Nucleophilic allylic systems

Interestingly, some nucleophiles attack the central carbon of the 7r-allyl system to form a palladacyclobutane 316 and its reductive elimination gives... 

No 0-allylation is observed in formation of the six-membered ring compound 79 by intramolecular allylation of the /3-keto ester 78(15,57]. Intramolecular allylation is useful for lactone fonnation. On the other hand, exclusive formation of the eight-membered ring lactone 81 from 80 may be in part derived from the preference for the nucleophile to attack the less substituted terminus of the allyl system[58]. 

The carbocations formed as intermediates when allylic halides undergo Stvfl reactions have their positive charge shared by the two end carbons of the allylic system and may be attacked by nucleophiles at either site Products may be formed with the same pattern of bonds as the starting allylic halide or with allylic rearrangement... 

Complexes 79 show several types of chemical reactions (87CCR229). Nucleophilic addition may proceed at the C2 and S atoms. In excess potassium cyanide, 79 (R = R = R" = R = H) forms mainly the allyl sulfide complex 82 (R = H, Nu = CN) (84JA2901). The reaction of sodium methylate, phenyl-, and 2-thienyllithium with 79 (R = R = r" = R = H) follows the same route. The fragment consisting of three coplanar carbon atoms is described as the allyl system over which the Tr-electron density is delocalized. The sulfur atom may participate in delocalization to some extent. Complex 82 (R = H, Nu = CN) may be proto-nated by hydrochloric acid to yield the product where the 2-cyanothiophene has been converted into 2,3-dihydro-2-cyanothiophene. The initial thiophene complex 79 (R = R = r" = R = H) reacts reversibly with tri-n-butylphosphine followed by the formation of 82 [R = H, Nu = P(n-Bu)3]. Less basic phosphines, such as methyldiphenylphosphine, add with much greater difficulty. The reaction of 79 (r2 = r3 = r4 = r5 = h) with the hydride anion [BH4, HFe(CO)4, HW(CO)J] followed by the formation of 82 (R = Nu, H) has also been studied in detail. When the hydride anion originates from HFe(CO)4, the process is complicated by the formation of side products 83 and 84. The 2-methylthiophene complex 79... 

Alkylation occurs predominantly or exclusively at the more substituted end of the allylic system regardless of the nucleophile. The steric course of the reactions is the same as that observed with palladium88 and molybdenum89 catalysts. 

The tertiary amines 303 and the acid chlorides 304 (X = Cl) initially formed acylammonium salts 305, which underwent a von Braun type degradation by an attack of the nucleophilic chloride ion at the allyl system to give allyl chlorides 306/307 and carboxylic acid amide functions. 

Scheme 7.4 illustrates some of the important synthetic reactions in which organolithium reagents act as nucleophiles. The range of reactions includes S/v2-(ype alkylation (Entries 1 to 3), epoxide ring opening (Entry 4), and formation of alcohols by additions to aldehydes and ketones (Entries 5 to 10). Note that in Entry 2, alkylation takes place mainly at the 7-carbon of the allylic system. The ratio favoring 7-alkylation... 

Due to the poor nucleophilicity of aliphatic alkoxides, the intermolecular O-allylation of aliphatic alcohols has been performed, for the most part, using a large excess of structurally simple primary alcohols (Equation (37))165 and/or unsubstituted allylic substrates.166,167 When allylic systems activated with an electron-withdrawing substituent were employed, only a slight excess of the alcohol was necessary to achieve complete stereospecificity, as exemplified by Equation (38).168,169... 

In addition to alkoxides, carbonyl oxygens have occasionally been recruited to function as nucleophiles in allylic etherification processes. The cyclization reactions of ketones containing internal allylic systems occur through O-allylation under Pd catalysis to give rise to vinyl dihydrofurans203 or vinyl dihydropyrans (Equation (51))204,205 in good yields. 

