Allyl compounds nucleophilic substitution

Alkyl halides can be hydrolyzed to alcohols. Hydroxide ion is usually required, except that especially active substrates such as allylic or benzylic types can be hydrolyzed by water. Ordinary halides can also be hydrolyzed by water, if the solvent is HMPA or A-methyl-2-pyrrolidinone." In contrast to most nucleophilic substitutions at saturated carbons, this reaction can be performed on tertiary substrates without significant interference from elimination side reactions. Tertiary alkyl a-halocarbonyl compounds can be converted to the corresponding alcohol with silver oxide in aqueous acetonitrile." The reaction is not frequently used for synthetic purposes, because alkyl halides are usually obtained from alcohols. 

In basic aqueous media, a kinetic study of the reaction between stannate(II) ions and alkyl halide shows that mono- and disubstituted organotin compounds are formed (Eq. 6.12a).27 The monosubstituted organotin compound is obtained after a nucleophilic substitution catalyzed by a complexation between the tin(II) and the halide atom. The disubstituted compound results from an electrophilic substitution coupled with a redox reaction on a complex between the monosubstituted organotin compound and the stannate(II) ion. Stannate(IV) ions prevent the synthesis of the disubstituted compound by complexation. Similarly, when allyl bromide and tin were stirred in D2O at 60° C, allyltin(II) bromide was formed first. This was followed by further reaction with another molecule of allyl bromide to give diallyltin(IV) dibromide (Eq. 6.12b).28... 

A typical second step after the insertion of CO into aryl or alkenyl-Pd(II) compounds is the addition to alkenes [148]. However, allenes can also be used (as shown in the following examples) where a it-allyl-r 3-Pd-complex is formed as an intermediate which undergoes a nucleophilic substitution. Thus, Alper and coworkers [148], as well as Grigg and coworkers [149], described a Pd-catalyzed transformation of o-iodophenols and o-iodoanilines with allenes in the presence of CO. Reaction of 6/1-310 or 6/1-311 with 6/1-312 in the presence of Pd° under a CO atmosphere (1 atm) led to the chromanones 6/1-314 and quinolones 6/1-315, respectively, via the Jt-allyl-r 3-Pd-complex 6/1-313 (Scheme 6/1.82). The enones obtained can be transformed by a Michael addition with amines, followed by reduction to give y-amino alcohols. Quinolones and chromanones are of interest due to their pronounced biological activity as antibacterials [150], antifungals [151] and neurotrophic factors [152]. 

Lewis acids are also effective to induce the nucleophilic substitution of allylic nitro compounds. These compounds react with allyltrimethylsilane,28 silyl enolates,28 or cy-anotrimethylsilane29 in the presence of SnCl4 to give substitution products, respectively (see Eqs. 7.24-7.26). 

Hetero-substituted allyl compounds obtained by electrophilic attack in the 1-position can be reduced to give the heteroalkyl compounds carrying the new substituent on the a-carbon atom ( ). In this case, the double bond was used as an activating substituent only, to achieve easier deprotonation and higher nucleophilicity. In both cases the synthetically important umpolung of reactivity was achieved20. 

Trost and his co-workers succeeded in the allylic alkylation of prochiral carbon-centered nucleophiles in the presence of Trost s ligand 118 and obtained the corresponding allylated compounds with an excellent enantioselec-tivity. A variety of prochiral carbon-centered nucleophiles such as / -keto esters, a-substituted ketones, and 3-aryl oxindoles are available for this asymmetric reaction (Scheme jg) Il3,ll3a-ll3g Q jjg recently, highly enantioselective allylation of acyclic ketones such as acetophenone derivatives has been reported by Hou and his co-workers, Trost and and Stoltz and Behenna - (Scheme 18-1). On the other hand, Ito and Kuwano... 

Asymmetric allylation of carbon nucleophiles has been carried out extensively using Pd catalysts coordinated by various chiral phosphine ligands and even with nitrogen ligands, and ee > 90% has been achieved in several cases. However, in most cases, a high ee has been achieved only with the 1,3-diaryl-substituted allylic compounds 217, and the synthetic usefulness of the reaction is limited, Therefore, only references are cited[24,133],... 

