Reaction of acylaminocyanoesters with 2,4-bis (4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide leading to substituted aminothiazoles. Crysta

2-Acylamino-2-cyanoacetic acid ethyl esters $\text{2a-c}$ react with 2,4-bis (4-methoxyphenyl)-1, 3, 2, 4-dithiadiphosphetane 2,4-disulfide $\text{1}$ in refluxing benzene with formation of 2-alkyl(aryl)-5-aminothiazole-4-carboxylic acid ethyl esters $\text{3a-c}$. Structure $\text{3}$ was established by spectroscopic means and an X ray crystallographic investigation of $\text{3a}$. X-Ray analysis revealed that the thiazole ring, exocyclic nitrogen and carbonyl group forming a hydrogen-bonded cycle are nearly coplanar. A resonance interaction is manifested by distinctly shortened /1.447 (3)/ C_(carbonyl)-C_(thiazole) distance.     

A short and efficient synthesis of 4-hydroxy-5-(1-hydroxyalkyl)-γ-butyrolactones

The cycloaddition of α,β-epoxyaldehydes or ketones ($\text{2}$) with the ketene acetal MeHC=C(OMe)₂ ($\text{1}$) gives epoxyoxetanes ($\text{3}$) in high yields. Without isolation they can be transformed into 4-hydroxy-5-(1-hydroxyalkyl)-γ-butyrolactones ($\text{6}$) via the epoxy esters $\text{4}$ and trihydroxy esters ($\text{5}$). The lactones $\text{6}$ appear to be valuable precursors for the synthesis of 5-(1-hydroxyalkyl)-3-methyl-2-5H-furanones ($\text{7}$) and 3-methyl-5-ylidene-2-5H-furanones ($\text{8}$)     

Synthesis of carboxylic esters using formaldehyde dimethyl dithioacetal S,S-dioxide

Formaldehyde dimethyl dithioaoetal S,S-dioxide ($\text{1}$) reacted uith an alkyl bromide or a 2-alkenyl bromide ($\text{8}$) under phase-transfer sonditions using 50% aq. NaOH to give an alkyl or 2-alkenyl derivative of $\text{1}$, whereas, in the reaction with $\text{8}$ in the presence of Kg₂CO₃KI in HMPA, $\text{1}$ formed a 1-alken-3-yl derivative. Transformation of these products into the corresponding carboxylio esters uae also described.     

Lewis acid promoted aldol additions of α-thiosilylketeneacetals to α-alkoxy aldehydes: diastereoselective synthesis of syn-α-methylene-β-hydroxy-∂-alkoxy esters.

MgBr₂ mediated addition of Methyl α-methylthio propionate silylketene acetal to α and α,β-alkoxy aldehydes is highly 3,4 $\text{syn}$-selective (18:1). $\text{syn}$-α- methylene-β- hydroxy-?-alkoxy esters (6) and (8) are synthesized.     

The invention of new radical chain reactions. part X: High yield radical addition reactions of αβ-unsaturated nitroolefins. An expedient construction of the 25-hydroxy-vitamin D3 side chain from bi

Radicals derived from thiohydroxamic esters $\text{3}$ readily add to nitroolefins $\text{5}$ (Z = NO₂) to give good yields of α-nitrosulphides. These adducts, where the structure permits, are easily oxidised to carboxylic acids $\text{8}$ by treatment with alkaline hydrogen peroxide. Reductive cleavage to the corresponding aldehydes or ketones $\text{9}$ is efficiently carried out by the action of TiCl₃. Addition of methyl magnesium iodide to the methyl ketone derived from 3α-acetoxy 11-oxo cholanic acid gives steroid $\text{10}$ possessing the 25-hydroxycholesterol side chain of the vitamin D₃ metabotites. Radical additions to 1-phenylthio-2-nitropropene $\text{11}$ have been briefly studied.     

