Pd -catalysed

These Pd-catalysed procedures appear to be preferable to earlier ones in which Cu(I)[3] or Hg(II)[4] were used to induce cyclization. Some additional examples are given in Table 2.3. 

Rctrosynthetic path a corresponds to Pd-catalysed exo-trig cyclization of o-halo-JV-allylanilines. Path b involves the endo-trig cyclization of o-halo-JV-vinyl anilines. Path c is a structurally similar cyclization which can be effected photochemically in the absence of an o-substituent. Retrosynthetic path d involves intramolecular Friedel-Crafts oxyalkylation followed by aromatiz-ation. 

Besides Pd-catalysed cyclizations, both radical[12] and organolithium[13] intermediates can give oxindoles by exo-trig additions. 

Lithiation at C2 can also be the starting point for 2-arylatioii or vinylation. The lithiated indoles can be converted to stannanes or zinc reagents which can undergo Pd-catalysed coupling with aryl, vinyl, benzyl and allyl halides or sulfonates. The mechanism of the coupling reaction involves formation of a disubstituted palladium intermediate by a combination of ligand exchange and oxidative addition. Phosphine catalysts and salts are often important reaction components. 

Vinylation can also be done by Pd-catalysed cross-coupling in which one component is used as a halide or triflate and the other as a stannane (Stille reaction) or boronic acid (Suzuki reaction). Entry 9, Table 11.3, is an example of the use of a vinylstannane with a haloindole. lndole-3-boronic acids, which can be prepared by mcrcuration/boration, undergo coupling with vinyl triflates (Entry 10). 

Indolyltrialkylstannanes are also potential reagents for Pd-catalysed coupling. 3-(Tri-n-butylstannyl)-l-tosylindole can be prepared by Pd-catalysed... 

Indoles with carbocyclic halogen or triflate substituents are potential starting materials for vinylation, arylation and acylation via palladium-catalysed pro-cesses[l]. Indolylstannanes. indolylzinc halides and indolylboronic acids are also potential reactants. The principal type of substitution which is excluded from such coupling reactions is alkylation, since saturated alkyl groups tend to give elimination products in Pd-catalysed processes. 

K. Yiokari, and S. Bebelis, In situ controlled electrochemical promotion of catalyst surfaces Pd-catalysed ethylene oxidation, /. Appl. Electrochem. 30, 1277-1283 (2000). 

Chromans have been obtained by the Pd-catalysed intramolecular cross coupling reaction involving aryl halides containing an ortto-hydroxyalkyl substituent <96JA10333>. 

Hie Pd-catalysed coupling of aiyl and heteroaryl halides with 2-hydroxyphenyl 2-propynyl ethers leads to (Z)-2-arylidene-l,4-benzodioxanes <96CC1067>. 

The Pd-catalysed Heck reaction performed with thiourea as the Ugand exhibit good activities for some catalysts. As for carbene ligands [104], steric hindrance improves catalytic results. Thus, thioureas wearing bulky substituents afford the formation of air- and moisture-stable Pd complexes [105]. For example, the catalyst obtained with 2mol% Pd(dba)2 and Ar,M -dimesitylene-ethylene thiourea (Scheme 24) was still active even after 2 months in an air atmosphere. 

In a very recent work, the Pd-catalysed cross-coupling reactions with arenediazonium salts under aerobic conditions in the presence of a chiral monothiourea ligand were reported (Scheme 25) [106]. Even if this Hgand bears four chiral centres, no test in asymmetric Heck-type reaction has been described so far. 

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

R = H, Me, MeO, PrO, MegN, Cl, F Scheme 5.35 NHC-Pd catalysed cycloisomerisation of aryl-substituted methylenecyclopropanes... 

R= Ph, 4-Me-Ph, 4-CI-Ph, Naphtyl, 3-MeO-Ph, 4-F-Ph Scheme 5.45 NHC-Pd catalysed ring closure of o-bromobenzyl ketones... 

Scheme 6.15 Pd-catalysed hydroarylation or norbornene using chelating NHC/P-Ugands...

