Aldehydes enolate equivalents from

Silyl enol ethers are other ketone or aldehyde enolate equivalents and react with allyl carbonate to give allyl ketones or aldehydes 13,300. The transme-tallation of the 7r-allylpalladium methoxide, formed from allyl alkyl carbonate, with the silyl enol ether 464 forms the palladium enolate 465, which undergoes reductive elimination to afford the allyl ketone or aldehyde 466. For this reaction, neither fluoride anion nor a Lewis acid is necessary for the activation of silyl enol ethers. The reaction also proceed.s with metallic Pd supported on silica by a special method[301j. The ketene silyl acetal 467 derived from esters or lactones also reacts with allyl carbonates, affording allylated esters or lactones by using dppe as a ligand[302]... 

Imine enolates can be prepared without self-condensation, yet they will add rapidly to carbonyl compounds. This circumvents the low reactivity of ketones toward carban-ions derived from nonactivated methylene compounds and permits addition of aldehyde enolate equivalents to ketones. 

Enolate Equivalents from Aldehydes with an o-Leaving Group... 

Enolate Equivalents from Aliphatic Aldehydes with Oxidant... 

Silyloxy)alkenes were first reported by Mukaiyama as the requisite latent enolate equivalent to react with aldehydes in the presence of Lewis acid activators. This process is now referred to as the Mukaiyama aldol reaction (Scheme 3-12). In the presence of Lewis acid, anti-aldol condensation products can be obtained in most cases via the reaction of aldehydes and silyl ketene acetals generated from propionates under kinetic control. 

Enantioselective -Functionalization of Aldehydes and Ketones The direct and enantiosective functionalization of enolates or enolate equivalents with carbon-, nitrogen-, oxygen-, sulfur- or halogen-centered electrophiles represents a powerful transformation of chemical synthesis and of fundamental importance to modem practitioners of asymmetric molecule constmction. Independent studies from List, J0rgensen, Cordova, Hayashi, and MacMiUan have demonstrated the power of enamine catalysis, developing catalytic enantioselective reactions such as... 

In 1997, Kobayashi and colleagues reported the first truly catalytic enantioselective Mannich-type reactions of aldimines 24 with silyl enolates 37 using a novel chiral zirconium catalyst 38 prepared from zirconium (IV) fert-butoxide, 2 equivalents of (R)-6,6 -dibromo-l,l -bi-2-naphthol, and N-methylimidazole (Scheme 13) [27, 28], In addition to imines derived from aromatic aldehydes, those derived from heterocyclic aldehydes also worked well in this reaction, and good to high yields and enantiomeric excess were obtained. The hydroxy group of the 2-hydroxyphenylimine moiety, which coordinates to the zirconium as a bidentate ligand, is essential to obtain high selectivity in this method. 

The use of hydrazones is particularly important to form die enolate equivalents of aldehydes. Aldehydes are quite reactive as electrophiles, so as soon as some enolate has been formed, it reacts witii die unreacted aldehyde present in solution. Conversion of die aldehyde to its /V, /V-dimetliy 1 hydrazone (=NNMe2) lowers the electrophilicity so that a-proton removal can take place and then the electrophile of choice can be added. Hydrolysis gives back the aldehyde. In this case the geometry of die hydrazone is unimportant since aldehydes have only one a position from which protons can be removed by base. 

Among the best enol equivalents for aldehydes are enamines.19 They are stable compounds, easily made from aldehydes 95 and secondary amines, reacting with electrophiles in the same way as enols 96 to give iminium salts 97, hydrolysed to substituted aldehydes 98. 

Hexyne has the triple bond in the middle of a carbon chain and is termed an internal alkyne. If, instead, an alkyne with the triple bond at the end of the carbon chain, a 1-alkyne or a terminal alkyne, were used in this reaction, then the reaction might be useful for the synthesis of aldehydes. The boron is expected to add to the terminal carbon of a 1-alkyne. Reaction with basic hydrogen peroxide would produce the enol resulting from anti-Markovnikov addition of water to the alkyne. Tautomerization of this enol would produce an aldehyde. Unfortunately, the vinylborane produced from a 1-alkyne reacts with a second equivalent of boron as shown in the following reaction. The product, with two borons bonded to the end carbon, does not produce an aldehyde when treated with basic hydrogen peroxide. 

