Transposition des oxirannes-ethanols par l'intermediaire d'alcoxyetains. Influence de la configuration de l'oxiranne

The transposition of oxirane-ethanols, through alkoxytin compounds, into oxetane-2-methanols and/or oxolan-3-ols (tetrahydrofuran-3-ols) is dependent upon the oxirane configuration. Cis configuration is more suitable for the formation of the smallest ring. Steric hindrance is not sufficient enough to explain the results.     

Rearrangement reactions of the molecular ions of some substituted aliphatic oxiranes

The fragmentation reactions of glycidic methyl ester (1) and of its derivatives (2–6) substituted by one, two and three methyl groups, respectively, at the oxirane ring, of the corresponding glycidols (7–12), and of the glycidyl ethers (13–16) in the 70 eV mass spectra have been studied using isotopic labelling and mass-analysed ion kinetic energy spectrometry. It is shown that the typical reaction of these aliphatic oxirane radical cations carrying a nucleophilic methoxy group and hydroxy group, respectively, at the side chain corresponds under high-energy conditions to a rearrangement by a methoxy group or a hydroxy group migration to the β-carbon atom of the oxirane moiety. This rearrangement is very likely mediated by the isomerization of the molecular ions into distonic ions via C? C bond cleavage within the oxirane ring.     

Stereoselective lithiation of α,β-epoxy-γ,δ-vinylsilanes and transformation into α-silylated ketones

A (cis)α,β-epoxy-γ,δ-vinyl-silane undergoes lithiation α to the silicon atom with retention of the configuration of the oxirane. This leads to new silylated vinyloxiranes with a quaternary silylated stereogenic carbon atom. We show here the possible and efficient rearrangement of a methyl substituted adduct into a β,γ-unsaturated-α-silylated ketone.     

Reaction of Optically Active Oxiranes with Thiofenchone and 1‐Methylpyrrolidine‐2‐thione: Formation of 1,3‐Oxathiolanes and Thiiranes

The SnCl₄‐catalyzed reaction of (?)‐thiofenchone (=1,3,3‐trimethylbicyclo[2.2.1]heptane‐2‐thione; 10 ) with (R)‐2‐phenyloxirane ((R)‐ 11 ) in anhydrous CH₂Cl₂ at ?60° led to two spirocyclic, stereoisomeric 4‐phenyl‐1,3‐oxathiolanes 12 and 13 via a regioselective ring enlargement, in accordance with previously reported reactions of oxiranes with thioketones (Scheme 3). The structure and configuration of the major isomer 12 were determined by X‐ray crystallography. On the other hand, the reaction of 1‐methylpyrrolidine‐2‐thione ( 14a ) with (R)‐ 11 yielded stereoselectively (S)‐2‐phenylthiirane ((S)‐ 15 ) in 56% yield and 87–93% ee, together with 1‐methylpyrrolidin‐2‐one ( 14b ). This transformation occurs via an S_N2‐type attack of the S‐atom at C(2) of the aryl‐substituted oxirane and, therefore, with inversion of the configuration (Scheme 4). The analogous reaction of 14a with (R)‐2‐{[(triphenylmethyl)oxy]methyl}oxirane ((R)‐ 16b ) led to the corresponding (R)‐configured thiirane (R)‐ 17b (Scheme 5); its structure and configuration were also determined by X‐ray crystallography. A mechanism via initial ring opening by attack at C(3) of the alkyl‐substituted oxirane, with retention of the configuration, and subsequent decomposition of the formed 1,3‐oxathiolane with inversion of the configuration is proposed (Scheme 5).     

Stereocontrolled synthesis of 3-amino-2-hydroxyalkyl diphenylphosphine oxides mediated by chiral azetidinium salts and epoxyamines

The stereocontrolled synthesis of amino hydroxyalkyl diphenylphosphine oxides has been achieved starting from (2S,3S)-N,N-dibenzyl-3-hydroxy-2-methylazetidinium bromide or (1R),[1′(S)-(dibenzylamino)ethyl]oxirane. The regioselective ring opening of both heterocyclic systems at the less substituted carbon atom with phosphorus nucleophiles proceeded with full stereochemical integrity.     

