Regioselectivity allylic anions

For carbanionic addition, the relative negative charge and the electron densities in the 1- and 3-position in the HOMO of the ambident allylic anion determine, in addition to steric effects, the regioselectivity of the hydroxyalkylation. According to the allopolarization principle13 the following generalizations can be made ... 

Cathodic substitution stands for C,C bond or C, heteroatom bond formation with cathodically generated anions. The question of regioselectivity is encountered in the reaction of such anions with allyl halides (path a) or in the reaction of allyl anions generated in an ECE process from allyl halides (path b). Cathodic reductive silylation of an allyl halide proceeds regioselectively at the less substituted position (Fig. 15) [91]. From the reduction potentials of the halides it is proposed that the reaction follows path b. 

The high selectivities found in the protonation experiments of the nitronate ions 44 suggested that also allyl anions 54 can be regioselectively protonated by a general acid protonation. Therefore, some lithium allyl compounds (Structures 6) were generated by deprotonation of alkenes with n-butyl lithium. 

Due to the low solubility of the concave pyridines 3 in diethyl ether, the corresponding pyridine buffers could not be compared with the experiments of Table 4. But when the protonations were carried out in other solvents, no influences of the acids (including the acids of Table 4) on the regioselectivity could be found. The exchange of diethyl ether by other solvents caused a color change of the allyl anion solution which indicated different structures for the anions in diethyl ether and in other, more polar solvents [44],... 

The degree of regioselectivity in the rearrangement of 2-methyl-7anti-cyclopentenyl-norbom-2-en-7syn-ol [240] is perhaps unanticipated. The C-2 methyl group is responsible for the predominant generation of the allyl anion on which it has minimal electronic interaction. 

Intramolecular hydroamination of cyclohexa-2,5-dienes has afforded the corresponding bicyclic allylic amines with high selectivity (Scheme 13).80 The reaction does not proceed through a direct hydroamination of one of the diastereotopic alkenes but more likely involves a diastereoselective protonation of a pentadienyl anion, followed by addition of a lithium amide across the double bond of the resulting 1,3-diene and a highly regioselective protonation of the final allylic anion. 

The mechanism does not proceed through a direct hydroamination of one of the diastereotopic alkenes, but involves a series of very selective processes including a deprotonation of (22), diastereoselective protonation of (26), intramolecular addition of lithium amide (27) to the 1,3-diene moiety, and final regioselective protonation of the allyl anion (28), all mediated by a substoichiometric amount of n-BuLi. 

We have now seen how the attraction of charges and the interaction of frontier orbitals combine to make a reaction between two such species as the allyl anion and allyl cation both fast and highly regioselective. We should remind ourselves that this is not the whole story another reason for both observations is that the reaction is very exothermic the energy of a full a bond is released with cancellation of charge, which would not be the case if reaction took place at C-2 on either component. Thus we are in the situation of Fig. 3.1a—the Coulombic forces and the frontier orbital interaction on one side, and the stability of the product on the other, combine to lower the energy of the transition structure. 

In organic syntheses allylsilanes and allylstannanes have been used extensively as allyl anion equivalents during the last two decades [187-190]. The regioselective attack of electrophiles, which finally yields products with allylic inversion (Scheme 43), has been explained by the hyperconju-gative stabilization of carbenium centers by the carbon-silicon or carbon-tin bond in the j3-position [191-196], which has initially been derived from solvolytic experiments [197-199]. 

Phen and the radical anion of the alkene. Secondary electron transfer from allylsilane to Phen produces the radical cation of allylsilane and neutral Phen. The radical cation of allylsilane is cleaved by assistance of acetonitrile to generate an allyl radical. The allyl radical adds to the radical anion of the alkene to give the allylated anion which is converted into the product upon protonation. Alkyl and arylmethyl radicals can be generated in a similar manner from tetraalkyl tin compounds and arylmethylsilanes, respectively [124]. These radicals add regioselectively to the -position to the cyano groups in the radical anions of alkenes. 

Copper salts such as CuCN, CuBr-SMc2 and CuCN-2LiCl were demonstrated to mediate the regioselective allylation, alkylation, and propargylation of the lithium anion of n-butylthiooxazole 128 providing 2,5-disubstituted systems 129. Desulfurization with deactivated W2-Raney nikel produced 5-substituted derivatives <03TL7395>. 