Electron transfer reactions between pentafluorobenzoyl peroxide and dimethoxybenzenes

Pentafluorobenzoyl peroxide (FBP) reacted rapidly with dimethoxybenzenes in F₁₁₃ (CCl₂FCClF₂) with kinetics of first order in each component. High yields of ring-substituted esters of $\text{m}$-dimethoxybenzene ($\text{m}$-DMB) and $\text{p}$-dimethoxybenzene ($\text{p}$-DMB) were obtained, whereas for 2,5-di-$\text{t}$-butyl-1,4-dimethoxybenzene (DBDMB), the $\text{t}$-Bu group was simultaneously eliminated. For 2,5-dimethyl-1,4-dimethoxybenzene (DMDMB), the benzylic hydrogen was substituted. Rate and product studies both indicate a rate-determining electron transfer step leading to radical ion pairs which collapse to products.     

The stereospecific synthesis of leukotriene A4 (LTA4), 5-epi-LTA4, 6-epi-LTA4 and 5-epi,6-epi-LTA4

The stereospecific syntheses of the four isomers of 6-formyl-5,6-epoxy hexanoic acid methyl ester $\text{8}$, $\text{15}$, $\text{23}$ and $\text{30}$ from Z-deoxy-D-ribose have allowed the preparation of methyl esters of LTA₄, $\text{1}$, and its three unnatural isomers.     

Acid - catalyzed rearrangement of butyl 2-0-acetyl-4,5-anhydro-3,6-dideoxy-hexaldonate. Synthesis of racemic epiallomuscarine and epimuscarine

Butyl 2-0-acetyl-4,5-anhydro-3,6-dideoxy-DL-xylo-hexaldonate ($\text{4}$) in the presence of SnCl₄ underwent an intramolecular rearrangement to give 2,5-anhydro ester $\text{7}$. On the other hand the lyxo epimeric epoxide $\text{5}$ under the same conditions afforded esters $\text{7}$ and $\text{8}$. Ester $\text{7}$ was transformed into racemic epiallomuscarine ($\text{12}$), whereas the isomer $\text{8}$ into racemic epimuscarine ($\text{13}$).     

Conjugate addition of (trimethylstannyl)copper reagents to α,β-acetylenic N,N-dimethylamides. Trapping of the intermediates with electrophiles

A study of the reaction of Me₃SnCu·.Me₂S (1) and [Me₃SnCuSPh]Li (2) with α,β - acetylenic N,N-dimethylamides 3 shows (a) that the overall process can be controlled experimentally so as to produce either N,N-dimethyl ($\text{E}$)-(4) or ($\text{Z}$)-3-trimethylstannyl-2-alkenamides (5), (b) that the initially formed intermediate derived from interaction of 2 and 3 is significantly more stable than that obtained by reaction of 2 and α,β-acetylenic esters, and (c) that the intermediate produced by treating 3 with 1 can be trapped with electrophiles other than proton.     

A convenient one-pot procedure for synthesis of thiol esters using magnesium ion as a catalyst

Various thiol esters (R¹ COSR²) were prepared in high yields by treatment of 1-acylimidazole with thiols in the presence of a catalytic amount of Mg(OEt)₂. Malonic half-thiol esters [R¹OCOCH(R³)COSR²] were also prepared in good yields by treating magnesium monoalkyl malonate [R¹ OCOCH(R³)COOMg$\text{1}\text{2}$] with carbonyl-1,1′-diimidazole followed by addition of thiols.     

Five ingol esters and a 17-hydroxyingenol ester from the latex of Euphorbia Kamerunica. Assignment of esters using 13C.N.M.R. methods.

The structures of five ingol esters and a 17-hydroxyingenol ester from the latex of $\text{Euphorbia kamerunica}$ have been determined. The ¹³C n.m.r. spectra of these compounds have been assigned using 2D δ_C/δ_H correlations. The specific positions of attachment of esters have been assigned unambiguously using ¹³C n.m.r. methods including 2D long range δ_C/δ_H correlation.     

