Nucleophilic Ring Opening Of Epoxides Research Articles

Unusual Regioselectivity in the Opening of Epoxides by Carboxylic Acid Enediolates

Addition of carboxylic acid dianions appears to be a potential alternative to the use of aluminium enolates for nucleophilic ring opening of epoxides. These conditions require the use of a sub-stoichiometric amount of amine (10% mol) for dianion generation and the previous activation of the epoxide with LiCl. Yields are good, with high regioselectivity, but the use of styrene oxide led, unexpectedly, to a mixture resulting from the attack on both the primary and secondary carbon atoms. Generally, a low diastereoselectivity is seen on attack at the primary center, however only one diastereoisomer was obtained from attack to the secondary carbon of the styrene oxide.

Efficient synthesis of a bacterial translocase MraY inhibitor

The bacterial translocase MraY has recently been demonstrated as a prime target for the development of new antibiotics. We describe a straightforward synthesis of a new inhibitor 1 of this enzyme. The two key steps involve a tandem nucleophilic epoxide ring opening of C2-symmetrical bis-epoxide and subsequent O-heterocyclisation, followed by O-glycosylation. The in vitro biological evaluation of 1 at 2 mM showed an 81% of inhibition of the MraY activity. Therefore, congeners of 1 should permit detailed SAR investigations for the discovery of novel antibacterials.

ChemInform Abstract: Enzyme‐Catalyzed Nucleophilic Ring Opening of Epoxides for the Preparation of Enantiopure Tertiary Alcohols.

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Enzyme‐Catalyzed Nucleophilic Ring Opening of Epoxides for the Preparation of Enantiopure Tertiary Alcohols

AbstractThe halohydrin dehalogenase from Agrobacterium radiobacter AD1 (HheC) catalyzes nucleophilic ring opening of epoxides with cyanide and azide. In the case of 2,2‐disubstituted epoxides, this reaction proceeds with excellent enantioselectivity (E values up to>200), which gives, by kinetic resolution, access to various enantiopure epoxides and β‐substituted tertiary alcohols (ee up to 99 %). Since the enzyme has a broad substrate range and because these tertiary alcohols are difficult to prepare in other ways, HheC is an attractive biocatalyst for the production of β‐cyano and β‐azido tertiary alcohols.

Aza-Michael Addition of Imidazoles to α,β-Unsaturated Compounds and Synthesis of β-Amino Alcohols via Nucleophilic Ring Opening of Epoxides Using Copper(II) Acetylacetonate (Cu(acac)2) Immobilized in Ionic Liquids

Efficient synthesis of N-substituted imidazoles via the conjugate addition of imidazoles (aza-Michael addition) to α,β-unsaturated compounds using Cu(acac)2 immobilized in ionic liquids under ambient conditions has been reported. Similarly, β-amino alcohols are also synthesized via nucleophilic ring opening of epoxides with amines. The use of ionic liquids allows easy separation of the product and recycling of the catalyst in both reactions.

Regioselective ring opening of epoxides with amines using monodispersed silica nanoparticles in water

Monodispersed silica nanoparticles were synthesized and used as catalyst for the regioselective synthesis of β-amino alcohols in water via nucleophilic ring opening of epoxides with amines under ambient conditions in shorter reaction times. The use of water as ‘green’ solvent allows easy recycling of the catalyst.

Indium(I) iodide promoted cleavage of dialkyl disulfides — Application of the Michael addition of thiolate anions to conjugated carbonyl compounds and regioselective ring opening of epoxides

Indium(I) iodide promotes cleavage of dialkyl disulfides generating thiolate anions that then undergo facile addition to α,β-unsaturated ketones, aldehydes, carboxylic esters, and nitriles under neutral conditions producing corresponding β-ketosulfides or β-cyanosulfides. This strategy has also been used for the regioselective nucleophilic ring opening of epoxides by thiolate anions in presence of indium(III) chloride producing corresponding β-hydroxyphenyl sulfides. The reactions are in general, very clean, high yielding, and reasonably fast. Thus, simple and convenient procedures for the synthesis of β-ketosulfides or β-cyanosulfides and β-hydroxyalkyl sulfides have been developed using this cleavage reaction.Key words: indium(I) iodide, Michael addition, β-ketosulfide, β-cyanosulfide, epoxide, β-hydroxy sulfide.

