Epoxide Reactions

5 Key excerpts on "Epoxide Reactions"

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  Lewis Base Catalysis in Organic Synthesis

  • Edwin Vedejs, Scott E. Denmark, Edwin Vedejs, Scott E. Denmark(Authors)
  • 2016(Publication Date)
  • Wiley-VCH

    (Publisher)

  23

  Reactions of Epoxides (n → σ* )

  Tyler W. Wilson1 and Scott E. Denmark2

  1 Gilead Sciences, Process Chemistry, 333 Lakeside Drive, Foster City, CA 94404, USA 2 University of Illinois, Department of Chemistry, 245 Roger Adams Laboratory, 600 South Mathews Avenue, Urbana, IL 61801, USA

  23.1 Introduction

  The availability and versatility of epoxides elevates them as a highly valued functional group in synthetic organic chemistry [1]. Epoxides are readily prepared by the direct oxidation of olefins and tremendous success has been achieved for both diastereoselective [2] and enantioselective preparations of oxiranes [3]. In parallel with advances for their synthesis, strategies for the site- and stereoselective opening of epoxides have been developed that harness their strain energy for myriad transformations [4]. For example, the ring opening of epoxides with nucleophiles, which can proceed with clean inversion of configuration by an SN 2 pathway, allows the construction of vicinal stereogenic centers with high stereochemical fidelity. Taken together, these processes of epoxidation and nucleophilic ring opening provide an extremely powerful method for transforming simple olefins into diverse arrays of chiral 1,2-difunctionalized building blocks.

  23.1.1 Lewis Acid-Catalyzed, Enantioselective Epoxide Opening

  The ability of chiral Lewis acids to catalyze the desymmetrization of meso-epoxides is now well established. Unlike most enantioselective transformations that involve enantiotopic face selection with compounds that contain no stereogenic centers, these reactions involve enantiotopic group selection with Cs -symmetric compounds containing two or more stereogenic centers. The power of this type of transformations is that a number of stereogenic centers can be unveiled in a single step (Eq. (23.1) ) [5]. The scope of the nucleophile for this process has evolved beginning with early studies by Nugent, who identified silyl azides as particularly effective nitrogen-based nucleophiles for epoxide opening using a zirconium alkoxide complex as the catalyst [6]. Later, Jacobsen greatly extended the field of meso-epoxide opening by employing chiral Cr- and Co-salen complexes for the reactions of epoxides with silyl azides, alcohols, and carboxylic acids [5a]. More recently, the scope of this process has been expanded to include phenols and sulfur-based nucleophiles by Shibasaki and coworkers, who described the use of a gallium–lithium BINOL complex as the catalyst [7]. These along with many other contributions have now made the Lewis acid-catalyzed opening of meso

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  Green Oxidation in Organic Synthesis

  • Ning Jiao, Shannon S. Stahl, Ning Jiao, Shannon S. Stahl(Authors)
  • 2019(Publication Date)
  • Wiley

    (Publisher)

  4 Green Oxidative Synthesis of Epoxides

  Miquel Costas

  Facultat de Ciències, Departament de Química I Institut de Química Computacional i Catàlisi, Universitat de Girona, Girona, Spain

  4.1 Introduction

  Epoxides are strained three‐membered heterocycles that have a high interest in organic synthesis because they exhibit a very versatile reactivity (Scheme 4.1 ). Most remarkably, they can be ring‐opened by a number of nucleophiles with high control over regio‐ and stereochemistry [1 ]. This aspect makes epoxides convenient starting points for the preparation of a number of 1,2‐difunctionalized products.

  Scheme 4.1

  Representative examples of the reactivity of epoxides.

  Epoxides are most commonly prepared by three different methods (Scheme 4.2 ).

  Scheme 4.2

  General methods for preparation of epoxides.

