Action des homocuprates sur les cetones α,α′-dibromees. Une nouvelle methode de synthese de cetones encombrees

The reaction between alkyllithium homocuprates and α,α′-dibromoketones permits the monoalkylation of ketones after hydrolysis of the reaction intermediate; the latter reacts with an excess of alkyl halide and gives the dialkylated product. Four alkylation reactions (methylation, ethylation, isopropylation and t-butylation) of α,α′-dibromoketones have been studied. While monoalkylation leads to secondary/primary and tertiary/secondary ketones from bis-primary and bis-secondary structures, dialkylation permits the synthesis of bis-secondary and bis-tertiary ketones. The introduction of two tertiary groups in the same structure is nevertheless impossible.     

Kinetics of the acetic acid-catalysed ring-opening reaction of 2-phenyl-4,4-dimethyl-2-oxazolin-5-one with some aminoacid ethyl esters in carbon tetrachloride

The kinetic behaviour of the acetic acid-catalysed reaction of 2-phenyl-4,4-dimethyl-2-oxazolin-5-one (1) with the ethyl esters of glycine (2), dl-α-aminobutyric acid (4), α-aminoisobutyric acid (5), dl-norvaline (6), dl-valine (7), dl-leucine (8) and dl-phenylalanine (9) has been investigated. Within the concentration ranges employed the reactions follow second order kinetics, with no dependence of the experimental rate constant on the initial concentration of 1, just as found previously for the ethyl ester of dl-alanine. To explain the function of the catalyst a cyclic intermediate has been compared with other intermediates proposed for similar reactions. A good correlation has been obtained between the rate constant for the catalysed reaction and Taft's σ* values, showing that the effects of the substituents on the esters are mainly polar and supporting the structure of the proposed intermediate.     

Stereochimie de l'action des organomagnesiens et des organolithiens sur les dimethyl-1,2 alcoxy-1 silacyclobutanes

The reaction of organomagnesium organolithium compounds (alkyl, aryl, allyl and benzyl derivatives) with 1,2-dimethyl-1-alkoxy-l-silacyclobutanes proceeds with retention of configuration at the silicon atom. Stereochemical results are discussed in terms of the S_N2Si mechanism. The proposed configurations are supported by ¹H and ¹³C NMR data.     

Mecanisme de formation et de transformation des spirophosphoranes—IX: Reactions des spirophosphoranes a liaison PH avec les ethers vinyliques et les enamines

The reaction of 1,4,6,9-tetraoxa-5-phospha(V)spiro[4,4]nonane 1 with ethyl vinyl ether gives a spirophosphorane containing a PC bond, 5-(β-ethosyethyl)-1,4,6,9-tetra-oxa-5-phospha(V) spiro[4,4]nonane 2 (radical reaction), and a tricoordinated phosphorus compound, 2-(3,5-di-oxa-4-methylheptanoxyl)-1,3,2-dioxaphospholane 3 (ionic reaction). 2,2,3,3,7,7,9-Heptamethyl-1,4,6-trioxa-9-aza-5-phospha(V) spiro[4,4]nonane 6 gives exclusively a spirophosphorane containing a PC bond, 5(β-ethoxyethyl)-2,2,3,3,7,7,9-heptamethyl-1,4,6-trioxa-9-aza-5-phospha(V)spiro[4,4]nonane 7. The reaction of 1 with alcohol or ethyleneglycol and enamine yields a pentaoxyspirophosphorane and an amine by an oxidation-reduction condensation. Suggested mechanisms of these reactions are presented.     

Selective rearrangements of 4a,5-epoxides of 4,4-dimethyl-1,2,3,4,6,8a-hexahydronaphthalenes.

Epoxidation selectivity of a number of 4,4-dimethyl-1,2,3,4,6,8a-hexahydronaphthalenes 4 were examined. Exposure of the isolated α-epoxides 7provided excellent yields (79–92%) or rearranged fused indene-oxetanes 8. Treatment of β-epoxides 5 with BF3·OEt₂ also yields oxetanes 8 and related alcohols 9 and 10.     

