Allyl halides reactions

Assuming a reactive oxonium ylide 147 (or its metalated form) as the central intermediate in the above transformations, the symmetry-allowed [2,3] rearrangement would account for all or part of 148. The symmetry-forbidden [1,2] rearrangement product 150 could result from a dissociative process such as 147 - 149. Both as a radical pair and an ion pair, 149 would be stabilized by the respective substituents recombination would produce both [1,2] and additional [2,3] rearrangement product. Furthermore, the ROH-insertion product 146 could arise from 149. For the allyl halide reactions, the [1,2] pathway was envisaged as occurring via allyl metal complexes (Scheme 24) rather than an ion or radical pair such as 149. The remarkable dependence of the yield of [1,2] product 150 on the allyl acetal substituents seems, however, to justify a metal-free precursor with an allyl cation or allyl radical moiety. 

A more versatile palladium-catalyzed formylation of organic halides takes place using tributyltin hydride and carbon monoxide (equation 7). The reaction works for a variety of substrates — aryl, benzyl and vinyl iodides, vinyl triflates and allyl halides. Reaction conditions are mild (1-3 bar CO, 50 °C), and a variety of functional groups can be tolerated. With unsymmetrical allyl halides formylation is regio-selective, taking place at the less-substituted allylic position with retention of geometry at the allylic double bond. 

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 reaction of allyl halides with terminal alkynes by use of PdClifFhCNji as a catalyst affords the l-halo-l,4-pentadienes 297. 7r-AlIylpalladium is not an intermediate in this reaction. The reaction proceeds by chloropalladation of the triple bond by PdCh, followed by the insertion of the double bond of the allyl halide to generate 296. The last step is the regeneration by elimination of PdCh, which recycles[148]. The cis addition of allyl chloride to alkynes is supported by formation of the cyclopentenone 299 from the addition product 298 by Ni(CO)4-catalyzed carbonylation[149]. 

Lithiated indoles can be alkylated with primary or allylic halides and they react with aldehydes and ketones by addition to give hydroxyalkyl derivatives. Table 10.1 gives some examples of such reactions. Entry 13 is an example of a reaction with ethylene oxide which introduces a 2-(2-hydroxyethyl) substituent. Entries 14 and 15 illustrate cases of addition to aromatic ketones in which dehydration occurs during the course of the reaction. It is likely that this process occurs through intramolecular transfer of the phenylsulfonyl group. 

Lithiation at C2 can also be the starting point for 2-arylatioii or vinylation. The lithiated indoles can be converted to stannanes or zinc reagents which can undergo Pd-catalysed coupling with aryl, vinyl, benzyl and allyl halides or sulfonates. The mechanism of the coupling reaction involves formation of a disubstituted palladium intermediate by a combination of ligand exchange and oxidative addition. Phosphine catalysts and salts are often important reaction components. 

Allylic brommations are normally carried out using one of a number of special ized reagents developed for that purpose N Bromosuccimmide (NBS) is the most fre quently used of these reagents An alkene is dissolved m carbon tetrachloride N bromo succimmide is added and the reaction mixture is heated illuminated with a sunlamp or both The products are an allylic halide and succimmide... 

The carbocations formed as intermediates when allylic halides undergo Stvfl reactions have their positive charge shared by the two end carbons of the allylic system and may be attacked by nucleophiles at either site Products may be formed with the same pattern of bonds as the starting allylic halide or with allylic rearrangement... 

This reaction illustrates a stereoselective preparation of (Z)-vinylic cuprates, which are very useful synthetic intermediates. They react with a variety of electrophiles such as carbon dioxide, epoxides, aldehydes, allylic halides, alkyl halides, and acetylenic halides they undergo... 

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... 

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 ... 

Displacement of an allylic halide is complicated by side reactions involving migration of the double bond. A good example is the reaction of 7a-bromo-3 -acetoxy-A -steroids (201) which gives, besides the expected... 

Codeposition of silver vapor with perfluoroalkyl iodides at -196 °C provides an alternative route to nonsolvated primary perfluoroalkylsilvers [272] Phosphine complexes of trifluaromethylsilver are formed from the reaction of trimethyl-phosphme, silver acetate, and bis(trifluoromethyl)cadmium glyme [755] The per-fluoroalkylsilver compounds react with halogens [270], carbon dioxide [274], allyl halides [270, 274], mineral acids and water [275], and nitrosyl chloride [276] to give the expected products Oxidation with dioxygen gives ketones [270] or acyl halides [270] Sulfur reacts via insertion of sulfur into the carbon-silver bond [270] (equation 188)... 

A two-step cyclization of an enamine with an electrophilic olefin has been reported in which the first step is alkylation by an allyl halide and the second step is alkylation by the electrophilic olefin (50). The reaction... 

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]. 

Conjugated dienes can be prepared by some of the methods previously discussed for preparing alkenes (Sections 11.7-11.10). The base-induced elimination of HX from an allylic halide is one such reaction. 

Allylic bromination, 339-340 mechanism of, 339-340 Allylic carbocation, electrostatic potential map of, 377, 489 resonance in, 488-489 SN1 reaction and, 376-377 stability of, 488-489 Allylic halide, S l reaction and. 377 S j2 reaction and, 377-378 Allylic protons, ]H NMR spectroscopy and, 457-458... 

Metzner and co-workers reported a one-pot epoxidation reaction in which a chiral sulfide, an allyl halide, and an aromatic aldehyde were allowed to react to give a trons-vinylepoxide (Scheme 9.16c) [77]. This is an efficient approach, as the sulfonium salt is formed in situ and deprotonated to afford the corresponding ylide, and then reacts with the aldehyde. The sulfide was still required in stoichiometric amounts, however, as the catalytic process was too slow for synthetic purposes. The yields were good and the transxis ratios were high when Ri H, but the enantioselectivities were lower than with the sulfur ylides discussed above. 

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. 

Phenyl-V-heptene Typical Procedure for the Reaction of RCu BE, with Allylic Halides and Allylic Alcohols 11 ... 

The reaction of allylic halides 1 with the zinc cuprate (R2CuZnCl), prepared by treatment of LiCuR2 with 1 equivalent of anhydrous zinc(II) chloride, affords the SN2 product 2 with 98% regioselectivity, and the diastercoselectivity is nearly 100% am/75. 

To a suspension of 1.10 mmol of eopper(I) bromide-dimethyl sulfide in 2 mL of THF arc added 2.20 mmol of Bul.i in hexane at — 70 C und the clear solution is stirred at — 40°C for 40 min. 1.15 mmol of freshly fused zinc(Il) chloride dissolved in THF (1 M, 1.15mL) are added at - 70°C and after 15 min 1.0 mmol of the allylic halide in 1 mL of 1HF are added. After 15 h at -702C, the reaction mixture is diluted with hexane washed with sat. aq NaHC03 and sat. aq NaCI and then dried over MgS04. Tile solvent is removed, the product ratio analyzed by GC and the product is purified by chromatography. 

An extensive study (6) of Sn displacement reactions of allyl halides using silyl anions/anionoids has provided the following regioselective alternatives ... 

Few reports describe the cross metathesis of allyl halides [88]. First-generation catalyst 9 does not seem to be sufficiently reactive to promote this reaction in preparatively useful yields and acceptable catalyst loadings, but second-generation catalyst 56d gives good results for allyl chloride. Cross-metathesis... 

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