Pd -catalysed reaction

Scheme 5.18 Examples of Pd-catalysed reactions in ionic liquids...

Coumarins are formed by the intramolecular hydroarylation of an activated alkyne. The basic starting materials for this fast, efficient and general Pd-catalysed reaction are phenols and alkynoic acids (Scheme 42), An intermolecular version in which electron-rich phenols react with 4-methoxycinnamic acid leads to high yields of 3,4-dihydrocoumarins... 

The dicarboxamide 443 could be sequentially lithiated and substituted twice under similar conditions and was reacted with several electrophiles . The sequence is shown in equation 120 for the synthesis of the bis(diphenylphosphine) 445. Only a little meso-445 is formed, removing most of the minor enantiomer of 445. The phosphines 444, 445 and meso-445 had been prepared earlier by Jendralla and Paulus applying the Snieckus method, and had been tested in enantioselective Pd-catalysed reactions . 

Thiochroman-4-ones result from the Pd-catalysed reaction of iodothiophenols with allenes and carbon monoxide <99JOC9646> and various thioflavonoids are accessible from acetoquinone via derived chalcones <99JOC359>. 

The Pd-catalysed reaction is possible with a stannylene on condition that it is carried out at low temperature, in order to avoid the competing uncatalysed formation of a polymeric product, and in the presence of a labile complex as catalyst (equation 6). The stannole 23... 

The Pd-catalysed reaction between ethyne and the germanorbomadiene derived from 1,1-dibutyl-2,3,4,5-tetraphenylgermole and benzyne gives a C-unsubstituted germole (17) (Scheme 5)24a. 

As a typical example of the catalytic cycle, the Pd-catalysed reaction of benzoyl chloride (99) with MeSnBu3 to afford acetophenone (100) is explained by the... 

Innovations in the chemistry of aromatic compounds have occurred by recent development of many novel reactions of aryl halides or pseudohalides catalysed or promoted by transition metal complexes. Pd-catalysed reactions are the most important [2,29], The first reaction step is generation of the arylpalladium halide by oxidative addition of halide to Pd(0). Formation of phenylpalladium complex 1 as an intermediate from various benzene derivatives is summarized in Scheme 3.1. 

Alkenyl halides and their pseudohalides also react with Pd(0) to form the alkenylpalladium intermediates 11, and their transformations are summarized in Scheme 3.4. In addition to alkenyl halides, the enol triflates 12 undergo oxidative addition, showing that carbonyl compounds are useful starting compounds for Pd-catalysed reactions. 

Scheme 4.2 Allylic compounds used for Pd-catalysed reactions...

Pd-catalysed allylation of amines proceeds smoothly. Allylamine (132) and di- and triallylamines are produced commercially by the Pd-catalysed reaction of ammonia with allyl alcohol using DPPB as a suitable ligand [69]. Allylic alcohols are rather unreactive substrates for 7r-allylpalladium complex formation under usual conditions. The intramolecular amination of 133 afforded the azaspiro ring 134 and the reaction was applied to the synthesis of perhydrohistrionicotoxin (135) [70]. Smooth Pd-catalyzed allylation of the purine base 136 gives 137, which is utilized for the synthesis of nucleosides [71]. 

However, whereas intermolecular insertion of alkene to 7r-allylpalladium is difficult, intramolecular insertion proceeds smoothly. This reaction is known as the metalla-ene (pallada-ene) reaction [124]. Use of AcOH as the solvent is crucial. The Pd-catalysed reaction of 277 under CO atmosphere affords the keto ester 279 by one-pot reaction... 

Pd-catalysed Reactions of Allyl 5-Keto Carboxylates, Malonates, and Enol Carbonates... 

Needless to say, /i-keto esters are important compounds in organic synthesis. Their usefulness has been considerably expanded, based on Pd-catalysed reactions of allyl / -keto carboxylates 399. Cleavage of the allylic carbon-oxygen bond and subsequent facile decarboxylation by the treatment of allyl / -keto carboxylates with Pd(0) catalysts generate the 7i-allylpalladium enolates 400, 401. These intermediates undergo, depending on the reaction conditions, various transformations which are not possible by conventional methods. Thus new synthetic uses of / -keto esters and malonates based on Pd enolates have been expanded. These reactions proceed under... 

The reductive coupling of the 7i-allylpalladium enolates 400 gives the allylated ketones 403. This reaction is also possible thermally and is called the Carroll reaction. Whereas the Carroll reaction proceeds by heating up to 200 °C, the Pd-catalysed Carroll-type reaction can be carried out under mild conditions (even at room temperature) by reductive elimination of the 7t-allylpalladium enolate 400 [177,178], The Pd-catalysed reaction is mechanistically different from the thermal reaction and more versatile, which is explained by the [3,3] sigmatropic rearrangement of the enolate form. For example, thermal Carroll rearrangement of the a,a-disubstituted keto ester 410 is not possible, because there is no possibility of the enolization. However, it rearranges to ketone 411 smoothly with the Pd catalyst, via the 7i-allylpalladium enolate. 

Various Pd-catalysed reactions of allyl (1-keto carboxylates, summarized in Scheme 4.3 and shown in the above clearly indicate that synthetic utility of /i-kcto esters and malonates has been expanded. 

