Allylic halide effect

Several Pd(0) complexes are effective catalysts of a variety of reactions, and these catalytic reactions are particularly useful because they are catalytic without adding other oxidants and proceed with catalytic amounts of expensive Pd compounds. These reactions are treated in this chapter. Among many substrates used for the catalytic reactions, organic halides and allylic esters are two of the most widely used, and they undergo facile oxidative additions to Pd(0) to form complexes which have o-Pd—C bonds. These intermediate complexes undergo several different transformations. Regeneration of Pd(0) species in the final step makes the reaction catalytic. These reactions of organic halides except allylic halides are treated in Section 1 and the reactions of various allylic compounds are surveyed in Section 2. Catalytic reactions of dienes, alkynes. and alkenes are treated in other sections. These reactions offer unique methods for carbon-carbon bond formation, which are impossible by other means. 

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. 

Similar kinetics are exhibited by the reduction of vicinal dihalides by Cr(II) , which proceeds 10-40 times faster than that of the allylic halides. Such activation by a second halogen atom suggests a neighbouring group effect, viz. 

Nickel carbonyl effects coupling of allylic halides when the reaction is carried out in very polar solvents such as DMF or DMSO. This coupling reaction has been used intramolecularly to bring about cyclization of to-allylic halides and was found useful in the preparation of large rings. 

Among all the nucleophilic addition reactions of carbonyl compounds, allylation reaction has been the most successful, partly due to the relatively high reactivity of allyl halides. Various metals have been found to be effective in mediating such a reaction (Scheme 8.4). Among them, indium has emerged as the most popular metal for such a reaction. 

Allylic halides (example 19, Table VII) carbonylate under very mild conditions. An inverse effect of the CO pressure was observed in reaction with Ni(CO)4, CO dissociation being required to allow coordination of the substrate (168). 

Allylation.2 Indium also effects addition of allyl halides to carbonyl compounds under mild conditions. 

Microwave spectroscopic studies of l-fluoro-2-propene show that the cis conformation is more stable than the gauche conformation by approximately 306 cal/mol293 However, when fluorine is replaced by chlorine, bromine, or iodine, the gauche conformation becomes more stable294. These results confirm our expectations that the conformational preferences of allyl halides may depend on a balance of nonbonded attractive effects and a—it interaction effects. 

Alkylation of P-dicarbonyl compounds and p-keto esters occurs preferentially on the carbon atom, whereas acylation produces the 0-acyl derivatives (see Chapter 3). There are indications that C- and 0-alkylated products are produced with simple haloalkanes and benzyl halides, but only C-alkylated derivatives are formed with propargyl and allyl halides [e.g. 90]. Di-C-alkylation frequently occurs and it has been reported that the use of tetra-alkylammonium 2-oxopyrrolidinyl salts are more effective catalysts (in place of aqueous sodium hydroxide and quaternary ammonium salt) for selective (-90%) mono-C-alkylation of p-dicarbonyl compounds [91]. 

In the carbonylation of allyl halides the highly toxic [Ni(CO)4] catalyst could be replaced by [Ni(CN)2], which yielded [Ni(CN)(CO)jr under the reaction conditions [17]. The cyanotricarbonylnickel(0) anion is a versatile catalyst of carbonylations under phase transfer conditions [18], however, hydroxycarbonylation of allyl chloride proceeds effectively without PT catalysts in a genuine biphasic system, as well. 

Examination of the stereospecificity of the etherification indicated that the reaction was subject to a dramatic halide effect (Tab. 10.9). Treatment of enantiomerically enriched allylic carbonate (R)-53 (94% ee) under optimized conditions furnished the allyl ether (R)-54 in 84% yield (2° 1° >99 1), although with poor enantiospecificity (41% cee ... 

For recent examples of halide effects on en-antioselectivity in transition metal-catalyzed allylic substitutions, see (a) Bartels, B. Helmchen, G. Chem. Commun. 1999, 741. (b) Burckhardt, U. Baumann, M. ... 

Instead of quenching with deuterium chloride, the intermediary organomonozinc compound can be used as a new nucleophile. Not only allylic halide but also alkenyl or aryl halide can be used as the first electrophile with bis(iodozincio)methane (3). In Scheme 23, examples for sequential coupling are summarized. In the case of coupling with bromoalkene, a nickel catalyst is more effective than a palladium catalyst. 

