Structure de la gouregine,alcaloïde orginal apparente aux cularines

The structure of guoregine, a new isoquinoline alkaloid from $\text{G}$$\text{u}$$\text{a}$$\text{t}$$\text{t}$$\text{e}$$\text{r}$$\text{i}$$\text{a}$$\text{o}$$\text{u}$$\text{r}$$\text{e}$$\text{g}$$\text{o}$$\text{u}$, Annonaceae, has been deduced by spectral analysis and confirmed by an X-ray structure determination. It is the first member of a new class of cularine-related alkaloids (α-$\text{g}$$\text{e}$$\text{m}$-dimetyltetradehydrocularines).     

Stereochemical studies 83 saturated heterocycles 76 : Preparation and conformational study of partially saturated 3,1-benzoxazines, 3,1-benzoxazin-2-ones and 3,1-benzoxazine-2-thiones

The $\text{cis}$- and $\text{trans}$-2-amino-4-cyclohexene-1-carboxylic acids $\text{1}$ and $\text{3}$ react with imidates to give the condensed-skeleton, bicyclic $\text{cis}$- and $\text{trans}$-pyrimidin-4-ones $\text{8}$ and $\text{9}$. The amino acids $\text{1}$ and $\text{3}$ were reduced to the $\text{cis}$-and $\text{trans}$-1, 3-aminoalcohoIs $\text{6}$ and $\text{7}$, which were cyclized by means of imidates to the bicyclic tetrahydro-4$\text{H}$-3,1-benzoxazines $\text{10}$ and $\text{11}$, or were converted, $\text{via}$ the corresponding carbamates $\text{14}$ and $\text{15}$ into the tetrahydro-4$\text{H}$-3,1-benzoxazin-2(1$\text{H}$)-ones $\text{16}$ and $\text{17}$. The 2-thioxo analogues $\text{18}$ and $\text{19}$ were prepared by cyclization of the dithiocarbamates obtained from the aminoalcohols $\text{6}$ and $\text{7}$ by treatment with carbon disulphide. The $\text{trans}$-aminoalcohol $\text{7}$ and its saturated analogue reacted with $\text{p}$-chlorobenzaldehyde to furnish the hexahydro $\text{13}$ and octahydro-4$\text{H}$-3,1-benzoxazine $\text{13a}$, respectively. ¹H and ¹³C NMR studies showed that, similarly to the earlier-investigated analogues containing oxygen or unsubstituted nitrogen at position 1, the synthesized $\text{cis}$ isomrs $\text{8}$, $\text{10}$, $\text{16}$ and $\text{18}$ occurred as the preferred conformer in the heterocyclic twist inverse form of $\text{N}$-inside type ($\text{quasiaxial}$ C₆-N bond) (B). In the $\text{trans}$ isomers containing a saturated C-2 atom ($\text{13}$ and $\text{13a}$), H-2 and H-6 are in $\text{cis}$ relative positions.     

On cyclopentadienone-ketals and their dimers. A novel rearrangement of α,β-unsaturated ketone dialkyl ketals

The dimers $\text{2a}$ & b) of dimethyl- and diethylcyclopentadienone ketals($\text{1a}$ & b) undergo a novel 1,3-alkoxy-rearrangement to $\text{4}$(a & b). Mild hydrolysis of $\text{2}$ or $\text{3}$ gives the monoketones ($\text{3}$a or b). On strong acid catalysed hydrolysis $\text{2}$, $\text{3}$ or $\text{4}$ afford the cyclopentadienone-dimer($\text{6}$.     