Reactivite des epoxydes—IV: Mise en evidence de complexes HMPT-lithium lors de l'ouverture des epoxydes par les amidures de lithium—interet sur la plan synthetique

The study of the ratio $\text{|HMPT|}\text{|Amide|}$ effect on the percentage of α-elimination products during the opening of 3,4-epoxycyclooctene 1 with Et₂NLi leads to notice the formation of two complexes: HMPT, Li⁺ and 2HMPT, Li⁺. The α-elimination is entirely suppressed when the second complex is formed. With 5,6-epoxycyclo-octene 2 as a substrate, the study of the ratio $\text{|HMPT|}\text{|Amide|}$ effect on the β-elimination evidences the formation of a third complex: 4HMPT. Li⁺; up to a concentration of |HMPT| = 2|amide| β-elimination is still possible, but for |HMPT|=4|amide| γ-elimination is mainly observed. These conclusions have been applied to 3-allyl epoxy-cylooctane 3 reaction which is able to lead to α, β and γ-elimination.     

Recherches sur la synthese totale des alcaloides appartenant a la serie de la carpaine et de la cassine—III : Deux methodes generales de synthese des ethylenedioxy-4,4 aldehydes

4,4-ethylenedioxy aldehydes 1 can be obtained readily from 1-ethoxycarbonyl 6-methyl hept-5-en 2-one 8 by C-alkylation, followed by hydrolysis, decarboxylation, dioxolane formation and ozonolysis. Alternatively, compounds 1 can be prepared by reacting the Grignard reagent of 1-bromo 4-methyl pent-3-ene 24 with an appropriate aldehyde, followed by oxidation, dioxolane formation and ozonolysis. Compounds of type 1 should prove useful in the total synthesis of carpaine, cassine and related alkaloids.     

Ions α-cetocarbenium. Influence de la structure sur l'evolution des ions α-cetocyclohexylcarbenium

α-Ketocyclohexylcarbenium ions are formed by dehalogenation in HgSbF₆Ch₂Cl₂ of the corresponding α-bromo carbonyl compounds 6,7, 8 and 9. In this medium they lead principally to bicyclic oxonium salts, the structure of which depends on the group adjacent to the carbonyl group, and positions of ring substituents. By a suitable choice of Y, it is possible to “functionalise” an α-keto cyclohexane system in either 3 or 4 positions.     

Réaction du diméthylcuprate de lithium avec les dérivés carbonylés α,β-insaturés α-fluorés et α-chlorés

Depending on the nature of the halogen, α-fluoro- and α-chloro-α,β-unsaturated carbonyl compounds (whose reduction potentials are greater than ? 2.4V) react in different ways with lithium dimethylcuprate. With α-fluoro derivatives, both 1,2- and 1,4-addition is observed, their ratios depend on the steric hindrance of the β-position. 1,4-Addition products are obtained from aldehydes and β-monosubstituted α-chloro-α,β-ethylenic ketones and esters. β,β-Disubstituted α-chloro ketones and esters give only reduction of halogen via halogen-metal exchange.     

Structure and isomerization in 4,4′-biimidazoles: a comparison of crystal structures and theoretical calculations of 2,2′-dimethyl-4,4′-biimidazole and 2,2′-dimethyl-4,4′-biimidazolium bis-trifluoroactate

The crystal structures of the compounds 2,2′-dimethyl-4,4′-biimidazole dihydrate (1) and 2,2′-dimethyl-4,4′-biimidazolium bistrifluoroacetate (2) have been determined. Compound 1 is linked into a three dimensional network via hydrogen bonding between the imidazole nitrogens and the water molecules, while compound 2 forms sheets through hydrogen bonding between the acetate and imidazolium ions. Theoretical calculations for 1 show that the particular prototropic tautomer observed in the crystal structure is not the lowest energy isomer. This observation is justified in terms of hydrogen bonding to the lattice water molecules.     

Condensation du complexe hexafluoroacetone - fluorure de potassium sur les cetones alpha - halogenees

During its condensation with α-halo ketones, the hexafluoro- acetone-potassium fluoride complex behaves as a weak nucleophile and a strong base. Nucleophilic substitution produces α-perfluoroalkoxy ketones. Abstraction of a proton α to the carbonyl function leads to the formation of ether-ketones substituted by the group C(CF₃)₂. In some cases, hydrogen halide elimination can occur.     