  The most common method is the direct epoxidation of olefins, by reaction with an oxidant, most commonly a peroxide or peracid (Scheme 4.2 a), but also via a metal‐catalyzed oxidation reaction with a number of oxidants [2 –4 ]. Epoxides can be also prepared by ring closing of halohydrins on reaction with a base (Scheme 4.2 b). Halohydrins are initially formed by reaction of an olefin and hypochlorous acid. Alternatively, the hypochlorous acid can be prepared in situ by reaction of Cl2 and water. This method is used in the large‐scale production of propene oxide and in the production of epichlorohydrin [5 –7 ]. Finally, epoxides can be also synthetized by reaction of aldehydes or ketones with ylides (Scheme 4.2 c) [8 ].

  Epoxidation of olefins is a well‐established and particularly useful reaction because olefins are largely available starting materials. However, the vast majority of current methods are far from satisfactory from a number of perspectives. In the first place, some epoxidizing agents exhibit poor atom economy in their reactions, and delivery of the oxygen atom occurs at the expense of the production of a large number of byproducts. In addition, because of the rich reactivity of epoxides, chemoselectivity remains a critical aspect in epoxidations with aggressive oxidants and acidic conditions. Paradigmatically, the epoxidation performed with peracids, known as the Prilezhaev reaction, is widely employed in organic synthesis [9 ]. For example, epoxidations with electron poor peracids, such as

  m‐chloro perbenzoic acid

  (MCPBA ), are reliable reactions, with a wide substrate scope. However, they produce the corresponding carboxylic acid as a by‐product. Peracetic acid is also employed in large‐scale epoxidations [2

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  Epoxy Resins

  • Michael Dornbusch, Ulrich Christ, Rob Rasing(Authors)
  • 2016(Publication Date)
  • Vincentz Network

    (Publisher)

  21 Properties and reactions of epoxy groups 2 Basic chemistry of the epoxy group Michael Dornbusch 2.1 Properties and reactions of epoxy groups Epoxides (oxiranes) are cyclic ethers that are characterised by high ring strain, which amounts to 114 kJ/mol in oxirane [1, 2] and 106 kJ/mol in oxetane [1] . The val-ues for cyclic hydrocarbons are in the same range: 115 kJ/mol for cyclopropane [1] and 111 kJ/mol for cyclobutane [1] . Equation 2.1: Important cyclic ethers and their systematic and trivial names The ring strain results from the bond angle of 60°, which is considerably less than the normal tetrahedral carbon angle of 109.5° and the C-O-C bivalent bond an-gle of 110° in ethers [7] . Small rings are stabilised by attached alkyl groups; thus the ring strain in 2-methyl-oxirane is 4 kJ/mol lower. The ring strain makes epoxides much more reactive than other cyclic ethers. The ring strain in oxetane also enables it to react in mild conditions; its reactiv-ity ranks between that of oxirane and open-chain ethers [1] . In contrast, the higher homologues of the cyclic ethers are good solvents and are largely inert. The key reactions of epoxides can be divided into two groups: • Reactions with nucleophiles in neutral solution and • Base-catalysed and acid-catalysed reactions M. Dornbusch, U. Christ, R. Rasing: Epoxy Resins © Copyright 2016 by Vincentz Network, Hanover, Germany Basic chemistry of the epoxy group 22 2.1.1 Reactions with nucleophiles As a general rule, ethers are inert to bases, which is why they serve as solvents in numerous organic reactions. By contrast, epoxides undergo ring opening in mild conditions when attacked by nucleophiles, such as alkyl amines, in what is for-mally an addition reaction without elimination (see Equation 2.2).

