A convenient synthesis of substituted γ-pyrones

An efficient and general synthetic method for various 2-mono- and 2,6-disubstituted γ-pyrones has been developed. This utilizes the $\text{C}$-acylation (70–85%) of β-methoxy-α,β-enone lithium enolates $\text{4}$ by acid chlorides $\text{3}$ followed by the acid-catalyzed cyclization (>80%) of the resulting enols $\text{5}$ to γ-pyrones $\text{6}$.     

Mise en evidence par rmn 13C et Ir d'enolates mixtes formes par reaction d'echange entre enolates lithiens et sels de metaux divalents

Mixed enolates (RO)₂LiMgBr $\text{4}$ and (RO)₂LiZnBr $\text{5}$ are obtained by addition of MgBr₂ or ZnBr₂ to the lithium enolate of 2,2-diMe pentanone-3

. The mixed magnesium enolate $\text{4}$ is further transformed to ROMgBr with an additional equivalent of MgBr₂ while $\text{5}$ is unchanged by additional ZnBr₂. The same mixed species are observed in the direct addition of preformed enolates.     

Acyclic stereoselection. 28. Use of stereoselective aldol methodology in the total synthesis of cladinose.

Reactions of ($\text{S}$)-2-benzyloxypropanal (4) with the lithium, magnesium, and zirconium enolates of methyl 2-methoxypropanoate (1) and with ketene acetals 2 and 3 have been studied and the stereostructures of the resulting products elucidated. The major stereoisomer resulting from the metal enolate additions has been converted into the branched sugar cladinose (5).     

Aldol diastereoselection via zirconium enolates. Product-selective,enolate structure independent condensations.

Both($\text{E}$)- and ($\text{Z}$)-zirconium enolates have been shown to undergo selective kinetic aldol condensation to give mainly $\text{erythro}$-β-hydroxy ketones, esters and amides.     

O-silylated ketene acetal chemistry; β-(alkoxycarbonyl)methyl O-silyl enolates,useful synthons for α-substituted-β-(alkoxycarbonyl)methylalkanones

Conjugate addition of O-silylated ketene acetals $\text{2}$ to α,β-unsaturated carbonyl compounds $\text{1}$ in acetonitrile gave quantitative yields of the corresponding β-(alkoxycarbonyl)methyl O-silyl enolates $\text{4}$. Site specific electrophilic substitutions of $\text{4}$ yielded the corresponding α-substituted β-(alkoxycarbonyl)-methylalkanones $\text{5}$, $\text{7}$, and $\text{8}$.     

Studies on 1-carbadethiacephems, part II: Reaction of 4-acetoxy-2-azetidinone with aluminium enolates

A procedure for the novel reaction of αβ-unsaturated ketones (as zinc-free aluminium enolates) with 4-acetoxy-2-azetidinone, giving products $\text{2}$, is reported. A 1-carbadethia-2-oxocephem derivative $\text{5}$ has been prepared from compound $\text{2b}$.     

Synthesis of di-t-alkylamines

Di-$\text{t}$-alkylamines can be synthesized efficiently by a three-step process: (1) oxidation of a $\text{t}$-alkylamine to a $\text{t}$-alkylnitroso compound with peracetic acid in ethyl acetate (2) conversion of the $\text{t}$-alkylnitroso compound to a tri-$\text{t}$-alkylhydroxylamine by successive trapping of two $\text{t}$-butyl radicals and (3) sodium naphthalide reduction to the di-$\text{t}$-alkylamine.     

Solvation of alkyllithium compounds. Steric effects on heats of interaction of bases with hexameric versus tetrameric alkyllithiums

