Regioselective Ring Opening Of Epoxides Research Articles

Active Copper Catalyzed Regioselective Ring Opening of Epoxides by Heterocyclic Amines: An Efficient Protocol for Synthesis of β-Amino Alcohols

The regioselective epoxide ring opening at less substituted carbon atom of epoxide were reported by nucleophiles like heterocyclic amines which gives well known 1,2-difunctionalized amino alcohols. These are present in many synthetic as well as natural products. The ring opening of epoxide is achieved by cleavage with amines in presence of copper(0) as a catalyst. It is observed that the lithium napthalenide reduction of copper(I) produces a highly reactive form of copper(0) that acts as a catalyst for ring opening of epoxides with an amine.

An alternative total synthesis of diplodialide-B

In this paper, an enantioselective synthesis of diplodialide-B has been described. To accomplish this target, a combination of regioselective ring opening of the chiral epoxide, Jacobsen hydrolytic kinetic resolution and Yamaguchi macrolactonization were used as the key steps.

Synthetic Studies toward the Total Synthesis of Tautomycetin.

The studies culminating in the synthesis of two large subunits of tautomycetin are described. The first one, fragment C1-C12 that has an anti-1,3-dimethyl system and a terminal diene unit, was accomplished in 10 linear steps in 7.4% overall yield. The second one, fragment C13-C25 which bears the sensitive anhydride framework and the majority of the stereogenic centers, was prepared in 13 linear steps (longest sequence) in 8% overall yield. Among the key transformations used, a regioselective epoxide opening, a Pd-catalyzed addition of terminal alkyne to acceptor alkyne, a Mukaiyama aldol reaction, a Yamaguchi esterification, and a homemade mild di-esterification can be cited. The chosen strategies allowed good yields, stereoselectivity, reproducibility, and scalability for several important intermediates.

Total synthesis of (±) aspidostomide B, C, regioisomeric N-methyl aspidostomide D and their derivatives

A full account of the total synthesis of aspidostomide B, C, their analogues and our synthetic efforts towards the synthesis of aspidostomide D, which led to the synthesis of regioisomeric N-methyl aspidostomide D, its analogues via epoxide opening strategy is presented. The synthesis of regioisomeric N-methyl aspidostomide D involves an efficient, five-step sequence, with 36.3% overall yield, starting from 3,4,5-tribromo-1H-pyrrole-2-carboxylic acid. The key features of this protocol are intramolecular cyclization, dehydration, oxidation, and a Lewis acid-mediated regioselective epoxide ring opening by C-3 position of 2,5-dibromo-1H-indole to furnish the title compounds.

Alternative total synthesis of dendrodolide-L

A new synthetic route for the total synthesis of dendrodolide-L has been developed from known chiral epoxides. The key reactions involved in this synthesis are regioselective ring-opening of epoxide, Yamaguchi esterification and ring-closing metathesis reactions (RCM) to result the target compound.

Desymmetrization‐Initiated Stereocontrolled Synthesis of (−)‐Kaitocephalin

AbstractA total synthesis of (−)‐kaitocephalin (1), the first naturally isolated glutamate receptor antagonist, is described. The key steps involved the enantioselective desymmetrization of the N‐Cbz‐protected seriol 42 to install the C4 quaternary chiral center and the intramolecular mercury(II)‐mediated N‐cyclization of (Z)‐alkene 44 followed by reductive demercuration to construct the pyrrolidine ring. As proposed, the quaternary asymmetric carbon induced the stereoselective epoxidation as well as the regioselective epoxide opening to generate the C2 and C3 stereocenters.

First Stereoselective Total Synthesis of Ciryneol C

The acetylene derivative Ciryneol C was isolated from the roots of C. japonicum. The asymmetric total synthesis of Ciryneol C was achieved in seven steps, with Horner–Wittig olefination, regioselective epoxide opening, and Cadiot–Chodkiewicz coupling reactions being the key steps.

Stereoselective total synthesis of C2-symmetric natural products pyrenophorol and its derivatives

A stereoselective total synthesis of 16-membered C2-symmetric macrodiolide Pyrenophorol, Tetrahydropyrenophorol and 4,4-diacetylpyrenophorol have been accomplished. The synthesis started from commercially available L-Aspartic acid and the key reactions involved are regioselective epoxide opening, CBS reduction, Pinnick oxidation and Mitsunobu dilactonization.

