Cyclic Epoxides Research Articles

Computational elucidation of the origins of reactivity and selectivity in non-aldol aldol rearrangements of cyclic epoxides.

The non-aldol aldol reaction of the isomeric epoxy silyl ethers is controlled by the conformation of the transition states leading to an internal hydride shift. One isomer rearranges to the β-silyloxy ketone whereas the other isomer gives a β-elimination product. Theoretical calculations show that the substrates with substituents that favor the formation of the chairlike transition state rearrange normally while those that do not undergo elimination instead.

Enantioselective desymmetrization of meso-epoxides with anilines catalyzed by polymeric and monomeric Ti(IV) salen complexes

The active catalysts for the enantioselective ring opening (ARO) of meso-stilbene oxide, cis-butene oxide, cyclohexene oxide, cyclopentene oxide, and cyclooctene oxide with various substituted anilines were generated in situ by the reaction of Ti(O(i)Pr)(4) with poly-[(R,R)-N,N'-bis-{3-(1,1-dimethylethyl)-5-methylene salicylidene} cyclohexane-1,2-diamine]-1 and (1R,2R)-N,N'-bis[3,5-di(tert-butyl)salicylidene] cyclohexane-1,2-diamine-2. These catalysts in the presence of nonracemic imine as an additive provided β-amino alcohol in excellent yield (99%) and chiral purity (enantiomeric excess (ee) up to 99%) for the ARO of meso-stilbene oxide with aniline. The same protocol was less effective for the ARO of cyclic epoxides; however, when triphenylphosphine was used as an additive, there was a significant improvement in catalyst performance for the ARO of cyclohexene oxide (yield, 85-90%; ee, 63-67%). Both in situ generated polymeric and monomeric catalysts performed in a similar manner except that the polymeric catalyst Ti(IV)-1 was more active and recycled several times with retention of enantioselectivity when compared with the monomeric catalyst Ti(IV)-2, which was nonrecyclable.

ChemInform Abstract: A New Method for the Synthesis of 3-Chromanol Derivatives by Sodium Iodide-Catalyzed Cyclization of Epoxide.

Treatment of 2-(2,3-epoxy) propylphenyl acetate derivatives with catalytic amounts of NaI in organic solvent gave directly the corresponding 3-chromanyl acetate derivatives in good yields (86.6-98.0%). Similar treatment of 2-(2,3-epoxy) propyl-6-methoxyphenyl N-mesyl-L-phenylalanylate gave a diastereomeric mixture of 8-methoxy-3-chromanyl N-mesyl-L-phenylalanylate, which was fractionated into both diastereomers by silica gel column chromatography. Subsequent hydrolysis of these isomers afforded the enantiomers of 8-methoxy-3-chromanol

ChemInform Abstract: Palladium-Catalyzed Stereospecific Cyclization of Hydroxy Epoxides. Stereocontrolled Synthesis of cis- and trans-2-Alkenyl-3- hydroxytetrahydropyrans.

Abstract Stereospecific constructions of the cis- and trans-2-alkenyl-3-hydroxytetrahydropyrans have been achieved by the one-pot procedure of desilylation-palladium catalyzed cyclization of the silyl ethers of ω-hydroxy trans- and cis-γ,°-epoxy-α,β-unsaturated esters, respectively.

ChemInform Abstract: Enzymic Cyclization of 2,3-Dihydrosqualene and Squalene 2,3-Epoxide by Squalene Cyclases: From Pentacyclic to Tetracyclic Triterpenes.

