Methyl esters, reductive carbonylation

Scheme 12.19 illustrates some cases in which ozonolysis reactions have been used in the course of syntheses. Entries 1 to 4 are examples of use of ozonolysis to introduce carbonyl groups under reductive workup. Entries 5 and 6 involve oxidative workup and give dicarboxylic acid products. The reaction in Entry 7 is an example of direct generation of a methyl ester by methoxide trapping. 

Acetaldehyde Production by Reductive Carbonylation of Methanol, Methyl Ketals, and Methyl Esters... 

Acetaldehyde is obtained from the reaction of synthesis gas with methanol, methyl ketals or methyl esters. The reactions are carried out with an iodide-promoted Co catalyst at 180-200 °C and 2000-5000 psig. In comparing the various feedstocks, the best overall process to make acetaldehyde involves the reductive carbonylation of methyl esters. In this case, acetaldehyde selec-tivities are > 95% ut acceptable rates and conversion. 

Me have studied the Co-I-PPh catalyzed reductive carbonylation of methanol, dimethyl ketalsf dimethyl carbonate and methyl esters ( 10 JL5 >2 ) 0 goal was to achieve high acetaldehyde... 

Reductive Carbonylation of Methyl Esters. The best alternative, and in our opinion, the best reported synthesis gas based process to produce acetaldehyde, is the reductive carbonylation of methyl esters. Equation 15 (16). 

A practicable strategy to provide access to chiral pyrazolidine-3-carboxylic acid (16) makes use of asymmetric dipolar cycloaddition of diazoalkanes to u,p-unsaturated carboxylic acid derivatives. For this purpose a chiral auxiliary of the alkene component is used, e.g. Op-polzer s1166 1671 (lf )-2,10-camphorsultam.t164l As shown in Scheme 7, by reaction of (tri-methylsilyl)diazomethane (41) with /V-( aery I oy I )cam p h ors u 11 am (42), the AL(4,5-dihy-dropyrazoline-5-carbonyl)camphorsultam (43) is obtained. Reduction of 44 with sodium cyanoborohydride leads to A-(pyrazolidine-3-carbonyl)camphorsultam (45) as the 35-dia-stereoisomer (ee 9 1) in 65 to 80% yields.[164] The camphorsultam 45 is then converted into the methyl ester 46 by reaction with magnesium methylate without racemizationj1641... 

Rhodium(II) acetate catalyzes C—H insertion, olefin addition, heteroatom-H insertion, and ylide formation of a-diazocarbonyls via a rhodium carbenoid species (144—147). Intramolecular cyclopentane formation via C—H insertion occurs with retention of stereochemistry (143). Chiral rhodium (TT) carboxamides catalyze enantioselective cyclopropanation and intramolecular C—N insertions of CC-diazoketones (148). Other reactions catalyzed by rhodium complexes include double-bond migration (140), hydrogenation of aromatic aldehydes and ketones to hydrocarbons (150), homologation of esters (151), carbonylation of formaldehyde (152) and amines (140), reductive carbonylation of dimethyl ether or methyl acetate to 1,1-diacetoxy ethane (153), decarbonylation of aldehydes (140), water gas shift reaction (69,154), C—C skeletal rearrangements (132,140), oxidation of olefins to ketones (155) and aldehydes (156), and oxidation of substituted anthracenes to anthraquinones (157). Rhodium-catalyzed hydrosilation of olefins, alkynes, carbonyls, alcohols, and imines is facile and may also be accomplished enantioselectively (140). Rhodium complexes are moderately active alkene and alkyne polymerization catalysts (140). In some cases polymer-supported versions of homogeneous rhodium catalysts have improved activity, compared to their homogenous counterparts. This is the case for the conversion of alkenes direcdy to alcohols under oxo conditions by rhodium—amine polymer catalysts... 

Chemoselective reduction of methyl ester 7 to aldehyde 2 is possible with DIB AH. The metallatcd hemiacetal that results from addition of DIBAII to the carbonyl group of ail ester usually decomposes rapidly in polar solvents like THF to an intermediate aldehyde This then competes with the ester and, as a result of its higher clcctrophilicity. js reduced by DIBAH to an alcohol. However, ester 7 bears a methoxymethyl residue in its a-position, which stabilizes the metallated hemiacetal by chelate formation. Chelate complex 22 is protolytically cleaved by way of the hemiacetal only in the course of aqueous workup, so in this case the DIBAH reaction produces only aldehyde 2, not the alcohol (see also Chapter 3), DIBAH, THF, -78 C 100. ... 

Reduction of the carbonyl group at C-15 and liberation of the hydroxy group at C-ll give a mixture of dl-PGE2- and dl-epi-PGE methoxime methyl ester which could be separated chromatographically. However, the authors did not succeed in cleaving the methoxime group127). 

Preparative Methods reaction of Phenylmagnesium Bromide with (S)-N-[(benzyloxy)carbonyl]proline methyl ester and subsequent reduction with Lithium Aluminum Hydride affords the title compound in 83% overall yield. 

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