Alder-Ene Reaction, Ene Reaction
The four-electron system including an alkene π-bond and an allylic C-H σ-bond can participate in a pericyclic reaction in which the double bond shifts and new C-H and C-C σ-bonds are formed. This allylic system reacts similarly to a diene in a Diels-Alder Reaction, while in this case the other partner is called an enophile, analogous to the dienophile in the Diels-Alder. The Alder-Ene Reaction requires higher temperatures because of the higher activation energy and stereoelectronic requirement of breaking the allylic C-H σ-bond.
The enophile can also be an aldehyde, ketone or imine, in which case β-hydroxy- or β-aminoolefins are obtained. These compounds may be unstable under the reaction conditions, so that at elevated temperature (>400°C) the reverse reaction takes place - the Retro-Ene Reaction.
Also like the Diels-Alder, some Ene Reactions can be catalyzed by Lewis Acids. Lewis-Acid catalyzed Ene Reactions are not necessarily concerted (for example: Iron(III) Chloride Catalysis of the Acetal-Ene Reaction).
The [1,2]-Brook Rearrangement of α-silyl carbinols is an intramolecular 1,2-anionic migration of a silyl group from carbon to oxygen in the presence of a catalytic amount of a base such as Et2NH, NaH or NaOH. The migratory aptitude is general over a range of homologues, and [1,n]-carbon to oxygen migrations are commonly referred to as Brook Rearrangements.
Mechanism of the Brook Rearrangement
The mechanism includes the formation of a cyclic pentavalent silicon species immediately following the deprotonation. Subsequent ring opening and irreversible, fast protonation of the carbanion by the starting alcohol or the conjugate base leads to the corresponding silyl ether:
The greater strength of the oxygen-silicon bond compared to the carbon-silicon bond provides the driving force for the conversion of silyl carbinols to the corresponding silyl ethers. An electron-withdrawing R group facilitates the kinetics of the carbanion formation.
In the presence of a strong base in stoichiometric amounts, the equilibrium between alkoxide and carbanion is relative to the stabilities of the corresponding anionic species.
Here, the presence of an electron withdrawing group R shifts the equilibrium to the right, whereas counterions that form strong ion pairs with oxygen such as lithium favor an oxygen to carbon silyl migration (retro-Brook Rearrangement). Destabilization of the alkoxides using polar solvents such as THF also shifts the equilibrium towards the silyl ethers.
The use of a stoichiometric amount of base and the control of the equilibrium enables tandem strategies to introduce electrophiles.The use of acylsilanes makes even more sophisticated tactics possible.
The acid-catalyzed reaction of ketones with hydroperoxide derivatives is known as the Baeyer-Villiger reaction. The rearrangement step is similar to that of a pinacol rearangement. Esters or lactones are the chief products from ketone reactants. In this a discrete oxacation is an intermediate, but it is more likely that the rearrangement is concerted. Once the peracid has added to the carbonyl group, the rearrangement may be facilitated by an intramolecular hydrogen bond, in the manner depicted in brackets on the right. The migratory aptitude of various substituent groups is generally: 3º-alkyl > 2º-alkyl ~ benzyl ~ phenyl > 1º-alkyl > methyl.
Stereoelectronic factors favor an anti-periplanar orientation of the migrating group to the leaving moiety, and will control the rearrangement in some cases. Peracid exchange with peracetic acid leads to an intramolecular Baeyer-Villiger reaction by way of the bicyclic acylperoxide drawn in brackets. Here stereoelectronics favor migration of the less substituted α-carbon. The lactone product was identified by esterification and ester exchange with methanol to give methyl 2-carbomethoxy-7-hydroxyheptanoate. Aldehydes are usually oxidized to carboxylic acids under the conditions used for the Baeyer-Villiger reaction.
Although hydrogen peroxide itself may be used in the Bayer-Villiger reaction, it may add at both ends to reactive carbonyl groups, producing cyclic dimeric, trimeric and higher addition compounds. Consequently, derivatives such as peracids (Z = RCO & ArCO above) are the preferred reagents for this reaction. Among the most common peracids used in this respect are: peracetic acid, perbenzoic acid & meta-chloroperbenzoic acid (MCPBA). In most of the examples the migrating group retains its configuration in the course of the rearrangement, as expected for a concerted process.
The Arndt-Eistert Reaction
The rearrangement of acyl nitrenes to isocyanates that is the crux of the Hofmann, Curtius and Lossen rearrangements, is paralleled by the rearrangement of acyl carbenes to ketenes, a transformation called the Wolff rearrangement. This rearrangement is a critical step in the Arndt-Eistert procedure for elongating a carboxylic acid by a single methylene unit. The starting acid, is converted first to an acyl chloride derivative, and then to a diazomethyl ketone. Diazomethane has a nucleophilic methylene group. Acylation of the methylene carbon produces an equilibrium mixture of a diazonium species and the diazomethyl ketone plus hydrogen chloride. If the HCl is not neutralized by a base, this mixture reacts further to give a chloromethyl ketone with loss of nitrogen. However, if the HCl is neutralized as it is formed, the relatively stable diazo ketone is obtained and may be used in subsequent reactions. Since diazomethane itself may function as a base, the course of a given reaction is established by the manner in which the reactants are combined. When an ether solution of diazomethane is slowly added to a warm solution of the acid chloride, nitrogen evolution is observed and the chloromethyl ketone is the chief product. One equivalent of diazomethane is required for this reaction. If the addition is reversed, so that a cold solution of the acid chloride is added slowly to an excess of diazomethane in cold ether solution, nitrogen evolution is again observed; but two equivalents of diazomethane are consumed. The products are the diazo ketone and methyl chloride (a gas) from the reaction of diazomethane with HCl..
To carry out the Arndt-Eistert reaction the diazo ketone is decomposed in the presence of a silver catalyst (usually AgO2 or AgNO3 ) together with heat or light energy. The resulting Wolff rearrangement generates a ketene, which quickly reacts with any hydroxylic or amine reactants that may be present in solution. The end product from the Arndt-Eistert reaction may be a carboxylic acid, an ester or an amide.