Heats of interaction of Lewis bases with hexameric and tetrameric alkyllithiums in hydrocarbon solution at 25° have been determined by high dilution solution calorimetry at low base to lithium atom ratios. The Lewis bases utilized include tetrahydrothiophene, tetrahydrofuran, triethylphosphine, triethylamine, and diethyl ether. The organolithiums investigated were $\text{n}$-butyllithium, ethyllithium, isopropyllithium, trimethylsilylmethyllithium, and $\text{t}$-butyllithium. The basicity order based on initial enthalpies of interaction is independent of the alkyllithium compound. Larger enthalpies of interaction were observed for the tetrameric $\text{versus}$ hexameric alkyllithiums with the exception of tetrameric $\text{t}$-butyllithium which does not interact significantly with these bases. The sensitivities of the enthalpies to the steric requirements of the base were probed by comparison of the enthalpies for tetrahydrofuran, 2-methyltetrahydrofuran, and 2,5-dimethyltetrahydrofuran. Base coordination to hexameric $\text{n}$-butyllithium is more sensitive to the steric requirements of the tetrahydrofuran bases than is coordination to tetrameric trimethylsilylmethyllithium or isopropyllithium. These results are interpreted in terms of coordination of tetrahydrofuran bases to the intact hexameric aggregate for $\text{n}$-butyllithium; however, it is concluded that the corresponding interaction with hexameric trimethylsilylmethyllithium leads directly to base-solvated tetramers.     

Generation of sec-thioamide dianions and their regioselective reaction with electrophiles.

The enolates of sec-thioamides $\text{8}$, which are generated by three different methods (scheme II and equation 1), are alkylated selectively at the α-carbon to the thiocarbonyl group. The unusual β′-lithiation to provide an intermediate $\text{11}$ is observed for N-methyl-α, β-dimetylthioacrylamide and N-methyl-thiocyclohexenecarboxamide.     

Asymmetric synthesis of α-hydroxy carboxylic acids: direct oxidation of chiral amide enolates using 2-sulfonyloxaziridines

The direct oxidation of chiral amide enolates to optically active mandelic acid using 2-sulfonyloxaziridine $\text{1}$ is described. The diastereoselectivity is counterion dependent.     

Stereospecific synthesis of cis-2-alkenylcyclopropane carboxylic acids; A total synthesis of (±)-cis-chrysanthemic acid

A stereospecific route to $\text{cis}$-2,2-dimethyl-3-alkenyl-cyclopropanecarboxylic Acids is illustrated by a total synthesis of (±)-$\text{cis}$-Chrysanthemic Acid (11). The key step consists of an alicyclic Claisen rearrangement of $\text{O}$-silyl enolates derived from appropriately substituted ($\text{Z}$)-4-hexen-6-olides [e.g.(9)].     

Addition of boron enolates to isoquinolinium salts: A facile synthesis of 1-β-keto substituted 2-ethoxycarbonyl-1,2-dihydroisoquinolines and their cyclization

An efficient method to synthesize 1-β-keto substituted 2-ethoxycarbonyl (or 2-acetyl)-1,2-dihydroisoquinolines ($\text{3}$) is described, utilizing boron enolates and isoquinolinium salts. The products were treated with sodium ethoxide to afford the corresponding cyclic compounds ($\text{6}$).     

Stereoselective methylation of β-hydroxylactone dianions

3-Alkoxy enolates of γ-butryrolactones are stereoselectively methylated at C-2 to give the corresponding $\text{trans}$-3-hydroxy-2-methyl-γ-butyrolactones.     

Stereospecific preparation of 1,2-epoxyalkyllithium reagents via the generalized lithiation of a-heterosubstituted epoxides1

A variety of α-heterosubstituted epoxides bearing triphenylsilyl, trimethylsilyl, diethoxyphosphinyl, phenylsulfonyl, phenyl, ethoxycarbonyl and cyano groups was found to undergo stereospecific α-lithiation by use of such bases as $\text{n}$-butyllithium, $\text{t}$-butyllithium or lithium diisopropylamide in solvent combinations of hexane with THF, ethyl ether or TMEDA at temperatures ranging from ?78° to ?110°C. The formation and stereochemistry of the resulting1,2-epoxyalkyllithium reagents were ascertained by quenching with deuterium oxide, methyl iodide or chloro(trimethyl)silane and analyzing the NMR spectra of the products isolated in 50–100% yields.     

Diastereoselective aldol condensations of tin enolates with aldehydes

The reaction of tin enolates of cyclohexanone or propiophenone with benzaldehyde at ?78°C gives predominately the $\text{threo}$ aldol diastereomer.     

