Ligand synthesis Wacker oxidation

This domino Wacker-Heck reaction is the key step of this total synthesis. In the presence of catalytic amounts of Pd(OTFA)2, the chiral ligand (S,S)-Bn-BOXAX (5) and j -benzoquinone (13) as reoxidant, phenol 19 first undergoes an intramolecular enantioselective Wacker oxidation and then reacts with methyl vinyl ketone (9) in a Heck reaction to afford chroman 22 with part of the vitamin E side chain in 84 % yield with 97 % ee. 

The Wacker oxidation [146], amongst other nucleophilic additions to alkenes, is the most important reaction based on a palladium(II) catalysis. It is also used industrially for the synthesis of acetaldehyde from ethene and water. This oxidative process has been combined with a Mizoroki-Heck reaction by Tietze and coworkers [13] for an enantioselective total synthesis of vitamin E (293) [147] using BOXAX ligand 291 [148]. In this way the chromane ring and parts of the side chain of vitamin E (293) can be introduced in one... 

The studies described in the last section provided the background for the development of a new asymmetric chlorohydrin synthesis. If the neutral ligand that encourages chlorohy-drin formation is made chiral, there is the possibility of forming chiral chlorohydrins. First, pyridine was replaced with chiral monodentate ligands such as (5)-(-)-Af, Af-dimethyl-l-phenethylamine.f f Scheme 23 shows the general reaction sequence. As might be expected the enantioselectivities were low 10-15% for propene. The Wacker oxidation product, acetone, was a side product in the reaction. 

In Leighton s total synthesis of dolabelide D, the Wacker-Tsuji oxidation diene 70 was achieved chemoselectively to produce methyl ketone 71.54 55 Furthermore, addition of (-)-sparteine as a ligand prevented olefin isomerization and led to selective formation of methyl ketone 71 from the terminal olefin in good yield.56... 

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... 

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