Intramolecular Epoxide Ring Opening Research Articles

Synthesis of 1,3-thiazolidine-2-thiones using CS2 and epoxy amines

An efficient method for the synthesis of 5-(hydoxymethyl)-1,3-thiazolidine-2-thiones is developed via the reaction of carbon disulfide with N-alkyl(aryl) epoxy amines. The reaction proceeds via intramolecular epoxide ring opening with in situ prepared dithiocarbamic acid. The products were obtained in good to high yields.

Synthetic and biosynthetic methods for selective cyclisations of 4,5-epoxy alcohols to tetrahydropyrans.

Tetrahydropyrans (THPs) are common structural motifs found in natural products and synthetic therapeutic molecules. In Nature these 6-membered oxygen heterocycles are often assembled via intramolecular reactions involving either oxy-Michael additions or ring opening of epoxy-alcohols. Indeed, the polyether natural products have been particularly widely studied due to their fascinating structures and important biological properties; these are commonly formed via endo-selective epoxide-opening cascades. In this review we outline synthetic approaches for endo-selective intramolecular epoxide ring opening (IERO) of 4,5-epoxy-alcohols and their applications in natural product synthesis. In addition, the biosynthesis of THP-containing natural products which utilise IERO reactions are reviewed.

Construction the A-B Bicyclic Ring Structure of Stemocurtisine

In this paper, the synthesis of the A-B bicyclic ring structure 3 of the natural product Stemocurtisine is described. The synthesis was accomplished in seven synthetic steps from commercially available L-glutamic acid. The key step involved a borono-Mannich reaction between the hemiaminal 6 and trans-β-styryl boronic acid and trans-β-styrylpotassiumtrifluoroborate to prepare the cis diene 4. Attempts to prepare the A-B-C ring compound 2 via intramolecular epoxide ring opening followed by rearrangement under different basic conditions were unsuccessful. The only unreactive starting material was recovered.

Base-mediated synthesis of benzimidazole-fused 1,4-benzoxazepines via sequential intermolecular epoxide ring-opening/intramolecular SNAr reactions

We have developed a transition-metal-free, practical route to benzimidazole-fused 1,4-benzoxazepines. Operationally, the protocol involves a K2CO3-mediated intermolecular ring opening of terminal epoxides by 2-(2-fluorophenyl)benzimidazole, followed by an intramolecular nucleophilic aromatic substitution (SNAr) reaction of the resulting products in the presence of NaH. We have also achieved an 11-step synthesis of a chroman-linked benzimidazole-fused 1,4-benzoxazepine using a phenoxide-ion induced 6-exo intramolecular epoxide ring-opening and an alkoxide-ion induced intramolecular SNAr reaction as key steps.

Synthetic approaches to phomactins: Late stage stereochemical and reactivity issues

Oxidation of a 15-methylenebicyclo[9.3.1]pentadeca-3,7-dien-14-ol with a 10-phenylsulfonyl substituent provided a 14-oxobicyclo[9.3.1]pentadeca-1(15),3,7-triene-15-carbaldehyde that on reduction with DIBAL-H was converted into a 15-hydroxymethylbicyclo[9.3.1]pentadeca-1(15),3,7-triene-14-ol with the relative configuration at C14 required for incorporation into a synthesis of phomactin A. The oxidation and reduction of an analogous 3,4-epoxide that lacked the 10-phenylsulfonyl group gave a diol with the opposite relative configuration at C14. However, the TPAP oxidation and DIBAL-H reduction of a 14-hydroxy-15-methylene-3,4-epoxide that still had the 10-phenylsulfonyl group gave a diol with the required configuration at C14 although the expected spontaneous participation of the 14-hydroxyl group in an intramolecular epoxide ring-opening was only observed under Lewis acidic conditions.

Intramolecular epoxide ring opening cyclisation reactions involving guanidines

The cyclisation of N-allyl- and N-homoallylguanidines using DMDO leading to the formation of novel 5- and 6-membered guanidine heterocycles is reported. Several of the products formed displayed weak inhibition of glycosidase enzymes.

Selective Synthesis of Seven- and Eight-Membered Ring Sultams via Two Tandem Reaction Protocols from One Starting Material

From one starting material, two tandem reaction protocols to synthesize seven- and eight-membered ring sultams were developed. One protocol employs intermolecular epoxide ring-opening by NaN3, followed by an intramolecular 7-endo-trig oxa-Michael addition reaction. The second protocol applies to intermolecular aza-Michael addition of a primary amine, followed by 8-endo-tet intramolecular epoxide ring-opening of the resultant amine intermediate. Both protocols afforded the respective sultams in good yields under mild reaction conditions.

ChemInform Abstract: Synthesis of Cyclic Sulfides by Intramolecular Ring Opening of Epoxides by Thiolates Generated by Nickel Complex Catalyzed Electroreduction of Thioacetates.

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Enantioselective Syntheses of Pachastrissamine and Jaspine AviaHydroxylactonization of a Chiral Epoxy Ester

A new enantioselective total synthesis of pachastrissamine (jaspine B) was achieved from a known alpha,beta-unsaturated aldehyde by utilizing Córdova's asymmetric epoxidation as the chirality-inducing step. The 2,3-cis stereochemistry of pachastrissamine was established via intramolecular epoxide ring opening of a gamma,delta-epoxy-alpha,beta-unsaturated ester intermediate coupled with oxy-Michael cyclization. Treatment of pachastrissamine with tetrahydro-2-furanol under acidic conditions led to smooth oxazolidine ring formation, furnishing jaspine A in a high yield.