An Alternative Approach to the Synthesis of Parvistone C

A stereoselective total synthesis of parvistone C, an oxygenated natural styryllactone, has been accomplished in excellent overall yield by employing asymmetric aldol reaction, asymmetric epoxidation and regioselective epoxide ring opening as the key steps. Our synthetic strategy is very simple, concise and no use of protecting groups.

Highly α-position regioselective ring-opening of epoxides catalyzed by halohydrin dehalogenase from Ilumatobacter coccineus: a biocatalytic approach to 2-azido-2-aryl-1-ols.

Halohydrin dehalogenases are usually recognized as strict β-position regioselective enzymes in the nucleophile-mediated ring-opening of epoxides. Here we found the HheG from Ilumatobacter coccineus exhibited excellent α-position regioselectivity in the azide-mediated ring-opening of styrene oxide derivatives 1a–1k, producing the corresponding 2-azido-2-aryl-1-ols 2a–2k with the yields up to 96%.

Caro's Acid-Silica Gel Catalyzed Regioselective Ring Opening of Epoxides with Indoles and Imidazoles under Solvent-Free Conditions

An efficient and facile procedure has been developed for the ring opening of epoxides with nitrogen heterocycles such as indole and imidazole in the presence of Caro's acid-silica gel (CA-SiO2) as catalyst in solventless system. The reactions were administered underneath Solvent-free conditions. The current methodology offers many benefits like good yields, easy procedure, simple work-up and ecofriendly reaction condition. The catalyst is well ready, stable and economical underneath the reaction conditions.

Epoxide ring opening with alcohols using heterogeneous Lewis acid catalysts: Regioselectivity and mechanism

Lewis acidic catalytic materials are investigated for the regioselective ring opening of epoxides with alcohols. For ring opening epichlorohydrin with methanol, the catalytic activity shows a strong dependence on the type of support and Lewis acidic species used. While Sn-SBA-15 is catalytically active, significantly higher catalytic activity can be achieved with hydrothermally synthesized zeolites of which Sn-Beta is 6 and 7 times more active than Zr-Beta or Hf-Beta, respectively. Sn-Beta is determined to be more active and more regioselective for epoxide ring opening of epichlorohydrin with methanol than Al-Beta. For Sn-Beta, the activation energy for the reaction between epichlorohydrin and methanol is determined to be 53 ± 7 kJ mol−1. For epichlorohydrin, the activation energy barrier and experimentally observed regioselectivity are found using DFT to be consistent with a concerted reaction mechanism involving activation of the epoxide on an alcohol adsorbed on the catalytic site and nucleophilic attack by a second alcohol. The epoxide is shown to impact the regioselectivity and the mechanism since isobutylene oxide is selectively ring opened by methanol to form the terminal alcohol. DFT calculations indicate the mechanism for isobutylene ring opening involves epoxide activation and ring opening on an alcohol adsorbed onto the catalytic site. Finally, catalyst reuse testing indicates that Sn-Beta can be used for multiple reactions with no decrease in activity and limited to no leaching of the tin site, demonstrating Sn-Beta is a promising catalytic material for epoxide ring opening reactions with alcohols.

Synthesis of Protected Amino Hexitol Nucleosides as Building Blocks for Oligonucleotide Synthesis.

A new synthesis protocol for the preparation of hitherto unknown 1',5'-anhydro-4'-amino-trityl/MMTr hexitol nucleosides has been developed. Key steps in the synthesis of the pyrimidine analogues (U and C) include the regioselective d- allo-hexitol oxirane and 2',4'-anhydronucleoside ring opening by uracil and azide, respectively. A different strategy using a regioselective epoxide ring opening of d- gulo-oxirane, followed by a SN2 type of azidation reaction, has been adopted for the purine analogues (A and G). These compounds can be easily converted to 6'-phosphoramidites for the solid-phase synthesis of N4' → P6' phosphoramidates of amino hexitol nucleic acids (AHNA).

Montmorillonite K10 catalyzed highly regioselective azidolysis of epoxides: A short and efficient synthesis of phenylglycine

A series of β‐hydroxyazides were effectively synthesized from the regioselective ring opening of epoxides by sodium azide using montmorillonite K10 as a novel heterogeneous catalyst in aqueous acetonitrile in good to excellent yields. The utility of this method has been demonstrated by achieving a short synthesis of phenylglycine in 33.5% overall yield.

