Synthesis of Carbonyl Compounds

This reaction was used as the basis for the development of a procedure for the synthesis of carbonyl compounds (182) from acetophenone derivatives (180) (386) (Scheme 3.138). 

The resulting radicals R efficiently alkylate BENAs (495) at the (3-C atom to give silyl derivatives of oximes (496) in good yields. The latter readily undergo deoximation in the presence of 1 M hydrochloric acid to give the corresponding carbonyl compounds (494). Thus, a convenient procedure was developed for the synthesis of carbonyl compounds (494) from secondary AN (493) through the intermediate terminal BENA (495) (527). 

Carbonylation is one of the most important reactions leading to C-C bond formation. Direct synthesis of carbonyl compounds with CO gives rise to carboxylic acids and their derivatives, such as esters, amides, lactones, lactams etc. The process can be represented by the simple reactions of Scheme 5.1. 

In summary, of the many chiral auxiliaries used in the asymmetric synthesis of carbonyl compounds via imines, those able to form a methoxymethyl-chclated azaenolate show the best enantioselectivities (see Tabic 7). The same is true for valine and im-leucine derivatives which form rigid chelates via their carboxyl groups. In particular, quaternary centers (see Table 6) and a-alkvl-/i-oxo esters arc effectively prepared using these chiral auxiliaries. 

Table 7. Chiral Auxiliaries Used in the Asymmetric Synthesis of Carbonyl Compounds by Alkylation of Imines...

D. Enders, Sel., Goal Synth. Effic., Proc. Workshop Conf. Hoechst 14th, 1983, S. 65-86 . .Asymmetric Synthesis of Carbonyl Compounds and Primary Amines". 

Functionalized organomagnesium compounds Synthesis and reactivity 559 4. Synthesis of carbonyl compounds... 

Alcohols are the most important precursors in the synthesis of carbonyl compounds, being readily available. More complex alcohols are prepared by reaction of Grignard reagents with simpler carbonyl compounds. Ordinarily MnO and Cx OY in acid are used to oxidize 2° RjCHOH to RjCO. However, to oxidize 1° RCHjOH to RCHO without allowing the ready oxidation of RCHO to RCOOH, requires special reagents. These include (a) pyridinium chlorochromate (pcc),... 

Varied oxidizing agents may be employed in the laboratory synthesis of carbonyl compounds. Styrenes undergo oxidative rearrangement when treated with Pb(OAc)4 in CF3COOH, but only aldehydes are produced in good yields 556... 

The most important use of 1,3-dithianes (792) stems from their ability to function as acyl anion equivalents (794 Scheme 184). Metallation of this heterocycle followed by alkylation of the anion and cleavage of the dithiane group produces a carbonyl compound. Since such aspects of dithiane chemistry have been extensively documented (69S17 75JOC231), only a few of the more current applications of these heterocycles are highlighted. We again note here that the application of heterocycles to the synthesis of carbonyl compounds has been the sole subject of an extensive review (77H(6)73l). 

H. M. Colquhoun, D. J. Thompson, M. V. Ttoigg, "Carbonyladon - Diiect Synthesis of Carbonyl Compounds, Plenum, New York (1991), Chpt 11... 

Recent developments in enantioselective protonation of enolates and enols have been reviewed, illustrating the reactions utility in asymmetric synthesis of carbonyl compounds with pharmaceutical or other industrial applications.150 Enolate protonation may require use of an auxiliary in stoichiometric amount, but it is typically readily recoverable. In contrast, the chiral reagent is not consumed in protonation of enols, so a catalytic quantity may suffice. Another variant is the protonation of a complex of the enolate and the auxiliary by an achiral proton source. Differentiation of these three possibilities may be difficult, due to reversible proton exchange reactions. 

Metalated Hydrazones, Formamides, Allylamines, and Aminonitriles in "Current Trends in Organic Synthesis", Nozaki, H., Ed. Pergamon Press Oxford, 1983 p. 151 (d) Enders, D. "Asymmetric Synthesis of Carbonyl Compounds and Primary Amines" in Selectivity - a Goal for Synthetic Efficiency", Bartmann, W. Trost, B. M., Eds. Verlag Chemie Weinheim, 1984 p. 65. (e) Enders, D. Chemiaa Seripta 1985, 25, 139. 

Acids can also be made by the oxidation of alcohols and acid derivatives are available from the acids via the acid chloride. Since acids can also be reduced to alcohols, there is a great deal of interdependence in all these methods. The synthesis of carbonyl compounds by one-group C-C disconnections is discussed more fully in chapter 13. 

For the Heck reaction as discussed in Section III.2.1 the final position of the olefi-nic double bond of the products must not necessarily be the same as in the starting materials (for example Schemes 8, 9, and 10 of Section III.2.1) [1], The selectivity is often driven by stereochemical requirements, because the /1-hydrogen elimination step which forms the double bond proceeds exclusively in a syn manner (if a trans /3-hydrogen is eliminated, one should suspect major deviations from the general mechanism of the Heck reaction, for example electrophilic substitution instead of carbopalladation). An impressive example of a double bond migration is depicted in Scheme 1 - instead of olefins the coupling reaction of iodobenzene 1 with the olefmic alcohol 2 results in the isomeric aldehydes 3 and 4 as final products [2], Reactions of this type have emerged as valuable tools for the synthesis of carbonyl compounds and also as crucial steps in domino processes. 

Imidazolium alkylselenite ionic liquids were found to be efficient catalysts/solvents for the oxidative carbonylation of amines,1371 but in general the synthesis of carbonyl compounds is carried out in the presence of a palladium catalyst. The first example of such a transformation stems from... 

The anodic oxidation of enol ethers in methanol yields a-methoxylated carbonyl conqKxinds, which are useful intermediates for the synthesis of carbonyl compounds utilizing the technique of oxidative cleavage of glycols (equation 4S). ... 

---