Photoaddition Reactions of 5-Fluoro-4,4-dimethyl-2-cyclopentenone

The photoaddition of 5-fluoro-4,4-dimethyl-2-cyclopentenone ( 4 ) to 2,3-dimethyl-2-butene leads specifically (in cyclohexane) and selectively (in acetonitrile) to the formation of the oxetanes 16 . The title compound is compared in its behaviour to the analogous 6-fluoro-4,4-dimethyl-2-cyclohexenone ( 1 ) and both α'-fluoro-4,4-dimethyl-2-cycloalkenones in turn are compared to the corresponding 2-cycloalkenones ( 6 and 3 ) and 4,4-dimethyl-2-cycloalkenones ( 5 and 2 ). The quantum yield for the addition of these enones to 2,3-dimethyl-2-butene and to cyclopentene are discussed.     

(R)- and (S)-3-Hydroxy-4,4-dimethyl-1-phenyl-2-pyrrolidinone as chiral auxiliaries in the enantioselective preparation of α-aryloxypropanoic acid herbicides and α-chlorocarboxylic acids

rac-α-Chlorocarboxylic acids, rac-9a–e, were formally deracemized by reaction of the corresponding acyl chlorides with the chiral auxiliaries (R)- and (S)-3-hydroxy-4,4-dimethyl-1-phenyl-2-pyrrolidinone, (R)- and (S)-4, followed by mild alkaline hydrolysis. The highest o.p. (99%) was obtained in the case of (S)-α-chloropropanoic acid, a known precursor for the synthesis of (R)-α-aryloxypropanoic acid herbicides such as dichlorprop-P, (R)-3a, or mecoprop-P, (R)-3b, which, together with their enantiomers, were also obtained in moderate e.e.s by dynamic kinetic resolution from (αRS,3S)-4,4-dimethyl-2-oxo-1-phenylpyrrolidin-3-yl α-bromopropanoate, (αRS,3S)-6, by reaction with the corresponding phenoxide followed by mild acid hydrolysis.     

Reactions de l'hexafluorure de molybdene avec les aldehydes et les cetones fonctionnels

The substituents F, Cl, Br, CN, NO₂, COOR, CONR₂, P(O)R₂ do not interfere with the reaction of MoF₆ with aromatic aldehydes and ketones yielding gem-difluoro compounds, but OH, NH, OR, NR₂, CC, react preferentially with MoF₆ and prevent the reaction at CO. Yields of gem-difluoro compounds are enhanced with electron-attracting substituents on the carbonyl derivative, and are lowered when the CO group is sterically hindered. The hydrolytic stability of the RCF₂R′ compounds vary widely with the nature of R and R′. Some reactions on R and R′ leave the CF₂ group unaffected. Thus a number of new CF₂ compounds are prepared including α,α-difluoroalkyl substituted benzyl alcohol32 benzylamines34, 36 benzaldehyde27, benzoic acids24, 28, 31, 35.¹H and¹⁹F NMR data are given for all the new derivatives. The mechanism of the conversion is tentatively postulated.     

Action du phenyltetrafluorophosphorane sur les α ou β hydroxy-esters, -cetones, -Nitriles, -ethers,et les nitroalcools. Acces a quelques derives fonctionnels α ou β fluores

The reaction of phenyltetrafluorophosphorane with secondary or tertiary α- or β -hydroxy esters, ketones, nitriles, ethers and nitro derivatives has been investigated. The formation of the alkoxyfluorophosphorane 3 has been established in several cases. Good yields of isolated fluoro compounds were obtained with MeCHFCOOEt, MeCHFCH₂COOEt and Me₂CFCH₂NO₂. These compounds eliminate HF readily.     