N-Acylated α-aminonitriles and their conversion into 5-aminooxazole, 5(4h)-oxazolone and 4(5h)-imidazolone derivatives

In contrast with the reaction of α-aminonitriles $\text{1}$a, the corresponding $\text{N}$-acylated α-aminonitriles $\text{1}$b-f and oxalyl chloride do not yield pyrazinone derivatives, but 5-aminooxazoles $\text{9}$-$\text{11}$ or 4(5$\text{H}$)-imidazolones $\text{12}$, the latter being converted in some cases into imidazo [2,1-$\text{a}$]isoquinoline-2,5,6(3$\text{H}$)-triones. Reactions of compounds $\text{1}$b-f and ethyl chlorooxoacetate provide evidence for a 5(4$\text{H}$)-iminooxazole intermediate $\text{7}$, which aromatizes to yield 5-aminooxazoles $\text{9}$-$\text{11}$; however, unaromatizable īntermediates of type $\text{7}$ - isolable as 5(4$\text{H}$)y-oxazolones $\text{13}$ after hydrolysis - undergo a catalyzed Dimroth-type rearrangement to give imidazolone derivatives $\text{12}$.     

12-S-CIS conformationally locked retinoids: Thermal and photochemical interconversions leading to new geometric isomers

For 12-$\text{s}$-$\text{cis}$ locked retinal analogues, thermal equilibria are established between 11-$\text{cis}$, 13-$\text{cis}$-1c and 13-$\text{cis}$-2c and between 9-$\text{cis}$, 11-$\text{cis}$, 13-$\text{cis}$-1d and 9-$\text{cis}$, 13-$\text{cis}$-2d; a photoisomerization occurs to transform 2c to $\text{all}$-$\text{trans}$-2a and 2d to 9-$\text{cis}$-2b     

Cycloaddition reactions of 2,3-didehydrothiophene generated by flow vacuum thermolysis of thiophene-2,3-dicarboxylic anhydride

Flow vacuum thermolysis (FVT) of thiophene-2,3-dicarboxylic anhydride ($\text{2}$) in the presence of 2,3-dimethylbutadiene ($\text{6}$) gives, in addition to 5,6-dimethylthianaphthene ($\text{9}$). small quantities of a dihydrodimethylthianaphthene ($\text{12}$) and another dimethylthianaphthene ($\text{13}$) which is probably also formed by dehydrogenation of $\text{12}$ with chloranil. The partial structures of these minor products are consistent with their being formed by a [2+2]-cycloaddition between $\text{6}$ and an intermediate aryne, 2,3-didehydrothiophene ($\text{1}$), followed by a rearrangement of the resulting adduct $\text{11}$ and dehydrogenation. FVT of $\text{2}$ in the presence of 2,5- ($\text{17b}$) or 3,4-dimethylthiophene ($\text{17c}$) also gave a mixture of the dimethylthianaphthenes ($\text{18}$$\text{22}$, $\text{23}$) which can be rationalized as arising by a [4+2]- and two [2+2]-cycloadditions of the aryne $\text{1}$ to the thiophenes $\text{17}$ with subsequent desulfurization. The lack of equilibration of the products $\text{18}$, $\text{22}$ and $\text{23}$, was demonstrated and their origin as a function of the structure and reactivity of the aryne $\text{1}$ discussed.     

Facile syntheses of 2,4,6-cycloheptatrienyl ketones

The synthesis of the 2,4,6-cycloheptatrienyl ketones $\text{1a}$–$\text{1e}$ by two alternative routes is reported: Route 1): The adducts $\text{3a–c}$ from the phenyl(trimethylsiloxy)-acetonitriles $\text{2a–c}$, known as “umpolung” reagents, and tropylium tetrafluoroborate are cleaved by triethylammonium fluoride to form the aromatic cycloheptatrienyl ketones $\text{1a}$–$\text{1c}$. Route 2): the phenyl, methyl, and cyclopropyl ketone ($\text{1a}$, $\text{1d}$, $\text{1e}$) are prepared by treatment of the acid chloride $\text{7}$ with the corresponding organomanganese iodides RMnI ($\text{8a}$, $\text{8d}$, $\text{8e}$). The Fe-catalyzed coupling reaction of the acid chloride $\text{7}$ with a Grignard reagent was also used for the preparation of ketone $\text{1b}$.     

