Alcohols oxycarbonylation

It has been reported that tertiary amines (as additives or as the solvent) lead to increased yields when etherifying tyrosine derivatives with polystyrene-bound benzyl alcohols [175]. Nevertheless, other phenols react smoothly without the addition of a base [47,176], When only a slight excess of phenol is used for the etherification of support-bound alcohols, AyV -bi s (eth oxycarbonyl)hydrazi n e (the by-product of the Mit-sunobu reaction) can compete with the phenol to a significant extent and become attached to the support. This reaction can be suppressed by the use of a greater excess of phenol [168]. 

The oxycarbonylation of propene under the same conditions results in the formation of crotonic acid as the major product instead of the more valuable methacrylic acid.439 When the oxycarbonylation of ethylene or terminal alkenes is carried out in anhydrous alcoholic solvents instead of acetic acid, dialkyl succinates and /3-alkoxy esters are the major products (equation 173).441,442... 

The synthesis of dialkyl oxalates by oxycarbonylation of alcohols in the presence of a dehydrating agent and a Wacker catalyst was first reported by Fenton in 1968 (equation 177).378,449 As for the previous oxycarbonylations, the presence of water is a strong inhibitor of the reaction and favors the side-formation of C02 (equation 178). Dehydrating agents such as triethyl orthoformate or boric anhydride are necessary to prevent water formation and subsequent deactivation of the... 

Substituents are given before the name of the diradical. Poly(vinyl alcohol) is thus correctly called poly(hydroxyethylene) (Example 9) and poly(methyl methacrylate) is called, according to lUPAC, poly[(l-meth-oxycarbonyl)- -methyl ethylene] (Example 10). 

Intramolecular reaction of allenes is known to proceed mainly by palladation at the central carbon to generate alkenylpalladium 235, which undergoes further reactions. Also TT-allylpalladium 236 is formed when a nucleophile attacks the central carbon. The intramolecular aminopalladation of the 6-aminoallene 237, followed by CO insertion, afforded the unsaturated amino ester 238. The reaction has been applied to the enantioselective synthesis of pumiliotoxin [103]. Oxycarbonylation of the allenyl alcohol 239 afforded the unsaturated ester 240 in 83 % yield using a catalytic amount of PdCl2 and 3 equivalents of CuCb in MeOH and is used for the synthesis of rhopaloic acid [104]. 

Another example of a regiodivergent qrdiTation of a racemic substrate is shown in Scheme 6.30 [51]. Racemic 140 was treated with Pd in the presence of chiral hgand 141, and the crude reaction mixture was oxidized using Dess-Martin periodinane (DMP) to form the bicychc products 143 (42% ee) and 144 (95% ee). Formation of the initial cydized product 142 is beheved to occur via the hemiacetal resulting from reversible addition of isopentanol to the ketone, followed by internal oxycarbonylation of the alkyne. Lower enantiomeric purity in 144 was observed when less bulky alcohols were used in place of the isopentanol. In contrast, the product 143 does not incorporate the alcohol and htde variation in enantiomeric excess was observed using different alcohols. 

The palladium(II)-catalyzed olefin carbonylation reaction was first reported more than 30 years ago in studies by Stille and co-workers and James et al. The reaction of carbon monoxide with cis- and tra 5-but-2-ene in methanol in the presence of palladium(II)-chloride and copper(II)-chloride yielded threo- and eryt/zro-3-methoxy-2-methyl-butanoate, respectively. The transformation that was based on the well-known Wacker process for oxidation of ethylene into acetaldehyde in water " is now broadly defined as the Pd(II)-catalyzed oxycarbonylation of the unsaturated carbon-carbon bonds. This domino reaction includes oxypalladation of alkenes, migratory insertion of carbon monoxide, and alkoxylation. Since the development of this process, several transformations mediated by palladium(II) compounds have been described. The direct oxidative bisfunctionalization of alkenes represents a powerful transformation in the field of chemical synthesis. Palladium(II)-promoted carbonylation of alkenes in the presence of water/alcohol may lead to alkyl carboxylic acids (hydrocarboxylation), diesters [bis(aIkoxycarbonyla-tion)], (3-alkoxy carboxylic acids (alkoxy-carboxylation), or (3-alkoxy esters (alkoxy-carbonylation or alkoxy-alkoxy-carbonylation). Particularly attractive features of these multitransformation processes include the following ... 

Boukouvalas and co-workers employed an intramolecular oxycarbonylation of benzyl alcohol 89 in the asymmetric synthesis of (—)-panacene, tetrahydrofuroben-zofuran derivative, which holds the prominent position of being the archetypical member of a family of marine bro-moallenes. ° The synthesis of the panacene building block 89 (Scheme 15.22) starts from the aldehyde 87, which is accessed from commercially available 2-methoxy-6-metyl-benzoic acid. An asymmetric alkynylation of 87 followed by reduction of the triple bond with hydrogen over Lindlar... 

The initial successes in the preceding section triggered several intensive studies in this area, which have not only made the Pd-oxycarbonylation chemistry synthetically usefiil and versatile but have also remitted the surprisingly intricate relationships between the chemistry of an a-allylic alcohols... 

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