Cell-free systems from the protozoon Tetrahymena pyriformis and the bacterium Alicyclobacillus acidocaldarius normally convert squalene into pentacyclic triterpenes of the gammacerane and hopane series. 2,3-Dihydrosqualene, a substrate analogue lacking one of the terminal double bonds of squalene and therefore making it impossible to form pentacyclic products, was converted unexpectedly into tetracyclic triterpenes, i.e. euph-7-ene by the T. pyriformis enzyme and a 1:1 mixture of (20R)-dammar-13(17)-ene and (20R)-dammar-12-ene by the system from A. acidocaldarius. Formation of a pentacyclic framework with six-membered D-ring might thus only depend on the assistance of the terminal double bond to the cyclization process, its lack of participation leading, probably spontaneously, to the formation of the thermodynamically favoured tetracyclic skeleton with a five-membered D-ring.The cell-free system from T. pyriformis was further, for the first time, directly shown to induce cyclization of (3S)-[3-3H]squalene epoxide into gammacerane-3β,21α-diol, and the (3R)-enantiomer into gammacerane-3α,21α-diol. The (3R)-enantiomer also afforded a novel monocyclic product with a 2,3,4-trimethylcyclohexanone structure. The enzymic cyclization of squalene epoxide is apparently exclusively initiated by an oxirane ring-opening, and not by a proton attack on the remaining terminal double bond of the molecule.

ChemInform Abstract: Friedel—Crafts Alkylation of Arenes with Epoxides Promoted by Fluorinated Alcohols or Water.

AbstractA series of 3‐chromanols (IV) is readily synthesized by stereoselective intramolecular cyclization of epoxides (III) in refluxing 1,1,1,3,3,3‐hexafluoro‐2‐propanol.

Synthesis of 1,4-Benzodioxanes via Epoxide Opening and Cyclization

Reported is the synthesis of 1,4-benzodioxanes through a tandem epoxide ring-opening and cross-coupling sequence. The current work demonstrates a significant improvement over this group’s previous procedure, whereby the methylene epoxide was attached to the opposite phenol (red above). This previous procedure gave both the six- and seven-membered ring products as an inseparable mixture. No such mixture was observed in the current work.

ChemInform Abstract: Zr-Catalyzed Kinetic Resolution of Allylic Ethers and Mo-Catalyzed Chromene Formation in Synthesis. Enantioselective Total Synthesis of the Antihypertensive Agent (S,R,R,R)-Nebivolol.

The first enantioselective total synthesis of the antihypertensive agent (S,R,R,R)-nebivolol (3) is described. The synthesis includes the efficient (EBTHI)Zr-catalyzed kinetic resolutions of cycloheptenyl styrenyl ethers 8 and 16, which are subsequently treated with 4 mol % Mo(CHCMe2Ph)(N(2,6-(i-Pr)2C6H3))(OCMe(CF3)2)2 to afford chiral nonracemic 2-substituted chromenes (R,R)-9 and (S,R)-17. Since the present retrosynthetic analysis dissects the molecule into two chromene fragments, both the (R) and (S) antipodes of (EBTHI)Zr catalyst are required. Accordingly, Buchwald's efficient resolution process is used to resolve rac-(EBTHI)ZrCl2 (from catalytic hydrogenation of commercially available rac-(EBI)ZrCl2), such that the two requisite transition metal chiral catalysts are obtained by a single process. Other noteworthy features of the synthesis include a highly efficient, regio- and stereoselective Pd-catalyzed opening of cyclic allylic epoxide 7 with diaryloxystannane 15 and a photochemical modification o...

ChemInform Abstract: Enantioselective Nucleophilic Opening of meso Epoxides by Organolithium Reagents.

Aryl lithium reagents, complexed with (-)-sparteine, react enantioselectively with cyclic meso epoxides, to afford chiral aryl cyclanols. The enantiomeric excess, though moderate (27-87%), is the best in the literature for such a reaction. Activation by BF3 · OEt2 is needed, and is compatible with a diamine such as (-)-sparteine.

ChemInform Abstract: Addition of a Grignard Reagent to Bis-spiroacetal Aldehydes: Appendage of a Tetrahydrofuran Ring.