Reactions of cyclo-octatetraene and its derivatives - X: 1,2,3,8-Tetraphenylcyclo-octatetraene and 2,3,4,5-tetraphenylcyclo-octa-1,3,5-triene

The reaction of tetracyclone $\text{1b}$ with the cyclo-octatetraene-dimethyl acetylenedicarboxylate adduct $\text{2}$ at $\text{ca}$. 110° produces, in addition to the $\text{exo}$[4+2] Π cycloadduct $\text{3b}$ (49%), 1,2,3,8-tetraphenylcyclo-octatraene $\text{5}$ (11%), together with the diketone $\text{11}$ (5%). In a similar reaction with the esterified cyclo-octatetraene-maleic anhydride adduct $\text{13a}$, the major product $\text{14}$ (82%) is accompanied by the cyclohexa-1,3-diene $\text{15}$ and the dihydrosemibullvalene derivative $\text{16}$. Thermolysis of $\text{3b}$ at $\text{ca}$. 145° leads to the cyclobutene $\text{12}$., which on catalytic hydrogonation followed by decarbonylation at 180°–190° gives 2,3,4,5-tetraphenylcyclo-octa-1,3,5-triene $\text{19}$. Attempted thermal conversion of $\text{19}$ into a dihydrosemibullvalene failed.     

Ylures sans sel,evolution en phosphoranes et equilibre ylure ⇌ phosphorane : I Synthese et structure

Synthesis of new salt-free ylids $\text{9}$,$\text{12}$ to $\text{16}$, $\text{19}$, $\text{20}$, $\text{22}$, $\text{27}$ and $\text{29}$ and phoiphoranes $\text{10}$, $\text{17}$, $\text{18}$, $\text{21}$, $\text{23}$, $\text{30}$ to $\text{33}$ by addition of a trivalent phosphorus compound (phosphites and amino-phosphines ) $\text{1}$ to $\text{7}$ with dimethyl acetylencedicartboxylate in presence of a protic trapping reagent are described. The results are consistent with trapping of carbanionic species. In relation with the. cyclic of acyclic structure of the triivalent phosphorus compound and the protic trapping reagent ie : methanol, phenol, carboxylic acid, etc.., several pathways are involved. Clearly), three phenomena are shown : one can obtain an ylid via a phosphorane or conversely a phosphorane via an ylid or an equilibrium Phoiphorane ? ylid. Results are dealing with thermodynamic or kinetically controlled reactions.     

Stereochemical studies—76 saturated heterocycles—63 : synthesis of cis- and trans-n-methyl- and n-benzyl-4.5- and 5,6-tetramethylenetetrahydro-1,3-oxazines; an x-ray study of n-benzyl-cis-4,5-tetramethylenetetrahydro-1,-3-oxazinium- picrate

- The corresponding $\text{cis}$- and $\text{trans-N}$-methyl- and $\text{N}$-benzyl-5,6- and 4,5-tetramethylenetetrahydro-l,3-oxazines $\text{(5a,b-8a,b)}$were synthesized from $\text{cis}$- and $\text{trans-N}$-methyl and$\text{N}$-benzyl-2- aminomethyl-1-cyclohexanols $\text{1a,b,2a,b}$, from $\text{cis}$- and $\text{trans-N}$-methyl- and $\text{N}$benzyl -2-hydroxymethyl-1-cyclohexylamines$\text{(3a,b,4a,b)}$ by reaction with formaldehyde. The aminoalcohols $\text{1a,2a,3a,b}$and $\text{4a,b}$ were prepared in considerably higher yields than in earlier procedures. NMR spectroscopy showed that the $\text{cis}$ isomers of the synthesized oxazines were conformationally homogeneous in solution, and their preferred conformation (inside or outside) depended on the steric requirement of the groups attached to the anellation points, whereas a bulky C-2 substituent had no influence on the predominant conformation. The structure of $\text{N}$-benzyl-$\text{cis}$-4,5-tetramethylenetetrahydro-1,3-oxaziniumpicrate $\text{(7b)}$. determined by X-ray diffraction analysis, was in agreement with the predominant N-outside conformation of the corresponding base, established by means of NMR spectroscopy.     

