Allyl halides epoxidation

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... 

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. 

These copper reagents do not react with epoxides, but they undergo SN2 reactions with allylic halides (equation II). These reagents also couple with acyl... 

Scheme 57 illustrates an example of this process coupling of the lithio reagent derived from vinyl stannane 237 with epoxide 242 leads to the C-disaccharide derivative 243 in good yield. A double transmetallation to give an organocopper reagent 244 can facilitate the C-glycosylation reaction with allyl halides [80] (Scheme 58). 

Benzyl methyl ether or allyl methyl ethers can be selectively metalated at the benzylic/allylic position by treatment with BuLi or sBuLi in THF at -40 °C to -80 C, and the resulting organolithium compounds react with primary and secondary alkyl halides, epoxides, aldehydes, or other electrophiles to yield the expected products [187, 252, 253]. With allyl ethers mixtures of a- and y-alkylated products can result [254], but transmetalation of the lithiated allyl ethers with indium yields y-metalated enol ethers, which are attacked by electrophiles at the a position (Scheme 5.29). Ethers with ft hydrogen usually undergo rapid elimination when treated with strong bases, and cannot be readily C-alkylated (last reaction, Scheme 5.29). Metalation of benzyl ethers at room temperature can also lead to metalation of the arene [255] (Section 5.3.11) or to Wittig rearrangement [256]. Epoxides have been lithiated and silylated by treatment with sBuLi at -90 °C in the presence of a diamine and a silyl chloride [257]. 

Fiirstner reported in parallel coupling reactions using 5 mol% of the isolated ferrate(-II) catalyst [Li(TMEDA)]2[Fe(C2H4)4] 4 in THF (Fig. 2) (entry 2) [45, 46], Primary and secondary alkyl bromides and iodides and allylic halides worked well, while alkyl chlorides and tertiary alkyl iodides were inert. Many sensitive functionalities like ester, nitrile, isocyanate, epoxide, and amine groups are tolerated. 

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. 

The complex formed on addition of cuprous iodide to a solution of a lithium dialkylamide in ether or tetrahydrofuran is effective in the reductive coupling of allylic halides to give 1,5-dienes with preservation of stereochemistry. This method has been used5 for the stereospecific synthesis of all-trans-squalene and (E,Z,Z,E) squalene from (E,E)- and (Z,JE)-farnesyl bromides, respectively. In an attempted synthesis of (3S)-squalene-2,3-epoxide, 4-[(4R)-2,2,5,5-tetramethyl-l,3-dioxolan-4-yl]butan-2-one (1) and the phosphonium iodide (2) were prepared.6 Unfortu-... 

Electrooxidation of halide salts is quite useful for the generation of reactive species of halogen atoms under mild conditions. Functionalization of alkenes involving the formation of halohydrins, 1,2-halides, a-halo ketones, epoxides, allylic halides and others has been achieved by electrochemical reactions and is well documented in the literature. On the other hand, electrogenerated carbenium ions can be captured by nucleophilic halide anions, providing a new route to halogenated compounds... 

The hydrosilation reaction is highly compatible with a number of functional groups including ether, epoxide, acetal, ketone, ester, nitrile, amine, amide, nitro, carbamate, isocyanate, phosphate, sulfide, sulfone, and others." As a consequence, it is a very attractive reaction for the construction of complex organic molecules. Sometimes allyUc displacement is observed as a side reaction, especially in the reaction of allyl halides. ... 

Vinylcopper reagents react with a wide variety of electrophilic reagents such as halogens, alkyl halides, allylic halides, acid chlorides, epoxides, a,(3-unsaturated ketones, and a,p-acetylenic esters with complete retention of the double bond stereochemistry. To enhance the reactivity of vinylcopper intermediates toward carbon electrophiles, the coupling is often carried out in the presence of activators such as HMPT, DMPU, and/or P(OEt)3 (triethylphosphite). Some representative examples of stereospecific... 

Other applications of carbanions a to a sulfone in total syntheses have recently been reported. Most of them used allylic sulfones or allylic halides. Two examples are reported here. In the synthesis of a precursor of cembranolides, a sulfone derived from geranyl bromide was coupled with an allylic alcohol epoxide (Scheme 65). An interesting point was that the coupling reaction gave high yields only when the lithiated sulfone was allowed to react with the epoxymagnesio alkoxide (the lithium salt of the epoxy alcohol did not react at all with the lithiated sulfone). 

Tt-Allylnickel halides. Billington has reviewed the preparation of these complexes from allylic halides using Ni(CO)4 or Ni(COD)2, and their use in synthesis, mainly of natural products (54 references). These complexes react with a wide range of both aliphatic and aryl bromides or iodides as well as aldehydes, ketones, epoxides, and quinones. One advantage is that both allyl ligands react. They do not react with acid chlorides, esters, ethers, nitriles, or acetals. 

The reactions between a-metalloalkyl sulfoxides and electrophiles have been extensively studied. Although alkylations of the sodium or potassium salts of dialkyl sulfoxides are not always very efficient since a,a -dialkylated sulfoxides are often produced (or stilbene in the case of methyl-sulfinyl carbanion and benzyl bromide ), those employing the lithioalkyl aryl sulfoxides work more efficiently with alkyl or allyl halides " and with epoxides. " " Typical examples of these alkylations, allylations and hydroxyalkylations (from epoxides) are illustrated in Scheme 86. 

---