Reactions with carbonyl compounds product isomerization

Furan has been found to form oxetanes with a variety of carbonyl compounds, e.g., ketones,202-205 aldehydes,206 and ethyl cyanofor-mate.207 In most reactions the (2 + 2)-cycloaddition occurred specifically to give a 2,7 dioxabicyclo[3.2.0]hept-3-ene (175) rather than the 2,6-isomer (176). Only the addition of ethyl cyanoformate yielded mixtures of 175 and 176 (R = OEt and R2 = CN), in a ratio of 2 l.207 Two subsequent (2 + 2)-cycloadditions of benzophenone and furans have been reported to give two isomeric products, 177 and 178.205 Substituted furans yielded similar oxetanes.203 Benzo[ >]furans, furo-coumarins, and furochromones also proved to undergo (2 + 2)-cyclo-addition reactions with carbonyl compounds such as ketones, aldehydes, and quinones. Invariably one type of oxetane was formed (179).,37,u3 ,44 200-202 208,20, In the case of 2-methoxycarbonylbenzo[6)-furan, evidence has been provided that the oxetane was produced by addition of the excited triplet state of the olefinic reactant to the ground state of the ketone.208... 

Since Theodor Curtius reported the synthesis of ethyl diazoacetate in 1883, Buchner had investigated its reactions with carbonyl compounds, alkenes, alkynes, and aromatic compounds for more than 30 years.His extensive contributions in this area resulted in two reactions named in his honor the Buchner-Curtius-Schlotterbeck reaction (formation of ketones from aldehydes and aliphatic diazo compounds) and the Buchner reaction. The prototypical example of the latter involves the thermal or photochemical reaction of ethyl diazoacetate with benzene to give (via norcaradiene 7) a mixture of four isomeric cycloheptatrienes 8-11. Initially, Buchner believed that a single norcaradiene product 7 was generated from this reaction, but later, he realized that the hydrolysis of the product afforded a mixture of four isomeric carboxylix acids. The norcaradiene formulation persisted until 1956 when Doering reinvestigated this reaction. ... 

Beside the Grignard and other C-C bond-forming reactions, a number of functional group transformations may also serve as an entry into allylic systems. Some of them, namely the reduction of a, -unsaturated carbonyl compounds (products of crotonic condensation), halogenation of alkenes at the allylic position with Af-bromosuccinimide (NBS) and epoxide isomerization, are shown in Scheme 2.56. 

This approach should be useful in determining the direction of hydrogenation for molecules in which the carbinol group is replaced by carbon-carbon or carbon-nitrogen double bonds. With an alkene, though, the simple conformational model would have to be used and the hydrogenation should be run under conditions that do not promote double bond isomerization, that is, not with palladium or nickel catalysts. With carbonyl compounds the preferred eonditions for selective reaction involve platinum, rhodium or ruthenium catalysts imder non-diffusion control conditions. The use of nickel catalysts, especially Raney nickel, with its basic components, can cause an equilibration of the alcohol product. 

The reactions of 2-aminobenzimidazoles have been reviewed <83S86l>. The compounds form Schiffs bases with carbonyl compounds, with isocyanates and isothiocyanates they give ureas and thioureas, they are subject to 1,3-dipolar addition reactions, and to the formation of carbamates on acylation and aroylation. When aminoimidazoles are acylated there is frequently competition between the annular and exocyclic nitrogen (see above). Add chlorides and anhydrides (soft) acylate the amino group chlorocarbonic acid esters (hard) are specific for the heteroatom <84CHE204>. When heated, the A -acyl products isomerize (Scheme 91). 

Anions derived from the aldimine of tiglaldehyde (14) react with carbonyl compounds preferentially at the a-position under conditions of kinetic control to give adducts (15), but products (16) derived from 7-attack are obtained under equilibrating conditions (Scheme 4). Addition of HMPA to the reaction or adduct mixture is required to promote isomerization of the initially formed a-adduct to the 7-product. There is also an increasing preference for 7-capture of the unsaturated imine anion as the degree of substitution a to the carbonyl function increases as in a-branched aldehydes and ketones (Table 2). Efforts to isomerize the initial a-adduct formed from reaction of the aldimine derived from crotonaldehyde with cyclohexanecarbaldehyde gave complicated mixtures. 

