Alcohols, carbonylation coupling with

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... 

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... 

One of the most gentle methods for the generation of reactive allylmetallic reagents was introduced in 1977 by Hiyama and Nozaki1,2,3,33. By the action of two equivalents of chromi-um(II) chloride on allylic halides in tetrahydrofuran at 0°C in the presence of a carbonyl compound, reductive coupling with the formation of a homoallylic alcohol takes place. 

Monometallic ruthenium, bimetallic cobalt-ruthenium and rhodium-ruthenium catalysts coupled with iodide promoters have been recognized as the most active and selective systems for the hydrogenation steps of homologation processes (carbonylation + hydrogenation) of oxygenated substrates alcohols, ethers, esters and carboxylic acids (1,2). 

Coupling of carbonyl compounds with alkenes.6 In the presence of Sml2, aldehydes and ketones couple with electron-deficient alkenes to form y-lactones. An alcohol functions as the essential proton donor. 

As already mentioned, it is the volatile constituents that serve to identify fruit type and variety. Broadly speaking, qualitative analysis will identify the principal substances present in the volatiles fraction as representative of a particular fruit type, but it is the relative proportions of these substances that will reflect the variety. Alcohols, volatile acids, esters, carbonyl compounds, and low-boiling hydrocarbons are the principal groups represented. Analysis by GC-MS (gas chromatography coupled with mass spectroscopy) can be used to provide quantification and identification of the various constituents. 

Reductive coupling of dialdehydes may also be accomplished by use of samarium(II) iodide514. The reactions is stereoselective and has been used to prepare myo-inositol derivatives (equation 132)515. The equivalent reaction, using low-valent titanium species as catalysts, results in a mixture of products516. The production of cyclic /1-amino alcohols may be accomplished in good yields, and with a high degree of cis selectivity by the treatment of carbonyl hydrazones with samarium(II) iodide (equation 133)517. This reaction is effectively equivalent to an aza-Barbier reaction. 

Indium-mediated Barbier-type coupling between carbonyl compounds and allyl halides has been revealed to proceed effectively in diverse reaction media. Even under solvent-free conditions, allylation works well, although no reaction is observed with benzyl bromide and a-halo carbonyl compounds.59 Various aldehydes react with allyl bromide mediated by indium in liquid carbon dioxide to give homoallylic alcohols (Scheme 1). In contrast to the corresponding neat allylation, the liquid C02-mediated reaction can allylate solid aldehydes successfully.60 Indium-mediated allylations of carbonyl compounds with allyl bromide proceed in room temperature ionic liquids. In [bmim][BF4] and [bmim][PF6] (bmin l-butyl-3-methylimidazolium), the desired homoallylic alcohols are formed with good levels of conversion.61 Homoallyllic alcohols are also prepared by the reaction of resin-bound aldehydes (Equation (l)).62... 

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. 

In certain cases, the selective protection of the closely similar sites offers an opportunity to achieve a reversal in selectivity from a common precursor. Thus, the monoketal derivative 228 (Scheme 2.94) can easily be prepared from the respective diketone owing to the steric shielding of the C-17 carbonyl. The opportunity, now, to reduce the non-protected carbonyl in 228 to form alcohol 229 should not be a surprise. However, it is truly remarkable that a selective reduction can also be achieved at the C-3 protected carbonyl. This paradoxical result is due to the utilization of the reagent H2Sil2, which selectively attacks the ketal moiety and induces its removal coupled with a reduction to form the iodo derivative 230. A successful and nearly quantitative reductive conversion at either C-17 or at C-3 is achieved in this manner. In this example, the protected carbonyl functionality served as a non-conventional functional group with a pattern of reactivity sharply differing from that of the unprotected group,... 

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