Application of Phenolate Ion Mediated Intramolecular Epoxide Ring Opening in the Enantioselective Synthesis of Functionalized 2,3-Dihydrobenzofurans and 1-Benzopyrans¹

The enantioselective synthesis of 2-isopropenyl-2,3-dihydrobenzofurans, 4-(2,3-dihydrobenzofuran-2-yl)-2-methylbut-3-en-2- ols, 2-hydroxymethylchromans, and 4-chroman-2-yl-2-methyl-but-3-en-2-ols has been achieved using Sharpless asymmetric epoxida- tion-derived enantiomerically enriched epoxy alcohols as chiral building blocks. A phenolate ion-mediated intramolecular epoxide ring opening reaction was the key step for every cyclization reaction.

Enantioselective Total Syntheses of Trichodermamides A and B

Starting from commercially available (-)-quinic acid, the enantioselective total syntheses of trichodermamides A and B were achieved. The key reactions involve the stereoselective construction of the oxazine ring via an intramolecular epoxide ring opening reaction and an EDCI-assisted peptide coupling reaction.

Synthesis of a Series of Structural Analogues of the Cinchona Alkaloids

Five olefins, each possessing an aryl (Ar) group, an aliphatic moiety, and a protected amino group as N-Teoc (-CO 2 (CH 2 ) 2 TMS) or N 3 at the aliphatic end, were converted to the corresponding epoxides with high ee. The amino group was generated by deprotection of the N-Teoc group with CsF or by Staudinger reaction of the azide group at elevated temperatures, under which the intramolecular epoxide ring-opening with the resulting amino group took place concomitantly to afford the analogues of the Cinchona alkaloids.

シンコナアルカロイドの合成

This review summarizes the synthesis of cinchona alkaloids, especially quinine. First, the synthetic efforts done by Rabe, Prelog, and Woodward are briefly mentioned. Described next are the achievements of Uskokovic in 1970 s, who found useful stereoselective transformations, introduced key intermediates, and established transformation of homomeroquinene to quinine, though as a mixture with quinidine. Then, the first completely stereoselective synthesis of quinine published by Stork in 2001 is presented, in which the key step is a stereoselective reduction of the substituted tetrahydropyridine (imine) to the piperidine by using NaBH4. Finally, syntheses of quinine and quinidine published by Jacobsen and by us are presented, both of which feature the stereoselective formation of the epoxide moiety on one of the side chains attached to the piperidine and subsequent intramolecular epoxide ring opening with the piperidine nitrogen, while the construction of the piperidine ring and the stereoselectivities accompanied with are different each other.

One‐Pot Regio‐ and Stereoselective Cyclization of 1,2,n‐Triols.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A new synthetic approach to enantiomerically enriched dihydrobenzofurans: use of a hydrolytic kinetic resolution and an intramolecular epoxide ring opening protocol using 1-benzyloxy-2-oxiranylmethylbenzenes

A novel approach towards the preparation of racemic 1-benzyloxy-2-oxiranylmethylbenzenes using dimethyldioxirane and their hydrolytic kinetic resolution using ( R, R)(Salen)Co(III)(OAc) (Jacobsen’s catalyst) to afford the ( R)-epoxides and ( S)-1,2-diols, enantioselectively, is described. The ( R)-1-benzyloxy-2-oxiranylmethylbenzenes were then cyclized via an intramolecular epoxide opening reaction to give ( S)-2-hydroxymethyl-2,3-dihydrobenzofurans.

Studies towards the Synthesis of Rapamycin: Regiocontrol in the Addition of Carbanions to Enantiomerically Pure Epoxides and the Formation of a Highly Substituted Tetrahydrofuran

Reaction of trimethylaluminium, dimethyllithium cuprate and lithium tetramethylaluminate with the homochiral epoxide 8 has been studied. Intermolecular epoxide ring-opening was observed with dimethyllithium cuprate and lithium tetramethylaluminate, but acetal ring-opening followed by intramolecular epoxide ring-opening was observed with trimethylaluminium.

One-Pot Regio- and Stereoselective Cyclization of 1,2,n-Triols

A simple and efficient process to cyclize triols containing a 1,2-diol functionality with a pendant hydroxyl group is presented. The one-pot procedure converts the 1,2-diol into an ortho ester in situ, which upon treatment with a Lewis acid generates a cyclic acetoxonium intermediate. This intermediate is subsequently trapped by the pendant hydroxyl group to generate a cyclic ether. The stereochemistry of the 1,2-diol is transferred to the product with complete fidelity (inversion at the site of cyclization), and the reaction proceeds with high regioselectivity. The process is akin to the Lewis acid-catalyzed intramolecular ring-opening of epoxides with hydroxyl groups yielding cyclic ethers of various sizes with regio- and stereochemical control.

Enantioselective Preparation of Ring-Fused 1-Fluorocyclopropane-1-carboxylate Derivatives: En Route to mGluR 2 Receptor Agonist MGS0028

[reaction: see text] An approach to the densely functionalized fluorocyclopropane 14, a key framework toward the synthesis of mGluR 2 receptor agonist MGS0028 (1) is reported. The Trost AAA reaction enantioselectively introduced the key allylic stereogenic center and the alpha-fluoroester moiety. Stereoselective epoxidation followed by intramolecular epoxide ring opening efficiently constructed the 1-fluorocyclopropane-1-carboxylate matrix. This route can potentially be a general methodology for a concise, highly enantio- and stereoselective synthesis of 1-fluorocyclopropane-1-carboxylate derivatives.

Intramolecular Guanidine Epoxide Ring Opening Reactions.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Intramolecular guanidine epoxide ring opening reactions

The synthesis of a range of cyclic guanidines via intramolecular ring opening of epoxides or iodocyclisation is reported. A preliminary investigation of the glycosidase inhibitory activity of these substances is also discussed.