N-allyl palladium

Kurosawa et al. have reported that the relative stability of the ti-allyl palladium thi-olate 39 and the allyl sulfide/Pd(0) was highly ligand dependent. In the presence of PPhs or P(OMe)3 the stability was in favor of reductive elimination (Eq. 7.28), while in the presence of olefin or in the absence of any additional ligand the stability was in favor of oxidative addition (Eq. 7.29) [38]. This can explain the reactivity of the n-allyl palladium thiolate 33 and 38 proposed in Eq. (7.24) and path (c) of Scheme 7-10. The complex 33 should react with PhSH, but C-S bond-forming reductive elimination has to be suppressed in order to obtain the desired product 32. On the other hand, the complex 38 requires the phosphine ligand to promote the C-S bond-forming reductive elimination. 

N2CHC02Et, cat PdCl2(PhCN)2 N2CHC02Et, cat n-allyl-palladium chloride N2CHC02Et, cat Cu... 

Stereoselective allylic alkylations have been carried out with the aid of palladium catalysts. The 17-(Z)-ethylidene groups of steroids (obtained from the ketones by Wittig olefination) form n-allyl palladium complexes in the presence of copper(n) salts (B.M. Trost, 1974, 1976). Their alkylation with dimethyl malonate anions in the presence of 1,2-ethane-diylbis[diphenylphosphine] (— diphos) gives a reaction exclusively at the side chain and only the (20S) products. If one starts with the endocyclic 16,17 double bond and replaces an (S)-20-acetoxy group by using tetrakis(triphenylphospbine)palladium,the substitution occurs with complete retention of configuration, resulting from two complete inversions (B.M. Trost, 1976). 

Carbonylation of (n-allyl)palladium dimers. Reaction of carbon monoxide in methanol with (7t-allyl)palladium dimers requires high pressure and results in modest yields of products. However, addition of the sodium salt of a carboxylic acid permits carbonylation at 25" under low pressure of CO and results in high, yields of fi.y-... 

The elegant asymmetrization methodology of a meso compound, achieved in high enantioexcess under chiral environment, was the highlight of the total synthesis of (+)-pancratistatin (94) reported by Trost and Pulley (31]. The synthesis commenced with ( )-conduritol-A (130), obtained from p-benzoquinone, (Scheme 18) which was converted into the acetonide 131 and thence, via the dialkoxide to the cis-bis carbonate 132 (Scheme 19). The chiral n-ailyl palladium complex A formed on treatment erf 132 with the catalyst generated from chiral bis-amide 133 and n-allyl palladium chloride underwent azide substitution from the less hindered face of the molecule to provide the monocarbonate 134 in excellent yield and with high optical induction. 

Reactions Involving n-Allyl Palladium Species as Intermediates 233... 

A three-component reaction based on the umpolung of re-allylpalladium (II) complexes indium metal was reported by Grigg and co-workers (Scheme 8.31) [74]. In this reaction, the electrophilic nature of the n-allyl palladium species generated from aryl halides and allenes is reversed by transmetallation with indium metal. The resultant nucleophilic allylindium reagent subsequently adds to the third component - aldehyde [75] or imine [76] - to give the corresponding homo-allylic alcohol 64 or amine 65 respectively. 

Here the Pd(0) complex reacts with diallyl carbonate to form a n-allyl palladium alkoxide that ligates to 16. The resulting intermediate then undergoes P-hydride elimination to produce the lactone and propene (Scheme 6.10). 

The palladium-catalyzed reaction of allyl chloride 11 with the benzyne precursor 104 to produces phenanthrene derivatives 131 is also known [83]. A plausible mechanism for this intermolecular benzyne-benzyne-alkene insertion reaction is shown in Scheme 38. Initially n-allyl palladium chloride la is formed from Pd(0) and 11. Benzyne 106, which is generated from the reaction of CsF and 104, inserted into la to afford the aryl palladium intermediate 132. A second benzyne insertion into 132 produce 133 and subsequent carbopalladation to the alkene afford the cyclized intermediate 134. f>- Iydride elimination from 134 followed by isomerization gave 9-methylphenanthrene 131. 