Telomerization with various nucleophiles affords interesting functionalized dimers 133 and 134 [50-54]. The Pd-catalyzed telomerizations of butadiene with various nucleophles gives 1-substituted 2,7-octadienes 133 as major products, and 3-substituted 1,7-octadienes 134 as minor products as summarized in Scheme 5.1. The telomers obtained by the Pd-catalysed reactions are useful building blocks. Natural products, such as steroids and macrolides, are synthesized efficiently using these telomers [55]. 

Formation of 2,7-octadien-l-ol (136) by the reaction of water attracts attention as a new commercial process for -octanol (155). The Pd-catalysed reaction of water under... 

Hydroboration proceeds without a catalyst, but hydroboration with less active catecholborane (225) is accelerated by catalysts. Usually 1,2-addition to conjugated dienes takes place, but the Pd-catalysed reaction of catecholborane (225) gives the 1,4-adduct 226. This reaction is not catalysed by Rh complexes [98], Hydroalumination of conjugated dienes catalysed by Cp2TiCl2 affords the allylic aluminium compounds 227 by 1,4-addition. The Pd-catalysed hydrostannation of isoprene with HSnBu3 affords the (Z)-2-alkenylstannane 228 with high regio- and stereoselectivities [99],... 

Propargylic compounds (2-alkynyl compounds) are derivatives of alkynes and they undergo several types of transformations in the presence of transition metal catalysts. However, catalytic reactions of propargylic compounds, particularly their esters and halides, clearly differ mechanistically from those of simple alkynes, except in a few cases. Therefore, the catalytic reactions of propargylic compounds are treated independently from those of simple alkynes. The most extensive studies have been carried out using Pd catalysts, and mainly Pd-catalysed reactions are treated in this chapter [1],... 

Organoboranes react with propargylic carbonates. Usually, addition of a base is indispensable for Pd-catalysed reactions of organoboranes with aryl, alkenyl and allyl halides. However, the reaction of organoboranes with methyl propargyl carbonates proceeds without addition of the base, because methoxide as the base is generated in situ from the carbonates. For example, the 1,2,4-alkatriene 127 is obtained by the reaction of alkenylboranes 126 with propargylic carbonate 125 under neutral conditions [32],... 

Nitrogen nucleophiles also react smoothly. The reaction of optically active propargyl mesylate 198 with aniline without a catalyst gives 200 with inversion. However, the Pd-catalysed reaction affords 199 with retention of stereochemistry [44], The 4-ethenylidene-2-oxazolidinone 202 is obtained by intramolecular reaction of the biscarbamate of the 2-butyn-l,4-diol 201 [45],... 

Reduction of propargylic compounds with Sml2 is possible in the presence of Pd catalysts. Propargylic acetates 233 are converted mainly to the allene 236 by Pd-catalysed reaction with Sml2 in the presence of a proton source [51]. In this reaction, the allenylpalladium 234 is reduced with Sm(II) to the allenyl anion 235, which is protonated to give allene 236. The alkyne 237 is a byproduct. 2,3-Naphthoquinodi-methane (240) as a reactive intermediate, can be generated by applying this reaction. 

As mentioned in Scheme 7.3, although thermal ene reaction of the 1,6-enyne 320 gives only 1,4-dienes 324, the 1,3-diene 325 is formed by the Pd-catalysed reaction. No thermal ene reaction is possible with 342, but the smooth Pd-catalysed cyclization affords the 1,3-diene system 343, which has a skeleton analogous to 325 in Scheme 7.3. Notably, the reaction proceeds with migration of vinylic hydrogen. The 1,3-diene system formed by the cyclization is useful for further modification, typically Diels-Alder reaction. The 1,3-diene 343 formed from 342 is converted to sterepolide (344) by Diels-Alder reaction [140]... 

Rh and Pd-catalysed Reactions of Diazo Compounds via Electrophilic Carbene Complexes... 

The usefulness of Pd-catalysed reactions is demonstrated amply in the total synthesis of clavicipitic acid [76]. The first step is intramolecular aminopalladation of the 2-vinyltosylamide 92 with Pd(II) to give the indole 93. Then stepwise Heck reactions of the iodide and bromide of 94 with two different alkenes 95 and 96 in the absence and presence of a phosphine ligand give 97. In the last step of the synthesis, the intramolecular aminopalladation of 97 with a catalytic amount of Pd(II) gives the cyclized product 99. It should be noted that the aminopalladation is a stoichiometric... 

The following Pd-catalysed stereoselective transformations of 142 and 143 are possible. The Pd-catalysed reaction of the cis product 143 with malonate gives the coproduct 148 with retention of the stereochemistry. However, reaction of 143 without the Pd catalyst affords the trans product 149. The cis product 142 is a mesa form and can be converted to the chiral half ester 150 by enzyme-catalysed partial hydrolysis. 

By changing the relative reactivity of the allylic leaving groups, namely acetate and the more reactive carbonate, either enantiomer of 4-substituted cyclohexenyl acetate is accessible by choice. The Pd-catalysed reaction of the allylic acetate moiety of 150 with malonate affords 151. Acetylation of 151 and Pd-catalysed 1,4-elimination of... 

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