Electrophilic reactions neutral allylation

The Pd(0)-catalyzed displacement of allylic acetates (297) with various nucleophiles via the allylic Pd(II) complex (298) is a well-established procedure (Scheme 114). Through attack of electrons (+2e ) in place of nucleophiles, (298) is expected to undergo a reductive cleavage providing allylic carbanions (299) and the acetate anion along with Pd(0) complexes. The latter can then be captured by various electrophiles (polarity inversion. Scheme 114) leading to (300) [434]. This procedure is useful for the deprotection of allyl esters under neutral conditions. Recently, a mechanistic study of the Pd-catalyzed reaction of allylic acetate (297), using carbonyl compounds as an electrophile, has been reported [435]. 

In intermolecular reactions, neutral aminyl radicals, R2N", react with n systems preferably by HAT. N-protonation increases the electrophUicity of the radical center, and successful addition of aminium radicals, R2NH, to 7t systems, usually alkenes, has been reported in the hterature." Compared to aminium radicals, amidyl and imidyl radicals, for example, RN C(0)R and [RC(0)]2N , are less electrophilic. Although they are delocahzed 7t-allyl radicals, they react exclusively at nitrogen." Only very few examples for radical cascades that are initiated by addition of A-centered radicals to alkynes have been reported. 

The cross-coupling reaction of organoboron compounds with organic halides or triflates proceeds selectively in the presence of a base, such as sodium or potassium carbonate, phosphate, hydroxide, and alkoxide [11, 45], The bases can be used in aqueous solution, or in suspension in dioxane or DMF. In contrast, the cross-coupling reaction with certain electrophiles, such as allylic acetates [45], 1,3-butadiene monoxide [49], and propargyl carbonates [50], occurs under neutral conditions without any assistance from a base. The transmetallation of organoboron compounds with palladium halides under basic or neutral conditions can be considered to involve three routes, 1, 2, and 3 (Schemes 2-18, 2-20, and 2-23, below). 

Allyl halides add to the more reactive d complexes. Both a- and w-allyl complexes are found, occasionally both in the same system. An example of this reaction with allyl chloride is that of 7r-cyclopentadienylcobalt dicarbonyl discovered by Fischer 58) and reinvestigated by Heck (66). Both cationic (XLI I) and neutral complexes (XLIII) are formed, depending on the conditions. The cationic sr-allyl complex (XLII) is interesting in that this is another example of the stepwise addition of an electrophile to a live-coordinate rf complex. The reader should remember that the formation of the TTrallyl group entails the loss of an additional neutral ligand. 

The scope of allylic electrophiles that react with amines was shown to encompass electron-neutral and electron-rich ciimamyl methyl carbonates, as well as furan-2-yl and alkyl-substituted allylic methyl carbonates. An ort/io-substituted cinnamyl carbonate was found to react with lower enantioselectivity, a trend that has been observed in later studies of reactions with other nucleophiles. The electron-poor p-nitrocinnamyl carbonate also reacted, but with reduced enantioselectivity. Allylic amination of dienyl carbonates also occur in some cases with high selectivity for formation of the product with the amino group at the y-position over the s-position of the pentadienyl unit [66]. Arylamines did not react with allylic carbonates under these conditions. However, they have been shown to react in the presence of the metalacyclic iridium-phosphoramidite catalysts that are discussed in Sect. 4. 

Because of the ability of some leaving groups to stabilize an a-carbanion, the pH at which the substitution is performed can be critical. Electrophiles with such leaving groups (e.g. R-N02 [36, 37], R-S(=0)2R [38, 39], R-S(=O)R[40]) will usually undergo substitution only under neutral or acidic conditions, what limits the choice of suitable nucleophiles. Some nucleophilic displacements of nitro and sulfonyl groups, both under acidic and basic reaction conditions, are shown in Schemes 4.6 and 4.7. Allylic nitro groups can also be readily displaced by catalysis with palla-... 

Vinyl epoxides and allylic carbonates are especially useful electrophiles because under the influence of palladium(O) they produce a catalytic amount of base since X- is an alkoxide anion. This is sufficiently basic to deprotonate most nucleophiles that participate in allylic alkylations and thus no added base is required with these substrates. The overall reaction proceeds under almost neutral conditions, which is ideal for complex substrates. The relief of strain in the three-niembered ring is responsible for the epoxide reacting with the palladium(O) to produce the zwitterionic intermediate. Attack of the negatively charged nucleophile at the less hindered end of the ic-allyl palladium intermediate preferentially leads to overall 1,4-addition of the neutral nucleophile to vinyl epoxides. 

The following series of allylic and 0-stannyl ketyl reactions is intended to provide insight into the reactivity and potential of these interesting synthetic intermediates. Various cyclizations, strained ring scissions, and electrophile trapping reactions will be demonstrated on diverse substrates such as ketones, aldehydes, enones and a-ketocyclopropanes. All of the chemistry described herein utilizes mild and neutral reaction conditions to accomplish a wide range of synthetic transformations. 

Similar to the reaction course of the allylic substitution, which involves formation of tr-allyl moieties followed by subsequent nucleophilic addition across the Jt-bond, the mononitrosyl iron(—II) complex was expected to be active in transesterifications involving activation of carbonyl group and nucleophilic addition to the electrophilic carbon atom [100]. This assumption could be verified by experimental tests. Under neutral conditions without addition of a ligand co-catalyst, the iron complex 31 exhibited high activity in the transesterification of vinyl acetate. Good to excellent yields were obtained affording a new ester bond, as depicted in Scheme 39. 

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