Synthetic approach towards cuparene-type sesquiterpenes via highly regioselective epoxide opening under acid catalysis

Obtaining cuparene-type sesquiterpenes is a significant synthetic challenge mainly because of the construction of the sterically hindered quaternary centres. We report herein the successful construction of such quaternary moiety by a highly regioselective opening of (+/−)-2,5-dimethoxy-4-methyl-α-methylstyrene oxide by the acetone silyl enol ether catalysed by Lewis acid. Additionally, an efficient epoxidation of the highly activated 2,5-dimethoxy-4-methyl-α-styrene was accomplished by modifications on the dioxirane-promoted epoxidation protocol. Intensive optimisations for both key steps allowed the synthesis of the desired branched homo-aldol adduct, proposed as a key intermediate for a short synthetic alternative towards enokipodins.

A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine.

Synthetic approaches towards N-acetylgalactosamine (GalNAc) have been attracting considerable interest since this compound is known for its pivotal role in cell–cell interaction and receptor induced cell signaling. Herein, we present a synthetic route in which two of the four stereogenic centers present in the target compound are derived from enantiopure tartaric acid being selectively converted to epoxy alcohols. The key step is the Pd-catalyzed, stereo- and regioselective epoxide opening and subsequent nucleophilic substitution of an azide functionality. This approach enables the synthesis of the naturally D- and unnaturally L-configured GalNAc, as well as both enantiomers of the largely unknown N-acetylidosamine (IdoNAc).

Total Synthesis of the Polyoxygenated Sesquiterpenes Guignarderemophilanes C and D

The total syntheses of the neural anti‐inflammatory agents guignarderemophilanes C and D have been accomplished for the first time starting from γ‐hydroxy carvone in 15 and 14 steps, respectively. The presented synthetic route proceeds via a known intermediate, whose synthesis has been elaborated in our group in the course of the total synthesis of the sesquiterpenoid periconianone A. Key for the successful conversion of this intermediate into both targets was finding a suitable strategy to install the 1,2,3‐trihydroxylated A‐ring scaffold. For this purpose, we effectively employed a Mitsunobu inversion, epoxidation, and regioselective epoxide opening sequence, before the bicyclic ring system was constructed by an aldol condensation reaction on a sterically demanding substrate. Our reported synthesis set the stage for SAR studies to prepare even more potent compounds by modification and derivatization of the natural product's scaffold.

Stereoselective Total Synthesis of the Non‐Contiguous Polyketide Natural Product (–)‐Dolabriferol

The stereoselective total synthesis of the non‐contiguous polypropionate dolabriferol has been accomplished in 17 steps, by an approach that is both divergent and convergent. The key reactions involved are enantioselective cross‐aldol coupling, aldol dimerisation of propionaldehyde, Sharpless asymmetric epoxidation, regioselective epoxide opening and Yamaguchi esterification. The effects of the protecting groups on the alcohol substrate on differential reactivity in Yamaguchi esterification were noteworthy.

Design and synthesis of N–acetylglucosamine derived 5a-carbasugar analogues as glycosidase inhibitors

An efficient synthesis of new six-membered carbasugars in both L-form and D-form starting from N–acetylglucosamine is described. The key synthetic steps involved regioselective protection and deprotection, Ferrier carbocyclization, Peterson olefination, hydroboration and stereoselective epoxidation followed by regioselective epoxide ring opening reactions. These six-membered carbasugars showed moderate glycosidase inhibitory activity and one of the compounds was found selective towards β-galactosidase inhibitory activity.

Stereoselective Synthesis of the Benzodihydropentalene Core of the Fijiolides.

An efficient stereoselective synthesis of the enantiomer of the benzodihydropentalene core of fijiolides A and B has been achieved. The asymmetric conjugate addition of styrylboronic acid to an indenone produced the first stereocenter. Ring C was installed by ring-closing metathesis of a cis disubstituted indanone. Regioselective epoxide opening by NaSePh and subsequent oxidative elimination produced an allylic alcohol. The final introduction of the cyclopentadiene was possible by elimination of an in situ formed triflate.