Alkylation of carbonyl compounds

Induction of Asymmetry by Amino Acids. No fewer than sis types of reactions can be carried out with yields of 75—100% usiag amino acid catalysts, ie, catalytic hydrogenation, iatramolecular aldol cyclizations, cyanhydrin synthesis, alkylation of carbonyl compounds, hydrosdylation, and epoxidations (91). 

O-Alkylation of carbonyl compounds with diazo alkanes... 

Ketones from Aoetylenes Alkylation of carbonyl compounds (p T 108) with propargyi halides gives 7,5-acetyienic ketones. Hydration then gives a 1,4-diketone of a type we shall use in Chapter T 25 as in the following example, ... 

The direct addition of simple alkyl groups onto aldehydes is the most challenging in water. Mitzel reported the indium-mediated alkylation of carbonyl compounds with a-sulfur stabilized systems.224 Recently, Li and co-workers reported an efficient addition of simple alkyl halides to aldehydes mediated by Zn/Cul with a catalytic amount of InCl in water (Eq. 8.89).225... 

TABLE 2-13. A Summary of Chiral Auxiliaries Reported To Be Useful in the a-Alkylation of Carbonyl Compounds... 

Chapter 2 provided a general introduction to the a-alkylation of carbonyl compounds, as well as the enantioselective nucleophilic addition on carbonyl compounds. Chiral auxiliary aided a-alkylation of a carbonyl group can provide high enantioselectivity for most substrates, and the hydrazone method can provide routes to a large variety of a-substituted carbonyl compounds. While a-alkylation of carbonyl compounds involves the reaction of an enolate, the well known aldol reaction also involves enolates. 

Covalently bonded chiral auxiliaries readily induce high stereoselectivity for propionate enolates, while the case of acetate enolates has proved to be difficult. Alkylation of carbonyl compound with a novel cyclopentadienyl titanium carbohydrate complex has been found to give high stereoselectivity,44 and a variety of ft-hydroxyl carboxylic acids are accessible with 90-95% optical yields. This compound was also tested in enantioselective aldol reactions. Transmetalation of the relatively stable lithium enolate of t-butyl acetate with chloro(cyclopentadienyl)-bis(l,2 5,6-di-<9-isopropylidene-a-D-glucofuranose-3-0-yl)titanate provided the titanium enolate 66. Reaction of 66 with aldehydes gave -hydroxy esters in high ee (Scheme 3-23). 

The chiral A/ -propionyl-2-oxazolidones (32 and 38) are also useful chiral auxiliaries in the enantioselective a-alkylation of carbonyl compounds, and it is interesting to observe that the sense of chirality transfer in the lithium enolate alkylation is opposite to that observed in the aldol condensation with boron enolates. Thus, whereas the lithium enolate of 37 (see Scheme 9.13) reacts with benzyl bromide to give predominantly the (2/ )-isomer 43a (ratio 43a 43b = 99.2 0.8), the dibutylboron enolate reacts with benzaldehyde to give the (3R, 25) aldol 44a (ratio 44a 44b = 99.7 0.3). The resultant (2R) and (25)-3-phenylpropionic acid derivatives obtained from the hydrolysis of the corresponding oxazolidinones indicated the compounds to be optically pure substances. 

The highly selective alkylation reaction of chiral imines, which in some cases occurs under complete asymmetric induction, as well as the simple introduction and recovery of the chiral auxiliaries, ensures that asymmetric alkylation of carbonyl compounds via their corresponding imines is a valuable tool in organic chemistry. 

Enol Ethers and Esters 0-15 O-Alkylation of carbonyl compounds with diazo alkanes 0-17 Transetherification 0-20 Reaction between acyl halides and active hydrogen compounds 0-23 Transesterification 0-24 Acylation of vinylic halides 0-94 Alkylation with ortho esters 0-107 O-Acylation of 1,3-dicarbonyl compounds... 

Unfortunately, alkylation reactions analogous to the base-catalyzed alkylation of carbonyl compounds generally are not useful for the synthesis of higher nitro compounds, because C-alkylation of the conjugate bases of primary nitro compounds is slower than O-alkylation. 

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