee.ss... 

Allylpalladium complexes with BOX-type ligands and glucopyrano-oxazoline-palladium catalysts were used as catalysts for enantioselective allylic substitution (277). A chiral bisoxazoline ligand (BOXBZ) developed by Pfaltz has been used for asymmetric carbo- and heteroannulation reactions (278). An axial binaphthyl-based ligand possessing oxazolyl substituents (BOXAX) was developed by Hayashi and co-workers and successfully applied for the asymmetric Wacker-type cyclization (279). 

However, Stahl et al. [41] could show that, with the structurally weU-defined pyridinyl oxazoline ligand 34, enantioselective aerobic amidation of alkenes can be achieved for a series of pyrrolidine-forming reactions to 36 from aminoalkenes 35 with up to 98% ee (Scheme 16.8). This regular high enantioselectivity is noteworthy and shows that general enantioselective aza-Wacker chemistry should be a feasible process. 

Michel BW, Steffens LD, Sigman MS (2011) On the mechanism of the palladium-catalyzed tert-butylhydroperoxide-mediated wacker-type oxidation of alkenes using quinoline-2-oxazoline ligands. J Am Chem Soc 133(21) 8317-8325... 

In contrast with the impressive evolution of asymmetric reactions with paUadium(0) catalyst, palladium(II)-catalyzed asymmetric Wacker-type oxidations have received only scant attention. For instance, Alper and Hamel and Cao and Zhang described asymmetric Pd(II)-catalyzed car-bonylation of aUyUc alcohols. Chiral bis(oxazolines) based on binaphtyl (Boxaxs ) or biphenyl backbone were also successfiiUy applied in the asymmetric Wacker-type cycUzation of aUylphenoIs. Sasai and co-workers reported on the oxidative cychzation of alkenyl alcohols with spiro bis(isoxazolines) (SPRIXs). ... 

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