Substitution palladium-catalyzed

As mentioned in Sect. 3.1.1, secondary phosphine-boranes also react efficiently with aryl iodides in palladium-catalyzed substitution reactions (Pd(PPh3)4) [73]. In all cases the boranato functional group remains unchanged. 

Palladium-catalyzed substitution can also be applied to nonbasic nitrogen heterocycles, such as indoles, in the absence of strong bases. 

B. Palladium-catalyzed substitution with nitrogen nucleophiles 4d... 

The palladium-catalyzed substitution of the less reactive racemic ethyl 3-cyclohexe-nyl carbonate could, in a similar fashion, be completed with dimethyl malonate, p-methoxyphenol, or phthalimide as nucleophiles, with satisfactory ee (Eq. 11.38) [55]. These reactions, when irradiated for 1 min with temperatures up to 100 °C, delivered yields (91-96%) and ee values (94—95%) identical with those performed in... 

Scheme 4.69 Highly enantioselective synthesis of allenes 272 by palladium-catalyzed substitution.

If allenes bear a potential leaving group in the a-position to the cumulene system, they are very attractive substrates for palladium-catalyzed substitutions. Examples are a-allenic acetates and particularly a-allenic phosphates, which react under palladium(O) catalysis with carbanions derived from /3-diesters, /i-keto esters, a-phenylsulfonyl esters and glycine ester derivatives. They lead to /3-functionalized allenes such as 86, 89 and 93 (Eqs. 14.9-14.11) [45 18]. 

Ceric ammonium nitrate promoted oxidative addition of silyl enol ethers to 1,3-butadiene affords 1 1 mixtures of 4-(/J-oxoalkyl)-substituted 3-nitroxy-l-butene and l-nitroxy-2-butene27. Palladium(0)-catalyzed alkylation of the nitroxy isomeric mixture takes place through a common ij3 palladium complex which undergoes nucleophilic attack almost exclusively at the less substituted allylic carbon. Thus, oxidative addition of the silyl enol ether of 1-indanone to 1,3-butadiene followed by palladium-catalyzed substitution with sodium dimethyl malonate afforded 42% of a 19 1 mixture of methyl ( )-2-(methoxycarbonyl)-6-(l-oxo-2-indanyl)-4-hexenoate (5) and methyl 2-(methoxycarbonyl)-4-(l-oxo-2-indanyl)-3-vinylbutanoate (6), respectively (equation 12). 

Van Heerden FR, Huyser JJ, Bradley D, Williams G, Holzapfel CW (1998) Palladium-catalyzed substitution reactions of geminal allylic diacetates. Tetrahedron Lett 39 5281-5284... 

When the allylic substituent is the source of chirality, then palladium-catalyzed substitutions can lead to good asymmetric induction (Schemes 16 and 17).109 In this example, the geometry of the double bond in the substrate controls the stereochemical outcome of the reaction. 

The generally accepted mechanism of the palladium-catalyzed substitution reaction is shown in Scheme 1. For a more detailed discussion, the reader is referred to the original chapter [1], A number of papers which probe the enanti-odetermining step for specific ligands have been published over the past four years but will not be discussed further [15-28]. The effect of catalyst loading [29], the ionization of I with different Pd° complexes [30,31], the mechanism of the q3-q -q3 isomerization [32] of intermediate II, and the behavior of the ole-fin-Pd(O) complex III have been studied [33]. 

The Suzuki reaction is a palladium-catalyzed substitution that couples an aryl or vinyl halide with an alkyl, alkenyl, or aryl boronic acid or boronate ester. Many variations on this fundamental reaction are possible, containing a wide variety of functional groups. 

Fig. 9. (A) A Pd-enolate complex observed by ESI(+)-MS during the palladium-catalyzed allylic substitution of l-acetoxy-l,3-diphenylpropene by acetylacetone 15. (B) A Pd-allyl complex observed by ESI(+)-MS during the palladium-catalyzed substitution of allylic acetates with sodium para-toluenesulfonate 20. ...

Palladium-catalyzed substitutions of allylic esters 93, which proceed via intermediate jz-allylpalladium complexes such as 94, are well established [178]. In contrast, the reactions proceeding through TT-allylpalladium intermediates, generated by addition of the palladium interaiediates from haloarenes, haloalkenes, or the corresponding triflates, to allene and substituted allenes 95 (Scheme 3-26), have scarcely been tapped [79]. 

Often catalyst variability is not mentioned at all, or found in notes buried within text. For instance, mention of the differing reactivities of batches of Pd(PPh3)4 is found in footnote a, Table 2 Aggarwal,V. K. Monteiro, N. Tarver, G. J. McCague, R., Scope and Limitations in Palladium-Catalyzed Substitution Reactions of Unsaturated Fused Lactones. / Org. Chem. 1997, 62, 4665. 

Using azide as the nucleophile, the palladium-catalyzed substitution of 1-alkenylcyclopropyl esters gave l-azido-l-alkeny cyclopropanes, e.g. 12, potential precursors to the corresponding... 

Allylic and dienyl sulfones have been prepared by conjugate addition to 1,3-dienes ". Phenylsulfonyhnercuration of conjugated dienes gives mercury adducts which can be treated with base to afford phenylsulfonyldienes. 2-(Phenylsulfonyl)-l,3-dienes can be stereo- and regioselectively functionalized via Michael addition of nucleophiles to give allylic sulfones. A key intermediate in the synthesis of a Monarch butterfly pheromone 4 was prepared by BackvaU and Juntunen by alkylation and subsequent palladium-catalyzed substitution of the allylic sulfone formed by Michael addition of dimethyl malonate to 2-(phenylsulfonyl)-l,3-butadiene (equation 10). 

Petrakis, K.S., and Nagabhushan, T.L., Palladium-catalyzed substitutions of triflates derived from tyrosine-containing peptides and simpler hydroxyarenes forming 4-(diethoxyphosphinyl)phenylala-nines and diethyl arylphosphonates, J. Am. Chem. Soc., 109, 2831, 1987. 

A similar triarylphosphane was introduced by Leitner for the performance of transition metal catalyzed reactions in supercritical CO2 [24]. Recently, this phosphane was used for palladium catalyzed substitutions of allylic substrates in perfluorinated solvents under fluorous biphase conditions [25], Therefore, the reaction of cinnamyl methylcarbonate (36) with several nucleophiles (Nu-... 

In this method the initial iodocyolization of a variety of propargylic anilines can be accomplished and followed by palladium-catalyzed substitution reactions to provide further elaboration of the... 

Sulfones are also useful as allylic leaving groups in palladium-mediated alkylations. In particular cyclic 2-sulfonyl-l, 3-dienes, which are readily available from a one-pot sulfonylmercura-tion/elimination of 1,3-dienes, are versatile starting materials107. The palladium-catalyzed substitution of allyl sulfones occurs with net retention of configuration and features attack on the least substituted 7i-allyl terminus108. 

The stereochemistry of Pd°-catalyzed allylic alkylation is net retention (equation 62). This arises from sequential inversion steps. Initially, the Pd° approaches from the face of the C3 unit opposite the leaving group, to form the n-allyl complex. Subsequently, the nucleophile adds to the face of the r-allyl opposite palladium. If a bulky or unreactive nucleophile is used with allylic acetates, the acetoxy group can add again to the complex. Ultimately, this results in the production of a mixture of stereoisomers upon nucleophilic addition. As an example of the range of allylic substrates that react, nitrogen nucleophiles, in particular primary and secondary amines, undergo palladium-catalyzed substitution with allylic alcohols, acetates, and ethers (equation 63). 

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