Synthesis of β-Amino Alcohols by Regioselective Ring Opening of Epoxides with Aromatic Amines Catalyzed by Tin (II) Chloride [1

Tin (II) chloride dihydrate catalyses the nucleophilic ring opening of epoxide by aromatic amines leading to an efficient synthesis of β-amino alcohols in very good yields. The reactions are completely antistereoselective, highly regioselctive and proceed at ambient temperature which make this procedure particularly an alternative strategy for the synthesis of β-amino alcohols. Keywords: β-amino alcohols, tin (II) chloride dihydrate (SnCl2.2H2O), aromatic amines, Epoxides

Enantioselective Ring Opening of Epoxides with Cyanide Catalysed by Halohydrin Dehalogenases: A New Approach to Non‐Racemic β‐Hydroxy Nitriles

AbstractHalohydrin dehalogenases (HheA, HheB and HheC) were found to efficiently catalyse a carbon‐carbon bond forming reaction between terminal aliphatic epoxides and cyanide, yielding β‐hydroxy nitriles. With all three enzymes nucleophilic ring opening of epoxides proceeds with high regioselectivity to the β‐carbon atom. Activity, enantioselectivity and enantiopreference depend on the type of enzyme and the substrate structure. HheC was found to be the most selective among the tested enzymes. The enantioselectivity toward monosubstituted epoxides varies from moderate to high (E=5–106), while resolution of 2,2‐disubstituted epoxides proceeds with very high enantioselectivity (E=141 and 200). The results show that halohydrin dehalogenases may become attractive catalysts for the facile preparation of enantiopure β‐hydroxy nitriles from racemic epoxides.

C-Glycosides and Aza-C-Glycosides as Potential Glycosidase and Glycosyltransferase Inhibitors

Glycosylation as one of most important post-translational modification of gene products is often critical to specific cellular biological functions. Since elevated glycoprocessing enzyme activities have been implicated in the development of various diseases including cancer metastasis, glycosidases and glycosyltransferases are considered as therapeutic targets. Azasugars, the first generation of enzyme inhibitors, have been extensively investigated and two azasugar-based drugs (Miglitol and Miglustat) have been approved. Aza-C-glycosides, molecules with an azasugar core and various C-aglycons attached at the pseudo anomeric center, have the potential to become the second-generation inhibitors with improved specificity and membrane permeability. In this review, C-glycosides, aza-C-glycosides, and aza-C-disaccharides are introduced as glycoprocessing enzyme inhibitors. The synthetic approaches toward those molecules are described based on the key reactions, which include reductive amination, nucleophilic ring opening of epoxides, nucleophilic addition to imines (C=N), and hetero-Michael additions. Aza-C-glycoside-based libraries are also described for the discovery of promising second-generation inhibitors.

Structural Basis for the Enantioselectivity of an Epoxide Ring Opening Reaction Catalyzed by Halo Alcohol Dehalogenase HheC

Halo alcohol dehalogenase HheC catalyzes the highly enantioselective dehalogenation of vicinal halo alcohols to epoxides, as well as the reverse reaction, the enantioselective and beta-regioselective nucleophilic ring opening of epoxides by pseudo-halides such as azide and cyanide. To investigate this latter reaction, we determined X-ray structures of complexes of HheC with the favored and unfavored enantiomers of para-nitrostyrene oxide. The aromatic parts of the two enantiomers bind in a very similar way, but the epoxide ring of the unfavored (S)-enantiomer binds in a nonproductive inverted manner, with the epoxide oxygen and Cbeta atom positions interchanged with respect to those of the favored (R)-enantiomer. The calculated difference in relative Gibbs binding energy is in agreement with the observed loss of a single hydrogen bond in the S bound state with respect to the R bound state. Our results indicate that it is the nonproductive binding of the unfavored (S)-enantiomer, rather than the difference in affinity for the two enantiomers, that allows HheC to catalyze the azide-mediated ring opening of para-nitrostyrene oxide with high enantioselectivity. This work represents a rare opportunity to explain the enantioselectivity of an enzymatic reaction by comparison of crystallographic data on the binding of both the favored and unfavored enantiomers.

