Carbonylative ketone synthesis

Competitive schemes similar to that shown in Scheme 1-51 must apply to other tandem processes in which reductive elimination is the Pd-releasing step. Indeed, the authors attempts to develop a carbonylative ketone synthesis similar to that shown in Scheme 1-50 using organozincs were largely unsuccessful due to competitive direct coupling, even though the Pd-catalyzed reaction of organozincs with acyl halides is very satisfactory [105]. 

Organoaluminum compounds such as triphenylaluminum (527) are used for ketone synthesis[387]. On the other hand, the reaction of /-BuiAl affords the corresponding alcohol 528 by reductive carbonylation[388]. 

Organotin compounds such as aryl-, alkenyl-, and alkynylstannanes are useful for the ketone synthesis by transmetallation of acylpalladium 529 and reductive elimination of 530 as shown[389-393]. Acetophenone (531) is obtained by the carbonylation of iodobenzene with Me4Sn. Diaryl ketones... 

Scheme 6.49 Cobalt carbonyl-mediated synthesis ofdiaryl ketones.

Hata, T., Hashizume, A., Nakajima, M., and Sekine, M., A convenient method of ketone synthesis utilizing the reaction of diethyl trimethylsilyl phosphite with carbonyl compounds, Tetrahedron Lett., 363, 1978. 

Michler s ketone (6.155) and related carbonyl compounds can be used to obtain colour salts directly by reaction with a reactive intermediate such as an aromatic amine (the ketone synthesis), as in the case of crystal violet (6.164 Cl Basic Violet 3) shown in Scheme 6.31. 

Among isolable metal homoenolates only zinc homoenolates cyclize to cyclo-propanes under suitable conditions. Whereas acylation of zinc alkyls makes a straightforward ketone synthesis [32], that of a zinc homoenolate is more complex. Treatment of a purified zinc homoenolate in CDC13 with acid chloride at room temperature gives O-acylation product, instead of the expected 4-keto ester, as the single product (Eq. (22) [33]). The reaction probably proceeds by initial electrophilic attack of acyl cation on the carbonyl oxygen. A C-acylation leading to a 4-keto ester can, however, be accomplished in a polar solvent Eq. (44)-... 

Organoboranes are used for ketone synthesis under basic conditions. The cyclic ketone 482 is prepared from alkenyl iodode 479. Hydroboration of terminal double bond, followed by carbonylation generates 480, and the cyclic ketone 482 is formed by intramolecular transmetallation of 480 to afford 481 [236],... 

Palladium-catalyzed ketone synthesis B. The reaction mixture is saturated with carbon monoxide, which intervenes in step 2 by forming a palladium(II) carbonyl complex. Before the transmetalation (above referred to as step 3) takes place a rearrangement is interposed. The ligand Rmisa rji cd undergoes a [l,2]-shift from Pd(II) to the carbon atom of carbon monoxide, leading to the formation of an acylpalladium(II) complex with the structure P lllsa llra cd-(C=0)-Pd(-X) L j. With regard to the above-mentioned steps 3-4 it behaves like the acyl-Pd(II) complex of the ketone synthesis A and, after reductive elimination, i.e. in step 5, yields... 

For the ketone synthesis via the present protocol, acid chlorides are useful precursors, in deed. Nevertheless, carbonylative cross coupling with organic halides is strategically the most simple and direct way to this purpose. The palladium-catalyzed carbonylative cross-coupling reaction with various organic halides has been extensively investigated, because of its merits from synthetic as well as phenomenal point of view. Acid chlorides are not always readily available, and their preparation is not always compatible with many sensitive functionalities. Therefore the development of this type of reaction widens the scope of the ketone synthesis in the present protocol because of the ready availability and storability of organic halides and pseudohalides. 

Other applications of this method include, e.g. the synthesis of the antibiotic A26771B (5i) [118] and the marine cembranolide isolobophytolide [119], Trost and Warner [120] reported that a-sulfonyl sulfones can also serve as the substrates of ir-allylpalladium complexes for macrocyclization. Furthermore, an a-hydroxy-carbonyl ketone was alkylated intramolecularly by a a-allylpalladium complex in the total synthesis of the macrocyclic sesquiterpene humulene [121]. 

Ma W, Li X, Yang J, Liu Z, Chen B, Pan X (2006) A convenient synthesis of aryl ferrocenylethynyl ketones and 2-ferrocenyl-4H-chromen-4-ones via palladium-catalyzed carbonylation coupling. Synthesis 2489-2492... 

Heasley VL, Buczala DM, Chappell AE, Hill DJ, Whisenand JM, Shellhamer DF (2002) Addition of bromine chloride and iodine monochloride to carbonyl-conjugated, acetylenic ketones synthesis and mechanisms. J Org Chem 67 2183-2187... 

The alkylation of protected cyanohydrin anions constitutes an excellent method for ketone synthesis. Generally the anions are generated from aliphatic or aromatic aldehyde protected cyanohyd with LDA under nitrogen at -78 C. The addition of an alkyl halide produces the protected ketone cyanohydrin. The carbonyl group is then liberated by successive treatment with dilute acid and dilute aqueous base. This method is applicable for the synthesis of buflomedil. ... 

Reaction with amides. Benzamides and thiobenzamides are converted to a,a-disubstituted benzylamines. Tertiary amides form ketones on reaction with RCeCl even when the reagent is present in large excess, therefore Weinreb amides are not necessary for the ketone synthesis. Enaminones are also attacked at the carbonyl group, and in the cases of a -silylated derivatives the reaction products are 3,y-unsaturated ketones. ... 

Tin hydride-mediated radical cyclizations onto a C-0 double bond, coupled with subsequent oxidation, can be applied to ketone synthesis. Fraiser-Reid and co-workers demonstrated that the radical cyclization onto an aldehyde carbonyl group is particularly useful for the construction of cyclohexanol derivatives [35]. Examples shown in Scheme 4-17 well feature the cyclization. As Beckwith s kinetic work predicts (Scheme 4-18) [36], when this method is applied to a five-membered ring system, the rapid ring opening hinders the formation of cyclopen-tanols. Accordingly, only cyclohexanols can be reliably prepared using this approach. 

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