The catalytic cycle of the palladium-catalyzed diacyloxylation follows the cycle depicted in Scheme 8-6 (X = RCOO, Y- = R COO ). The coordination of a quinone in the n-allyl)palladium intermediate was demonstrated by NMR studies including 7j measurements [58]. Attack by the second nucleophile results in the formation of the 1,4-addition product and a palladium(0)-benzoquinone complex. In an independent mechanistic study, it was shown that such Pd(0)-benzoquinone complexes, which are stable at neutral conditions (pH 7), react with weak acids to give hydroquinone and the palladium(II) salt of the acid [Eq.(36)] [59]. 

Trost proposed the following mechanism to explain formation of n -allyl complexes from alkenes.271.216 Initial reaction with PdCl4 generates a n -alkene complex (352), which is in equilibrium with the n-allyl palladium hydride complex 353. The presence of a base (such as an amine or a phosphine) or CuCl2 led to removal of the hydrogen from Pd—H to give the n -allyl palladium dimer 354. The CuCl2 oxidative procedure is more efficient than addition of a base. 

Initial reactions with n-allyl palladium complexes involved treatment of this stabilized cation with nucleophiles. Trost found that 355 reacted with diethyl sodiomalonate in the presence of triphenylphosphine (PPh3). The phosphine acted as a basic ligand and coordinated with the palladium. The major product from reaction with sodium malonate was 356, formed in 68% yield.220 This reaction completes the initially set goal (in... 

An interesting generalization of the above reactions consists in the inclusion of an alkyne among the reagents. Since n-allyl palladium complexes have low reactivity as regards the intermolecular insertion of ordinary alkynes, this makes controlled benzyne-alkyne-alkene insertion possible (Scheme 41) [76]. 

Oh et al. observed that 1,6-allenynes 131 and 135 underwent cyclization to afford six-membered-ring products 132-134 and 136-138 depending on the catalyst and additives used (Scheme 57) [35]. These products may be formed via the intermediacy of n-allyl palladium intermediate 139, which was formed... 

Trimethylenemethane (TMM) derivatives, such as n-allyl palladium species, are much used in [3+2] cycloadditions. Trost showed that the methodology can also be applied in certain cases to [4+3] cycloadditions (Eq. 41). ... 

In the Mitsunobu reaction with the allylic alcohols [2] and [5a,b] as with the palladium(0)-catalyzed reaction, good yields are obtained for the monomers [23] and [27] with an excess of nucleophile [22]. The dimers [24] and [28], however, ean be prepared only in moderate yields. Beeause the reaction does not proeeed via a n-allyl palladium complex with two reaetion sites, additional isomers are not produeed in this reaction. The conversion of [2] therefore yields only [27] and [28] as product. 

We recently studied if it is possible to device a selection strategy based on the relative stability of the intermediate of a reaction [24]. It is known that in the palladium-catalyzed allylic substitution, the rate-determining step is the attack of the nucleophile on the n-allyl-palladium species. The transition state of this step is believed to be late when carbon nucleophiles are used. In this scenario, an inverse correlation of the energy of the intermediate and the reaction rate is expected, as the transition state is more product-like (see Figure 4.10). Based on this hypothesis, the selection of catalyst among a dynamic mixture of palladium complexes was studied. 

Synthesis of homoallylamines by catalytic asymmetric allylation of imines with allyl silanes using a chiral bis n-allyl palladium complex, also using allylstannanes (see 1st edition). 

In 1983, Dieck and co-workers studied the reactions between aryl and vinyl halides with 1,3-dienes and amines. The catalytic formation of n-allylic palladium complexes via addition reactions to 1,3-dienes was involved, then the complexes formed reacted with amines and gave the final products. In order to explore the potential value of this methodology in organic synthesis, they tested 2-iodoaniline as a substrate as well. % using isoprene and 1,3-cyclohexadiene as the coupling partner, the desired cyclized produets were formed in good yields (Scheme 2.80). 

Larock and cmworkers described a palladium-catalyzed annulation of 1,4-dienes with ort/zo-functionalized aiyl halides in 1993. The reactions go through a (n-allyl)palladium intermediate the corresponding six-membered... 

There have been further papers on the synthesis of carbovir. Roberts and coworkers have described in full their routes both to the bioactive (-)- isomer 171 and to its enantiomer using enzymic resolutions (see Vol. 24, p. 239-40 and Vol. 25, p. 261). 99 One of their routes relied upon n-allyl palladium intermediates, and other workers have described a amilar approach for making... 

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