Enolates fonnation

Both parts of the Lapworth mechanism, enol fonnation and enol halogenation, are new to us. Let s examine them in reverse order. We can understand enol halogenation by analogy to halogen addition to alkenes. An enol is a very reactive kind of alkene. Its caibon-caibon double bond bears an electron-releasing hydroxyl group, which makes it electron-rich and activates it toward attack by electrophiles. 

Our experience to this point has been that C—H bonds aie not very acidic. Com-paied with most hydrocaibons, however, aldehydes and ketones have relatively acidic protons on theii a-caibon atoms. pK "s for enolate fonnation from simple aldehydes and ketones aie in the 16 to 20 range. 

The slow step in base-catalyzed enolization is fonnation of the enolate ion. The second step, proton transfer from water to the enolate oxygen, is very fast, as aie almost all proton transfers from one oxygen atom to another. 

In a reiterative approach, enol ether epoxidation with DM DO has been coupled with C-C bond fonnation and ring-closing metathesis to provide trans-fused THP ring systems [82],... 

Upon fonnation of intermediate LI, conjugate addition to a chalcone and subsequent proton transfer is proposed to lead to enolate LIII (Scheme 37). An intramolecular aldol addition provides activated carboxylate LIV in which alkoxide acylation regenerates the catalyst and delivers p-lactone LVI which, upon decarboxylation, gives rise to a trisubstituted cyclopentene. 

Another attractive domino approach starts with an aldol reaction of preformed enol ethers and carbonyl compounds as the first step. Rychnovsky and coworkers have found that unsaturated enol ethers such as 2-237 react with different aldehydes 2-238 in the presence of TiBr4. The process consists of an aldol and a Prins-type reaction to give 4-bromotetrahydropyrans 2-239 in good yields, and allows the fonnation of two new C-C-bonds, one ring and three new stereogenic centers (Scheme 2.56) [131]. In the reaction, only two diastereomers out of eight possible isomers were fonned whereby the intermediate carbocation is quenched with a bromide. 

A common procedure in C-C-bond formation is the aldol addition of enolates derived from carboxylic acid derivatives with aldehydes to provide the anion of the (3-hydroxy carboxylic acid derivative. If one starts with an activated add derivative, the fonnation of a (3-lactone can follow. This procedure has been used by the group of Taylor [137] for the first synthesis of the l-oxo-2-oxa-5-azaspiro[3.4]octane framework. Schick and coworkers have utilized the method for their assembly of key intermediates for the preparation of enzyme inhibitors of the tetrahydrolipstatin and tetrahydroesterastin type [138], Romo and coworkers used a Mukaiyama aldol/lac-tonization sequence as a concise and direct route to (3-lactones of type 2-253, starting from different aldehydes 2-251 and readily available thiopyridylsilylketenes 2-252 (Scheme 2.60) [139],... 

A combination of a Pd-catalyzed arylation of a ketone followed by intramolecular cyclization of the fonned enolate with an allylic silyl ether moiety in one of the substrates led to the direct fonnation of a 1 -vinyl-111-isochromene, as described by Wills and coworkers [164],... 

Alternatively, diltiazem (21) has been prepared using the Evans auxiliary 22 derived from L-valine (Seheme 5) [50], After dehydration of the adduct from the condensation of 22 with anisaldehyde through the mesylate, the enol ether was formed with a Z E ratio of 4 1. This imide was then treated with 2-aminothi-ophenol in the presence of 0.1 equivalents of 2-aminothiophenoxide with no change in the isomer ratio. The auxiliary was removed with trimethylaluminum, with concomitant fonnation of the lactam. After separation by crystallization, the correct diastereoisomer was converted to diltiazem in > 99% ee. 

See Section 362 (Ester-Alkene) for the fonnation of enol esters and Section 367 (Ether-Alkenes) for the fonnation of enol ethers. Many of the methods in Section 60A (Protection of Aldehydes) are also applicable to ketones. 

Talcing our earlier work into account, we proposed a mechanism for the NOx reduction by C .dUOM, which can be described by a simplitled reaction scheme, shown in Scheme 2. The reaction starts with the fonnaiioii of both ad.sorbed nitrates via NO oxidation by (). and enolic species and acetate via the partial oxidation of C dCOH over Ag/AI O . The reaction between the two kinds of adsorbed species then leads to the fonnalion of NCO directly, or via organo-nitrogcn compounds (such as R-ONO and R-NO ). which is widely accepted in the studies of the S( R of NOx 15.22.43.46.66). Subsetiuenily. NCO reacts w ith NO - O and nitrates to yield N,. It should be pt>inted out that the acetate formed by the reaction of C H.OII O alsi> reads toward NO O to produce NC O. However, as a result of its low adiviiy, this parallel reaction dt>es not play an important role in the fonnation of NCO. 

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