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.     

The facile (<−50°C) formation of cis-bicyclo[6.1.0]nona-2,4,6-trienes from cyclonona-1,3,5,7-tetraenes: A symmetry - forbidden reaction

The formation of the $\text{cis}$-bicyclo [6.1.0] nona-2,4,6-trienes $\text{4a}$-$\text{c}$ is not due to the sequence $\text{1}$ → $\text{2}$ → $\text{4}$, which would involve the symmetry-forbidden reaction $\text{2}$ → $\text{4}$ even at ?50°C. Rather, reaction of RX at C^4–7 of $\text{5}$, which is formed together with $\text{1}$, leads (probably via $\text{6a}$-$\text{c}$ and $\text{7a}$-$\text{c}$ to $\text{4a}$-$\text{c}$.     

Photochemical valence tautomerization of berberinephenolbetaines to 8,14-cycloberbines,versatile aziridine derivatives for spirobenzylisoquinolines

Irradiation of the berberinephenolbetaines ($\text{8}$$\text{a}$, $\text{8}$$\text{b}$, and $\text{8}$$\text{c}$) effected valence tautomerization to give the 8,14-cycloberbines ($\text{9}$$\text{a}$, $\text{9}$$\text{b}$, and $\text{9}$$\text{c}$), the aziridine derivatives, in high yield. The 8,14-cycloberbines were efficiently converted to the spirobenzylisoquinolines by regioselective C bond cleavage.     

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 $\text{12}$.     

Addition conjuguee d'equivalents d'acyles aux cyclohexen-2 ones et a la Δ1(9) octalone-2: Synthese de dicetones 1–4.

The synthesis of 3-acetylcyclohexanones $\text{11}$, $\text{12}$, $\text{13}$ has been realized by conjugate addition of lithiated cyanohydrin ether $\text{1a}$ to 2-cyclohexenones $\text{2}$, $\text{3}$, $\text{4}$ in THF-HMPA, even if 3-substituted. 3-benzoylcyclohexanones $\text{14}$, $\text{15}$, $\text{16}$ are obtained from $\text{1b}$ and $\text{2}$, $\text{3}$, $\text{4}$ in THF with excellent yields.     

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.     

Cycloaddition reactions of 1,3-benzothiazines - 6. Reactions of 1,3-benzothiazine derivatives with substituted acetyl chlorides

6, 7-Dimethoxy-2$\text{H}$-l,3-benzothiazine derivatives ($\text{1}$, $\text{8}$) react with substituted acetyl chlorides to give angularly condensed β -lactams ($\text{3a}$-$\text{d}$, $\text{10}$, $\text{11}$). The $\text{cis}$ compound $\text{11}$ was epimerised to the $\text{trans}$ derivative $\text{12}$. From the interaction of 2-phenyl-6,7-dimethoxy-4$\text{H}$-1,3-benzothiazine ($\text{7}$) and α -chloro-phenylacetyl chloride two stereoisomeric β -lactam derivatives ($\text{9a}$, $\text{b}$) were isolated, whereas in the other cases studied the reactions leading to β -lactams proved to be stereospecific. Analogous reactions of $\text{4}$-methyl-6,7-dimethoxy-2$\text{H}$-l,3-benzothiazine ($\text{5}$) furnished the enamides $\text{6a}$,$\text{c}$, $\text{d}$. Structures of the new compounds and configurations of the diastereomers were elucidated by IR and NMR spectroscopy.     

Substituted cyclononatetraenes and nonafulvenes

Reaction of $\text{cis}$,$\text{cis}$,$\text{cis}$,$\text{cis}$-[9]annulene anion ($\text{1}$) with electrophiles ($\text{2a}$-$\text{d}$) leads to substituted $\text{cis}$,$\text{cis}$,$\text{cis}$,$\text{cis}$-1,3,5,7-cyclononatetraenes ($\text{3a}$-$\text{d}$) which are precursors for the preparation of 10- and 10,10′-donor-substituted nonafulvenes (e.g. $\text{7b′}$$\text{e′}$). The influence of solvent and temperature on the ¹H-nmr spectra of the nonafulvenes $\text{7b′}$-$\text{h′}$ has been investigated.     

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).     

Investigations on diazo compounds and azides- LXII.: Synthesis and reactions of a-diazo phosphonates with a conjugated 1,3-diene unit

α-Diazo phosphonates with a conjugated 1,3-diene unit are synthesised by the Bamford-Stevens reaction ($\text{2}$ →$\text{4}$→$\text{3}$). They undergo [4+2]-cycloadditions with the dienophile $\text{5}$ to form the tetrahydrotriazolopyridazines $\text{8}$, which possess an unchanged diazo group. In contrast, dimethyl acetylenedicarboxylate ($\text{9}$) reacts exclusively with the diazo dipole of $\text{3}$ to yield the 3H-pyrazoles $\text{10}$, which rearrange to $\text{11}$ by sigmatropic PO-shifts and hydrolyse to form $\text{13}$. The diazo compound $\text{3b}$ isomerises to the pyrazole $\text{16}$ when heated in benzene.     

