Wacker stereoselective

Stereoselective aldol condensation. 2-Butenyllilhium (1) reacts with aldehydes to form the threo- and erythro-fl-methyl alcohol in equal amounts. However, if a trialkylboranc is present, r/ireo-products predominate. Presumably an allylboronate complex (a) is involved.1 An example is formulated in equation (1). The products are converted into 0-hydroxy ketones (4) by a Wacker-type oxidation.2... 

Acetals result from oxidative coupling of alcohols with electron-poor terminal olefins followed by a second, redox-neutral addition of alcohol [11-13]. Acrylonitrile (41) is converted to 3,3-dimethoxypropionitrile (42), an intermediate in the industrial synthesis of thiamin (vitamin Bl), by use of an alkyl nitrite oxidant [57]. A stereoselective acetalization was performed with methacrylates 43 to yield 44 with variable de [58]. Rare examples of intermolecular acetalization with nonactivated olefins are observed with chelating allyl and homoallyl amines and thioethers (45, give acetals 46) [46]. As opposed to intermolecular acetalizations, the intramolecular variety do not require activated olefins, but a suitable spatial relationship of hydroxy groups and the alkene[13]. Thus, Wacker oxidation of enediol 47 gave bicyclic acetal 48 as a precursor of a fluorinated analogue of the pheromone fron-talin[59]. 

Given this problem, the attachment of the butanone synthon to aldehyde 74 prior to the methyl ketone aldol reaction was then addressed. To ovenide the unexpected. vTface preference of aldehyde 74, a chiral reagent was required and an asymmetric. syn crotylboration followed by Wacker oxidation proved effective for generating methyl ketone 87. Based on the previous results, it was considered unlikely that a boron enolate would now add selectively to aldehyde 73. However, a Mukaiyama aldol reaction should favour the desired isomer based on induction from the aldehyde partner. In practice, reaction of the silyl enol ether derived from 87 with aldehyde 73, in the presence of BF3-OEt2, afforded the required Felkin adduct 88 with >97%ds (Scheme 9-29). This provides an excellent example of a stereoselective Mukaiyama aldol reaction uniting a complex ketone and aldehyde, and this key step then enabled the successful first synthesis of swinholide A. 

Introduction Chemo-, Regio-, and Stereoselectivity Chemoselectivity Controlling Chemoselectivity Regioselectivity Markovnikov Hydration Mercuration-reduction Wacker oxidation... 

An illustration that demonstrates stereoselectivity as well comes in Ikegama s synthesis of coriolin.12 Allylation of the sodium enolate of cyclopentanone 77 gives one diastereoisomer of the precursor 78 for a Wacker oxidation and cyclisation to give the tricyclic intermediate 79. 

For the stereoselective synthesis of C-glycosides, deoxygenation of hemiketals, obtained from Wacker oxidation of sngar-derived olefin alcohols, was envisaged as an easy and efficient protocol. In our earlier study on the synthesis of 4-epiethisolide, attempted PdCV mediated conversion of the terminal olefin (1), obtained from sugar chiron into a methyl ketone (2) resulted in the exclnsive formation of an anti-Markovnikov product (3), which happened to be the first report in the literature (Scheme 22.1). 

In 2008, Tietze et al. [466] reported on the stereoselective synthesis of 4-dehydroxydiversonol (413) utilizing pathways involving both Pd-catalyzed domino-Wacker-Heck and domino-Wacker-carbonylation reactions. The Wacker-Heck substrate 410 was treated with methyl acrylate in the presence of Pd ditriflate and the (S,S)-Bn-BOXAX ligand 411 along with p-benzoquinone (as a catalyst reoxidant), giving the chromane 412 with 80% ee in 55% yield (Scheme 8.82). 

An efficient method to prepare l /f-spiro-[indoline-3,3 -quinoline]-2, 4 -diones and their trifluoromethylated products was developed hy Wang and co-workers in 2014. The reaction proceeds via a palladium-catalyzed Sono-gashira coupling-Wacker-type ojqqjalladation-cyclization cascade reaction sequence. The amount of water in the reaction system played an important role in the in situ trifluoromethylation reaction, and the trifluoromethylation exhibited excellent molecular self-induced stereoselectivity. 

A somewhat related intramolecular oxy-carbopaUadation reaction described for a series of hydroxy 5mones 86 leads to a vinylpaUadium intermediate that cannot undergo p-elimination and adds onto ethyl acrylate 87 (foUowing a Pd(II)-catalyzed cascade Wacker-Heck reaction) to afford, stereoselectively, dihydropyranones 88 (Scheme 44) [79]. 

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