Allylic halides, substitution

Standard techniques are used to substitute on nitrogen. Allyl and substituted allyl halides substitute directly, whereas alkyl and CPM functions are best introduced via the acyl halide followed by LAH reduction.(61) Reaction of norbenzomorphans with N-nitrourea or with urea, acetic acid, and HC1 affords N-carbamoylbenzomorphans.(65,66) N-Arylamidinobenzomorphans have also been reported.(67)... 

In contrast to allyl halides substituted with one ASG, the cyclopropanation reaction proceeds relatively smoothly when a second ASG is present. Generally, the best results are obtained with sodium borohydride, sodium cyanide, potassium cyanide, and the sodium salts of alcohols or thiols as the nucleophilic species (Table 22, entries 3-26). Even spiroalkanes can be synthesized with the nucleophiles described above (Table 23). Examples illustrating this route are the conversion of a tetracyclic enamino ester with potassium cyanide to the corresponding electrophilic cyclopropane 2, and the facile one-pot synthesis of 1,1 -bis(hydroxymethyl)cyclo-propanes 3 by reduction of halogenated alkylidene malonates with lithium aluminium hydride. ... 

Substituted allylic halides give mixtures of products resulting from bond formation at both C-1 and C-3 of the allylic system, with the product ratio favoring the product formed by reaction at the less substituted site. The portion of the product formed by reaction at C-1 in allylic systems may result from direct substitution, but it has also been suggested that a... 

These mechanisms ascribe in jortance to the Lewis acid-Lewis base interaction between the allyl halide and the organolithium reagent. When substitution is complete, the halide ion is incorporated into the lifliium cluster in place of one of the carbon ligands. 

A similar transformation results when trimethylsilyloxy-substituted allylic halides react with silver perchlorate in nitromethane. The resulting allylic cation gives cycloaddition reactions with dienes such as cyclopentadiene. The isolated products result from desilyla-tion of the initial adducts ... 

Cuprates react rapidly witli allylic halides for acetates) [17, 23], propargyl halides for acetates) [ 106-108], and vinyloxiraties, often witli S 2 regioselectivity iSclieme 10.9) [17]. Hie reaction takes place witli emit stereodieniistry iwitli respect to tlie leaving group), while syn substitution occurs when an allylic carbamate is employed as tlie substrate [109]. 

Symmetric allylsilanes and unsymmetric allylsilanes, in which the silyl substituent is at the less substituted end of the allyl fragment, are available from allyl halides and trimethylsilylmetal reagents13. 2-Chloro-l-cyclohexenes react with inversion of configuration and a 1,3-shift, with better results in the presence of coppcr(l) iodide14. 

Allylstannanes can be prepared by treatment of allyl halides with trialkyl- or triaryltin lithium reagents. Displacement of primary allyl halides tends to be regioselective for formation of the less substituted allylstannane, and takes place with useful retention of double-bond geometry14-16. 

Stoichiometric organocoppcr reactions become more y selective in the presence of boron trifluoride or trialkylboranes1Thus, RCu BF3 gives y substitution with allylic halides, alcohols, carboxylates and mesylates1119. 

Allyl- and substituted allylstannanes89 as well as allylcobaloximes90-92 undergo substitution with sulfonyl halides ... 

The difference in reactivity between the anions generated from LDA and LHMDS is difficult to rationalize, but nonetheless reproducible. The same effect has been observed with substituted allyl halides and propargyl halides. Instability of the product under the reaction conditions may account for this phenomenon. Thus, for alkylation of allylic and propargylic halides, LHMDS and KHMDS are the bases of choice. 

Entries 3 to 6 are examples of ester enolate alkylations. These reactions show stereoselectivity consistent with cyclic TSs in which the hydrogen is eclipsed with the enolate and the larger substituent is pseudoequatorial. Entries 4 and 5 involve SN2 substitutions of allylic halides. The formation of the six- and five-membered rings, respectively, is the result of ring size preferences with 5 > 7 and 6 > 8. In Entry 4, reaction occurs through a chairlike TS with the tertiary C(5) substituent controlling the conformation. The cyclic TS results in a trans relationship between the ester and vinylic substituents. 

Allylic stannanes can be prepared from allylic halides and sulfonates by displacement with or LiSnMe3 or LiSnBu3.146 They can also be prepared by Pd-catalyzed substitution of allylic acetates and phosphates using (C2H5)2AlSn... 

Regio- and Stereoselectivity. For the allylation of carbonyl compounds mediated by indium and other compounds in aqueous media, usually the carbon-carbon bond forms at the more substituted carbon of the allyl halide, irrespective of the position of halogen in the starting material. However, the carbon-carbon bond forms at the less-substituted carbon when the y-substituents of allyl halides are large enough (e.g., trimethylsilyl or tert-butyl) as shown by Chan et al.139 (Scheme 8.10). The following conclusions can be drawn ... 

It is possible to combine both the type I and the type II situations in the coupling of a chiral aldehyde with a substituted allylic halide. Such is the case in the coupling of unprotected aldoses (e.g., glyceraldehyde)... 

In contrast to the zirconium compounds the chromium halides are less active than pure Cr(allyl)3 Cr (allyl) Cl2 seems to be completely inactive. The only other element known in which halide substitution of the corresponding allyl compound results in activation is hafnium, suggesting the effect may be confined to group IVa. 

Chemical reactions are used to modify existing polymers, often for specialty applications. Although of considerable importance for plastics, very few polymer reactions (aside from crosslinking) are important for elastomers. Chlorination and bromination of Butyl rubber to the extent of about one halogen atom per isoprene unit yields elastomers which are more easily crosslinked than Butyl rubber. Substitution occurs with rearrangement to yield an allylic halide structure... 

The primary (7, 47) and most commonly used organonickel compounds have been the dimeric 7r-allyl- (or substituted Tr-allyl-) nickel halides (1) (Scheme 1) or their monophosphine adducts (2) in the presence of Lewis acids such as aluminum halides or alkylaluminum halides (4, 48-53). The... 

Allylphosphonium salts are synthesized by substitution of allyl halides with PPh3. The use of allyl alcohol, allyl acetate, or nitropropene with a palladium catalyst has also been reported.19 It is shown in this study that the organophosphorous compounds can be obtained by a palladium-catalyzed addition to an allene. A notable aspect of this method is that it can control the stereochemistry of the phosphonium salt, and that (Z)-allylphosphonium salts have been obtained in pure form for the first time. 

Extension of this reaction to electrophiles other than aldehydes was unsuccessful [22, 23], However, propargylic boronates were found to react with allylic halides and various carbonyl compounds [23], The boronates were prepared by lithiation of a methyl-substituted alkyne with t-butyllithium followed by treatment with a trialkylborane. The propargylic boronate preferentially reacts with the electrophile at the y-position to yield propargylic products (Eq. 9.20). The methodology has also been applied to alanates with comparable results. 

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. 

Fig. 16 Regioselective cathodic addition of allyl substituted allyl halides to carbonyl compounds [93].

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