Vinylic epoxides allylic alkylation

Trimethylsilyl alkyl and aryl sulfides were found to function as latent sources of a sulfide nucleophile when used in conjunction with allyl carbonates or vinyl epoxides with Pd catalysts (equation 64).223... 

Trimethylsilyl alkyl and aryl sulfides react with allyl carbonates and vinyl epoxides to deliver the alkyl or aryl sulfide to the allyl unit. These species show typical regioselectivities by (i) adding to the less substituted end of alkyl substituted allyls (equation 290) (ii) adding to the allyl terminus more distant from remote oxygen functionality (equation 291) and (iii) showing substantial endocyclic addition to methylenecyclohexane-derived allyls (equation 292).223... 

Vinyl epoxides react with Pd(0) to yield electrophilic allyl complexes which can convert alcohols and phenols into allyl ethers (Scheme 4.80). These alkylations usually yield 2-alkoxy-2-vinylethanols, and if the Pd-mediated etherification is performed in the presence of a chiral, enantiomerically pure diphosphine, enantiomeri-cally enriched ethers may be obtained (Scheme 4.80) [356, 357]. 

An unusual syn addition to epoxides occurs when 1,3-diene monoepoxides are treated with organozinc reagents. Thus, the cyclic vinyl epoxide 72 was converted to the cis-ethyl-cyclohexenol 75 with diethyl zinc in methylene chloride and trifluoroacetic acid. The syn addition is believed to derive from an initial coordination of the oxiranyl oxygen to the organozinc compound, which then delivers the alkyl group to the same face. This transfer is facilitated by a relaxation of the sp3 hybridization brought about by the Lewis acidic zinc center and the allylic character of the incipient carbocation <020L905>. 

Vinyl epoxides and allylic carbonates are especially useful electrophiles because under the influence of palladium(O) they produce a catalytic amount of base since X- is an alkoxide anion. This is sufficiently basic to deprotonate most nucleophiles that participate in allylic alkylations and thus no added base is required with these substrates. The overall reaction proceeds under almost neutral conditions, which is ideal for complex substrates. The relief of strain in the three-niembered ring is responsible for the epoxide reacting with the palladium(O) to produce the zwitterionic intermediate. Attack of the negatively charged nucleophile at the less hindered end of the ic-allyl palladium intermediate preferentially leads to overall 1,4-addition of the neutral nucleophile to vinyl epoxides. 

Trost and Scanlan reported a Pd-catalyzed condensation of a vinyl epoxide 75 and an allyl sulfone 76 in the presence of dppf under neutral conditions [231]. This alkylation allows a room temperature entry to a basic indolizidine ring system as a step towards the synthesis of (+)-aj//o-Pumiliotoxin 339B [232], The modification of allylic alkylations by condensation of a diene 77 with a pronucleophile 78 also leads to C-C bond formation at the allylic position in both 1 1 (79 and 80) and 2 1 (81 and 82) products [233]. Reactions between ketene silyl acetals 83 with allyl... 

When the substrate is a vinylic epoxide, Grignard reagents generally give a mixture of the normal product and the product of allylic rearrangement (152). Butyllithium reacted with a difluoroalkylidene epoxide (F2C=CR epoxide) and Sn2 displacement gave alkylation at the difluoro carbon and opened the... 

On treatment with a palladium(O) catalyst, vinyl epoxides undergo facile unimolecular rearrangement to give dienols or enones depending on the substitution pattern of the substrate. In the presence of an active methylene compound in the reaction system, however, a single alkylation product is formed. Cyclic and acyclic vinyl epoxides participate equally well. The reaction proceeds with clean alkylation from the same face as the oxygen of the epoxide, and proceeds with allyl inversion (Scheme 22). ... 

The resulting derivatives were applied with success in the standard asymmetric allylic alkylation (up to 97 % ee) [134, 136] or in transformations involving either specific allylic substrates (2-cycloalkenyl derivatives, up to >99% ee) [135, 137], unsymmetrical substrates (monosubstituted allyl acetate, up to 83% ee) [140], or especial nucleophiles (nitroalkanes [141], iminoesters [138 a], or diketones [139, 140, 142]). Such ligands were also effective in the formation of quaternary chiral carbon through allylic substitution (eq. (6)) [138, 143], deracemiza-tion of vinyl epoxides (up to 99% ee) [144], or alkylation of ketone enolates [138 b], and deracemization of allylic derivatives [145]. 

Alkylation of allylic acetates also occurred under these conditions, NEt3 - or better l,8-diazabicyclo[5.4.0]undec-7-ene (dbu) - being used as the base, as well as that of vinyl epoxides. 

Alkylation of allylic acetates or vinyl epoxide occurred also under these conditions,... 