The HDO and isomerization reactions were previously described as bimolecular nucleophilic substitutions with allylic migrations-the so-called SN2 mechanism (7). The first common step is the fixation of the hydride on the carbon sp of the substrate. The loss of the hydroxyl group of the alcohols could not be a simple dehydration -a preliminar elimination reaction- as the 3-butene-l-ol leads to neither isomerization nor hydrodehydroxyl at ion (6). The results observed with vinylic ethers confirm that only allylic oxygenated compounds are able to undergo easily isomerization and HDO reactions. Moreover, we can note that furan tetrahydro and furan do not react at all even at high temperature (200 C). 

Although this catalytic reaction appeared to be of synthetic interest, it has since then neither been applied in synthesis nor further developed. This might be attributed in part to problems with reproducibility and catalyst stability under the reaction conditions, although the Hieber complex was used in a stoichiometric manner for the preparation of a variety of 7i-allyl-Fe complexes. These latter compounds served as starting materials for a plethora of subsequent reactions [34]. The results obtained by Nakanishi and coworkers on the stability and reactivity of n-allyl-Fe-nitrosyl complexes proved such intermediates to be reactive towards a variety of nucleophiles however, the Fe complexes formed upon nucleophilic substitution were catalytically inactive. Hence, in order to maintain the catalytic activity, the formation of intermediate 7i-allyl-Fe complexes had to be circumvented. About 3 years ago we started our research in this field and envisioned the use of a monodentate ligand to be a suitable way to stabilize the proposed catalytically active G-allyl complex. The replacement of one CO by a non-volatile basic ligand was thought to prevent the formation of the catalytically inactive 7t-allyl-Fe complex (Scheme 7.21). 

Four reviews on allylic and vinyl substitution have been published.20-23 The use of pentamethylcyclopentadienylruthenium catalysts for the. S n reactions of allyl substrates has been reviewed.20 The Sn reactions of allyl substrates in the presence of ruthenium catalysts occur primarily at the most substituted position of the allylic group. All the catalysts involve formation of an intermediate where the allyl compound becomes associated with the Ru atom in the catalyst. The regiospecificity (50-98%) depends on the structure of the allylic substrate, the nucleophile, the solvent, the temperature, and the catalyst. These catalysts have also been used for protection of allylic alcohol and amino groups. Some of the reactions are stereospecific. 

An excellent review21 outlining the mechanism of diphenylphosphinobenzoic acid-based palladium-catalysed asymmetric substitution of allyl compounds with nucleophiles has been published. The mechanistic model developed for these reactions allows one to predict the stereochemistry of the product(s). 

If the add is HBr, then nucleophilic attack by Br on the cation follows. The cation is attacked at the less hindered end to give the important compound prenyl bromide. This is very much the sort of reaction you met in Chapter 17—it is the second half of an S>jl substitution reaction on an allylic compound. 

The study of PVC stabilisation by stannic compounds in the presence of HC1 scavengers shows that the essential stabilisation process is nucleophilic substitution of the allylic chlorine by the thioglycolate or mercaptopropionate groups. It is claimed that their capability to form complexes with HC1 and transport this degradation catalyst to HC1 scavengers are essential for the marked synergism observed between these two types of stabilisers. 14 refs. 

Recently Rinctionalized octa[(propyl)-silsesquioxanes] were obtained by hydrosilylation of Hg(SiO, 5)5 [3] with hinctionalized allylic compounds [4-8], In the following, the preparation of new functionalized propyl-silsesquioxanes by nucleophilic substitution or partial rearrangement of octa-[(3-chloropropyl)-silsesquioxane] is reported. 

The corresponding ferrilactams (156), which have also been the subject of much attention, are available by the nucleophilic substitution of (155) by amines in the presence of a Lewis acid, usually ZnCb. The substitution occurs with allylic transposition,that is, attack at C-3 of (155). In selected cases, compounds of the type (156) have been prepared by oxidative addition of vinylaziridines or m-4-amino-l-butenols with (2). A bridged ferrilactam bonded through C-2 of the allyl (157) unit has been reported recently and was prepared by way of oxidative addition of a cyclic allylic... 

AUyl compounds are highly reactive towards nucleophiles and examples of dissociative (5 1) and associative (5 2) reactions, and nucleophilic substitution with rearrangement are well documented . Differentiation between these mechanisms when azide ion is the nucleophile is cften extremely difficult due to the possibility of rearrangement of the allylic azide resulting from substitution, and for this reason the relative nucleophilic strength of azide ion in allylic 5n reactions has not been delineated. 

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