The first example of a NHC-Pd catalysed Stille reaction between aryl bromides and aryl stannanes was reported by Herrmann in 1999 [120]. Summarised in Scheme 6.36 are the best results obtained when the weU-defined pre-catalyst 22 was employed. Unfortunately, the coupling of aryl chlorides was not possible. 

Scheme 6.36 First example of a NHC-Pd catalysed Stille coupling...

The widespread use of aryl boronic acids or aryl boronates in various metal-catalysed C-C bond-forming reactions has created a substantial demand for these versatile nncleophiles. A general procedure for the preparation of these compounds, based on a NHC/Pd catalysed coupling, has been reported by Fiirtsner and co-workers nsing aryl chlorides and the tetraalkoxy diboron derivative 27 as conpling partners. Very good yields were obtained in several cases especially when electron poor aryls were employed [169]. Milder reaction conditions can be achieved when diazonium salts are used instead of chlorides [170] (Scheme 6.51). 

Scheme 8.1 General mechanistic cycle proposed for Ni and Pd catalysed hydrodehalogenation...

Table 8.1 Comparison of Ni and Pd catalysed hydrodechlorination of aryl chlorides...

The oxidation of alcohols to the corresponding carbonyl compounds is one of the key reactions in organic synthesis and nnmerous methods have been developed over the years to accomplish this transformation [16], A general mechanism for Pd-catalysed aerobic oxidation is shown below (Scheme 10.5). 

Another more specific characteristic can allowed the differentiation between homogeneous and colloidal catalysts. In Pd-catalysed allylic alkylation rac-3-acetoxy-1,3-diphenyl-l-propene with dimethyl malonate, homogeneous and colloid species reacts at different rates with both substrate enantiomers, obtaining in the case of Pd colloids an excellent kinetic resolution (see Section 4) [44]. 

Enriched I (more than 75% (5)-I) was used as substrate for Pd-catalysed allylic alkylation, using both colloidal [Pd/l]coii and molecular [Pd/lj oi catalysts. As observed in Scheme 3, the colloidal system reacts more slowly with (S)-I enantiomer only 8% of (R)-l is present in the starting substrate, leading to a substrate conversion of ca. 10% with an ee of the remained substrate higher than 99% (S), in agreement with the relative rate calculated previously, k((/J)-I)/k((S)-I) 12 (see above). This relative rate is actually smaller for the molecular catalyst (see above) and consequently a higher conversion was obtained in this case 67% conversion is achieved after 30 h of reaction from a starting substrate constituted by 88.5 R)-I and 11.5(5)- . 

Scheme 3. Pd-catalysed allylic alkykation using an enriched substrate (a) colloidal catalyst (Pd/l/I = 1/1.05/100) (b) molecular catalyst (Pd/l/I = 1/1.25/10,000).

Monflier et al. (1997) have suggested Pd catalysed hydrocarboxylation of higher alpha olefins in which chemically modified P-cyclodextrin (especially dimethyl P-cyclodextrin) is u.sed in water in preference to a co-solvent like methanol, acetone, acetic acid, acetonitrile, etc. Here, quantitative recycling of the aqueous phase is possible due to easy phase separation without emulsions. A similar strategy has been adopted by Monflier et al. (1998) for biphasic hydrogenations for water-in.soluble aldehydes like undecenal using a water-soluble Ru/triphenylphosphine trisulphonate complex with a. suitably modified p-cyclodextrin. 

Scheme 1.1 Mechanism for Pd-catalysed allylic substitution with soft nucleophiles.

Scheme 1.2 Test reaction Pd-catalysed allylic alkylation of 1,3-diphenylpropenyl acetate with dimethyl malonate.

Scheme 1.4 Pd-catalysed allylic alkylations with dithioether ligands.

In 2004, Shi et al. reported Pd-catalysed asymmetric allylic substitutions using axially chiral S/S- and S/O-heterodonor ligands based on the binaphthalene backbone. The test reaction was performed in the presence of... 

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