Nucleophilic reaction of fluoroolefins. V. Regioselectivity and stereochemistry in the reactios of 1-phenylpentafluoropropenes with lithium dialkylamides

1-Phenylpentafluoropropenes $\text{1}$ readily react with lithium dialkylamides to give, in most cases, mixtures of 1-aminosubstituted alkenes $\text{2}$ and 2-amino-substituted alkenes $\text{3}$, with the latter being the favoured products. The reactions with bulky lithium diethylamide and lithium 2-methylpiperidinoamide gave exclusively 1-amino-substituted products $\text{2}$. The effect of the increased bulk of N-nucleophiles is opposite to that observed for the reactions of alkenes $\text{1}$ with C-nucleophiles Increasing electronegativity of the phenyl ring substituents in alkenes $\text{1}$ shifts the regioselectivity of the attack of lithium amides towards the C2 carbon atom. The E to Z isomer ratios of enamines $\text{2}$ were found to be time dependent and the slow isomerisation of the kinetic isomers E to the thermodynamic isomers Z was observed, while the ratio of isomers of enamines $\text{3}$ did not change with time.A concerted, single-step process is suggested for the reactions of alkenes $\text{1}$ with lithium dialkylamides, and a tentative explanation of the different stereochemistry of enamines $\text{2}$ and $\text{3}$ is given.     

Oxygenation of 4-(N-alkylimino)methyl-2,6-di-t-butylphenols mediated by Co(II)-Schiff base complex

4-(N-Alkylimino)methyl-2,6-di-$\text{t}$-butylphenols ($\text{1}$), Schiff bases of 3,5-di-$\text{t}$-butyl-4-hydroxybenzaldehyde can be oxygenated in the presence of Co(Salpr), a five coordinate Co(II)-Schiff base complex to give N-alkyl-3-$\text{t}$-butyl-5-formyl-2-hydroxy-2-pivaloyl-1,2-dihydropyridines ($\text{2}$ as the main product together with 3-formyl-2,5-di-$\text{t}$-butyl-2,4-cyclopentadienone ($\text{3}$) and 2,6-di-$\text{t}$-butyl-4-formyl-6-hydroxy-4,5-epoxy-2-cyclohexenone ($\text{4}$). These products result from dioxygen incorporation into the ortho position of $\text{1}$.     

Enantioselective Michael reactions. Stereoselective addition of enolates of phenmenthol esters to crotonates

A method is described for enantioselective synthesis which is based on the stereoselective Michael addition of phenmenthol enolates such as 5 to $\text{E}$-crotonate esters. A stereomechanistic rationale is presented.     

A new route to 3-alkyl-2,5-di-t-butyl-2,4-cyclopentadienones from 4-alkyl-2,6-di-t-butylphenols

Base-catalyzed reaction of 5-acylmethyl-2,5-di-$\text{t}$-butyl-4-oxa-2-cyclopentenones selectively derived from 4-alkyl-2,6-di-$\text{t}$-butylphenols $\text{via}$ three steps involving oxygenation, acetylation, and acid-treatment gave 3-alkyl-2,5-di-$\text{t}$-butyl-2,4-cyclopentadienones in excellent yield.     

Reactivite des β-cyclopropyl α-enones—I: Etude des transferts electroniques par voltametrie cyclique et de la reduction par l'electron solvate dans l'ammoniac liquide

Species produced by electron transfer to variously substituted bicyclo[3.1.0]hex-3-en-2-ones provide a better insight into the origin of 1,6-addition products sometimes observed by reaction of lithium diorganocuprates with β-cyclopropyl α-enones. Cyclic voltammetry of eight such bicyclohexenones show that the half-lives of the corresponding anion radicals are very short (t_{$\text{1}\text{2}$}?10^?4s) except when the initial molecule is phenyl substituted at C-4. In such cases the anion radicals are very stable (t_{$\text{1}\text{2}$}?6s) owing to the greater charge delocalization and we observe a second wave corresponding to the formation of the Dianion. The reduction of the same substrates by the solvated electron in liquid ammonia exhibits the same difference of behaviour. The molecules giving strongly reactive anion radicals only lead to the straight-forward product expected by conjugate reduction; while the 4-phenyl substituted substrates yield a mixture of products from normal conjugate reduction and rearrangement. This correlation strongly suggest that these last products arise from the rearrangement of the dianion.