Aryl halides enolates

Lewis acids catalyse the cyclocondensation of acid chlorides and aldehydes to give lactones (83) and (84). Aluminium chloride catalysis favours the 1 1 product (84), via a ketene pathway, while the large ring is the predominant product using e.g. TiCl2(OPr )2, where aryl halide enolates are implicated as intermediates. 

Aryl halides react with a wide variety of aryl-, alkenyl- and alkylstan-nanes[548-550]. Coupling of an aryl tritlate with an arylstannane is a good preparative method for diaryls such as 688. The coupling of alkenylstannanes with alkenyl halides proceeds stereospecifically to give conjugated dienes 689. The allylstannane 690 is used for allylation[397,546,551-553]. Aryl and enol triflates react with organostannanes smoothly in the presence of LiCl[554]. 

Vinylic and aryl halides can be used to vinylate or arylate carboxylic esters (but not ketones) by the use of NiBr2 as a catalyst. " However, ketones have been vinylated by treating their enol acetates with vinylic bromides in the presence of a Pd... 

An example of this displacement between a pyridine nitrogen atom and an aryl halide is shown in Scheme 21. When 2-pyridyl acetates 138 were C-acylated with 2-halobenzoyl chlorides, the enolized products 139 resulting from the reaction suffered an intramolecular nucleophilic attack of the pyridine nitrogen atom onto the ipso-position to give benzo[c]quinolizinium salts 140 as intermediates. Loss of HC1 gas from 140 afforded benzo[c]quinolizine derivatives 141 <2002JOC2082>. 

Commensurately with the development of various catalyst systems, the Pd-catalyzed G-O cross-coupling has found a number of synthetic applications. Examples include the syntheses of the protein kinase G (PKC) activator (+)-decursin,104 the natural product heliannuol E,105 a chiral 2-methyl chroman,106 and a series of aryloxy and alkoxy porphyrins.107 The Buchwald-Hartwig coupling has also been utilized in the preparation of a heterocycle library.108 Intramolecular O-arylation has also been achieved in the reactions of enolates with aryl halides leading to benzofur-ans.109,110 Finally, a double cross-coupling between an 0-dibromobenzene and a glycol has also been applied for the preparation of benzodioxanes (Equation (16)).1... 

The radical-chain 5 rnI reaction is a useful method for the formation of new carbon-carbon bonds reactions of the enolate ions of 2-acetylthiophene and 2-acetylfuran with aryl halides have been investigated using photo-initiation and also iron(II) initiation. ... 

The relative reactivities of the enolate ions of acetophenone and 2-acetylnaphthalene towards phenyl radicals have been explored in order to determine their suitability as electron donor initiatiors of 5 rnI reactions of enolate ions of 2-acetylthiophene and 2-acetyl fiiran with aryl halides Phl. ... 

As the last example of C-C bond-formation reactions catalyzed by alkaline earth hydroxides, we mention the recently reported a-arylation of diethyl malonate in the presence of a palladium catalyst and a base in a separate phase 299). The arylation of carbonyl compounds is a carbon-carbon coupling reaction between an aryl halide and an enolate, which is usually catalyzed by palladium salts in the presence of an appropriate base (300,301). The arylation of diethyl malonate with bromobenzene (Scheme 48) was performed with tetrachloropalladate as the... 

An interesting arylation of the silyl enolate of Ley s dioxanone 133 in the presence of a catalytic amount of Pd2(dba)3 (5 mol%) and P(/-Bu)3 (10 mol%) with 0.5 equiv of Znp2 or Zn(0-/-Bu)2 provides a single diastereoisomer of the coupled products 134 (dba = dibenz[ , ]anthracene). A variety of electronically and sterically distinct aryl halides, including those containing electrophilic functional groups, have been introduced (Equation 20) <2004JA5182>. 

Bromination of the enol ether product with two equivalents of bromine followed by dehydrobromination afforded the Z-bromoenol ether (Eq. 79) which could be converted to the zinc reagent and cross-coupled with aryl halides [242]. Dehydrobromination in the presence of thiophenol followed by bromination/dehydrobromination affords an enol thioether [243]. Oxidation to the sulfone, followed by exposure to triethylamine in ether, resulted in dehydrobromination to the unstable alkynyl sulfone which could be trapped with dienes in situ. Alternatively, dehydrobromination of the sulfide in the presence of allylic alcohols results in the formation of allyl vinyl ethers which undergo Claisen rearrangements [244]. Further oxidation followed by sulfoxide elimination results in highly unsaturated trifluoromethyl ketonic products (Eq. 80). 

