Synthesis of 2,5-piperidinediones. regioselectivity in the dieckmann cyclization

Dieckmann cyclization of ethyl N-benzyl-N-[(ethoxycar-bonyl)methyl]succinamate ($\text{2}$) with sodium ethoxide gave regioselectively β-keto ester $\text{3}$, whereas when using potassium tert-butoxide or potassium hydride as a base the regioisomer $\text{4}$ was isolated as the main product. Transesterification of ethyl β-keto esters $\text{3}$ and $\text{4}$ with benzyl alcohol followed by hydrogenolysis and decarboxylation of the resulting benzyl esters $\text{5}$ and $\text{6}$ led to 1-benzyl- 2,5-piperidinedione ($\text{1}$). The preparation of some 4-alkyl- and 4-alkoxycarbonylalkyl derivatives was achieved by alkylation of $\text{5}$ with the appropriate halide and further hydrogenolysis.     

A direction controlled Dieckmann type cyclization of half-thiol diesters

A direction controlled Dieckmann type cyclization was performed on treatment of the half-thiol diesters($\text{1}$) with base to give exclusively the β-keto esters ($\text{2}$.     

Stereoselective synthesis of the optically active functionalized 1,3,5-all-anti-triol

The optically active 1,3,5-$\text{all}$-$\text{anti}$-triol $\text{20}$ was synthesized starting from ($\text{S}$)-(-)-malic acid with complete stereoselection, based on the stereoselective reduction of cyclic β-keto acetal and successive transthioacetalization.     

Trimethylsilyl trichloroacetate: a new reagent for salt-free silylations

Trimethylsilyl trichloroacetate ($\text{1}$) is a convenient reagent for the silylation of phenols, carboxylic acids, mercaptans, amides, acetylenes, and β-keto esters, while the reaction of $\text{1}$ with aldehydes and ketones affords silylated trichloromethyl carbinols ($\text{5}$).     

Total synthesis of (+--oudemansin

($\text{+}\text{-}$)-Oudemansin has been synthesized starting from $\text{trans}$-cinnamaldehyde by a route involving the stereoselective Zn(BH₄)₂ reduction of β-keto ester.     

α-Fluorination of β-keto sulfoxides

We have developed an efficient new procedure for α-fluorination of β-keto sulfoxide enolate anions which are generated $\text{in situ}$ via nucleophilic addition reactions to cyclopentenone sulfoxide 7. Perchloryl fluoride is used as the fluorinating agent. Characterization of the product α-fluoro β-keto sulfoxides includes ¹⁹F NMR spectroscopy.     

Acid-catalyzed decomposition of an α-keto diazo endoperoxide

Two different decomposition modes of α-keto diazo endoperoxide $\text{1}$ are described. One is the Brønsted acid-catalyzed elimination of the diazo group leading to rearranged peroxides $\text{2}$. Deuterium labeling clearly shows the path of the rearrangement. The other reaction is a catalyzed cleavage of the peroxide bond to form diazoketone $\text{3}$.     

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 reduction of β-keto esters with zinc borohydride. stereoselective synthesis of erythro-3-hydroxy-2-alkylpropionates

$\text{Erythro}$-3-hydroxy-2-alkylpropionates were prepared in high stereoselectivity and in high isolated yield by zinc borohydride reduction of the corresponding β-keto esters.     

Intramolecular diels-alder reaction with furan-diene: Total synthesis of (±)-11-ketotestosterone and (±)-adrenosterone

A novel D → BCD → ABCD route to 11 -keto steroids is reported involving a high yield stereoselective intramolecular Diels-Alder reaction of furan-diene $\text{12}$ in water as a key-step. The dienophilic side chain is readily introduced starting from $\text{8}$ via a sequence involving alkylation with ethyl ($\text{E}$)-3-ethoxy-4-iodo-2-butenoate, reduction and acid hydrolysis. The reduced adduct $\text{14}$ is further converted into (±)-adrenosterone ($\text{6}$) via $\text{24}$, the dienediolate equivalent of which is a known intermediate in corticosteroid synthesis.     

lα-hydroxy previtamin D3, and its selective formation from 1-keto previtamin D3

An efficient method for the preparation of crystalline α-hydroxy previtamin D₃ is described. Also the stereoselective reduction of 1-keto previtamin $\text{9}$ is discussed; it was observed that with aluminum hydride $\text{7}$ is the most abundant product. This stands in contrast with previously reported LiAlH₄ and NaBH₄ mediated reductions.     

A ring transformation of 1-substituted 3,5-dinitro-2-pyidones

Reaction of 1-substituted 3,5-dinitro-2-pyridones with sodium salts of β-keto esters gave the ring transformation products, phenol derivatives and $\text{N}$-substituted nitroacetamides. Nonionic bicyclic intermediates could be isolated.     

Reaction of silylketene acetals with 3,3-dimethylacryloyl chloride.

The reaction of silylketene acetals with 3,3-dimethylacryloyl chloride in acetonitrile gave <,δ-ethylenic β-keto esters $\text{3}$. Application to a new synthesis of (?)-turmerone is described.     

Synthesis of 3-keto-4-diazo-5-α-dihydrosteroids as potential irreversible inhibitors of steroid 5-α-reductase

3-Keto-4-diazo-5-α-dihydrosteroids are prepared using the Hendrickson diazo transfer reaction on the corresponding β-diketones, which are available from 3-ketoΔ-4-steroids $\text{via}$ Li/NH₃ reduction and acylation of the kinetic enolate.     

Steric and kinetic effects of changing solvent and reactant in grignard reactions: Conformationally mobile versus rigid δ-keto esters

trans-7α-carbomethoxy-decal-1-one (2) yields a mixture of the two oxy-esters 6 and 7 on reacting with MeMgX. Ratios $\text{6}\text{7}$ were measured for reactions performed in benzene (with X = I) and in THF (with X = Cl). The small variations of the ratios $\text{6}\text{7}$ as compared to those obtained in analogous experiments performed with methyl (2-oxo-cyclohexyl)-propionate 4 and methyl 4-methyl-5-oxo-hexanoate 5 suggest that conformational mobility plays a fundamental role in determining the variations of stereospecificity with varying the reaction conditions. Competitive Grignard reactions among 2,4 and 5 show that their reactivities are in the order 4>2>5 ($\text{K}{}_4\text{k}{}_2$ = 1.7; $\text{k}{}_5\text{k}{}_2$=0.8) when reactions are performed in benzene with X  I and 2>4>5 ($\text{k}{}_4\text{k}{}_2$= 0.56; $\text{k}{}_5\text{k}{}_2$=0.25) when reactions are performed in THF with X  C1. The experimental data are interpreted in terms of anchimeric assistance given by the ester group to the reactions of the keto group in conformationally mobile δ-keto esters. The occurrence of this effect depends on the reaction conditions which can favour, or not, folded transition states.     

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.     

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.     

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).     

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.     

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.