Vicinal dialkylation

A recently disclosed transformation describes an interesting oxovanadium(v)-induced vicinal dialkylation of cyclic enones by dialkylzincs.317 The method is based on the previous finding of the same authors that oxidation of... 

The general reaction sequence has been named more specifically as tandem vicinal dialkylation, nucleophilic-electrophilic carbacondensation,11 dicarbacondensation1213 or conjugate addition-enolate trapping,14 usually in reference to the fact that most of the reaction examples available create two new vicinal carbon-carbon bonds. Many noncarbon nucleophiles and electrophiles also are known, resulting... 

Esters are far less reactive as electrophiles when compared to aldehydes and ketones. Successful tandem vicinal dialkylations are possible using alkyl formates,67 but most esters lack the needed reactivity. More reactive thioesters can serve as electrophiles in these sequences.208 Presence of a potentially electrophilic ester group as a substituent in the conjugate enolate permits very efficient Dieckmann cycliza-tion to take place as the second step of a MIRC sequence (e.g. equations 5118 and 52).24 Ortho esters are far more reactive, giving p-keto esters as adducts when used in sequences that employ enones as substrates.230... 

Michael addition.1 This ketene silyl acetal undergoes Michael addition to a,fl-enones in acetonitrile in the absence of a Lewis acid to afford the corresponding O-silylated Michael adduct in high yield. These O-silyl enolates undergo site-specific electrophilic substitution. This sequence was used for vicinal dialkylation of cyclohexanone (equation I) and of cyclopentanone. It is particularly useful for synthesis of methyl jasmonate and related compounds from cyclopentenone. 

C-Trapping. Alkylation or hydroxy alkylation (i.e., reaction with RCHO) of enolates derived from conjugate addition of organocuprates affords vicinal dialkylated products. However, the reaction is confined to highly reactive alkylating agents such as methyl, allyl, propargyl, benzyl, and a-halocarbonyl compounds or aldehydes. 

A useful technique to accomplish overall vicinal dialkylation of enones is to trap the enolate initially formed in the conjugate addition with TMS-Cl, and then regenerate the enolate under suitable conditions for its alkylation. Lithium 1-enolates of 3,5-dialkylcyclohexanones generated from the reaction of the corresponding TMS enol ethers with lithium amide in liquid ammonia-THF can be alkylated efficiently in liquid ammonia-THF, even with an unreactive alkylating agent such as n-butyl iodide (Scheme 10). ... 

Vicinal dialkylation. The oxovanadium-induced reaction of cyclic enones with dialkylzinc reagents is followed by oxidation of the alkylzinc enolates and another C—C bond formation process, resulting in the generation of vicinal dialkylation products. 

Lithium n butyl (phenylthio) cuprate has been used in nucleophilic substitution reactions of arenesulfonyl fluorides, al-lylic acetates, 9 BBN, propargyllc carbamates, and bromo-alkenes, as well as in nucleophilic additions to acetoxy-epoxides. It Is a good choice for 1,4-addItIon of an n-Bu group, having been used in 1,4 addition-elimination reactions of a-oxoketene dithloacetals and 3-halo-2-cycloalkenones, and in tandem vicinal dialkylation reactions of 5-methyleneoxa-zolones and alkynes. A typical example Is the use of the reagentin the stereospecific synthesis of (, -2-heptenoicacidfrom acetylene (eq 1). ... 

Scheme 2.80 Vicinal dialkylation via conjugate addition and ligand coupling...

Scheme 2.81 Oxovanadium-induced vicinal dialkylation of cychc a,f)-unsaturated carbonyl...

Scheme 2.82 Oxovanadium-induced vicinal dialkylation of 2-cyclohexenone with triethylaluminum or triethylborane...

Scheme 2.83 Oxovanadium-induced vicinal dialkylation of cyclic a,p-unsaturated carbonyl compounds with RaZnLi...

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