The resolution of racemic 2-alkyl-1-aminocyclopropane-1-carboxylic acids

Practical procedures for the resolution of racemic modification of (1$\text{R}$, 2$\text{S}$)-and (1$\text{S}$, 2$\text{R}$)-1-amino-2-ethylcyclopropane-1-carboxylic acid $\text{1a}$,$\text{b}$,(1$\text{R}$, 2$\text{S}$)- and (1$\text{S}$, 2$\text{R}$)-1-amino-2-methylcyclopropane-1-carboxylic acid $\text{2a}$,$\text{b}$, and (1$\text{R}$, 2$\text{R}$)- and (1$\text{S}$, 2$\text{S}$)-1-amino-2-methylcyclopropane-1-carboxylic acid $\text{3a}$,$\text{b}$ are described; the structures as $\text{1a}$,$\text{2a}$, and $\text{3a}$ were confirmed by X-ray-crystallographic methods.     

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.     

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.     

Amino substituted 1-oxa-3-azabutatrienium salts: preparation, structure and reaction with carbonyl compounds

N,N-Dimethylformamide ($\text{4a}$) and N,N-dimethylpivalamide ($\text{4b}$) react with carbonyl chloride isocyanate ($\text{5}$) in the presence of antimony pentachloride to afford the amino substituted 1-oxa-3-azabutatrienium hexachloroantimonates $\text{6a}$,$\text{b}$. An X-ray diffraction analysis of $\text{6a}$ confirms the proposed structure. The heterocumulenes $\text{6a}$,$\text{b}$ react with aldehydes, ketones and tertiary carboxamides to give the amino substituted 2-azaallenium salts $\text{13a}$-$\text{O}$ in high yields.     

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     

De novo-synthese von verzweigten dl-pseudoglycalen

Z-1-Methoxybutenyne $\text{1}$ was used for the synthesis of Z,E-1-methoxybutadiene derivatives $\text{2}$–$\text{7}$. Hetero-Diels-Alder reactions with diethyl mesoxalate $\text{8}$ led to the C-4 branched pseudoglycals $\text{9}$–$\text{14}$, $\text{16}$ and to the glycal $\text{15}$, respectively. The bicyclic lactone $\text{17}$ was obtained by dealkoxycarbonylation of $\text{16}$.     

Oxygenated limonene analogs. Preparation of tetramethylated carvone and carveols via regiocontrolled opening of tetramethyllimonene oxide.

Regioselective opening of trans epoxide $\text{2}$ gave $\text{endo}$ and $\text{exo}$ tetramethylated $\text{trans}$ carveols $\text{3t}$ and $\text{4t}$ respectively, which were oxidized to tetramethylcarvone ($\text{5}$) and its unstable exocylic isomer $\text{6}$; reduction of $\text{5}$ with DIBAH gave tetramethylated $\text{cis}$ carveol $\text{3c}$ exclusively, whilst analogus reduction of $\text{6}$ produced an epimeric mixture of $\text{4c}$:$\text{4t}$=85:15.     

Synthetic studies on β-lactam antibiotics. Part 16. synthesis of 1-carba-2-penem-3-carboxylic acid esters from penicillins utilizing a carbon-carbon coupling reaction

Allylazetidinones $\text{9}$, $\text{10}$, prepared by coupling of allylcoppers $\text{8}$ with chloroazetidinones $\text{6}$, $\text{7}$, were converted into carbapenem esters $\text{16}$, $\text{28}$–$\text{31}$ using an Emmons-Horner reaction to introduce the 6-side chain and an intramolecular Wittig reaction to form the carbapenem ring system.     

Per - bicyclophosphoranylation d'alditols

Reaction of bicyclophosphane $\text{1}$ with glycol $\text{2}$, glycerol $\text{3}$, erythritol $\text{4}$, L(-)arabitol $\text{5}$ and dulcitol $\text{6}$ leads to the corresponding per-alkoxybicyclophosphoranes $\text{2p}$ - $\text{6p}$ which are in tautomeric equilibrium with the phosphates forms $\text{2p}$′ - $\text{6p}$′.The amount of these latters increases regularly from traces to 24%.     

Stereochemical studies—971a. Saturated heterocycles—991b : An unusual ring-opening reaction of 2-methylthio-3,1-perhydro-benzoxazines. A comparative study of the 3,1 and 1,3-isomers

In the reactions of 2-thioxo-$\text{cis}$- and $\text{trans}$-3,1-perhydrobenzoxazines ($\text{3}$, $\text{4}$) with methyl iodide the hydrogen iodide formed in the S-methylation process brings about ring-opening and gives iodomethylthiolcarbamates ($\text{7}$, $\text{8}$). Under similar conditions, the thioether salts ($\text{15}$, $\text{16}$) of the structurally isomeric $\text{cis}$- and $\text{trans}$-2-thioxo-1,3-perhydrobenzoxazines, corresponding to the unstable intermediates in the former reactions, are stable. Under more vigorous conditions, the $\text{cis}$ isomer thioether salt $\text{15}$ is transformed into the corresponding $\text{cis}$-and $\text{trans}$-l,3-perhydrobenzoxazin-2-ones ($\text{17}$, $\text{18}$) by ring-opening and subsequent ring-closure, whereas the $\text{trans}$ isomer $\text{16}$ gives only $\text{trans}$-1,3-perhydrobenzoxazin-2-one ($\text{18}$).