Keto acids from alkenes

Of trialkyl phosphites the most frequently used is triethyl phosphite (EtO)3P (M.W. 166.16, b.p. 156°, density 0.969) which combines with sulfur in thiiranes [291, 294] and gives alkenes in respectable yields. In addition, it can extrude sulfur from sulfides [295], convert a-diketones to acyloins [296], convert a-keto acids to a-hydroxy acids [297], and reduce nitroso compounds to hydroxylamines [298] Procedure 47, p. 111). 

A simple, efficient, one-step synthesis of quinoxaline 1,4-dioxides from the reaction of benzofurazan oxide 179 with activated alkenes such as enamines was named the Beirut reaction in honor of the city of its discovery. Developments up to 1993 were surveyed by Haddadin and Issidorides <1993H(35)1503>, who first demonstrated this reaction. The benzofurazan oxide 179 (Scheme 52) also condenses with 1,3-diketones <1995M1217, 1996JHC1057, 1999CHE459, 2003EJM791, 2005H(65)1589>, /3-keto acid derivatives <1995H(41)2203,... 

The oxidative cleavage of unsaturated ketones takes place under the same conditions as that of alkenes or other unsaturated derivatives. The fate of the primary fission product depends on the position of the double bond with respect to the carbonyl group and on the subsequent reactions. Ozonization of A -cholestenone in acetic acid and ethyl acetate, followed by treatment with 30% hydrogen peroxide, gives a keto acid, evidently resulting from the decomposition of the primarily formed diketo acid (equation 444) [1176]. 

The required aldehs de or keto-acid can be made in a number of ways with the cb-alkene probably best derived from an alkyne. Here are two possibilities. 

More complex products are obtained from cyclizations in which the oxidizable functionality and the alkene are present in the same molecule. y9-Keto esters have been used extensively for Mn(III)-based oxidative cyclizations and react with Mn(OAc)3 at room temperature or slightly above [4, 10, 11, 15], They may be cyclic or acyclic and may be a-unsubstituted or may contain an a-alkyl or chloro substituent. Cycloalkanones are formed if the unsaturated chain is attached to the ketone. y-Lactones are formed from allylic acetoacetates [10, 11]. Less acidic /3-keto amides have recently been used for the formation of lactams or cycloalkanones [37]. Malonic esters have also been widely used and form radicals at 60-80 °C. Cycloalkanes are formed if an unsaturated chain is attached to the a-position. y-Lactones are formed from allylic malonates [10, 11]. yff-Diketones have been used with some success for cyclizations to both alkenes and aromatic rings [10, 11]. Other acidic carbonyl compounds such as fi-keto acids, /3-keto sulfoxides, j8-keto sulfones, and P-nitro ketones have seen limited use [10, 11]. We have recently found that oxidative cyclizations of unsaturated ketones can be carried out in high yield in acetic acid at 80 °C if the ketone selectively enolizes to one side and the product cannot enolize... 

P-keto-acids, and the saponification of only one cyano-function in the reaction with malononitrile is difficult to rationalise. Treatment of compounds containing active methylene groups with cupric acetate in the presence of an alkene can lead to a cyclopropane (8—66%) by a radical route.1,3-Debromination, by sodium, of suitable precursors has led to a series of new spirans, and a new synthesis of cyclopropane from 3-bromopropyne and allylic zinc bromides has been claimed. Miscellaneous Methods.—Pyrolysis of (144) leads to carbonylcyclopropane, which undergoes ready dimerization on warming to ambient temperatures. The ketone... 

Keto-enol tautomerism of carbon) ] compounds is catalyzed by both acids and bases. Acid catalysis occurs by protonation of the carbonyl oxygen atom to give an intermediate cation that Joses H+ from its a carbon to yield a neutral enol (Figure 22.1). This proton loss from the cation intermediate is similar to what occurs during an El reaction when a carbocation loses H+ to form an alkene (Section 11.10). 

The synthesis of bicyclo[3.2.2]non-6-en-3-one (192) and the spiro-substituted derivatives (195) can be achieved via similar methodology. Thus, thermolysis of the enol silyl ether (190), which is readily derived from the ketone (189), gives the bicyclic substance (191). Mild acid hydrolysis of (191) affords (192 Scheme 27). In a similar fashion the exo-ketones (193) have been converted, via the enol silyl ethers (194), into the tricyclic keto alkenes (195). ... 

The pathway in Scheme 3 relates mainly to alkenes activated by keto or aldehyde groups, for reduction in hydroxylic solvents. Under these conditions, radical anions derived from carbonyl compounds are protonated at oxygen, and the resulting enolic radical, HI, is more difficult to reduce than the starting compound. Consequently, fast dimerization of the enol radicals may compete with further reduction. For other substrate types, especially in aprotic solvents containing added acids, proton transfer is to carbon... 

As discussed in Section 3.1.11.1, which covers the reductive cleavage of the 3-hydroxy sulfone derivatives to alkenes, the Julia reaction proceeds by the formation of an anion that is able to equilibrate to the thermodynamic mixture prior to elimination. Therefore, there is no inherent advantage in producing the erthyro- or threo-fi-hydroxy sulfone selectively fix>m the keto sulfone. The ( )/(Z)-mixture of alkenes should be the same. This method is used to produce alkenes in cases where the acid derivative is more readily available or more reactive. The reaction of the sulfone anion with esters to form the keto sulfone, followed by reduction with metal hydrides has been studied. The steric effects in the reduction do become important for the reaction to produce vinyl sulfones, which are formed from the anti elimination of the 3-hydroxy sulfone adduct, as mentioned in Section 3.1.11.6.2. Some examples of the use of esters are presented below. 

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