Stereochemistry-60 : Kinetic control of asymmetric induction during oxazolidine formation from (-)-ephedrine and aromatic aldehydes

Kinetically controlled oxazolidine formation was observed with aromatic aldehydes substituted by electron-withdrawing groups. The stereoselectivity is solvent dependent: non-stereoselective ring closure occurred in chloroform while a high diastereodifferentiation was observed in methanol. The first oxazolidine showing an unambiguous 2R configuration was synthesized from p-bromobenzaldehyde and (-)-ephedrine in alcohol medium. A mechanism involving a nucleophilic assistance by alcoholic solvents is suggested in order to clarify the differences in stereoselectivity.     

The rearrangement of 2,3-epoxysulfonates and its application to natural products syntheses: formal synthesis of (-)-aphanorphine and total syntheses of (-)-alpha-herbertenol and (-)-herbertenediol

The Lewis acid treatment of 2,3-epoxysulfonates with 2,3-dialkyl substituents or 2-alkyl-3-aryl substituents produced the rearrangement products via C3-cleavage of the oxirane ring in high yields. On the other hand, 2-aryl-3-alkyl-2,3-epoxysulfonates produced the products via C2-cleavage of the oxirane ring. The sulfonyloxy groups of the alpha-sulfonyloxy ketones, having a chiral benzylic quaternary carbon center obtained by the rearrangement of 2-alkyl-3-aryl-2,3-epoxysulfonates, were reductively eliminated to give the ketones with a chiral benzylic quaternary carbon center. The method was applied to the formal synthesis of (-)-aphanorphine and total syntheses of (-)-alpha-herbertenol and (-)-herbertenediol.     

Conformational studies of small ring derivatives by x-ray crystallography—I: The crystal structure of p-nitrostyrene oxide

The crystal structure of p-nitrostyrene oxide has been determined at room temperature from three-dimensional X-ray diffractometer data, and refined by full-matrix least-squares to a final R = 0·045. The crystals are monoclinic, space group P2₁/c with unit-cell dimensions a = 7·8244(2), b = 7·1277(2), c = 14·2059(4) Å, β = 104·193(3)°. The value of the dihedral angle formed by the phenyl ring and the oxirane ring (80·2°) can be rationalised on the basis of pseudoconjugation between the two rings, and of non-bonding interactions of one of the ortho-hydrogens of the phenyl ring with the hydrogens of the oxirane ring. The oxirane ring contains a short CC bond of length 1·448(4) Å.     

Synthese radicalaire d'analgesiques potentiels: aryl-4 piperidines substituees en 2 et benzomorphanes

The synthesis of a series of 3-aryl 5-hexenyl amines and the cyclisations of the corresponding N-chloroamines are described. When the ring closure results from the amino radical addition to the ethylenic double bond, 2-chloromethyl 4-phenyl piperidines are obtained. These compounds lead by intramolecular Friedel-Craft reaction to varied substituted 6,7-benzomorphanes. When the phenyl ring is substituted with a methoxyl group, the cyclisation proceeds via homolytic aromatic substitution and 4-allyl tetrahydroquinolines are formed.     

Stereospecific cycloaddition of heterocumulenes to oxiranes catalyzed by organotin halide complexes

Stereospecific cycloaddition of 2,3-disubstituted oxiranes to heterocumulenes, including carbodiimides, isocyanates and carbon dioxide, is catalytically promoted by dialkyltin diiodide-hexamethylphosphoric triamide (HMPA) system, producing various five-membered heterocycles, where the configuration of the carbons in the oxirane ring is retained. In particular, the addition of isocyanates to oxiranes gave stereo-specifically two types of products, dioxolan-2-imines and oxazolidin-2-ones independently, while the rearrangement of the former to the latter product has been already proposed.     

Synthesis of N,4-diaryl substituted β-lactams via Kinugasa cycloaddition/rearrangement reaction

The methodology of construction of N,4-diaryl substituted β-lactam framework, based on the Kinugasa cycloaddition/rearrangement sequence is presented. The series of protected chiral propargyl alcohols was treated with diaryl nitrones to afford mainly the cis-I adduct, providing direct access to the highly-functionalized azetitidin-2-one derivatives with a well-defined stereochemistry. Under the optimized reaction conditions, the unprotected chiral propargylic alcohols were also found to be suitable precursors of β-lactams. The absolute configuration of adducts was determined by CD or HPLC-CD technique, which was shown to be reliable method of determination of the configuration at C-4 of 4-aryl-substituted azetidin-2-ones. Epimerization of the cis adduct to the respective trans isomer could be easily done by the oxidation of hydroxyl group next to the four-membered β-lactam ring to the ketone, followed by a base-mediated epimerization of the malonyl fragment.     