Recently, a new ruthenium catalyst that also provides regioselective allylic alkylation has been reported. In DMF, a highly branched alkylation product of cinnamyl carbonate vsdth malonate anion was obtained in quantitative yield (branched/line-ar = 14/1) within 30 min in the presence of 1 mol% of [(C5Me5)Ru(MeCN)3]PF6 catalyst (Eq. 5.30) [46]. 

Directed lithiations of a,3- and -y.b-unsaturated amides " have been extensively studied. Illustrative examples are shown in Scheme 44. Prior complexation of the alkyllithium base with the amide carbonyl oxygen directs the base to the thermodynamically less acidic -position in a,3-unsaturated amide (31), which adds to benzophenone and subsequently lactonizes. Analysis of the NMR spectrum reveals that the organolithium added the benzophenone in the equatorial position. A Afferent kinetic deprotonation is seen in y,8-unsaturated amide (32), where -lithiation to form an allylic anion predominates over a-lithiadon to form an enolate. > Addition of the lithium anion to acetone affords poor regioselectivity, but transmetalation to magnesium before carbonyl addition yields a species which adds exclusively at the 8-position. ... 

By using a Pd/Sml2 system as catalyst, allylic acetates can be converted regioselectively to the corresponding allylic selenides, most probably by selenation of allylic anion intermediates (Scheme 15.80) [160]. 

The most useful of all allyl anion equivalents are the allyl silanes.20 This is because it is easy to make them regioselectively, because they do not undergo allylic rearrangement (silicon does not do a [1,3] shift) and because their reactions with electrophiles are very well controlled addition always occurring at the opposite end to the silicon atom. Symmetrical allyl silanes can be made from allyl-lithiums or Grignards by displacement of chloride from silicon. A useful variant is to mix the halide with a metal, e.g. sodium, and Me3SiCl in the same reaction, rather after the style of the silicon acyloin reaction,21 as in the synthesis of the acetal 80. 

Anions of allyl sulfides have been quite widely used but their regioselectivity is unpredictable and the vinyl sulfides 107 Z = SR resulting from y-addition are difficult to hydrolyse.32 Anions of allyl ethers are more difficult to prepare, but generally better behaved.33 A study of such anions led Still to propose that allyl anions with very anion stabilising substituents Z = COR 118, S02Ph 119, +PPh3120 etc, react a with all electrophiles, those with moderately anion-stabilising substituents... 

From this point on, the regioselectivity of substituted allyl anions is much less regular, and somewhat less explicable. For a start, X-substituted allyl anions react with carbonyl electrophiles with a selectivity. This is explicable, but it is determined by the site of coordination by the metal, not by the frontier orbitals. We can contrast the reaction of the oxygen-substituted lithium anion 4.57 with an alkyl halide, which is y selective, as usual, and the reaction of the zinc anion 4.58 with a ketone, which is a selective.304 The oxygen substituent coordinates to the zinc cr-bound at the y position, and the aldehyde is then delivered to the a position in a six-membered cyclic transition structure 4.59. The same reaction with the lithium reagent 4.57 gives a 50 50 mixture of a and y products, and so lithium is not so obviously coordinated in the way that the zinc is. This type of reaction is often brought under control in the sense 4.59 for synthetic purposes by... 

C-Substituted Allyl Anions—Pentadienyl Anions.315 Allyl anions with C-substituents pose a different problem. Both a attack and y attack are known, as illustrated by the reactions of the open-chain C-substituted anions 4.66,316 and 4.67.317 The problem is not only that the regioselectivity is irregular, but explaining it is not straightforward either. Simple predictions based on the n orbitals suggest that the... 

A stereo- and regio-selective synthesis of rrans-2,5-dialkylpyrroiine structures is accomplished via the A-substituted allylic anion intermediates (Scheme 12). The a-regioselective alkylation is presumably due to the presence of the electron-withdrawing methoxycarbonyl group. The piperidine ring system... 

Allyl anions (38a),(38b) and (38c) exhibit a similar regioselectivity toward electrophiles, and thus serve as homoenolate synthons. Addition of titanium tetraisopropoxide to (39) followed by condensation with aldehydes gives the anti adducts exclusively, which can be converted to the (Z)-1,3-dienes upon treatment with methyl iodide (Scheme 18). The ( -1,3-dienes can be prepared from the lithiated allyldiphenylphosphine oxide. The stabilized allylic phosphonate anion (40) condenses with carbonyl... 

---