Oxidative alkyl electrophiles

Subsequent ion exchange of the metal cation with the quaternary ammonium ion catalyst provides a lipophilic ion pair (step 2), which either reacts with the requisite alkyl electrophile at the interface (step 3) or is partitioned into the electrophile-containing organic phase, whereupon alkylation occurs and the catalyst is reconstituted. Enantioselective PTC has found apphcation in a vast number of chemical transformations, including alkylations, conjugate additions, aldol reactions, oxidations, reductions, and C-X bond formations." ... 

Whereas allyl, benzyl and propargyl electrophiles are among the most reactive towards Pd, Ni and other transition metals, ordinary alkyl halides and related alkyl electrophiles that are not /3, -unsaturated are among the least reactive carbon electrophiles with respect to oxidative addition to Pd or Ni. Most of the alkyl derivatives are also associated... 

Another major approach to the Pd- or Ni-catalyzed alkylation with alkyl electrophiles is to use bulky and highly nucleophilic trialkylphosphines to promote slow oxidative addition. Screening of several trialkylphosphines as well as several widely used tri-arylphosphines for the Pd-catalyzed reaction of n-BuZnBr with Br(CH2)3OBn led to the following results Firstly, most of the conventional triarylphosphines including PPh3, TFP... 

Very few examples of electrophilic attack at sulfur(II) have been reported for these systems, with the exception of oxidation. Alkylation of the benzothiadiazine (88) with trimethyloxonium tetrafluoroborate gave a poor yield of the imino ether (89). The major product (90) resulted from alkylation at sulfur followed by hydrolytic ring opening of the resulting azasulfonium salt (79JCR(S)214). 

The industrially important direct methane conversion processes comprise oxidative coupling, reductive coupling including pyrolysis reactions, partial oxidation, halogenation and oxyhalogenation,26 and ammoxidation. Other direct conversions include alkylation, electrophilic substitution, and C-H bond activation over various complex and super acid catalysts. Several of these direct conversion technologies remain to be exploited to achieve their full commercial potentials. 

Trimethylsilyl)-l,3-oxathianyllithium 332 was obtained by deprotonation of compound 323 with s-BuLi at —78 °C and reacted with different electrophiles such as deuterium oxide, alkyl iodides, dimethyl disulfide and carbonyl compounds, providing the corresponding products 333 in moderate to good yields. However, the reaction with benzonitrile, followed by acid hydrolysis, gave 2-benzoyl-l,3-oxathiane 334 (X = H) (Scheme 87)503,504. When the last reaction was quenched with methyl iodide before... 

Secondary amines an easily converted into formamidines reaction with amidines (equation 24). Deprotonation and addition of electrophiles, including alkyl halides, acyl halides, aldehydes and dise-lenides, permit the introduction of various groups adjacent to the amino center, and therefore can be considered as an oxidation. Alkylation with dihalides gives intermediates which lead to new caibocyclic rings after removal of the formamidine group (equation 2S). ... 

Pioneering studies by Stille in the 1970s established that the oxidative addition of benzyl chlorides and bromides (activated alkyl electrophiles) to Pd(0)/PPh3 complexes occurs predominantly with inversion of stereochemistry at the elec-... 

Kinetics studies of the oxidative addition of a variety of unactivated primary alkyl electrophiles to several PdL2 complexes (L=trialkylphosphine) have been described [46]. For the reaction depicted in Eq. 17, the activation parameters are AU =20.8 kcal mol" (20 °C) AH =2A kcal mol" AS =-63 eu. The large negative AS" value that is observed is consistent with an associative pathway for oxidative addition. The rate of addition increases as the solvent polarity increases, as would be expected for the postulated 8 2 mechanism, and is not affected by added P(f-Bu)2Me, indicating that the alkyl bromide oxidatively adds to PdL2 (not PdLi or PdL3) [47]. 

Finally, the dependence of the rate of oxidative addition on the choice of tri-alkylphosphine has been quantified (Table 11). Consistent with the reactivity patterns that have been observed in Pd/trialkylphosphine-catalyzed cross-coupling processes of alkyl electrophiles (e.g.. Scheme 1), Pdl2 complexes derived from P(t-Bu)2Me and PCy3 undergo relatively facile oxidative addition (entries 1 and 2), whereas those based on P(t-Bu)2Et and P(f-Bu)3 are essentially unreactive (entries 3 and 4). 

Some appropriately heteroatom-substituted alkyl electrophiles undergo oxidative addition to Pd. For example, the carbonylative synthesis of a-amino acids from aldehydes and carboxamides shown in Scheme 5 must involve oxidative addition of 1 formed by the reaction of an aldehyde and a carboxamide to Pd to produce an a-amidoalkylpalla-dium species 2 as intermediate. It is likely that many other proximally heteroatom-substituted alkyl electrophiles will be found to undergo oxidative addition to Pd. 

Oxidative addition can also occur between anionic metal complexes and alkyl electrophiles. In this case, the halide becomes a byproduct, rather than a ligand, in the final metal complex. One well-studied example of oxidative addition to an anionic metal complex by an Sj 2 pathway involves the "supernucleophile" Fe(CO) ". This complex reacts rapidly with most organic halides, including hindered halides containing strong C-X bonds, such as neopentyl chloride. The products from multistep reactions of this complex are consistent with 100% inversion in the oxidative addition step. This and the other evidence in Figure 7.1 support reaction by a classic S 2 pathway. 

As an example, this apply to enols or tautomeric enols such as maleic acid derivatives. While with a chemical reagent (cerium ammonium nitrate) the only process occurring is oxidative dimerization, when aromatic nitriles are used as the photochemical oxidant, selective trapping of the radicals by an electrophilic alkenes or by the nitrile itself occurs. Under these conditions, both the alkylation of alkenes and the oxidative alkylation/dimerization of dienes have been smoothly obtained (see Scheme 8) and side processes such as double alkylation or polymerization often occurring with other methods have been avoided. A three-component (Nucleophile-Olefin Combination, Aromatic Substitution) process is also possible. ... 

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