Alkylation of allylic halides and alcohols (8, 334 335). Complete details of the reaction of RC.u BF3 with allylic halides and alcohols are now available. The reagent is probably an ate complex, RBF3 Cu 1, at least at low temperatures. In the case of allylic halides, THF is superior to ether for effecting /-substitution. However use of ether is essential for the direct alkylation. Addition of BF3 (even 2 equivalents) has no effect on reactions of C6II5Cu.5... 

Selective reduction of t-alkyl halides. The ate complex of B-butyl-9-BBN with n-BuLi selectively reduces tertiary alkyl halides to hydrocarbons in high yield without effect on primary or secondary halides. It does not reduce aryl or vinyl halfdes, but does reduce benzyl and allyl halides. The reduction involves a carbonium ion, and thus can proceed with Wagner-Meerwein rearrangements in certain systems. 

Amino acid synthesis (8, 389). Alkylation of the aldimine (1) from glycine ethyl ester and /j-chlorobenzaldehyde under phase-transfer conditions offers a general route to amino acids. Either liquid-liquid phase-transfer or solid-liquid phase-transfer catalytic conditions are satisfactory with active halides, but alkylation with allylic halides and less active alkyl halides is best effected under ion-pair extraction conditions (6,41), with 1 equiv. of tetra-n-butylammonium hydrogen sulfate (76-95% yields).1... 

Catalyst screening experiments resulted in the discovery that copper(salen) complex 33 was a highly effective catalyst for the conversion of alanine derivative 16b into (f )-a-methyl phenylalanine 17 under the conditions shown in Scheme 8.16. The presence of just 1 mol% of catalyst 33 was sufficient to induce the formation of compound 17 with up to 92% ee and in >70% yield [33]. Allyl bromide, 1-chloromethylnaphthalene and ethyl iodide also reacted with substrate 16b to give the corresponding (H)-a-methyl a-amino acids in the presence of 2 mol % of complex 33 [34], Complex 33 also catalyzed the asymmetric mono-alkylation of glycine-derived substrate 34 by benzylic or allylic halides, to give (H)-a-amino acid derivatives 35 with 77-81% ee. and in greater than 90% yield, as shown in Scheme 8.17. 

Allylation of imines.1 A low-valent Ti(0) species generated by reduction of TiCl4 with aluminum foil in THF can effect allylation of imines with allyl bromide, even when used in catalytic amounts (0.05 equiv.). This combination of a catalytic amount of TiCU with 1 equiv. of aluminum presumably generates Al(III) and Ti(0), which reacts with the allyl halide to form an allyltitanium, the reactive species. 

When the halide is bonded to an allylic system (CH CH-CH -X) an alkoxide ion will react analogously to the previously described S 2 displacement on an alkyl halide. The most significant difference is the rate enhancing effect of the alkene moiety which has been attributed to a decrease in the activation energy of the reaction (9). A second possible mode of reaction is available with allylic halides. This mode of displacement is usually called S 2 and, in general, will be promoted relative to the normal displacement when there are substituents on the alpha carbon which tend to inhibit the normal SN2 pathway by inductive or steric effects (Reaction VII). 

The UPS of the haloethenes was reviewed by Wittel and Bock in Supplement D of this Series4. The haloethenes for which UPS data are available constitute less than half of the 174 compounds which can be made by substituting different combinations of H, F, Cl, Br and I atoms on the C=C bond. However, the valence electronic structures and the nature of the ncc orbitals appear to be well understood. Nonetheless, if the past be any guide, some unexpected results will turn up. Thus, tetrafluoroethene was among the first compounds in which a perfluoro effect was observed. The TS interaction between fluorine atoms was discovered in ds,-difluoroethene. Some data for haloethenes and allyl halides are given in Table 6. 

Burton has investigated the alkylation of allyl halides with perfluoroorganocoppers. Both perfluoroalkylcoppers and perfluoroalkenylcoppers couple with allyl bromide in high yield the former also couples effectively with allyl chloride (equation 38)51 13. Doublebond stereochemistry is preserved with alkenylcopper reagents, while issues of a-/y-regio-selectivity of attack on the allyl unit have yet to be addressed. 

---