Reactions of o-tolyl isocyanide with isocyanate and isothiocyanate syntheses of n-substituted indole-3-carboxamides and indole-3-thiocarboxamides

o-Lithomethylphenyl isocyanide is reacted at ?78° with isocyanates and isothiocyanates to produce o-isocyanophenyl-acetamides $\text{(2a)}$ and -acetothioamides $\text{(2b)}$. Isocyanides $\text{(2a)}$ and $\text{(2b)}$ are cyclized to indole-3-carboxamides $\text{(3a)}$ and -3-thiocarboxamides $\text{(3b)}$ via lithiathion, respectively. Isocyanides $\text{2a}$ are also cyclized by Cu₂O catalyst to produce 4,5-dihydro-1,3-benzodiazepin-4-ones $\text{(4a)}$ with $\text{(3a)}$.     

The synthesis of γ-fluoroisoleucine

Condensation of 3-fluoro-2-butanone ($\text{2}$) with alkyl diethylphosphonoacetates ($\text{4a–d}$) gave alkyl 4-fluoro-3-methyl-2-pentenoates ($\text{5a–d}$). Addition of bromine yielded alkyl-2,3-dibromo-4-fluoro-3-methylpentanoates ($\text{6a,b}$) which were dehydrobrominated to alkyl 2-bromo-4-fluoro-3-methyl-2- pentenoates ($\text{7a,b}$). Since these compounds could not be hydrogenated to the desired alkyl 2-bromo-4-fluoro-3-methylpentanoates ($\text{8a,b}$), another route was taken. The esters $\text{5a–d}$ were hydrogenated to alkyl 4-fluoro-3- methylpentanoates ($\text{11a–c}$) which were converted to their carbanions. Treatment with bromine gave esters $\text{8a–c}$, and iodine gave alkyl 4-fluoro-2-iodo- 3-methylpentanoates ($\text{12a,b}$). Esters $\text{8a–c}$ and $\text{12a,b}$ were converted to alkyl 2-azido-4-fluoro-3-methylpentanoates ($\text{13a–c}$) whose hydrogenation gave alkyl 2-amino-4-fluoro-3-methylpentanoates ($\text{14a–c}$). Hydrolysis afforded γ-fluoroisoleucine ($\text{1}$).     

Oxidative decarboxylation of [n.2.2]propellane carboxylic acids with lead tetraacetate. rearrangement approach to bicyclo [n.2.2.]bridgehead alkenes.

Oxidative decarboxylation of [n.2.2]propellane carboxylic acids ($\text{1a}$-$\text{c}$) with lead tetraacetate gave the bicyclic acetates ($\text{2b}$, $\text{c}$) having a bridgehead double bond and/or the tricyclic acetates ($\text{3a}$, $\text{b}$) in good yields. Vapor phase thermolysis of $\text{3a}$ or $\text{3b}$ afforded the bridgehead olefin $\text{2a}$ or $\text{2b}$ quantatively.     

An adamantane rearrangement. A new pathway

Tricyclo(4.2.2.o^1,5)decane ($\text{7}$) in the presence of AlBr₃ rearranges partly “forwards” to adamantane ($\text{1}$) and partly “backwards” to tetrahydrodicyclopentadiene ($\text{2}$, largely the oxo isomer). Intermediate $\text{14}$, characterizing the $\text{7}$→exo-$\text{8}$→$\text{14}$→$\text{3}$→$\text{1}$ forward pathway, is found only in small amounts. The detection of a new intermediate, $\text{12}$, also shows that a second major rearrangement route from $\text{7}$ to $\text{1}$ is being utilized (see dashed lines in Figure 1).     

Photochemical studies. Irradiation induced transformations of 1,2-dihydrophthalides

The photochemical behavior of $\text{cis}$-1,2-dihydrophthalide ($\text{1}$) and its 1,2-trimethylene derivative ($\text{4}$) was studied. Besides bicyclo[2.2.0]hexene formation in both cases, ($\text{1}$) transforms into its $\text{trans}$ isomer ($\text{3}$) whereas ($\text{4}$) undergoes a 1,2-shift to ($\text{7}$).     