In the examples presented so far, only two enantiomeric products have been possible in each case, since the substrates have all contained identical substituents on the Cl and C3 positions. However, a more complex situation occurs when the allyl system is unsymmetrically-substituted, as in 43a or 43b (Scheme 12).1161 Here, nucleophilic addition to the corresponding ri3-allyl intermediate 44 may afford an achiral, linear product 45, in addition to the pair of enantiomeric branched products 46. 

Asymmetric allylic substitutions are widely applied in organic synthesis, using various metal complexes, chiral ligands, nucleophiles and allyl systems [39]. Although Pd is often the metal of choice, this is not the case for monosubstituted allylic substrates, where most Pd catalysts predominantly produce the achiral linear product. In contrast. Mo, W and Ir catalysts preferentially give rise to the desired branched products and, in recent years, a number of very effective Ir catalysts for various substrates have been developed [40]. Since, to the best of our... 

Although both Sn2 and SnI mechanisms might be formnlated for such reactions, all the available evidence favours an Sn 1 process. This is rationalized in terms of formation of a favourable resonance-stabilized allylic cation by loss of the leaving gronp. In the majority of natnral prodnct structures, the nucleophile has attacked the allylic system on the same carbon that loses the diphosphate, bnt there are certainly examples of nncleophilic attack on the alternative tertiary carbon. 

The possibility of nucleophilic attack on different carbons in the resonance-stabilized carbocation facilitates another modification exploited by nature during terpenoid metabolism. This is a change in double-bond stereochemistry in the allylic system. The interconversions of geranyl diphosphate, linalyl diphosphate, and neryl diphosphate provide neat but satisfying examples of the chemistry of simple allylic carbocations. 

The palladium catalysed substitution reaction of allylic systems has also been utilised in the formation of five membered rings. Intramolecular nucleophilic attack of the amide nitrogen atom on the allylpalladium complex formed in the oxidative addition of the allyl acetate moiety on the catalyst led to the formation of the five membered ring (3.63.). In the presence of a copper(II) salt the intermediate pyrroline derivative oxidized to pyrrole.80... 

Answer. The Lewis acidity depends on the interaction energy ( ) from the interaction of the LUMO of the acid with the HOMO of the nucleophile. The interaction is of a type, with the base HOMO (usually a nonbonded p or spn hybrid) interacting end on with the LUMO, which for the methyl cation is a single 2p orbital and for the allyl system is a linear combination of 2p orbitals. The LUMOs of the two systems are shown below. 

An elegant example of a stereo relay in a nonrigid system employed a chiral vinyl lactone 430 For the relay to be completely successful (i) the ionization of the vinyl lactone must occur from one conformation, (ii) the intermediate ir-allylpalladium complex must retain its stereochemistry, and (iii) the nucleophile must attack regioselectively at the carbon of the allyl system distal to the incipient carboxylate. This distal transfer of chirality was achieved as shown in equation (346). This same process has been utilized in a synthesis of an optically active vitamin E side chain from D-glucose.431... 

When a prochiral nucleophile is reacted with 1,3-disubstituted allylic systems, the issue of diastereo- as well as enantioselectivity arises. In the alkylation of a tetralone, both the acyclic... 

The double stereodifferentiation is also found in the reactions of acyclic nucleophiles (Scheme 8E.42). Whereas the alkylation of W-imino(methylphosphonates) affords the simple allylated product in poor enantioselectivity (11% ee) using ligand 38a, excellent enantioselec-tivity and good diastereoselectivity can be obtained from the alkylation with the 1,3-diphenyl-allyl system [188],... 

As is readily noted from the results summarized in Table 8E.13, enantioselectivity is very sensitive to a variety of factors such as the nucleophile and the nature of the allylic system as well as the ligand used. As expected, the enantioselectivity varied greatly with the structure of the nucleophile. Higher enantioselectivities were consistently obtained from the reactions of 2-cyclopentenyl phenyl ether than from the corresponding reactions of 2-cyclohexenyl ether. The biphenyl-derived DiPHEMP (7a) proved to be more effective than closely related BINAP (4) for this reaction. 

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