The synthesis of tetracyclic polyethers 16 and 17, which are closely related to the polyether antibiotics epi-17-deoxy-(O-8)-salinomycin 3 and CP44,161 4, is described. The key step involved Barbier–Grignard addition of bromide 8 to bis-spiroacetal aldehyde 7a which proceeded via chelation control to provide erythro alcohol 9a as the major product. Addition of the Grignard reagent derived from bromide 8 to the isomeric bis-spiroacetal aldehydes 7b,7c,7d also afforded erythro alcohols 9b,9c,9d, respectively as the major products. A rationale for this observed stereoselectivity is provided. Attempts to effect iodoetherification of alkene 9a resulted in decomposition of the sensitive bis-spiroacetal ring system, however, epoxidation followed by acid catalyzed cyclization of the resultant epoxides 14,15 afforded bis-spiroacetal tetrahydrofurans 16,17. Attempts to effect ring expansion of tetrahydrofuran alcohols 16,17 to tetrahydropyrans 18,19 were unsuccessful.

Acid Rearrangment of Epoxy-germacranolides and Absolute Configuration of 1β,10α-Epoxy-salonitenolide

The acid-catalyzed cyclization of mono epoxides of cnicin acetonide (3) was investigated. Several 6,12-eudesmanolides were obtained, and their stereochemistry established by extensive spectroscopic analyses. Chemical correlations also led to the assignment of the absolute configuration of 1beta,10alpha-epoxy-salonitenolide (13), a previously isolated natural product. The cytotoxic activities of some compounds were determined against A549 and MCF-7 tumor cell lines. The esterified germacranolides 2-6 were selectively cytotoxic against the MCF-7 breast cancer cell line.

Essential Oils From Myrtaceae Species of the Brazilian Southeastern Maritime Forest (Restinga)

The leaf oils from five Myrtaceae species growing in the restinga forest of Carapebus, on the southeastern Brazilian coast, were obtained by hydrodistillation and analyzed by GC/MS. Eugenia punicifolia oil contained only sesquiterpenes, with predominance of β-elemene (22.1%) followed by β-caryophyllene (8.5%) and components of the selinane (24.8%) and cadinane (14.0%) skeletal-types. Eugenia sulcata oil had the highest content of monoterpenes, among which α-pinene (12.2%), β-pinene (10.8%) and 1,8-cineole (19.6%) predominated. This profile was completed with 23.5% of caryophyllane and humulane derivatives. α-Pinene also appeared significantly (18.8%) in Eugenia rotundifolia, followed by small amounts of α-terpineol (4.4), while limonene (4.7%) and 1,8-cineole (6.8%) were the main monoterpenes in Myrciaria floribunda. The chemical profile of Neomitranthes obscura was also dominated by selinane-type sesquiterpenes: α-cadinene (23.4%), selina-3,7(11)-diene (13.9%), β-selinene (8.5%) and α-selinene (5.5%), followed by traces of pinenes, limonene and 1,8-cineole (2.4%). Total cyclic sesquiterpene alcohols, esters and epoxides decreased from 55.5% in E. rotundifolia to 8.6% in M. floribunda. However, the latter species contained 26.9% of (E)-nerolidol in the oil composition. Traces of ketones (up to 3.1%) are present in E. punicifolia, N. obscura and M. floribunda.

Desymmetrization of Medium-Ring Cyclic Epoxides with SiCl4 and Chiral Mono-N-Oxide Lewis Base

Desymmetrization of Medium-Ring Cyclic Epoxides with SiCl₄ and Chiral Mono-<i>N</i>-Oxide Lewis Base

Enantioselective Ring Opening of Epoxides by Fluoride Anion Promoted by a Cooperative Dual-Catalyst System

An enantioselective method for the synthesis of beta-fluoroalcohols by catalytic nucleophilic fluorination of epoxides is described. Mild reaction conditions and high selectivity are made possible by the use of benzoyl fluoride as a soluble, latent source of fluoride anion. A chiral amine and chiral Lewis acid serve as cooperative catalysts for desymmetrizations of five- through eight-membered cyclic epoxides, affording products in up to 95% ee. The cocatalytic protocol is also effective for kinetic resolutions of racemic terminal epoxides, which proceed with k(rel) values as high as 300.