Biomimetic reactions of germacrenes

The biomimetic reactions of epoxygermacrene-D ($\text{1}$) with basic alumina afforded three new interesting compounds ($\text{4}$, $\text{5}$, and $\text{6}$), two of which ($\text{4}$ and $\text{6}$) have the same carbon skeleton as that of periplanone-A ($\text{3}$), a sexual stimulant for the American cockroach. The remaining one ($\text{5}$) is a bicyclo[3.1.0]hexane derivative, from whch an axisonitrile-3 type compound ($\text{14}$) has been produced. Finally, preisocalamendiol ($\text{2}$) was also converted into $\text{6}$.     

Stereochemical studies — 79 synthesis and kinetic study on the retrodiene decomposition of norbornene-condensed 1,3-oxazin-4-ones

The $\text{cis}$-$\text{cxo}$- amino acid $\text{c}$ with norbornene skeleton was converted into 2-aryvl-$\text{cis}$-$\text{cxo}$-1,3-oxazin-4-ones $\text{5a}$-$\text{d}$. These compounds, similarly to the $\text{diendo}$ isomers $\text{1a}$-$\text{d}$ studied by us earlier, undergo retrodiene decomposition under mild conditions to give 2-aryl-6$\text{2}$-l,3-oxazin-6-ones ($\text{2}$$\text{a}$-$\text{d}$) in 50-60% yield. The ratio of the decomposition rate constants of the tricyclic $\text{diendo}$ and $\text{diexo}$-1,3-oxazin-4-ones, measured in toluene solution, is about 2.     

Ritter-reaction on steroids: Ring expansion of steroid oxethans into dihydrooxazines

The 3β-acetoxy-16β,17β-epoxymethyleneandrost-5-ene ($\text{1}$) transforms into the dihydrooxazine condensed to the sterane skeleton ($\text{4}$$\text{a}$,$\text{b}$,$\text{c}$,$\text{e}$,$\text{g}$,$\text{i}$) in a ring-expansion reaction with alkyl and aryl nitriles in the presence of HBF₄— diethyletherate The 3β-acetoxy-16α, 17α-epoxymethyleneandrost-5-ene ($\text{9}$) undergoes a Wagner-Meerwein rearrangement under similar conditions.     

Pheromone XXXVII. Eine stereospezifische synthese der komponenten des sexualpheromons von antherea polyphemus, (E)-6,(Z)-11-hexadecadienylacetat und (E)-6,(Z)-11-hexadecadienal.

Starting from the aldehydes $\text{2}$ and $\text{9}$ the acetylene $\text{16}$ is prepared via the borane $\text{15}$ by means of a combined Wittig reaction-hydroboration reaction sequence. $\text{16}$ may be converted into the (E)-6,(Z)-11-hexadecadienylacetate ($\text{18}$) and the corresponding aldehyde $\text{19}$. The synthetic route proceeds with high stereospecifity (isomeric purity of $\text{18}$ and $\text{19}$ ? 97%).     

Radical-initiated polyolefinic cyclizations in linear triquinane synthesis. model studies and total synthesis of (±)-hirsutene

Details of a novel radical-initiated polyolefinic cyclization approach to linear condensed cyclopentanoids are reported. The strategy is executed in three stages: (1) Sn2′-anti opening of a vinyl lactone to produce a trans-3,5-disubstituted cyclopentene, (2) rapid elaboration to a cyclization precursor, and (3) single step tandem radical cyclization to produce a cis-anticis tricyclo[3.3.0]undecane. Model substrates $\text{16a}$ and $\text{16b}$ give high yields of tricyclic products $\text{17}$ and $\text{18}$, respectively. An effort to rationalize the interesting endo selectivity via the Beckwith transition state model is proposed. Cyclizations of $\text{28}$ and $\text{29}$ to $\text{30}$ and $\text{31}$ demonstrate the viability of a tandem hexenyl-hexynyl cyclization. The work culminates with a total synthesis of (±)hirsutene. A selective approach to methyl substituted vinyl lactones by Claisen rearrangement-phenylselenolactonization-elimination of acetoxy cyclopentenols is exemplified by the synthesis of $\text{12}$. Tandem cyclization of $\text{38}$ produces hirsutene ($\text{1}$) in a single step. Alternatively, cyclization of $\text{37}$ yields trimethylsilyl hirsutene.