Scheme 12.41 Mechanism of the allylic alkylation with vinyl epoxides [77]. 12.2.3...

Reactions that proceed under neutral conditions are highly desirable. An important event in TT-allylpalladium chemistry is the introduction of highly reactive allylic carbonates (Sect. V.2.1.3), Their reactions can be carried out under mild neutral conditions. " Also, reactions of allylic carbamates, " allyl aryl ethers, and vinyl epoxides proceed without addition of bases. As shown by the mechanism in Scheme 6, the oxidative addition of allyl methyl carbonates is followed by decarboxylation as an irreversible process to afford TT-allylpalladium methoxide, and the generated methoxide picks up a proton from pronucleophiles (NuH), such as active methylene compounds. This in situ formation of the alkoxide is the reason why the reaction of aUyl carbonates can be carried out without addition of bases from outside. Alkoxides are rather poor nucleophiles, and alkyl allyl ethers are not formed from them. In addition, formation of TT-allylpalladium complexes from allylic carbonates involving decarboxylation is irreversible. In contrast, the formation of TT-allylpalladium acetate from allyl acetate is reversible. 

The reaction of alkenyl epoxides with organometallic species (lithium, magnesium, copper, and boron) affords allylic alcohols, following an Sn and/or Sn mechanism. These processes can accommodate only little organic functionality and exhibit low regio- and/or stereoselectivity. Under smooth conditions, C—C bond formation proceeds by nucleophilic alkylation of vinyl epoxides in the presence of catalytic amounts of zerovalent palladium. Regio- and stereoselectivity can be achieved via the formation of a Tr-allylpal-ladium complex. Trost and Molander and Tsuji and co-workers simultaneously reported the first studies in 1981. Since then, numerous papers have dealt with this subject. Essentially, after chelation and oxidative addition of the palladium onto the vinyl epoxide, the zwitterionic 7r-allylpalladium complex deprotonates the nucleophile, which can in principle attack either carbon 2 (proximal attack) or 4 (distal attack) (Scheme 1). 

The research groups of Trost and Tsuji have shown that in the presence of a palladium(O) catalyst vinyl epoxides can be regio- and stereo-selectively alkylated with various carbon acids under neutral conditions the main products are E-allylic alcohols resulting from 1,4-addition, e.g. (107) - (108). The reaction tolerates ester and ether groups. In the presence of a base, alkyl-lithiums... 

The radical-induced epoxide ring-opening of a,/3-epoxy-0-thiocarbonyl-imidazolides (23) [equation (3)] has been reported to be a convenient alternative to the Wharton rearrangement (action of hydrazine on epoxides of a,/3-unsaturated ketones) for production of allylic alcohols. /3,y-Disubstituted allylic alcohols with Z-conhguration are the major products formed on addition of alkyl-lithiums to the vinyl epoxide (24) [equation (4)]. ... 

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... 

In Entry 5, the carbanion-stabilizing ability of the sulfonyl group enables lithiation and is then reductively removed after alkylation. The reagent in Entry 6 is prepared by dilithiation of allyl hydrosulfide using n-bulyl lithium. After nucleophilic addition and S-alkylation, a masked aldehyde is present in the form of a vinyl thioether. Entry 7 uses the epoxidation of a vinyl silane to form a 7-hydroxy aldehyde masked as a cyclic acetal. Entries 8 and 9 use nucleophilic cuprate reagents to introduce alkyl groups containing aldehydes masked as acetals. 

The regioselectivity in palladium-catalyzed alkylations has been attributed to the dynamic behavior of trihapto pentadienyl metal complexes60. For example, competing electronic and steric effects influence product formation in dienyl epoxides, but in palladium-catalyzed reactions steric factors were often found to be more important. Thus, alkylation of dienyl epoxide 76 with bulky nucleophiles such as bis(benzenesulfonyl)me-thane in the presence of (Ph3P)4Pd occurred exclusively at the terminal carbon of the dienyl system producing allyl alcohol 77 (equation 39). However, the steric factors could be overcome by electronic effects when one of the terminal vinylic protons was replaced with an electron-withdrawing group. Thus, alkylation of dienyl epoxide 78 affords homoal-lylic alcohol 79 as the major product (equation 40). 

Since the starting tellurides are easily prepared (see Section 3.1.3.2) from the corresponding alkyl bromides and tellurolate ions, and -hydroxyalkyl tellurides by the opening of epoxides with the same reagents, the combined procedures furnish a method for the dehydrobromination of alkyl bromides and for the conversion of epoxides into allylic alcohols. Moreover, combining the telluroxide elimination with the methoxytelluration of olefins (see Sections 3.9.3.2 and 4.4.8.3), allylic and vinylic ethers are easily prepared. 

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