Alkyl homoallylic iodide

The first approach to oxa-[3 + 3] annulation precursor 8 would rely on late-stage oxidation of the cyclohexanone motif in 10 to the diketone, and 10 can be accessed through a sequence of 1,4-conjugate addition of a Me-nucleophile followed by trapping with a homoallyl electrophile 9 to set the A-ring stereochemistry (Scheme 8.1). Unfortunately, while the addition of Me2CuLi proceeded smoothly, no alkylation using iodide 9 was observed instead, only a mixture of 2,3-dimethylcyclohexanones and recovered iodide were isolated. 

Using an alternative method, homoallylic iodides are efficiently transformed into cyclopropylmethyl acetates using silver acetate in anhydrous benzene (Table 1). y-Disubstituted or conjugated homoallylic iodides are particularly reactive and rearrange quantitatively. y-Monosub-stituted iodides afford mixtures of cyclopropylmethyl and homoallyl acetates in a 1 1 ratio, whereas the absence of a y-alkyl or aryl group in the homoallylic iodides leads to elimination, only. 

It is noteworthy that diethyl 1-(ethoxycarbonyl)methylphosphonate can be first metallated, then alkylated by an homoallyl iodide to give 4,5-unsaturated phosphonate, and further converted into epoxides by treatment with MCPBA in CH2CI2 in 93% yield. ... 

Homofamesyl iodide 7 was prepared by the reaction sequence shown in the margin. Of interest here is the two-step transformation of an alkyl halide into a Crextended alkyl halide.9 Compound 30 is first subjected to a nucleophilic substitution by an urganolithium species with formation of a homoallylic phenyl thioether This is then methylated in a second step to an intermediate sulfonium salt. The final SN2 reaction with an iodide ion releases thioanisol as a stable leaving group to give compound 7. 

Second, if tin(II) catecholate is ligated by an optically active dialkyl tartrate, it will react with an allylic bromide or iodide and an aldehyde, in the presence of Cul as catalyst, to give the optically active homoallylic alcohol. The enantioselectivity is highest when the alkyl groups of the tartrate are bulky (t-butyl or cyclohexyl). Aromatic aldehydes give higher enantioselectivities than do aliphatic aldehydes, and the reaction is also successful with a-carbonylketones 74... 

Costa et al. developed an efficient pathway utilizing a chiral auxiliary to enter the monobutyrolactone skeleton, Scheme (9) [56]. The carboxylic acid 48 was transformed into the corresponding acyl chloride and then esterified using a homochiral enantiomeric alcohol 49. The resulting ester 50 was deprotonated with LDA and alkylated with piperonyl iodide providing the alkylated ester 51 in 62% yield and high diastereomeric excess (94% de). Ester 51 was reduced to the homoallylic alcohol 52 and finally transformed into the desired lactone 29 either by ozonolysis of the... 

Under conditions of high dilution to prevent intermolecular reactions, two allylic halide groups in the same molecule can be coupled to give a cyclic product. Macrocyclic lactones have been made in this way. Coupling occurs only at the primary centres. Note that the nickel reagents do not attack ester groups. Neither do they react with acid chlorides, ethers, nitriles, olefins or alkyl, aryl or vinyl chlorides (in contrast to bromides or iodides). Aldehydes and cyclic ketones are attacked, however, above 40°C affording homoallylic alcohols. 

It was not possible to get clean reactions between aldehydes and alkyl halides in the presence of Smij. The reason is the very fast Meerwein-Ponndorf reaction quoted in section 4.3.5. It was, however, found that halides such as allyl iodide or benzyl bromide are so reactive towards aldehyde groups that the secondary samarium alkoxide which appears in the solution cannot compete for the remaining aldehyde (Souppe et al., 1982). In this way several homoallylic or homobenzylic alcohols could be obtained. Some examples are listed in table 10. The reaction failed on aromatic aldehydes because the pinacol formation is faster. 

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