546-49-6

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Enethiolizable β-oxodithioesters allowing the successive formation of carbon-carbon bonds at the carbonyl and at the thiocarbonyl sites, are precursors of α-unsaturated dithioesters and can be used as a3d1 or a3a1 synthons.

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The major components of the isoprenoid-rich essential oil of Artemisia annua L. accumulate in the subcuticular sac of glandular secretory trichomes. As part of an effort to understand isoprenoid biosynthesis in A. annua, an expressed sequence tag (EST) collection was investigated for evidence of genes encoding trichome-specific enzymes. This analysis established that a gene denoted Adh2, encodes an alcohol dehydrogenase and shows a high expression level in glandular trichomes relative to other tissues. The gene product, ADH2, has up to 61% amino acid identity to members of the short chain alcohol dehydrogenase/reductase (SDR) superfamily, including Forsythia × intermedia secoisolariciresinol dehydrogenase (49.8% identity). Through in vitro biochemical analysis, ADH2 was found to show a strong preference for monoterpenoid secondary alcohols including carveol, borneol and artemisia alcohol. These results indicate a role for ADH2 in monoterpenoid ketone biosynthesis in A. annua glandular trichomes.

Indium mediated coupling of allylic bromide with acyloyl-imidazoles or pyrazoles in aqueous media gives the corresponding tertiary alcohols or ketones in good yield. The reaction provides a facile regioselective synthesis of P,β,γ-unsaturated ketones and its usefulness is demonstrated by the synthesis of the monoterpene artemesia ketone.

Allylic mercuric iodides are readily prepared by the reaction of mercury(0) and allylic iodides.They undergo efficient acylation with allylic rearrangement upon reaction with acyl chlorides and aluminium chloride to provide a convenient synthesis of allylic ketones.Artemisia ketone is prepared in two steps by this approach.

TiCl4 induced rearrangement of α-allyl α′-vinylβ-trimethylsilyl ketones 3c,d,c,g leads to rearranged α-allyl α′-vinyl ketones 4c, d, e or 2-vinylcyclopentanone 9 resulting of an acyl shift with silyl control.

Lithium enolates of carboxylic and thiocarboxylic esters react with nucleophiles to afford ketone and aldehyde enolates and subsequently their enol silyl ethers diastereoselectively.This reaction is applied to the synthesis of γ-damascone, α-damascone, β-safranal, and artemisia ketone.

Allylic mercurials, readily available from allylic halides and mercury(0), react with acyl chlorides and AlCl3 under mild reaction conditions to afford high yields of allylic ketones.

The reactivity of α-unsaturated N-phenyl imidothioesters towards organomagnesium and lithium compounds was studied.From an α or β-non ramified imidothioester (methyl N-phenyl 2-butenimidothioate) 1,4-additions were observed with alkyl-, vinyl- and aryl-Grignard reagents, alkyllithium and lithiated limonene, and with benzenethiolate and benzenesulfinate anions.After sulfhydrolysis, new β-ramified or functionalized dithioesters were isolated and one of them was used in a synthesis of 2,6-dimethyl-1,7-octadiene-4-one.A 1,2-addition, with inversion of the allylic chain, was observed with allylic Grignard reagents, followed by a second 1,2-addition to the imine formed after elimination of magnesium methylthiolate.This double addition was not observed with prenylmagnesium bromide, the reaction of which with methyl 3-methyl N-phenyl 2-butenimidothioate led, after hydrolysis, to artemisia ketone.The regoiselectivities of the additions of organometallics to methyl 2-butenedithioate (prepared in situ from methyl phenylsulfonyl-3 butanedithioate) were also examined and they appeared completely different to those observed with the corresponding imidothioester; a thiophilic addition was the first step in the reaction of methyllithium or ethylmagnesium bromide and 1,4-γ-additions were observed with allylic Grignard reagents.

The novel reagents formed by combination of Grignard reagents (RMgX) with lithium diisopropylamide (LDA) convert non-enolizable carboxylic esters or carboxamides into ketones which are protected from further reaction by their in situ conversion into enolates.These enolates can be trapped with electrophiles such as Me3SiCl and allyl bromide.The scope of this Grignard mono-addition is illustrated by two direct synthesis of artemisia ketone (14).

Mesyltriflone (CF3SO2CH2SO2CH3) is developed as a nuclear synthon reagent capable first of multiple constructions such as alkylations then of Ramberg-Baecklund elimination to a substituted olefin.The alkylations are clean and regiospecific, often amenable to one-pot operation, and in most cases the elimination is smooth.A variety of examples is presented to establish the scope of the method, and the mechanism and stereochemistry are discussed.

The sequential dialkylation of dimethylaminoacetonitrile with first methallylchloride and then prenylbromide is performed at room temperature using K2CO3 in DMF.Subsequent hydrolysis and isomerisation afford artemisia ketone in 77percent overall yield.

The condensation of a Grignard reagents with hindered acid chlorides in THF at low temperature, yields ketones which are generally difficult to obtain and avoids the side reaction caused with a CuCl catalyst.Applied to unsaturated Grignard reagents and acid chlorides, this method also yields unsaturated ketones, such as the Artemisia ketone.

5,6-Epoxy-3,3,6-trimethyl-hept-1-en-4-one, a novel aliphatic epoxy-ketone, has been found to possess useful odor and flavor properties. It can be advantageously used as perfume and flavor-modifying ingredient. Perfume and flavor-modifying composition containing same and process for its preparation.

Allylsilanes show in certain cases a behaviour towards electrophiles which is opposite to that of its carbon homologues.Theoretical calculations using Dewar's MINDO/3 method performed on 3-methyl 3-butenyl trimethyl-silane and 2-methyl 2-butene show that geometrical optimization leads to a silicon-allylic carbon bond nearly parallel to the double bond ? cloud, and both net atomic charges and HOMO coefficients indicate an inversion between these two substrates.