Allyl halides, electrophilic addition

Both resonance forms of the allylic carbocation from 1 3 cyclopentadiene are equivalent and so attack at either of the carbons that share the positive charge gives the same product 3 chlorocyclopentene This is not the case with 1 3 butadiene and so hydrogen halides add to 1 3 butadiene to give a mixture of two regioisomeric allylic halides For the case of electrophilic addition of hydrogen bromide at -80°C... 

The prime functional group for constructing C-C bonds may be the carbonyl group, functioning as either an electrophile (Eq. 1) or via its enolate derivative as a nucleophile (Eqs. 2 and 3). The objective of this chapter is to survey the issue of asymmetric inductions involving the reaction between enolates derived from carbonyl compounds and alkyl halide electrophiles. The addition of a nucleophile toward a carbonyl group, especially in the catalytic manner, is presented as well. Asymmetric aldol reactions and the related allylation reactions (Eq. 3) are the topics of Chapter 3. Reduction of carbonyl groups is discussed in Chapter 4. 

Pentafluorophenylcopper exhibits high reactivity towards a variety of organic substrates such as aryl, vinyl, alkynyl, allyl halides etc. [226,227,229,235-238] (Scheme 77). Similar to trifluorovinylcopper, pentafluorophenylcopper readily adds to hexafluoro-2-butyne to form the syn addition product, which can be quenched with electrophiles [230] (Scheme 78). 

OxazoIones are alkylated at position 4 by alkyl halides, allyl halides and electrophilic alkynes, such as methyl propiolate (equation 36). In contrast, 2-phenyloxazolones react with methyl vinyl ketone at both C(4) and C(2) to yield a mixture of Michael adducts (equation 37). If the phenyl substituent is replaced by the bulky 2,4,6-trimethylphenyl group the addition is directed exclusively to C(4) (81CB2580). Alkylation of 5(4//)-oxazolones is a key step in the synthesis of ketones from a-amino acids (Scheme 16). The outcome of this sequence is the union of the electrophilic fragment R3 with the group R2CO the amino acid thus functions as the equivalent of an acyl anion (78AG(E)450). 

This reaction illustrates a stereoselective preparation of (Z)-vinylic cuprates, 5 which are very useful synthetic Intermediates. They react with a variety of electrophiles such as carbon dioxide,5,6 epoxides,5,6 aldehydes,6 allylic halides,7 alkyl halides,7 and acetylenic halides 7 they undergo conjugate addition to a,6-unsaturated esters,5 6 ketones,6 aldehydes,6 and sulfones.8 Finally they add smoothly to activated triple bonds6 such as HCSC-OEt, HC3C-SEt, HC=C-CH(0Et)2. In most cases these cuprates transfer both alkenyl groups. The uses and applications of the carbocupration reaction have been reviewed recently.9 The configurational purity in the final product 1s at least 99.951 Z in the above transformations. 

Perfluorophenyl)copper exhibits high reactivity towards organic substrates. and reacts with fluorinated or nonfluorinated aryl iodides (e.g., formation of 5), fluorinated vinyl iodides, al-kynyl bromides and iodides, allyl halides, alkanoyl halides, and iodomethane to afford the corresponding coupled products in good yields. (Perfluorophenyl)copper readily undergoes addition in a syn fashion to perfluorobut-2-yne to form a perfluorovinylcoppcr reagent 6, which can be quenched by electrophiles (e.g. formation of 7). Recall that (per-fluorophcnyl)coppcr reacts with (trifluoromethyl)copper to form (perfluorophenethyl)copper (Section 2.1.1.3.3.). 

In most cases, treatment of allylic halides containing one ASG with a nucleophile does not result in formation of electrophilic cyclopropanes (MIRC product) instead, other reaction pathways are followed, e.g. addition, substitution, rearrangement and elimination reactions.However, with certain alkenes or nucleophiles or under the appropriate conditions a conjugate addition-nucleophilic substitution pathway is favored, resulting in cyclopropanes substituted with one ASG. Representative examples are compiled in Tables 20 and 21 where organometallic compounds or active methylene compounds are used as the nucleophilic species in combination with allyl bromides containing an ester or a sulfone as ASG. 

It is often difficult to make a comparison between the various results obtained for the same polyenes as different reaction conditions (ratio of reactants, temperature, time) were used in each case. The addition of dichlorocarbene (chloroform/base/phase-transfer catalysis) to straight chain and cyclic unconjugated di- and trienes, carried out under identical conditions but varying the catalysts, showed the peculiar properties of tetramethylammonium chloride. Under precisely tailored conditions, either highly selective mono- or polyaddition of dichlorocarbene to the polyenes is possible tetramethylammonium chloride was the most efficient catalyst for monocyclopropanation. (For the unusual properties of tetramethylammonium salts on the phase-transfer catalyzed reaction of chloroform with electrophilic alkenes see Section 1.2.1.4.2.1.8.2. and likewise for the reaction of bromoform with allylic halides, see Section 1.2.1.4.3.1.5.1.). For example, cyclopropanation of 2 with various phase-transfer catalysts to give mixtures of 3, 4, and 5, ° of 6 to give 7 and 8, ° and of 9 to give 10 and 11. °... 

Allylic barium reagents prepared in this way can realize highly a-selective reactions with different electrophiles, e.g. cross-coupling reactions with allylic halides or allylic phosphates, additions to carbonyl compounds or imines, and ring opening of epoxides. A selective Michael addition reaction with an a,/ -unsaturated cy-cloalkanone can also be performed by use of an allylic barium reagent. 

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