Homologated ketones

Diazomethane reacts with ketonic compounds according to the reactions to give epoxides and homologated ketones. If the ketone employed is cyclic, only a single... 

Treatment of benzaldehydes with ethyl diazoacetate and a catalytic quantity of the iron Lewis acid [ -CpFe(CO)2(THF)]+BF4 yields the expected homologated ketone (80). However, the major product in most cases is the aryl-shifted structure (81a), predominantly as its enol tautomer, 3-hydroxy-2-arylacrylic acid (81b). This novel reaction occurs via a 1,2-aryl shift. Although the mechanism has not been fully characterized, there is evidence for loss of THF to give a vacancy for the aldehyde to bind to the iron, followed by diazoacetate attachment. The product balance is then determined by the ratio of 1,2-aryl to -hydride shift, with the former favoured by electron-donating substituents on the aryl ring. An alternative mechanism involving epoxide intermediates was ruled out by a control experiment. 

Reaction of carbonyl compounds with aliphatic diazo compounds to deliver homologated ketones. 

The product epoxy pyrroles such as 8 can be efficiently converted to the alcohol 9, the homologated ester 10, and the homologated ketone 11. 

It was amply emphasized above that the formation of homologous ketones is the principal competing reaction in this condensa-tJoor4M,e To explain this observation it has become customary to invoke a transient intermediate zwitterion, termed by Arndt and Eistert 4 5 a diazomum betaine which can collapse into an epoxide with attendant nitrogen expulsion, or can undergo rearrangement to (me or two possible oarbonyl compounds. The process may be represented schematically as shown in Eq. (284). 

Enamidines can be converted to homologated ketones by alkylation of the anion (t-butyllithium) followed by hydrazinolysis and subsequent cleavage (equation III). 

Finally, we wish to report that the Horner-Wittig reaction has been extended to a-alkyl and a-aryl substituted a-aminomethylphos-phine oxides. After a facile hydrolysis, the homologous ketones are obtained in excellent yields (85-95%). 

An improved synthesis of Uhle s ketone (54), a useful intermediate in ergoline synthesis, has been described,36 in which the closure of the ketone ring is accomplished by the Dieckmann reaction this route is also applicable to the homologous ketone. 

Homologation of aldehydes or ketones. These reagents react with aldehydes or ketones to form homologated ketones. 

Carbonylalion followed by oxidation gives the homologated ketone (3). Yields arc in the range of 60 75%. An overall process can be presented as ... 

Addition of the diazoalkane nucleophile is followed by an reaction with ring-closure or a homologous ketone is formed with a 1,2-alkyl rearrangement (shift). Spirooxiranes are produced from cyclic ketone derivatives with diazomethane (Eq. 86). ... 

An epoxidation reaction utilizing a complex diazo compound is shown in equation (30)." The addition of diazomethane to highly electron-deficient esters has been reported to yield 2-alkoxy-2-substituted epoxides (equation 31)." The stereoselectivity of the addition of diazomethane to pentulose derivative (20) was shown to be superior to that obtained using sulfur ylides, giving ratios of 95 5 in favor of (21 equation 8). However, the yields were unstated, and the products were accompanied in most cases by significant amounts of homologous ketone. ... 

The semipinacol rearrangement is not restricted to 2-heterosubstituted alcohols. Thus, the addition of diazoalkanes to ketones yields homologated ketones (equation 4), via rearrangement of the adduct (3). This process is closely related to the rearrangement of 2-amino alcohols on treatment with nitrous acid (equation 5). Similarly, 2-hydroxyimines undergo rearrangement to 2-amino ketones in a related process (equation 6). 

Rearrangement is sometimes observed on the addition of sulfur ylides to ketones, yielding a homologated ketone rather than the expected epoxide (equation 30). Hydroxy sulfides can undergo elimination to form alkenes, but the conditions are quite specific and require derivatization at oxygen or sulfur. ... 

The diazonium betaines formed are sometimes reasonably stable. The rearrangements which occur with evolution of nitrogen and formation of homologous ketones or aldehydes are described in detail on page 1092 it suffices in this Section to mention the formation of oxiranes (epoxides), which can also occur on evolution of nitrogen ... 

The reaction of ketones with diazomethane has been thoroughly studied (55) homologous ketones or epoxides are the usual reaction products. With acylmetalloids two alternative ketones could be formed, depending on whether the silyl (or germyl) group or the (R ) group attached to the carbonyl underwent the 1,2-migration. 

The homologated ketones are synthesized by adding the a-bromoketone and potassium f-butoxide simultaneously to the B-R-9-BBN at 0 °C. This simultaneous addition procedure provides good yields of the desired ketone with an additional alkyl group (Chart 7.3) [2a],... 

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