Alcohols, carbonylation coupling

The alcohol-unsaturate couplings developed in our laboratory provide products of carbonyl addition. In contrast, related hydrogen auto-transfer processes provide products of alcohol substitution via pathways involving oxidation-condensation-reduction and the use of preactivated nucleophiles. For recent reviews, see [22-25]. 

A similar carbonylative coupling reaction was applied to the kinetic resolution of secondary alcohols [63]. In the presence of a Pd catalyst ligated by chiral oxazolinylferrocenylphosphine, the pentavalent Ph3Bi(OAc)2 and carbon monoxide effectively benzoylated secondary alcohols, and up to 48% enantiomeric excess (ee) was attained (Scheme 47). Although the enantioselectivity is not satisfactory, this is a unique new procedure for the kinetic resolution. 

Scheme 47 Kinetic resolution of secondary alcohols by carbonylative coupling reaction of Ph3Bi (OAc)2...

Palladium-catalysed coupling also proceeded readily, carbonylative coupling in the presence of alcohols affording some particularly useful C-3 building blocks (Sect. 4.6) (Eq. 71) [224]. A metal-free method for generation of the trifluoroacetimidoyl carbanion has also been reported involving silic-ate formation and trapping [225]. 

Termination of the autoxidation chain process occurs as peroxyl radicals couple to yield non-radical products. This reaction takes place through an unstable tetroxide intermediate. Primary and secondary tetroxides decompose rapidly by the Russell termination mechanism to yield three non-radical products via a six-membered cyclic transition state (Fig. 95). The decomposition yields the corresponding alcohol, carbonyl compound, and molecular oxygen (often in the higher energy singlet oxygen state) three... 

Mechanistically, alcohol carbonylation reactions catalyzed by the HCo(CO)4/ Co(CO)4 system appear to be governed by several features which are unique to this system. In particular, the high inherent acidity of the HCo(CO)4 species (45), coupled with the nucleophilicity of the conjugate base (55), is responsible for the activation of the substrate and formation of the alkyl-cobalt bond. In addition, the facility of homolytic cleavage of cobalt-carbon bonds (46, 47) may be responsible for the complications in selectivity not normally observed with other systems. 

The hydroxypentanoic acid segment was obtained via metalation and carbonylation of l-silyloxy-3-butyne (141). Conjugate addition of lithium dimethylcuprate followed by reduction provided a 45% yield of allylic alcohol 142. Coupling with alcohol 140 was effected via conversion of 142 to the... 

Chiral oxazolines Stille carbonylative coupling,4 Pd-catalyzed carbonylative coupling of Inflates of ketones and phenols with chiral amino alcohols provides )3-hydroxy amides, which cyclize to chiral oxazolines when treated with thionyl chloride. 

Palladium acyl species can also undergo intramolecular acyl-palladation with alkenes to form five- and six-membered ring y-keto esters through exocyclic alkene insertion (eq 12). The carbonylative coupling of o-iodoaryl alkenyl ketones is also promoted by Pd(dba)2 to give bicyclic and polycyclic quinones through endocyclization followed by /3-H elimination. Sequential carbonylation and intramolecular insertion of propargylic and allylic alcohols provides a route to y-butyrolactones (eq 13). ... 

There has been a review of palladium-catalysed carbonylative coupling reactions of aryl halides with carbon nucleophiles in the presence of carbon monoxide. It has been shown that rhodium is an efficient catalyst for the homocoupling reaction of arylzinc compounds in the presence of 1 atm of carbon monoxide to give diaryl ketones. Under similar conditions, palladium and nickel catalysts yield biaryls. The beneficial catalysis by rhodium is likely to derive from the ease of migration of the aryl ligand to carbon monoxide in the rhodium(III) intermediate. A rhodium catalyst has also been used in the formation of indole-3-carboxylates by reaction of indoles with alcohols in the presence of carbon monoxide. The catalytic cycle. Scheme 5, is likely to involve metallation of the indole at the 3-position, followed... 

A Pd-catalyzed carbonylative coupling reaction of propargyl alcohols and thiols has been developed by using different reaction conditions. Monothioesters, dithioesters, or sulfur-containing furanones can be produced in good to excellent yield and selectivity. This methodology is attractive for the preparation of thioesters and sulfur-substituted... 

HMPA, through which a carbonylative coupling of aUyl and alkyl groups proceeds to provide unsymmetrical ketone and Pd(0) species. On the other hand, in the absence of HMPA, an alkyl-allyl exchange reaction takes place between I and organozinc and gives rise to the mixture of symmetrically substituted dialkylpalladium HI and allylzinc. Car-bonylation of the intermediate HI produces symmetrical ketone and regenerates Pd(0). Allylzinc thus formed is responsible for the formation of the lactones and the homoallyl alcohol in Scheme 26. ... 

This case study highlights the formidable challenge posed by epimerization en route to the synthesis of nonpeptidic fragments of cyclic peptide natural products. (3S,4R,7S)-HTMMD was prepared from (R)-4-methyl-5-valerolactone 74 in nine steps (Scheme 8.6a). After convenient synthesis of aldehyde 77 and its asymmetric aldol condensation with the ketene acetal 79, HTMMD skeleton 80 was isolated as a single isomer. After installation of allyl ester, the alcohol was coupled with Fmoc-Ala-Cl in the presence of DMAP/DIPEA (4-dimethylaminopyridine/diisopropylethylamine) followed by fluorenylmethyloxy-carbonyl (Fmoc) deprotection to afford the ester segment 81b in excellent yield. The amount of DMAP and temperature (—15 °C) were critical to avoid racemiza-tion. Modified Tsunoda s diastereoselective aza-Claisen rearrangement [145] was used as the key step in the 13-step synthesis of N-methylhydroxyisoleucine 86b... 

Moderate yields of acids and ketones can be obtained by paHadium-cataly2ed carbonylation of boronic acids and by carbonylation cross-coupling reactions (272,320,321). In an alternative procedure for the carbonylation reaction, potassium trialkylborohydride ia the presence of a catalytic amount of the free borane is utilized (322). FiaaHy, various tertiary alcohols including hindered and polycycHc stmctures become readily available by oxidation of the organoborane iatermediate produced after migration of three alkyl groups (312,313,323). 

Muzart et al. described the coupling of aryl iodides and bromides with allylic alcohols to give the corresponding (3-arylated carbonyl compounds [87]. Calo et al... 

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