Highly stereocontrolled synthesis of (2e,4z)-dienic esters by alumina catalyst

Thermal treatment of β-allenic esters ($\text{2}$) with alumina catalyst in aprotic solvents yielded (2E,4Z)-dienoic esters ($\text{3}$) in 57-58% yield with 91-100% stereoselectivity.     

Eugenol and safrole as starting materials for the synthesis of 3-alkyl muconic acid mono and dimethyl esters and 4,4-dialkyl butenolides

Compounds $\text{1b-e}$ and $\text{2b-d}$ prepared from eugenol ($\text{1a}$) and safrole ($\text{2a}$) respectively were submitted to ozonation in methanol at 0°C. The 3-alkyl muconic acid dimethyl esters $\text{4b-e}$ were produced from $\text{1b-e}$ (～ 45%), while starting from $\text{2b-d}$ the 3-alkyl muconic acid monomethyl esters $\text{6b-d}$ were obtained regiospecifically (～ 75%). These latter compounds were transformed (～ 85%) into the 4,4-dialkyl butenolides $\text{7b-d}$.     

β-Carbonyl radicals as three-carbon building blocks for carbon-carbon bond forming reactions

From aldehydes, ketones and esters β-carbonyl radicals $\text{47}$ can be generated via enolization, cyclopropanation, solvomercuration and reduction with NaBH₄. Radicals $\text{47}$ react with electron-poor alkenes $\text{27}$ to give products of CC-bond forming reactions (Tables 1–3). Carbonyl compounds are therefore precursors of three-carbon building blocks. The products result from reactions with “Umpolung”.     

Alkylation of sulfonate anions via substrate-reagent ion-pair (srip) reactions of [2]betylates. Preparation of alkyl esters of hydroxyalkanesulfonic acids

[2]Bety1ate sulfonates ($\text{4}$ or $\text{8}$) give alkyl sulfonate esters ($\text{6}$) in refluxing toluene or benzene, chiral esters being formed with inversion. Preparation of alkyl hydroxyalkanesulfonates in this way (a) is a simple route to a little-known class of compounds, and (b) shows sulfonate anions to be more nucleophilic than hydroxyl groups in this system.     

On the lithium dimethylcuprate induced conversion of propargylic esters into allenes using a steroidal C/D fragment derived from vitamin D3 as a stereochemical probe.

The reactions of (CH₃)₂CuLi with various C-8 epimeric propargylic esters derived from Grundmann's ketone, a C/D steroid fragment originating from vitamin D₃, lead to the corresponding allenes, the stereochemistry of which indicate a preferred $\text{anti}$ 1,3-substitution.     

Synthesis of 2-oxo-bisnorpenicillin G esters

Using penicillin G as starting material, a synthetic route for the novel 2-oxo-bisnorpenicillin G esters $\text{1}$ has been developed. These oxopenams are precursors of 2-alkoxypenems $\text{2}$.     

The synthesis and rearrangement of epoxypyrones

The oxidation of 5-acyl-4-oxo-pyran-2-carboxylic acid esters $\text{1}$,$\text{2}$ to novel epoxypyrones and subsequent rearrangement to the previously inaccessible 6-substituted-5-hydroxy or 5-chloropyrones $\text{6}$ - $\text{9}$ are described.     

[2,3] Sigmatropic rearrangement of S-(3-chloroallyl) thiocarbamate sulfoxides followed by a 1,2-elimination reaction yielding unsaturated aldehydes and acid chlorides

Peracid oxidation of $\text{S}$-(2,3-dichloroarryl) was $\text{S}$-(2,3,3-trichloroallyl) thiocarbamates yields 2-chloroacrolein and 2-chloroacrylyl chloride, respectively, via intermediate $\text{S}$-allyl thiocarbamate sulfoxides and $\text{S}$-$\text{O}$-allyl thiocarbamate sulfenate esters.     

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 ($\text{1}$).