Stereoselective synthesis of bioactive natural spiroacetals aculeatins A and B

The stereoselective synthesis of two naturally occurring bioactive spiroacetals, aculeatins A and B has been accomplished using 1-tetradecanal as the starting material. The sequence introduces diastereoselective iodine-induced electrophilic cyclization and ring opening of epoxide with 1,3-dithiane as the key steps.

Regioselective Reductive Cleavage of Bis-benzylidene Acetal: Stereoselective Synthesis of Anticancer Agent OGT2378 and Glycosidase Inhibitor 1,4-Dideoxy-1,4-imino-l-xylitol

A highly regioselective reductive cleavage of the bis-benzylidene acetal of D-mannitol was performed using a BF(3) x Et(2)O/Et(3)SiH reagent system. A chiral intermediate 6 thus obtained was efficiently utilized in the stereoselective synthesis of the anticancer agent OGT2378 (3) and glycosidase inhibitor derivative N-tosyl 1,4-dideoxy-1,4-imino-L-xylitol (22). Chemoselective reduction of azido epoxide 10 followed by regioselective intramolecular cyclization of amino epoxide 11 resulted in the exclusive formation of deoxyidonojirimycin derivative 12. By changing the order of deprotection, the chiral intermediate 6 was readily transformed to glycosidase inhibitor derivative 22.

Theoretical conformational study of six-membered cyclic allyl epoxides

Accurate “ab initio” calculations (MP2 method) were performed to outline the conformational profile of a number of six-membered cyclic allyl epoxides differing either in the nature of the cycle fragment (Y) bound to the unsaturation, or in the substitution at the endocyclic carbon bound to the epoxy ring and bridging the epoxy ring with the Y fragment. In particular, we calculated structures 4 (Y=CH2), 5 (Y=O), 6 (Y=NH), 7 (Y=S), 8 (Y=CF2), 9 (Y=NH2 +), 10 (Y=CO), 11 (Y=BH) and 12 (Y=NCOOH), where the fragment of the endocyclic carbon bridging “Y” and the epoxy fragment is either non-substituted (4a – 12a) or bears a methyl side chain trans (4b–12b) or cis (4c–12c) to the epoxidic oxygen. Saturated analogs (Y=O and Y=CH2) were also computed to test the method and to evaluate the conformational profile in the absence of the unsaturation. Minimum energy conformations were found which differ in the relative position of the Y group and the epoxy oxygen, with respect to a plane containing the epoxy ring carbons and the adjacent saturated endocyclic carbon: they may be on the same side (conformer A) or on opposite sides (conformer B). Conformers A are generally more stable. The conjugation effect of Y with the double bond lowers the barrier between the two conformers to the extent that in a few cases only conformer A is associated with a minimum of energy. On the basis of the elongation of the allylic oxirane C–O bond, we postulated the order of reactivity of epoxides 4–12 in the oxirane ring-opening process, and a mechanism based on the more reactive conformer A. A comparison was also made between MP2 and DFT calculation methods.

Titanocene(III)-catalyzed formation of indolines and azaindolines.

Reductive cyclization of epoxides tethered to substituted anilines and aminopyridines in the presence of 3 mol % of titanocene dichloride and stoichiometric manganese metal promotes a radical annulation to form 3,3-disubstituted indolines and azaindolines.

Intramolecular Azide−Alkyne Cycloaddition for the Fast Assembly of Structurally Diverse, Tricyclic 1,2,3-Triazoles

The synthesis of novel tricyclic 1,2,3-triazoles starting from cyclic epoxides via the sequential azidolysis, propargylation and 1,3-dipolar cycloaddition is described. Derivatization by N-arylation reaction and the synthesis of enantiomerically pure compounds is also reported. Some of these compounds exhibit significant affinity for the sigma-1 receptor.

ChemInform Abstract: Titanocene(III)‐Mediated Radical Cyclizations of Epoxides for the Synthesis of Medium‐Sized Cyclic Ethers.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.