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  Mechanisms in Homogeneous and Heterogeneous Epoxidation Catalysis

  • S. Ted Oyama(Author)
  • 2011(Publication Date)
  • Elsevier Science

    (Publisher)

  The ketones are difficult to obtain by conventional means. In summary, epoxides are produced not only as endproducts, but also as intermediates because they are valuable building blocks in synthetic organic chemistry [82–84] (Table 1.3). Until recently, epoxide intermediates were pro-duced by direct oxygen transfer to olefins by a variety of stoichiometric methods. Recently, considerable efforts have been made to conduct the transformations selectively under catalytic conditions. Because epoxides are reactive substances, they can undergo diverse transformations by reactions with acids and bases, and their reactivity has been exploited to form a diverse range of products by so-called click chemistry [85,86], which combines the breadth of combinatorial methods with the precise synthesis of organic chemistry. TABLE 1.2 Terpenic compounds: Epoxidation reactions and catalysts Reactant Catalyst and conditions References Limonene [PW 4 O 24 ] 3 -Amberlite IRA-900/H 2 O 2 ; 33 C, 1 atm, CH 3 CN solvent, 24 h; conv. 77%, select. 93% ( endo epoxide); 59% H 2 O 2 select., TOF ¼ 5.8 10 –4 s 1 [62,63] OH H Isopulegol Limonene Ti-MCM-41/H 2 O 2 ; 90 C, 1 atm, CH 3 CN solvent, 24 h. Limonene: conv. 59%; select. 90% ( endo ); TOF ¼ 3.1 10 –4 s 1 . Isopulegol: conv. 71%; select. 80%; TOF ¼ 3.3 10 –4 s 1 [55] OH H OH a -Terpineol Terpinen-4-ol Ti-MCM-41/H 2 O 2 ; 90 C, 1 atm, CH 3 CN solvent, 24 h. a -Terpineol: conv. 86%; select. 51%; TOF ¼ 2.6 10 –4 s 1 . Terpinen-4-ol: conv. 74%; select. 61%; TOF ¼ 2.7 10 –4 s 1 [55] OH H OH H Carveol Carvotanacetol Ti-MCM-41/H 2 O 2; 90 C, 1 atm, CH 3 CN solvent, 24 h. Carveol: conv. 78%; select. 73%; TOF ¼ 3.4 10 –4 s 1 . Carvotanacetol: conv. 84%; select. 64%; TOF ¼ 3.2 10 –4 s 1 [55] 10 S. Ted Oyama

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  Applications of Domino Transformations in Organic Synthesis, Volume 1

  • Prof. Scott A. Snyder(Author)
  • 2015(Publication Date)
  • Thieme

    (Publisher)

  1.2 Cation– ð Cyclizations of Epoxides and Polyepoxides K. W. Armbrust, T. Halkina, E. H. Kelley, S. Sittihan, and T. F. Jamison General Introduction Domino reactions of polyepoxides are of general interest for the synthesis of a variety of polycyclic ethers, including polyether ionophores, squalene-derived polyethers, and ma-rine ladder polyethers. [1] A number of biosynthetic hypotheses invoke polyepoxide cas-cades to rapidly generate complex polyethers; the two most cited are the Cane–Celmer– Westley and Nakanishi proposals. Respectively, these hypotheses account for the ob-served formation of all-exo and all-endo cascade products, borrowing terminology from Baldwin)s classification of ring-closing processes. [2–4] In general, smaller-ring products (formed by what is generally termed an exo pathway) are kinetically favored over larger-ring products ( endo ). That is, five-membered tetrahydrofuran rings form preferentially to their six-membered tetrahydropyran counterparts. Similarly, six-membered tetrahydro-pyrans form preferentially to seven-membered oxepane rings. A number of total synthe-ses have been inspired by these proposed cascades, and many creative methods have been developed to generate either exo or endo products in a selective fashion. The polyepoxide starting materials are often prepared via the powerful Sharpless and Shi asymmetric ep-oxidations of alkenes. [5,6] Complete transfer of stereochemical information is generally observed, as most epoxide openings proceed with stereospecific inversion of configura-tion. For the large majority of cascades discussed in this review, mechanistic details re-main unresolved, but most can nonetheless be categorized on the basis of how they are designed.

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