Carbonyl alkylation

COOR esters alkoxy carbonyl alkyl -oate or carboxylate ... 

One of the oldest and best known carbonyl alkylation reactions is the malonic ester synthesis, a method for preparing a carboxylic add from an alkyl halide while lengthening the carbon chain by two atoms. 

It is believed that the primary step involves excitation of the acyl complex via a metal-to-terminal CO charge transfer (755). The molecule then loses CO and rearranges to the carbonyl alkyl, as shown in Eq. (43). However, it... 

Several modifications have been made to organoaluminum-based catalysts. Methylaluminum bis(2,6-di-tert-butyl-4-alkylphenoxide) (MAD) shows high diastereofacial selectivity in carbonyl alkylation (Scheme 72).31 11 Aluminum tris(2,6-diphenylphenoxide) (ATPH) has been developed as a catalyst for conjugate addition reactions. Since a carbonyl group is stabilized by steric effect of ATPH, the 1,4-adduct is obtained selectively.312... 

This reaction occurs thermally in toluene at 30°C with an equilibrium constant (K) equal to 1.5 (13). Both bis(phosphine) and (carbonyl)phosphine Soret bands are present in the active catalyst solutions (see Decarbonylation Procedure), together with the unassigned, and likely critical, band at 420 nm. This could be due to some species giving rise to, or resulting from, a RuII + RCO reaction this is equivalent, of course, to a (Ru H-COR) acyl or a RuIII(C0)R (carbonyl)alkyl species, and the final elimination reaction after loss of CO could be written as ... 

Carbonyl alkylation and condensation reactions are always of great value in synthesis, and the formation of o-ANIS ALDEHYDE via 4,4-dimethyl-2-oxazoline, 2,2-DIMETHYL-3-PHENYLPROPION-ALDEHYDE via alkylation of the magnesio-enamine salt and threo-4-HYDROXY-3-PHENYL-2-HEPTANONE via a directed aldol... 

A general method for converting an aldehyde to a ketone consists of the transformation of the aldehyde to a 1,3-dithiane (183), removal of a proton by butyllithium, and alkylation, followed by hydrolysis. The method is known as the umpolung (reversed) carbonyl alkylation.279... 

Pichler and Schulz were the first to suggest that the initial step in metal-catalyzed CO/H2 reactions might be the migration of catalyst-bound hydride to CO to yield a formyl intermediate [Eq. (1)] (3). The alkyl ligand in many isolable metal carbonyl alkyls can similarly be induced to migrate to coordinated CO (4. ). Thus, Eq. (1) has some precedent in homogeneous chemistry. Other suggestions for the involvement of formyl intermediates have come from Wender (6) and Henrici-Olive and Olive (7). 

Keh, C. C. K. Wei, C. Li, C.-J. The Barbier— Grignard-type carbonyl alkylation using unactivated alkyl halides in water. J. Am. Chem. 

Sequential nucleophilic and electrophilic alkylations of 1,3-dicarbonyl compounds with a trimethylenemethane zwitterion equivalent lead to [3 + 2]-annulation. The nucleophilic carbonyl alkylation step has been carried out via an indium-mediated allylation in water (Equation (30)).200 Indium-mediated allylation of a-chlorocarbonyl compounds with allyl bromides in aqueous media gives the corresponding homoallylic chlorohydrins, which can be transformed to allyloxiranes (Equation (31)).201 Allylation of the G3 position of the cephem nucleus has been accomplished by indium-mediated allylation reaction in aqueous media (Equation (32)).202... 

Almost every metal in the Periodic Table has been coordinated to a porphyrin of one sort or another. The complexes are usually made by interaction of the ligand with a metal salt in a solvent such as DMF other ways include interaction of the H2porph with metal carbonyls, alkyls, hydrides, or acetylacetonates. The radius of the central hole is fixed, but puckering of the rings can alter it normally it lies between 1.929 and 2.098 A. It is also common for larger metal ions to sit above... 

Products isolated from the insertion of SO2 into transition metal-carbon bonds have been shown to adopt structures (I), (III), and possibly, (IV). The first mode of bonding, expected of class b (la) or soft metals (105), is by far the most common one encountered. In fact, oxygen-bonded insertion products have been isolated only for titanium and zirconium (131, 132). However, recent spectroscopic studies have demonstrated that (III) is the kinetic product of the insertion with a number of metal carbonyl alkyls and aryls it then isomerizes to (I) (72, 73) ... 

Re Carbonyl Alkyls, Aryls, Acyls, and Related Complexes... 

Despite such intensive studies on MPV reduction chemistry, the corresponding alkylation, i.e., MPV alkylation had never been realized, mainly because of the inertness of alkyl transfer [C] compared with the facile hydride transfer [B] in the MPV reduction, until Maruoka presented the first example of MPV alkynylations for various aldehydes [34]. This truly represents a non-organometallic way of effecting carbonyl alkylation of aldehydes. The success of the approach relies heavily on the discovery of a ligand-accelerated mode for the MPV alkynylations, which has a beneficial effect on the rate of alkynyl transfer. 

This hypothesis has been supported by experiments with a modified bimetallic, two-center system. Initial treatment of bis(dimethylaluminum) derivative 188 with 1 equiv. MeLi generates a new amphiphilic alkylation system 199 which has both electrophilic and nucleophilic centers in one reagent (Sch. 150). This system is found to be much more effective than symmetric 188, and the carbonyl alkylation of aldehydes proceeds even at -78 to -40 °C. A similar process with monoalmninum derivative 190 and its complex with MeLi, however, gave a trace of methylation product 200 (R = Ph) (< 3 % yield), indicating that appropriate internal arrangement of the two metal centers is essential to achieve this remarkable rate enhancement in the new amphiphilic alkylation. 

The best method for the preparation of A-alkylamide peptides employs 5-(4- [[(9//-fluoren-9-ylmethoxy)carbonyl](alkyl)amino]methyl -3,5-dimethoxyphenoxy)valeric acid [(R)-PAL handle, 29],f l which is derived from the PAL handle. The (R)PAL handle, when used in the same way as PAL, would transfer the alkylamine to the peptide. Similarly, the use of N-alkyl XALP 1 or A-alkyl Rink resinst °°l also gives rise to A-alkylamide peptides. The same conditions as those used to release peptides from PAL, Rink, and XAL apply for the A-alkyl analogues. The preparation of A/,A-dialkylamide peptides requires a backbone attachment strategy (see Section 4.3.1.2.5).f l... 

The ability of the trisylhydrazone dianion to undergo alkylation further enhances the synthetic potential of the Shapiro reaction. The initial carbonyl alkylation of acetone trisylhydrazone dianion, followed by fragmentation to the functionalized alkenyllithium reagent and subsequent trapping with carbon diox-... 

In essence, these are the cis and trans conformers of the ester, as the ester alkyl group is either adjacent to the carbonyl alkyl group or is opposite it. Suggest which one is the favoured conformer. 

Metal-carbonyl-alkyl complexes undergo photoinduced loss of CO in preference to photoreactions involving the alkyl ligand, at least in the primary photoprocess , e.g., in h -CjHjMCRXCO), (R = Me, n-pentyl M = Cr, Mo, h -CjHjMCCO),-... 

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