Carbonyl compounds, addition reactions Wittig reaction

Addition of phosphorus ylide to carbonyl compounds Wittig reaction... 

The reaction of triphenyl-/ -phosphanes with carbonyl compounds, the Wittig olcfmation reaction, involves addition to the carbonyl carbon in a reaction closely related to the aldol condensation. Triphenyl-2 -phosphanes, derived from alkyltriphenylphosphorus salts, react with 1,1,1-trifluoroacetonc or other trifluoromethyl ketones " - to give products 29. 

Abstract Phosphacumulene ylides of the general formula Ph3P=C=C=X [X=0, S, NR, (0R)2] are versatile C2-building blocks. They can act either as C-nudeophiles-only in a manner typical of phosphorus ylides, or as cumulenes undergoing [2 + n -cycloadditions with other cumulenes such as CO2, COS, RNCO etc. Most prominent is their tandem addition-Wittig alkenation of hydroxy- or amino-substituted carbonyl compounds. With aptly chosen reaction partners all these pathways may lead to heterocyclic products. Some recent applications of these methods to the syntheses of azetidines, five-membered lactams, lactones, tetramates, tetronates and pyrroles as well as to six-membered quinolones and to macrolides are delineated. 

The Julia-Lythgoc olefination operates by addition of alkyl sulfone anions to carbonyl compounds and subsequent reductive deoxysulfonation (P. Kocienski, 1985). In comparison with the Wittig reaction, it has several advantages sulfones are often more readily available than phosphorus ylides, and it was often successful when the Wittig olefination failed. The elimination step yields exclusively or predominantly the more stable trans olefin stereoisomer. 

With respect to the carbonyl substrate, a variety of additional functional groups is tolerated, e.g. ester, ether, halogen. With compounds that contain an ester as well as a keto or aldehyde function, the latter usually reacts preferentially. Due to its mild reaction conditions the Wittig reaction is an important method for the synthesis of sensitive alkenes, as for example highly unsaturated compounds like the carotinoid 17 shown above. 

The Peterson olefination reaction involves the addition of an a-silyl substituted anion to an aldehyde or a ketone followed by the elimination of silylcarbinol either under acidic (awP -elimination) or basic (syn-elimination) conditions to furnish olefins178. Thus, Peterson olefination, just like Wittig and related reactions, is a method for regioselective conversion of a carbonyl compound to an olefin. Dienes and polyenes can be generated when the Peterson reaction is conducted using either an ,/l-unsaturated carbonyl compound or unsaturated silyl derivatives as reaction partners (Table 20)179. 

Despite the apparent generality of this Wittig-type process, it must be noted that the reactions of Ph3P=C=PPh3 with transition-metal carbonyl compounds do not always result in the formation of phosphonioacetylide moieties. Thus, replacement of, instead of addition to (see Scheme 24), the CO group has been observed in some... 

Nucleophilic Addition to Carbonyl Compounds and -Unsaturated Carbonyl Compounds.—Although the reactions of 17-oxo-steroids with various carbanion reagents are reported to have varying success/ the use of alcohols or DMF as solvents appears to facilitate the Wittig-Horner reaction/ For example, the ketone (97) was converted with (Et0)2P0CHC02Et into the E-ethyl ester (98) in... 

Much better known are the fluorinatedphosphoranes, which have been widely used m the Wittig reaction for the preparation of fluoroolefms Dtfluoromethylena tion reactions have been effected by using a variety of conditions Treatment of dibromodifluoromethane with two equivalents of tns(dimethylamino)phosphine m carefully dried tnglyme yields a solution of bromodifluoromethylphosphonium broomide, which very effectively converts ketones to difluoromethylene derivatives A more sensitive reagent is prepared by the addition of two eqm valents of the phosphine to the reaction mixture of fluorohalomethane and a carbonyl compound [39, 401 (equation 40) (Table 14)... 

Alternatively it is possible to have both steps, addition and elimination, occur spontaneously if appropriate reagents are employed. There are two common strategies in use the Wittig reaction and the Wittig-Horner reaction. The Wittig olefination uses a phosphorus-stabilized carbanion (ylid) as a nucleophile and a carbonyl compound as an electrophile. Typically the ylid is generated in situ from a triphenylphosphonium salt and a strong base such as LDA or an alkyl lithium. 

Wittig reactions.3 Yields in the reaction of an aldehyde with cyclopropyltri-phenylphosphonium bromide (2,95-96) under the usual conditions (NaH, DMF) are negligible, but can be improved to about 15% by addition of 18-crown-6. A dramatic increase in yield is obtained by use of NaH in THF with TDA-1 as a transfer catalyst. Best results are obtained by heating the phosphonium salt suspended in THF with TDA-1 before addition of the carbonyl compound. With this technique, alkylidenecyclopropanes can be obtained from carbonyl compounds in yields of 60-95%. 

So far, most of the reactions presented in the book that are useful in synthesis have made C-O, C-N, or C-halogen bonds and only a few (Wittig, Friedel-Crafts, and reactions of cyanides and alkynes) make C-C bonds. This limitation has severely restricted the syntheses that we can discuss in this chapter. This is by design as we wanted to establish the idea of synthesis before coming to more complicated chemistry. The next four chapters introduce the main C-C bond-forming reactions in the chemistry of enols and enolates. You met these valuable intermediates in Chapter 21 but now you are about to see how they can be alkylated and acylated and how they add directly to aldehydes and ketones and how they do conjugate addition to unsaturated carbonyl compounds. Then in Chapter 30 we return to a more general discussion of synthesis and develop a new approach in the style of the last synthesis in this chapter. 

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