Synthese et transposition thermique d'alcools α-ethyleniques β'-alleniques

Thirteen variously substituted α-ethylenic β'-allenic alcohols (1,5,6-triene-3-ols) have been synthesized by three different methods, for two of which the key step was the reaction of an organo copper reagent with a derivative of a β-hydroxy γ-ethylenic alcohol (1-ene-5-yne-3,7-diol). The[3,3]-sigmatropic rearrangement of these alcohols, following the heating of their solution in diglyme, leads to γ-dienic aldehydes and ketones. The yields are best (60–70%) for tertiary alcohols substituted on carbon 5. Comparisons of the reactivities of these 13 alcohols show that the mechanism of this rearrangement can probably vary, following the substitution from a cyclohexadiyl biradical process to a concerted pathway involving a cyclohexane transition state.     

Regio- and Stereoselective Formation of 1,3-Oxathiolanes by Reactions of Thiocarbonyl Compounds with Oxiranes

Abstract

Lewis acid-catalyzed reactions of oxiranes with a variety of C═S compounds yield 1,3-oxathiolanes. The ring enlargement of monosubstituted oxiranes occurs regioselectively via cleavage of the O,C(3) bond of alkyl substituted oxiranes and the O,C(2) bond of phenyl oxirane. Furthermore, the reaction proceeds with inversion of the configuration at the center of the nucleophilic attack by the S-atom. The formation of thiocarbonylium ions as intermediates is supported by Wagner–Meerwein-type rearrangements. Enolized thioketones react with oxiranes to give enesulfanyl alcohols, which undergo an acid-catalyzed cyclization to yield 1,3-oxathiolanes.     

Hydrolysis oxirylcarbinyl tosylates1

The participation of the oxirane carbon-carbon bond during the hydrolysis of oxirylcarbinyl tosylates gives rise to a 2-oxocyclobutyl cation which is further hydrolyzed to β-ketols. The reaction is stereospecific for the threo isomers which give only one diastereoisomer, while erythro isomers yield a diastereoisomeric mixture of β-ketols. The difference in the hydrolysis rates (threo isomers react 1.2–3.6 times faster than erythro isomers) can be related to the more important non-bonded interaction in the transition state arising in the erythro isomer. A Taft-Streitwieser treatment shows an anchimeric assistance by the oxiryl ring of small amplitude (<15). This new transposition allows to isomerise an ethylenic ketone by exchanging two substituents.     

Stereoselective synthesis and transformations of pinane-based 1,3-diaminoalcohols

A library of pinane-based 1,3-diaminoalcohols and 5-aminomethyloxazolidin-2-ones was developed from commercially available (1R)-(?)-myrtenol which was transformed to N-trichloroacetyl protected allyl amine via Overmann rearrangement followed by stereoselective epoxidation with mCPBA resulting in key intermedier epoxy-amine. In order to obtain the diaminoalcohol moiety, aminolysis and azidolysis of the oxirane ring was performed. The cleavage of the oxirane ring proceeded regioselectively, affording N-trichloroacetyl protected 1,3-diaminoalcohols and oxazolidin-2-ones, which were obtained also via a thermal cyclisation. Since N deprotection of diaminoalcohols was unsuccessful under varied conditions, the protecting group was changed and Boc-protected analogues were synthesised. In this case, removal of the Boc protecting group was successful resulting in the planned diamino alcohols. An unexpected extreme δ Me_α-9 value (0.11 ppm) was measured for the dibenzylaminomethyl-substituted oxazolidine-2-one, and the stereostructure was refined by means of DFT geometry optimization. The obtained potential catalysts were applied in the test reaction of benzaldehyde and diethylzinc with low to moderate enantioselectivities (up to 74% ee).     

Acid-Catalyzed Rearrangements of 3-Aryloxirane-2-Carboxamides: Novel DFT Mechanistic Insights

Efficient synthesis of 3-arylquinolin-2(1H)-ones and N-(2-carboxyaryl)-oxalamides from protic acid-catalyzed rearrangements of 3-aryloxirane-2-carboxamides was achieved recently but not well understood. In contrast to the classical Meinwald rearrangement, extensive DFT calculations reveal that the proximal aryl and amide groups have strong synergetic effects to control the amide-aided and aryl-directed oxirane-opening and further rearrangement sequences. The ortho-nitro substituent of the proximal aryl is directly involved in a nucleophilic oxirane ring-opening, the amide C=O is an important proton shuttle for facile H-shifts, while the N-aryl may act as a potential ring-closing site via Friedel-Crafts alkylation. The mechanistic insights are useful for rational design of novel synthesis by changing the aryl and amide functional groups proximal to the oxirane ring.     

