Carbonyl addition-elimination-hydrogenation

Seconday and tertiary alcohols readily react with Martin s sulfurane to yield trisubstituted alkenes. These eliminations preferentially provide more highly substituted and conjugated olefins. In his recent synthesis of monopyrrolinone-based HIV-1 protease inhibitors, Smith used sulfurane 1 as part of a three-step carbonyl addition-elimination-hydrogenation sequence (43—>44—>45). The sulfurane-mediated elimination step proceeded... 

Ca.ta.lysis, Iridium compounds do not have industrial appHcations as catalysts. However, these compounds have been studied to model fundamental catalytic steps (174), such as substrate binding of unsaturated molecules and dioxygen oxidative addition of hydrogen, alkyl haHdes, and the carbon—hydrogen bond reductive elimination and important metal-centered transformations such as carbonylation, -elimination, CO reduction, and... 

Double-bond isomerization can also take place in other ways. Nucleophilic allylic rearrangements were discussed in Chapter 10 (p. 421). Electrocyclic and sigmatropic rearrangements are treated at 18-27-18-35. Double-bond migrations have also been accomplished photochemically, and by means of metallic ion (most often complex ions containing Pt, Rh, or Ru) or metal carbonyl catalysts. In the latter case there are at least two possible mechanisms. One of these, which requires external hydrogen, is called the nwtal hydride addition-elimination mechanism ... 

At the outset it is important to clarify the scope of this discussion by the elimination of areas which will not be considered. When one notes that the term "activation of carbon monoxide" may mean a process as little perturbative of the C-0 bond as its end-on attachment to a metal atom in carbonyls, or as strongly perturbative as its dissociation to atoms on a metal surface, the need for limits becomes obvious. In this discussion we will consider only the activation of carbon monoxide in the sense that isolable products are formed by the addition of hydrogen to the molecule without complete rupture of all carbon-oxygen bonds, oxygenates are formed. 

Cyanohydrin derivatives have also been widely used as acyl anion synthons. They are prepared from carbonyl compounds by addition of hydrogen cyanide. A very useful variant is to use trimethylsilyl cyanide with an aldehyde to produce a trimethylsilyloxy cyanide. The cyano group acidifies the a position (pKA 25) and the a proton can be removed by a strong base. Alkylation of the anion and unmasking of the hydroxy group cause elimination of cyanide and re-formation of the carbonyl group. 

Previous reactions in this chapter have involved only addition of the nucleophile and a hydrogen to the carbonyl group. In this reaction, addition is followed by elimination of the oxygen to form a double bond between the carbonyl carbon and the nucleophile. Such an addition-elimination reaction occurs when the nucleophile has or can generate (by the loss of a proton or a phosphorus group) a second pair of electrons that can be used to form a second bond to the electrophilic carbon. In the case of the Wittig reaction, the phosphorus and the oxygen are eliminated to form the alkene. The forma-... 

The naphthylamines may be prepared by reduction of the corresponding nitro compound, but they are readily accessible from naphthois by the Bucherer reaction The naphthol is heated, preferably under pressure in an autoclave, with ammonia and aqueous sodium hydrogen sulfite solution, when an addition-elimination sequence occurs. The detailed mechanism is not completely elucidated, but the Bucherer reaction is restricted to those phenols that show a tendency to tautomerize to the keto form, such as the naphthois and 1,3-dihydroxybenzene (resorcinol). Using 1-naphthol for illustration, the first step is addition of the hydrosulfite across the 3,4-double bond of either the enol or keto tautomer (Scheme 12.9). Nucleophilic attack by ammonia at the carbonyl group... 

The other is a two-step, elimination-addition mechanism. In the elimination step, / elimination occurs by an E2 mechanism to give a ketene, a very reactive compound that is not usually isolable. In the addition step, the alkoxide adds to the electrophilic carbonyl C of the ketene to give the enolate of an ester. Acyl chlorides lacking a-hydrogens (t-BuCOCl, ArCOCl), of course, can react only by the addition-elimination mechanism. 

Table 7-2 summarizes kinetic data for the reaction of O2 with esters, diketones, and carbon dioxide.35,37-39 Esters react with superoxide ion to form diacyl peroxides or the carboxylate and the alcohol. Initial reaction occurs via a reversible addition-elimination reaction at the carbonyl carbon (Scheme 7-9). This conclusion is supported by the products that are observed in the gas-phase reaction of O2 with phenyl acetate and phenyl benzoate, which has been studied by Fourier-transform mass spectrometry.40 in effect, there is a competition between loss of O2 and loss of the leaving group. Carbanions are poor leaving groups, so that simple ketones without acidic a-hydrogen atoms are unreactive. The KC(O)OO- radical should be a reactive intermediate for the initiation of the autoxidation of allylic hydrogens (see Chapter 5). 

Sometimes, although the first step in the reaction may be addition of hydrogen to carbonyl, the overall reaction involves elimination of the carbonyl oxygen as water ... 

HCI + CH2 CH2 CHaCHja An example of nucleophilic addition is the addition of hydrogen cyanide across the carbonyl bond in aldehydes to form cyanohydrins. Addition-elimination reactions are ones in which the addition is followed by... 

The enolate attacks the carbonyl carbon of another ester molecule, forming a tetrahedral intermediate. The tetrahedral intermediate expels an alkoxide ion, resulting in substitution of the alkoxide by the group derived from the enolate. The net result is nucleophilic addition-elimination at the ester carbonyl group. The overall equilibrium for the process Is unfavorable thus far, however, but it is drawn toward the final product by removal of the acidic a hydrogen from the new... 

Heck has formulated a mechanism which accounts for hydroformylation of olefins catalyzed by cobalt carbonyl (68). A modification of this mechanism is presented in Fig. 5. Cobalt octacarbonyl reacts with hydrogen to form the tetracarbonyl hydride. It is proposed that this coordinatively saturated complex loses a CO group to form the four-coordinate hydride (LX). Coordination of an olefin yields the olefin complex (LXI). Migration of hydride yields an unsaturated alkyl complex (LXII). Further insertion of a CO group (undoubtedly by a migration mechanism) affords the four-coordinate acyl cobalt(I) complex (LXIII). Oxidative addition of hydrogen affords the hypothetical dihydride (LXIV), which eliminates the product aldehyde and regenerates the cobalt(I) hydride catalyst (LX). This latter... 

The mechanism of this reaction is only slightly more complicated than the usual reaction of nucleophiles with acid chlorides (p. 854). Diazo compounds are nucleophiles at carbon and add to the carbonyl group of the reactive acid chloride. Chloride ion is expelled in the elimination phase of this normal addition-elimination process. In the only new step of the reaction, chloride removes the newly acidic hydrogen to give the diazo ketone (Fig. 18.64).This hydrogen is acidic because the conjugate base is stabilized by resonance. 

---