Stereochimie de la cycloaddition sur les ethers butadienyliques d'alcools chiraux. Derives en 4 et 6 de glucosides perbenzylés

Two partially protected derivatives of α-D-glucose with one free OH group function, benzyl 2,3,6-tri-O--α-D-glucopyranoside 2 and benzyl-2,3,4-tri-$\text{O}$-benzyl-α-D-glucopyranoside 4 were prepared. Base-catalysed addition of the diyne-diol 5 onto these sugars gave trans-cis mixtures of enynyl ethers, 6 and 8 from compound 2, and 7 and 9 from compound 4. Catalytic partial hydrogenation gave the corresponding butadienyl ethers 10 and 12 from 6 and 8, and 11 and 13 from 7 and 9. All trans-cis mixtures obtained could be readily separated by fractionnal crystallisation or column chromatography, thus making for the first time pure trans and cis enynyl ethers readily available in quantity. The cycloaddition of butyl glyoxylate onto the trans dienes led to mixtures of dia-stereoisomeric, dihydropyrannyl ethers, 14 (β-L) 18 (α-D) and 22 (β-D) from diene 10, and 16 (β-L), 20 (α-D) and 24 (β-D) from diene 11. Configurations were ascribed by the use of already described methods. This study brings to a number of five all examined reactions of cycloaddition onto butadienyl ethers of chiral alcohols. In each case a strong preference is observed for one of the faces of the prochiral butadienyl ether, but no great preference for the endo path of cycloaddition.     

Rearrangement spinal du dimethyl-4,4 epoxy-6α,20α (5α)androstane avec le trichlorure de bore

A backbone rearrangement of 4,4 dimethyl 6α,20α epoxy (5α)androstane with BCl₃, is described. The structures of the resulting compounds have been elucidated either by synthesis from 3β-acetoxy (5α)pregnane 20-one, or by X rays diffraction.     

Total synthesis of the sesquiterpene (±)-hirsutene using an organoselenium-mediated cyclization reaction

Cyclization of 2-carbomethoxy-3-(4',4'-dimethylcyclopent-2-enylmethyl)cyclopentanone (4) with N-phenylselenophthalimide and tin(IV) chloride affords cis-syn-cis-1β-carbomethoxy-4,4-dimethyl-3β-phenylselenotricyclo [6.3.0.0^2,6]undecan-11-one (8) and cis-anti-cis-1β-carbomethoxy-4,4-dimethyl-3α-phenylselenotricyclo [6.3.0.0^2,6]undecan-11-one (9). Both of these selenides can be elaborated to cis-anti-cis-4,4-dimethyl-1β-methyltricyclo [6.3.0.0^2,6]undecan-11-one (13) which upon treatment with CH₂Br₂/ TiCl₄/Zn affords the sesquiterpene (±)-hirsutene (1) in 20% overall yield.     

Synthesis and alkylation of new functionally substituted 4,4-dimethylpiperidin-2-ones

The reaction of ethyl isopropylidenecyanoacetate with ethyl 3-amino-3-thioxopropanoate gave rise to ethyl 4,4-dimethyl-6-oxo-2-thioxo-5-cyanopiperidine-3-carboxylate whose alkylation provided ethyl 2-benzylsulfanyl-4,4-dimethyl-6-oxo-5-cyano-1,4,5,6-tetrahydropyridine-3-carboxylate, ethyl 5-benzyl-2-benzylsulfanyl-4,4-dimethyl-6-oxo-5-cyano-1,4,5,6-tetrahydropyridine-3-carboxylate, and ethyl 7,7-dimethyl-5-oxo-6-cyano-3,5,6,7-tetrahydro-2H-thiazolo[3,2-a]pyridine-8-carboxylate.     

4,4-Disubstituierte Imidazol-Derivate aus der Umsetzung von 3-Amino-2H-azirinen mit Salicylamid

4,4-Disubstituted Imidazole Derivatives from the Reaction of 3-Amino-2H-azirines with Salicylamide Reaction of 3-amino-2H-azirines 1a–c with salicylamide ( 7 ) in MeCN leads to imidazoles 10 and 11 in different rates, depending on the conditions. In the case of 1a and 1b, 11a and 11b , respectively, have been obtained as the main product at 50°; in reactions at 80°, 10a and 10b are the favored products (Tables 1 and 2). 2,2-Dimethyl-3-(N-methyl-N-phenylamino)-2H-azirine ( 1c ) reacts with 7 in MeCN mainly to 2-(2-hydroxyphenyl)-5,5-dimethyl-3,5-dihydroimidazol-4-one ( 10a ); in boiling toluene, 11c is formed with low preference (Table 3). The structure of the products has been established by spectroscopic means, and in the case of 10b and 11c , by X-ray crystallography. Two different reaction mechanisms for the formation of the products are discussed (Scheme 2).