Ring‐Opening Lithiation–Borylation of 2‐Trifluoromethyl Oxirane: A Route to Versatile Tertiary Trifluoromethyl Boronic Esters

Stereogenic trifluoromethyl‐substituted carbon centers are highly sought‐after moieties in pharmaceutical and agrochemical discovery. Here, we show that lithiation–borylation reactions of 2‐trifluoromethyl oxirane give densely functionalized and highly versatile trifluoromethyl‐substituted α‐tertiary boronic esters. The intermediate boronate complexes undergo the desired 1,2‐rearrangement of the carbon‐based group with complete retentive stereospecificity, a process that was only observed in non‐polar solvents in the presence of TESOTf. Although the trifluoromethyl group adversely affects subsequent transformations of the α‐boryl group, Zweifel olefinations provide trifluoromethyl‐bearing quaternary stereocenters substituted with alkenes, alkynes and ketones.     

Experimental and Theoretical Studies on the Rearrangement of 2‐Oxoazepane α,α‐Amino Acids into 2′‐Oxopiperidine β2,3,3‐Amino Acids: An Example of Intramolecular Catalysis

Enantiopure β‐amino acids represent interesting scaffolds for peptidomimetics, foldamers and bioactive compounds. However, the synthesis of highly substituted analogues is still a major challenge. Herein, we describe the spontaneous rearrangement of 4‐carboxy‐2‐oxoazepane α,α‐amino acids to lead to 2′‐oxopiperidine‐containing β^2,3,3‐amino acids, upon basic or acid hydrolysis of the 2‐oxoazepane α,α‐amino acid ester. Under acidic conditions, a totally stereoselective synthetic route has been developed. The reordering process involved the spontaneous breakdown of an amide bond, which typically requires strong conditions, and the formation of a new bond leading to the six‐membered heterocycle. A quantum mechanical study was carried out to obtain insight into the remarkable ease of this rearrangement, which occurs at room temperature, either in solution or upon storage of the 4‐carboxylic acid substituted 2‐oxoazepane derivatives. This theoretical study suggests that the rearrangement process occurs through a concerted mechanism, in which the energy of the transition states can be lowered by the participation of a catalytic water molecule. Interestingly, it also suggested a role for the carboxylic acid at position 4 of the 2‐oxoazepane ring, which facilitates this rearrangement, participating directly in the intramolecular catalysis.     

Chiral spiro-connected 2,3,3-trisubstituted oxiranes New dopants for induced ferroelectric phases

Abstract

The synthesis, phase behaviour and spontaneous polarization of a new class of chiral dopants for induced ferroelectric phases of general structure A and B, possessing a 2,3,3-trisubstituted oxirane ring spiro-connected with four-, five- or six-membered carbocycles are described. In a series of these compounds with the same mesogenic building blocks the one with the five-membered carbocycle exhibits the highest induced spontaneous polarization. Introduction of a carbonyl group adjacent to the oxirane ring leads to an increased induced spontaneous polarization. The sign of the helical twisting power is positive for compounds with a cyclobutane ring and negative for those with a cyclopentane or a cyclohexane ring, although the absolute configuration at the chiral carbon is the same for all compounds.     

Five- and six-membered ring formation from the intramolecular reaction of a protonated oxirane and alkene

Computational studies of competing five- and six-membered cyclisation of alkenyloxiranes 1a-d show that intramolecular reaction of a protonated oxirane and alkene is a concerted, single-step, exothermic process. The reactions proceed via reactant-like transition states, but where the oxirane C-O bond is considerably stretched. Two factors are seen to affect the regiochemistry: (1) stabilisation of the transitory positive charge in the transition state favours cyclisation to the more highly substituted oxirane carbon; and (2) there is an inherent stereoelectronic preference for six-membered cyclisation over five-membered cyclisation. The inherent preference for six-membered cyclisation has a parallel in Baldwin's rules for six-membered ring closure of a carbocation with an alkene, rather than Baldwin's rule for intramolecular nucleophilic reaction of three-membered rings, suggesting that the protonated oxirane mimics a carbocation. The electronic and stereoelectronic effects for cyclisation are modified by steric interactions of axial methyl groups. These systems provide a model for the A-ring cyclisation of oxidosqualene.