Polymer supported ferric chloride: Regiospecific nucleophilic ring opening of epoxides

Cross-linked polystyrene, 4-vinyl pyridine copolymer beads were prepared, characterized and were used to complex ferric chloride. This polymer metal complex was used as a heterogeneous, recoverable and reusable Lewis acid in nucleophilic ring opening of different epoxides to prepare β alkoxy alcohols and β azidohydrins in good to excellent yields.

Lithium Bromide: A Versatile Reagent in Organic Synthesis

(A) LiBr catalyzes the nucleophilic ring opening of epoxides with various aliphatic and aromatic amines to give b-amino alcohols. Aromatic and aliphatic amines react with cyclohexene oxides, providing exclusive formation of trans-2-aryl(alkyl)aminocycloalkanols in high yields. Excellent (98‐100%) selectivity in favor of nucleophilic attack at the benzylic carbon of styrene oxide is observed with aromatic amines. The chelation effect of the Li + ion enables selective opening of the epoxide ring in 3-phenoxypropylene oxide in the presence of styrene oxide. 1

Transition Metal Based Lewis Acid Catalyzed Ring Opening of Epoxides Using Amines under Solvent‐Free Conditions.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Microwave‐Assisted Ring Opening of Epoxides with Pyrimidine Nucleobases: A Rapid Entry into C‐Nucleoside Synthesis.

Microwave irradiation strongly accelerates the regioselective nucleophilic ring opening of epoxides by pyrimidine nucleobases. In the presence of tetrabutylammonium bromide (TBAB), various bases were elaborated to determine the proper base in which it can activate N 1 rather than N3 for alkylation. It was shown that MgO not only could serve as an eligible base, but also enhanced the selectivity and tendency of N1 for alkylation as compared with N3. The use of microwave irradiation provided dominant regioselective synthesis of N1-β-hydroxyalkylpyrimidines in moderate to good yields with a reaction time of less than 7 minutes.

Synthesis of 1′‐Homo‐N‐nucleosides from Hexitols.

AbstractFor Abstract see ChemInform Abstract in Full Text.

ZrCl4 as a New and Efficient Catalyst for the Opening of Epoxide Rings by Amines.

Zirconium(IV) chloride catalyses the nucleophilic opening of epoxide rings by amines leading to the efficient synthesis of β-amino alcohols. The reaction works well with aromatic and aliphatic amines in short times at room temperature in the absence of solvent. Exclusive trans stereoselectivity is observed for cyclic epoxides. Aromatic amines exhibit excellent regioselectivity for preferential nucleophilic attack at the sterically less hindered position during the reaction with unsymmetrical epoxides. However, in case of styrene oxide, selective formation of the benzylic amine was observed during the reactions with aromatic amines.

Transition Metal-based Lewis Acid Catalyzed Ring Opening of Epoxides Using Amines under Solvent-Free Conditions

Corrected by: Transition Metal-based Lewis Acid Catalyzed Ring Opening of Epoxides Using Amines Under Solvent-Free ConditionsSynlett 2004; 2004(06): 1122-1122DOI: 10.1055/s-2004-822910

Microwave-Assisted Ring Opening of Epoxides with Pyrimidine Nucleobases: A Rapid Entry into C -Nucleoside Synthesis

Microwave irradiation strongly accelerates the regio­selective nucleophilic ring opening of epoxides by pyrimidine nucleobases. In the presence of tetrabutylammonium bromide (TBAB), various bases were elaborated to determine the proper base in which it can activate N1 rather than N3 for alkylation. It was shown that MgO not only could serve as an eligible base, but also enhanced the selectivity and tendency of N1 for alkylation as compared with N3. The use of microwave irradiation provided dominant regioselective synthesis of N1-β-hydroxyalkylpyrimidines in moderate to good yields with a reaction time of less than 7 minutes.

Zinc‐Catalyzed Aminolysis of Epoxides.

AbstractFor Abstract see ChemInform Abstract in Full Text.