Stephen L. Buchwald at MIT has reported (Org. Lett. 2004, 6, 4809) a complementary approach. Enantioselective conjugate reduction of the inexpensive 3-methylcyclopentenone 4 led to the silyl enol ether 5, Pd-mediated coupling of which with the aryl halide gave the product 6. 3-Methylcyclohexenone gave the analogous product in 84% . 

Vinylic and aryl halides can be used to vinylate or arylate carboxylic esters (but not ketones) by the use of NiBr2 as a catalyst.1463 However, ketones have been vinylated by treating their enol acetates with vinylic bromides in the presence of a Pd compound catalyst.1464 Also as in 0-94, this reaction can be used to close rings.1465 In one example of this, rings have been closed by treating a diion of a dialkyl succinate with a l,cu-dihalide or ditosylate,1466, e.g. ... 

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.

Vinyl substitution of primary or secondary allylic alcohols with aryl halides usually produces 3-aryl aldehydes or ketones, respectively. The reaction is believed to involve an addition of the intermediate arylpalladium halide to die double bond, placing the aryl group mainly on the more distant carbon from the hydroxy group, followed by palladium hydride elimination, a reverse readdition and another elimination with a hydrogen atom on the carbon bearing the hydroxy group. The product is probably a ir-com-plex of the enol which ultimately either dissociates or collapses to a a-complex with palladium on the... 

A procedure has been developed for the palladium-catalysed a-arylation of amides by aryl bromides using the zinc enolates of the amides. The reaction works well with bromoarenes carrying a variety of ring substituents and with bromopyridine. In addition, the reaction has been shown to be effective with morpholine amides to give products which are precursors for aldehydes and ketones.39 A new method has been reported for the allylation of aryl halides using homoallyl alcohols as the allyl source the palladium-catalysed reaction, which may be both stereo- and regio-sepecific, uses a retro-allylation reaction to form a a-allyl(aryl)palladium intermediate.40... 

A new type of triaryl phosphine-functionalized imidazolium salt containing cations such as (6) has been prepared. Palladium complexes of (6) generated in situ have been used successfully in Heck-type reactions of aryl halides with acrylates and of 4-bromotoluene with styrene derivatives.34 The first Heck-type reaction of aryl halides with allenes has been reported. 1,3-Double arylations were observed with 3-substituted-l,2-allenyl sulfones, while 1-monoarylation was favoured with 3,3-disubstituted-l,2-allenyl sulfones.35 It has been shown that the a-arylation of methane-sulfonamides (7) may be achieved using palladium catalysis reaction proceeds through the sulfonamide enolates.36 It is also reported that palladium cross-coupling of alkynes with /V - (3 - i odophe n y I an i I i ncs) may lead to the formation of substituted carbazoles.37... 

Alkyl aryl ketones are known to be arylated at the a-position of the alkyl groups, via the corresponding enolates, by treatment with aryl halides in the presence of palladium catalysts [4, 9]. The ortho arylation of alkyl aryl ketones is also possible. For example, in the reaction of benzyl phenyl ketones with bromobenzenes, the arylation first occurs at the benzylic position the ortho positions are then arylated via C-H bond cleavage (Eq. 8) [15]. The ortho arylation is believed to occur after coordination of the enol oxygen to ArPd(II), which is followed by ortho palladation as in the reaction of 2-phenylphenols shown in Scheme 2. 

The Reformatsky reagents, i.e. zinc enolates of esters, undergo Ni catalysed cross-coupling with aryl halides.53 The Ni catalysed reaction of arylzincs with a-bromoacetates also permits a-arylation of esters54 (Scheme 11.13). However, a-alkenylation of enolates of ketones, aldehydes, and esters has been less satisfactory. Its further development is clearly desirable. Alternatively, a-alkenylation of a-iodoenones in conjunction with conjugate reduction discussed earlier should be considered. 

Ferrayoli, C.G., Palacios, S.M. and Alonso, R.A. (1995) Alternative synthesis of 2-Aryl propanoic adds from enolate and aryl halides. Journal of the Chemical Society, Perkin Transactions 1, 1635-1638. 

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