Nucleophilic attack on allylic compounds

The allylic bromides that can be made by these radical reactions display interesting regio-selectivity. We shall start with some substitution reactions with which you are familiar from Chapter 15. There we said that allyl bromide is about 100 times more reactive towards simple Sn2 reactions than is propyl bromide or other saturated alkyl halides. 

There is an alternative mechanism for this reaction that involves nucleophilic attack on the alkene instead of on the saturated carbon atom. This mechanism leads to the same product and is often called the Sn2 (pronounced S-N-two-prime ) mechanism. 

We can explain both mechanisms in a unified way if we look at the frontier orbitals involved. The nucleophile must attack an empty orbital (the LUMO), which we might expect to be simply a (C-Br) for the 5 2 reaction. But this ignores the alkene. The interaction between n (C=C) and the adjacent o (C-Br) will as usual produce two new orbitals, one higher and one lower in energy. The lower-energy orbital, k + a, will now be the LUMO. To construct this orbital we must put all the atomic orbitals parallel and make the contact between n + a a bonding interaction. 

If the allylic halide is unsymmetrically substituted, a question of regioseiectivity arises. The products from Sn2 and Sn2 are different and the normal result is that nucleophilic attack occurs at the less hindered end of the allylic system, whether that means 5 2 or Sn2. This important allylic bromide, known as prenyl bromide, normally reacts entirely via the 5, 2 reaction. 

The two ends of the allylic system are contrasted sterically direct (5 2) attack is at a primary carbon while allylic ( n2 ) attack is at a tertiary carbon atom so that steric hindrance favours the Sn2 reaction. In addition, the number of substituents on the alkene product means that the Sn2 product is nearly always preferred—5 2 gives a trisubstituted alkene while the Sn2 product has a less stable monosubstituted alkene. 

The double bond stabilizes the 5 2 transition state by conjugation with the p orbital at the carbon atom under attack. This full p orbital (shown in yellow in the diagram below) forms a partial bond with the nucleophile and with the leaving group in the transition state. Any stabilization of the transition state win, of course, accelerate the reaction by lowering the energy barrier. 

We can explain both mechanisms in a unified way if we look at the frontier orbitals involved. The nucleophile must attack an empty orbital (the LUMO) which we might expect to be simply (C-Br) for the Si f2 reaction. 

---

Toyota, Ihara, and coworkers demonstrated that silyl enol ethers undergo Pd -promoted intramolecular nucleophilic attack on alkenes [18]. Allhough early examples required stoichiometric Pd [167], they have also shown that Pd(OAc)2 in DMSO is an effective catalyst in the presence of an aerobic atmosphere (Eq. 38) [168-170]. The reaction is proposed to proceed through an oxo-jt-allyl intermediate that can undergo competitive alkene insertion or P-hydride elimination (Scheme 11). The latter reaction is the basis for the synthetically useful conversion of silyl enol ethers to a,P-unsaturated carbonyl compounds (see below). Efforts to use BQ as an oxidant were not described. 

Palladium-catalyzed allylic oxidations, in contrast, are synthetically useful reactions. Palladium compounds are known to give rise to carbonyl compounds or products of vinylic oxidation via nucleophilic attack on a palladium alkene complex followed by p-hydride elimination (Scheme 9.16, path a see also Section 9.2.4). Allylic oxidation, however, can be expected if C—H bond cleavage precedes nucleophilic attack 694 A poorly coordinating weak base, for instance, may remove a proton, allowing the formation of a palladium rr-allyl complex intermediate (89, path by694-696 Under such conditions, oxidative allylic substitution can compete... 

Nucleophilic attack on ( -alkene)Fp+ cations may be effected by heteroatom nucleophiles including amines, azide ion, cyanate ion (through N), alcohols, and thiols (Scheme 39). Carbon-based nucleophiles, such as the anions of active methylene compounds (malonic esters, /3-keto esters, cyanoac-etate), enamines, cyanide, cuprates, Grignard reagents, and ( l -allyl)Fe(Cp)(CO)2 complexes react similarly. In addition, several hydride sources, most notably NaBHsCN, deliver hydride ion to Fp(jj -alkene)+ complexes. Subjecting complexes of type (79) to Nal or NaBr in acetone, however, does not give nncleophilic attack, but instead results rehably in the displacement of the alkene from the iron residue. Cyclohexanone enolates or silyl enol ethers also may be added, and the iron alkyl complexes thus produced can give Robinson annulation-type products (Scheme 40). Vinyl ether-cationic Fp complexes as the electrophiles are nseful as vinyl cation equivalents. ... 

In contrast to the allyl halides with one EWG, nucleophilic attack on double bond activated allyl halides (291) normally gives rise to substituted electrophilic cyclopropanes (293) or compounds derived therefrom (equation 87). The formation of these cyclopropanes is strongly dependent on the reaction conditions, the nature of the nucleophiles, the... 

The catalytic processes for allylation reactions are composed of the allylic C-0 bond cleavage and nucleophilic attack on the r 3-allyltransition metal complexes formed to give various organic allylation compounds (Scheme 3). 

Scheme 1.9. Oxidative addition of an ally lie compound to Pd(0) complex and nucleophilic attack on the -allyl ligand.

Scheme 1.10. Stereochemistry of oxidative addition of aUylic compounds to L M to give allyl complexes and nucleophilic attack on the -aUyl ligand.

Stereochemistry of Pd-catalyzed allylation of nucleophiles has been studied extensively. In the first step, formation of 7r-allylpalladium complexes 37 by the attack of Pd(0) on allylic compounds 36 proceeds with inversion of configuration (anti attack). Subsequent reaction of 37 with nucleophiles occurs in different stereochemistry depending on the nature of the nucleophiles. The soft (stabilized) nucleophiles which are derived from conjugate acids with < 25, such as active methylene compounds, attack 37 from the backside of the Pd atom to give 38 with inversion of stereochemistry. Thus overall retention is observed. On the other hand, hard nucleophiles (pK > 25), typically organometallic compounds of main group metals (Mg, Zn, B, Sn and others) generate 39 by transmetallation, and subsequent reductive elimination affords 40. Both the transmetallation and... 

The most important feature that makes CpMo(CO)2(7i-allyl) useful in organic synthesis is its facile transformation to the CpMo(CO)2(Jt-di-ene) cation. This reaction is particularly suitable for ring systems with six or seven members because their a-methylene protons adjacent to the Mo-Jt-allyl moiety are subject to Ph3CBF4-promoted hydride abstrac-tion. For an acyclic system, this method is successful in only a few cases, mainly on simple molybdenum (ji-onfi-crotyl) compounds (Eq. 2, Scheme 15). The molybdenum-Jl-diene cation is useful because of its reasonable reactivity to nucleophilic attack on carbanions and common... 

Nucleophilic attack on the central allyl carbon atom of (T) -allyl) palladium and platinum compounds was employed in the synthesis of cyclopropanes from allylic electrophiles and silyl enolates. Treatment with base of (r) -allyl) palladium and platinum complexes bearing a methoxymethoxy group at the 2-position afforded the corresponding oxodimethylenemethane complexes in contrast to the formation of 2-hydroxysubstitutcd-(Ti5-allyl) complexes which was observed under acidic conditions. 

From an allyl compound by nucleophilic attack on the metal ... 

---