Asymmetric Wacker cyclization

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). 

Trend, R. M., Ramtohul, Y. K., Ferreira, E. M., Stoltz, B. M. Palladium-catalyzed oxidative Wacker cyclizations in nonpolar organic solvents with molecular oxygen A stepping stone to asymmetric aerobic cyclizations. Angew. Chem., Int. Ed. Engl. 2003,42, 2892-2895. 

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. 

In 2003, Stoltz at CalTech described a palladium-catalyzed oxidative Wacker cyclization of o-allylphenols such as 55 in nonpolar organic solvents with molecular oxygen to afford dihydrobenzofurans such as 56.44 Interestingly, when (-)-sparteine was used in place of pyridine, dihydrobenzofuran 56 was produced asymmetrically. The ee reached 90% when Ca(OH)2 was added as an additive. Stoltz considered it a stepping stone to asymmetric aerobic cyclizations. In 2004, Mufiiz carried out aerobic, intramolecular Wacker-type cyclization reactions similar to 55—>56 using palladium-carbene catalysts.45 Hiyashi et al. investigated the stereochemistry at the oxypalladation step in the Wacker-type oxidative cyclization of an o-allylphenol. Like o-allylphenol, o-allylbenzoic acid 57 underwent the Wacker-type oxidative cyclization to afford lactone 58.47... 

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... 

Complexes 24, 25, and 26 aU possess two neutral and two anionic ligands, respectively, and they are included in this section although they do not have halide ligands. Each of C2-symmetric bisoxazoline complexes 24 and 25 has two tiifluoroacetate ligands and is a good catalyst for asymmetric Wacker-type cyclization. Complex 26, applied to the asymmetric Fujiwara-Moritani reaction, is a rare example of having anionic chelate... 

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). 

Uozumi Y, Kato K, Hayashi T. Catalytic asymmetric Wacker-type cyclization. 7. Am. Chem. Soc. 1997 119 5063-5064. 

Hosokawa T, Uno T, Inui S, Murahashi S-I. Palladium (II)-catalyzed asymmetric oxidative cyclization of 2-aUylphenols in the presence of copper(II) acetate and molecular oxygen. Study of the atCalysis of the Wacker-t) pe oxidation. J. Am. Chem. Soc. 1981 103 2318-2323. 

Aral MA, Kuraishi M, Aral T, Sasai H. A New asymmetric Wacker-type cyclization and tandem cyclization promoted by Pd(II)-spiro bis(isoxazoline) catalyst. J. Am. Chem. Soc. 2001 123 2907-2908. 

The asymmetric Wacker-type cyclization of phenolic olefins (93) using the chiral tetraoxazoline ligand (95) has been developed the resulting pyran derivatives (94) were obtained in <92% ee. ... 

Uemura s discovery also opened the door to direct 02-coupled asymmetric catalytic oxidative kinetic resolution (OKR) of alcohols with catalytic amounts of chiral ligands. Simultaneously both Stoltz and Sigman reported the aerobic OKR of secondary alcohols using catalytic Pd[(-)-sparteine]Q2 with the addition of catalytic (-)sparteine, 36 (Scheme 5.18E) [66]. Mechanistic studies on this system performed by Sigman and coworkers have found the chiral amine to have a dual role as a hgand and an exogenous base [66e,hj. This system has been further apphed to asymmetric Wacker-type cyclizations [2 c, 22a,bj. 

It is of particular value from a synthetic viewpoint that, under Wacker-type conditions the cyclization is catalytic [Pd(OAc)2/Cu(OAc)2/MeOH,H20/ air/55°C]121 albeit not by a Wacker-type mechanism.123 Addition of the chiral alkene, (- )-/l-pinene, to the catalyzed cyclization of 2-(but-2-enyl)phenol causes asymmetric induction with an optical yield of 12%... 

Asymmetric induction has also been achieved in the cyclization of aliphatic alcohol substrates where the catalyst derived from a spirocyclic ligand differentiates enantiotopic alcohols and alkenes (Equation (114)).416 The catalyst system derived from Pd(TFA)2 and (—)-sparteine has recently been reported for a similar cyclization process (Equation (115)).417 In contrast to the previous cases, molecular oxygen was used as the stoichiometric oxidant, thereby eliminating the reliance on other co-oxidants such as GuCl or/>-benzoquinone. Additional aerobic Wacker-type cyclizations have also been reported employing a Pd(n) system supported by A-heterocyclic carbene (NHC) ligands.401,418... 

In fact, the role of copper and oxygen in the Wacker Process is certainly more complicated than indicated in equations (151) and (152) and in Scheme 10, and could be similar to that previously discussed for the rhodium/copper-catalyzed ketonization of terminal alkenes. Hosokawa and coworkers have recently studied the Wacker-type asymmetric intramolecular oxidative cyclization of irons-2-(2-butenyl)phenol (132) by 02 in the presence of (+)-(3,2,10-i -pinene)palladium(II) acetate (133) and Cu(OAc)2 (equation 156).413 It has been shown that the chiral pinanyl ligand is retained by palladium throughout the reaction, and therefore it is suggested that the active catalyst consists of copper and palladium linked by an acetate bridge. The role of copper would be to act as an oxygen carrier capable of rapidly reoxidizing palladium hydride into a hydroperoxide species (equation 157).413 Such a process is also likely to occur in the palladium-catalyzed acetoxylation of alkenes (see Section 61.3.4.3). 

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>. 

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