Enolates arylations

In the presence of sulfide or sulfhydryl anions, the quinonemethide is attacked and a benzyl thiol formed. The P-aryl ether linkage to the next phenylpropane unit is broken down as a result of neighboring-group attack by the sulfur, eliminating the aryloxy group which becomes reactive phenolate ion (eq. 2). If sulfide is not present, a principal reaction is the formation of the stable aryl enol ether, ArCH=CHOAr. A smaller amount of this product also forms in the presence of sulfhydryl anion. 

The reaction between acyl halides and alcohols or phenols is the best general method for the preparation of carboxylic esters. It is believed to proceed by a 8 2 mechanism. As with 10-8, the mechanism can be S l or tetrahedral. Pyridine catalyzes the reaction by the nucleophilic catalysis route (see 10-9). The reaction is of wide scope, and many functional groups do not interfere. A base is frequently added to combine with the HX formed. When aqueous alkali is used, this is called the Schotten-Baumann procedure, but pyridine is also frequently used. Both R and R may be primary, secondary, or tertiary alkyl or aryl. Enolic esters can also be prepared by this method, though C-acylation competes in these cases. In difficult cases, especially with hindered acids or tertiary R, the alkoxide can be used instead of the alcohol. Activated alumina has also been used as a catalyst, for tertiary R. Thallium salts of phenols give very high yields of phenolic esters. Phase-transfer catalysis has been used for hindered phenols. Zinc has been used to couple... 

A promising recent development is the extension of Pd-catalyzed cross coupling to simple enolates and enolate equivalents. This provides an important way of arylating enolates, which is normally a difficult transformation to accomplish. Use of tri-/-butylphos-phine with a catalytic amount of Pd(OAc)2 results in phenylation of the enolates of... 

An interesting organometallic reaction is the Heck Arylation (Eqn. 1) (ref. 5), which is commonly run using a Pd(OAc>2 catalyst. This reaction is used to prepare aryl enol ethers which can be valuable synthetic intermediates in that they can be hydrolyzed to aldehydes or ketones, species which can be useful themselves or as intermediates in further reactions. The influence of reaction parameters on the rate and selectivity of this reaction was reported in a series of papers (refs. 2, 3). In these a brief mention in some tables was made that Pd/C was able to catalyze this reaction but no discussion of the use of this catalyst was included. We have found, though, that this reaction is readily promoted over dispersed Pd catalysts. When run with Pd(OAc)2 as the catalyst, the Heck reaction gives as the primary products the E (1) and Z (2) aryl P enol ethers in about a 2 1 ratio. The a isomer, 3, and ester, 4, are also produced but in much smaller amounts. When the reaction is run over Pd/A Oj, the same products are obtained but the P enol ethers 1 and 2 are produced in nearly a 3 1 ratio. Table 1 lists the product compositions of these reactions. 

When a series of STO characterized Pd/A Og catalysts were used to promote the Heck reaction (Eqn. 1) the amount of the fi aryl enol ethers, 1 and 2, formed after a 60 minute reaction was directly related to the comer site densities on these catalysts. Thus, this reaction and presumably, others such as the diene cyclization shown in Eqn. 2, which require the adsorption of two reactive species on a single surface atom, must take place on the more coordinatively unsaturated comer atoms. 

Scheme 2 shows a similar mechanistic pathway for a Heck reaction taking place on a Pd octahedral comer. This mechanism is based on that established for soluble Pd catalysts (ref. 5). Adsorption of the aryl halide (or aryl acid chloride after decarbonylation) gives the aryl Pd halide, 15, by way of the adsorbed intermediate, 14. Vinyl ether adsorption, as in 16, takes place as described in Scheme 1. Aryl insertion gives the halometalalkyl, 17, which on f) elimination to the available 4dxy orbital gives the aryl enol ether, 2 (or 1 depending on which hydrogen is eliminated in 17). The resulting halo palladium hydride, 18, then reacts with the tertiary amine to give the amine hydrochloride and regenerates the octahedral comer for further reaction.

Results of semiempirical calculations and deuterium exchange experiments indicate that the succinyl transfer from aryl enol succinates to the enolates of aryl ketones occurs by an addition-elimination mechanism and does not involve a retro-ene process.38... 

Enantioselective protonation reactions are not limited to dienols, however, but also function well with simple enols, e.g. the aryl enol 23. The aryl enol 23 was... 

The arylation of enol esters has also been improved (95). Previously a wide range of products were produced including j8-aryl carbonyls, arylated enol esters, styrene, and stilbene derivatives (96). It has also been found that arylated enol esters can be obtained as major products if the reactions are carried out with stoichiometric amounts of aryl mercuric acetate and palladium acetate in anhydrous acetonitrile or in excess enol ester solution. The products are those arising from addition of the phenyl group to the carbons not containing the ester. Thus, with vinyl acetate and phenyl mercuric acetate, the product is the enol acetate of phenyl acetaldehyde ... 

Arylation. Enolates derived related systems are arylated at deconjugated products. 

The asymmetric hydrogenation of cyclic enol acetate has also proven to be a challenging problem. In this respect, Me-PennPhos 125 was shown to be an effective ligand in the rhodium-catalyzed asymmetric hydrogenation of five- or six-membered cyclic enol acetates such as 172. " In addition, Tang et al. found that the TangPhos-Rh catalyst system provided good-to-excellent (92%-99%) enantioselectivities for a diverse set of aryl enol acetates. ... 

On the other hand, van Otterlo and coworkers utilized an isomeriza-tion/RCM strategy for the synthesis of substituted benzofurans (03TL6483, 05T7746). Isomerization of the aUyl groups in precursor 38 was performed using a ruthenium complex 39 to form the aryl enol ethers 40 subsequent RCM with catalyst 3 then provided the desired benzofurans 37 in excellent yields (Scheme 11). 

It is noteworthy that compounds homologous with (1) couple with Grignard reagents in the presence of nickel-phosphine complexes to produce alkylated and arylated enol ethers (eq A) ... 

PdBr2 with an ammonium bromide in NMP provides an active catalyst enabling the oxidative insertion into the aryl enol esters, which then undergo decarbonylative (with formation of... 

Kotsuki, H., Datta, P.K. and Suenaga, H. (1996) An efficient procedure for palladium-catalyzed hydroformylation of aryl/enol triflates. Synthesis, 470-472. 

The addition of carbon nucleophiles under the form of organolithium reagents to a,p-unsaturated carbonyl compounds is of limited scope for the generation of lithium enolates due to the prevailing 1,2-addition. In certain cases oftritylenones and sterically demanding aryl enolates, the Michael reaction is enforced so that... 

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