In this section more mechanistic detail is provided concerning the isomerization of vinyl alcohols (enois) to carbonyl compounds. This isomerization, although it favors the keto structure, allows small concentrations of enois to be in equilibrium with carbonyl coinpouiuls, and thc.se cnols can lead to productive chemical reactions. 

The importance of the dipolar resonance forms is reflected in the stabihties of isomeric carbonyl compounds. Propanal is approximately 27 kj mole" less stable than propanone. For addition reactions, two isomeric products with different stabihties also form. Therefore, we also have to consider the relative stabihties of the products. Hydrogenation of propanal and propanone gives isomeric alcohols. 1-Propanol is approximately 16 kJ mole" less stable than 2-propanol. Since the difference in the stabihties of the reactants is greater than the difference in the stabilities of the products, the equihbrium constants for the addition reactions of carbonyl compounds depend on more differences in the structure of the carbonyl compound than on the differences in the structure of the addition product. Thus, because ketones are more stable than aldehydes, the addition reactions of ketones are less favorable (have smaller equihbrium constants) than addition reactions of aldehydes. 

Certain starting materials may give rise to the non-selective formation of regioisomeric enolates, leading to a mixture of isomeric products. Furthermore a ,/3-unsaturated carbonyl compounds tend to polymerize. The classical Michael procedure (i.e. polar solvent, catalytic amount of base) thus has some disadvantages, some of which can be avoided by use of preformed enolates. The CH-acidic carbonyl compound is converted to the corresponding enolate by treatment with an equimolar amount of a strong base, and in a second step the a ,/3-unsaturated carbonyl compound is added—often at low temperature. A similar procedure is applied for variants of the aldol reaction. 

In water-heptane biphasic systems, allylic alcohols underwent rearrangement to the corresponding carbonyl compounds with a catalyst prepared in situ from RhCU.aq and TPPTS. The reactions proceeded very fast (TOP up to 2500 h ) and in most cases provided the carbonyl products quantitatively. The industrially interesting geraniol was isomerized mostly to citronelM, albeit octatrienes and tricyclene were also produced. With an increase of the pH of the aqueous phase the yield of isomerization decreased somewhat (from 48 % to 40 %), however the selectivity towards the... 

In the presence of excess monoalkylamine, carbonyl compounds in aqueous solution are in equilibrium with the corresponding imine. In most cases these imines cannot be isolated but they are reduced at a less negative potential than the carbonyl compound. Selective reduction of such equilibrium mixtures is a useful route to alkylamines from ketones in yields of 70-90%. The process fails with hindered ketones such as camphor and with bulky amines such as fert.-butyl amine. Overall the reaction has advantages of lower costs and simpler work-up compared to the use of cyanoborohydride reducing agents. In the electrochemical reaction, protonation of carbanion intermediates occurs from the more hindered side and where two isomeric products are fomied, the least hindered amine predominates [193]. 

Sarel and co-workers have examined some reactions of alkynylcyclopropanes with iron carbonyl compounds [1]. Treatment of cyclopropylacetylene (5) with iron pentacarbonyl under photolytic conditions gives, after cerium(IV) oxidation, isomeric quinones 6 and 7, derived from two molecules of 5 and two carbonyls with both cyclopropane rings intact [6]. Furthermore, the photoreaction of dicyclopropylacetylene (8) with iron carbonyl gives some ten different products depending on the reagents and the reaction conditions, and some of them have the cyclopentenone skeleton formed by the opening of cyclopropane ring coupled with carbonyl insertion [7] (Scheme 2). 

Thus, the observations that (a) dienes quench the photoreduction reaction (b) the isomerization and dimerization of dienes is sensitized by the it,n carbonyl triplet and (c) there is a lack of photocycloaddition products with dienes, taken in conjunction with the relative energy levels of carbonyl compounds and dienes, form a consistent picture. 

---