Methyl carbonylation

The unstable CH TiCl [12747-38-8] from (CH3 )2 2n + TiCl forms stable complexes with such donors as (CH2)2NCH2CH2N(CH2)2, THF, and sparteine, which methylate carbonyl groups stereoselectively. They give 80% of the isomer shown and 20% of the diastereomer this is considerably more selective than the mote active CH MgBt (201). Such complexes or CH2Ti(OC2H2 methylate tertiary halides or ethers (202) as follows ... 

Rather limited information is available on how the nature of R affects the rate of CO insertion, all other factors being constant. A generalization that ethylmetal complexes react faster than the corresponding methyl carbonyls derives from investigations on four systems RIr(CO)2(AsPh3)Cl2 (92), RMn(CO)5 (51), CpFe(CO)2R (98), and CpMo(CO)jR (80). When R = Et the reactions with CO or P and As donor ligands proceed at least 6 times faster than when R = Me. 

Evidence was shown for migration of an alkyl group in carbonyl insertion, and deinsertion steps between the methyl carbonyl rhodium complex [ r/Vi/ -Indenyl-l -(CH2)3PPh2 Rh(CO)-Me](BF4) and the acetyl rhodium complex [ r/5 r/l-(Indenyl-l -(Cl I2)3PPh2) RhI(COMe)] by crystallography as well as by 1H NMR spectroscopy.28... 

Fig. 9.8 presents another, more complex type of phosphate prodrugs, namely (phosphoryloxy)methyl carbonates and carbamates (9-26, X = O or NH, resp.) [84], Here, the [(phosphoryloxy)methyl]carbonyl carrier appears quite versatile and of potential interest to prepare prodrugs of alcohols, phenols, and amines. The cascade of reactions leading from prodrug to drug as shown in Fig. 9.8 involves three steps, namely ester hydrolysis, release of formaldehyde, and a final step of carbonate hydrolysis (X = O) or A-decar-boxylation (X = NH). Three model compounds, a secondary alcohol, a primary aliphatic amine, and a primary aromatic amine, were derivatized with the carrier moiety and examined for their rates of breakdown [84], The alcohol, indan-2-ol, yielded a carrier-linked derivative that proved relatively... 

Bianchini has reported that the migratory insertion reactions of [Pd(R)(CO)(P-P)]+ complexes (R = Me, Et) are reversible and follow first-order kinetics irrespective of the chelating diphosphine (P-P = dppp, dppe, meso-dppb, rac-dppb, meso-bdpp, rac-bdpp) [5e, f]. The free energies of activation for these reactions were calculated from the half-life times (tj 2) obtained by P( H HP NMR spectroscopy as all the rates of conversion of the methyl carbonyl complexes were independent of the CO pressure. Therefore, the AG values associated with the migratory insertion of the methyl carbonyl complexes could be straightforwardly calculated from the values using the equation AG = RT(ln k -ln kT/h) with = In First-order... 

It has been shown that different methods may ascribe different bond lengths to the 0-0 and C—O bonds and that the medium and substituents affect the electronic behaviors of carbonyl oxides." For example, recent computational studies (B3LYP/6-31 + G (d, p)) of carbonyl oxides, syn- and awri-methyl carbonyl oxides and dimethylcarbonyl oxides in gas and solution reveal that dipolar character increases with the number of methyl groups, and the ionic configuration is stabilized in a polar medium. These effects result in a weakened 0 0 bond and an increased double-bond character in the CO bond. ... 

Dialkylboron trifluoromethanesulfonates (triflates) are particularly useful reagents for the preparation of boron enolates from carbonyl compounds, including ketones, thioesters and acyloxazolidinones.4 Recently, the combination of dicylohexylboron trifluoromethanesulfonate and triethylamine was found to effect the enolization of carboxylic esters.5 The boron-mediated asymmetric aldol reaction of carboxylic esters is particularly useful for the construction of anti (3-hydroxy-a-methyl carbonyl units.6 The present procedure is a slight modification of that reported by Brown, et al.2... 

By comparisons among the spectra of large numbers of compounds of known structure, it lias been possible to recognize, at specific positions in the spectrum, bands which can be identified as characteristic group frequencies associated with the presence of localized units of molecular structure in the molecule, such as methyl, carbonyl, or hydroxyl groups. Many of these group frequencies differ in the Raman and infrared spectra. 

The products of oxidative addition of acyl chlorides and alkyl halides to various tertiary phosphine complexes of rhodium(I) and iridium(I) are discussed. Features of interest include (1) an equilibrium between a five-coordinate acetylrhodium(III) cation and its six-coordinate methyl(carbonyl) isomer which is established at an intermediate rate on the NMR time scale at room temperature, and (2) a solvent-dependent secondary- to normal-alkyl-group isomerization in octahedral al-kyliridium(III) complexes. The chemistry of monomeric, tertiary phosphine-stabilized hydroxoplatinum(II) complexes is reviewed, with emphasis on their conversion into hydrido -alkyl or -aryl complexes. Evidence for an electronic cis-PtP bond-weakening influence is presented. 

Stavropoulos et al. [162] synthesized the methyl, carbonyl, hydride, and acetyl coordinated complexes of the compound shown in Scheme 8 as models of a possible pathway to the formation of a thioester. The tripodal ligands N(CH2CH2SR)3 are biologically relevant in using N and S coordination. Further, the sequence of reactions... 

Reacts with enolate ions to yield a-methylated carbonyl compounds (Section 22.7). 

SYNS FLUORID KYSELINY OCTOVE METHYL-CARBONYL FLUORIDE... 

Alkoxycyclopropanes are commonly prepared from alkyl enol ethers by one of the Simmons-Smith modifications (see Chapter 7). According to Wenkert and coworkers they are cleaved by strong acids to the a-methylated carbonyl compound, thus establishing an overall a-methylation of a ketone or an aldehyde (equation 64). This method has often been used for natural product synthesis (e.g. valerane " ). 

This sensitive test permits use of the readily available sodium hypochlorite in place of sodium hypoiodite for recognition of methyl carbonyl or methylcarbinol structures. It is useful also when detection of a haloform by infrared spectroscopy or gas-liquid chromatography is unsatisfactory, as may happen in certain reactions in which haloform-type cleavage occurs to a slight extent. ... 

Synthesis of a-Methylated Carbonyl Compounds from Cyclopropanols, Cyclopropylamines... 

The Masamune aldol condensation, in common with the Evans aldol condensation, involves a boron enolate of an ester containing a norephedrine derived chiral auxiliary however, unlike the latter, the Masamune aldol delivers a 3-hydroxy-2-methyl carbonyl moiety with the an/z-stereochemistry. Crucial to the success of this reaction is the use of dicyclohexylboron triflate to generate the boron enolate. Note in the Evans aldol condensation, dibutylboron triflate is utilized. 

Although the tetrahedral carbon of an acetal or ketal is bonded to two oxygen atoms, causing us to predict that the acetal or ketal is not stable, the acetal or ketal can be isolated if the water eliminated from the hemiacetal (or hemiketal) is removed from the reaction mixture. This is because, if water is not available, the only compound the acetal or ketal can form is an 0-methylated carbonyl compound, which is less stable than the acetal or ketal. 

Dimethyl-1-butene will not yield a methyl carbonyl compound upon ozonolysis with reductive workup. Hence, it will subsequently not give a positive iodoform reaction. 

Dimethylamino)propyl]diinethylaluniii Methylation. Carbonyl compounds iJehydes require activation with AlCl,. 

Methylation Carbonyl compounds are attacked by this reagent (1), but aryl... 

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