Silyl enolates react with acyl cation equivalents to give the C- and/or O-acylated products (Equation (90)).333 Fluoride-catalyzed reaction using acyl fluorides is valuable for O-acylation of silyl enolates derived from aldehydes and ketones.334 CuCl also promotes the 0-acylation with acyl chlorides.335 The CuCl-promoted reaction of ester silyl enolates results in exclusive (7-acylation. Combined use of BiCfl and Znl2 (or Nal) effects catalytic (7-acylation of ketone silyl enolates with acyl chlorides. 

The conjugated ylides derived from aldehydes, ketones, and esters are all sufficiently stable to be commercially available as the ylids—one of the few examples of specific enol equivalents that you can actually buy. The ylid corresponding to the enolate of acetaldehyde is a solid, m.p. 185-188 °C that reacts well with other aldehydes, even if they are enolizable. 

Other useful specific enol equivalents of aldehydes and ketones are enamines and aza-enolates, which you saw in use in alkylation reactions in Chapter 26. Aza-enolates—the lithium enolates of imines—derived from aldehydes are useful too in aldol reactions. 

For the synthesis of the pyrrolizidine fragment (2), we identified maleic anhydride (5, 7 /kg), aminobutyric acid (6, 120 /kg) and trienal 7 as readily available starting materials. In the most ambitious disconnection, the racemic pyrrolizidine carboxylic acid 4a, could be assembled, in principle, in a single step from 4-aminobutyric acid (6) and maleic anhydride (5). A subsequent kinetic resolution via oxa-Michael addition would then generate an enantiomerically enriched enolate equivalent, which could in turn add to the aldehyde 3. However,... 

Compared to the great variety of Lewis acid catalysts for the catalytic asymmetric aldol reaction the field of nucleophilic (Lewis base) catalysts is less explored. This strategy involves the transient activation of the latent enolate equivalent via Lewis base coordination to the silyl enol ether (Scheme 9) [3], For instance the tri-chlorosilyl enol ether 50 is able to expand its valency at the silicon atom from four to five and six. It reacts with an aldehyde (51), proceeding through a closed Zimmerman-Traxler-like transition state (54), to give 53 after quenching with saturated aqueous NaHCO, [16]. 

Enantioselective cross aldol reactions. A 3-acylthiazolidine-2-thione can be used as an equivalent of an aldehyde or carboxylic arid in cross aldol reactions to provide p-hydroxy aldehydes or carboxylic acids. The tin enolates formed from Sn(OTf), react with aromatic and aliphatic aldehydes with high svn-selectivity (equation I),... 

Silyl enol ethers are versatile reagents in organic synthesis [83]. They are used as isol-able enolate equivalents and many useful reactions have been developed using silyl enol ethers [83]. As a new approach to exploit an efficient method for combinatorial synthesis [84], silyl enol ethers were successfully immobilized on to a polymer. Polymer-supported silyl enol ethers (PSSEEs) were prepared according to Sch. 10 [85]. In aldol reactions of PSSEEs with aldehydes, it was again found that Sc(OTf)3 was an efficient catalyst [86]. An example of the preparation of a 1,3-diol library by use of PSSEEs is shown in Sch. 11. In all cases, the reactions proceeded smoothly to afford the corresponding 1,3-diols in good yields. 1,3-Diols are successfully cleaved from the... 

Since we shall reduce all the carbonyl groups to alcohols, it doesn t really matter which route - follow. Compound A would require a crossed aldol reaction between two aldehydes so we ll ave r that Compound B is easier as we can use a specific enol equivalent (we have chosen the zinc enout as it is less basic than most see p. 706) from an ester to add to the aldehyde. 

The condensation of enolates derived from malonic esters and other active methylene compounds with a,p-unsaturated aldehydes, ketones, esters, or nitriles proceeds exclusively by 1,4-addition. The conjugate addition to a,(3-unsaturated compounds, often called Michael acceptors, is promoted by treatment of the active methylene species with either an excess of a weak base (e.g., Et3N or piperidine) or using a stronger base in catalytic amounts (e.g., 0.1-0.3 equivalents NaH, NaOEt, or r-BuOK). 

The fact that ketones, aldehydes, and geminal diacetates are readily available from these reactions illustrate their complementarity to reactions with allylsilanes. Specifically, the equivalency of allylic ethers to homoenolates allows for the formation of compounds extended by one carbon unit as compared to the products of couplings with enolate equivalents already discussed. 

The best specific enol equivalents for aldehydes are enamines (75) and these are also very useful for ketones. They are easily made from the carbonyl compound and a secondary amine, are stable isolable compounds, and react... 

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