Epoxides mono-substituted

Slightly more exotic carbon-centered nucleophiles can also participate in the ring-optening of epoxides. For example, the vinyl metallate 81, prepared by the treatment of the alkenyl acetal 86 with Schlosser s reagent, attacks mono-substituted epoxides 82 at the C-2 position to give the labile homoallyl alcohols 83 in fair to very good yields <96TET1433>. 

The allyloxy and propargyloxy compounds are easily prepared by the opening of mono-substituted epoxides with sodium aryl tellurolates, followed by allylation and propargyla-tion of the obtained -hydroxytellurides, submitted to irradiation with a sun lamp in the presence of hexabutylditin, and suffer group-transfer cyclization under 5-exo-mode to give the 2,4-disubstituted tetrahydrofuran derivatives. ... 

Azidoalcohols (79, 81) can be accessed directly through the cerium-catalyzed addition of sodium azide onto mono-substituted epoxides. When the substituent is a simple alkyl or aryl group, nucleophilic attack at the more substituted epoxide carbon was observed i.e., 78 -> 79). However, when a phenoxy group was incorporated into the side chain (e.g., 80), a crossover to attack on the unsubstituted methylene carbon was encountered <99SC561>. 

Vandenberg, E. J. Organometallic Catalysts for Polymerising Mono-substituted Epoxides. J. Polymer Sci. 47, 486 (1960). 

Water conjugation Water Epoxide hydrolase (microsomes) Arene oxides, cis-disubstituted and mono-substituted oxiranes Benzopyrene 7,8-epoxide, styrene 1,2-oxide, carbamazepine epoxide... 

The analogy between this type of C-C disconnection and 1,2-diX disconnections was explained at the start of this chapter with compounds 5, 6 and 7. The epoxide route works particularly well if the epoxide is mono-substituted as the reaction with nucleophilic carbon should then be regioselective. Alcohol 53 is used in perfumery and can be disconnected 53a at the next-but-one bond to the alcohol group with the idea of using the epoxide 54 made from the but-l-ene. 

Varying degrees of substrate enantioselectivity have been described for microsomal epoxide hydrolases. For example, for benzo(a]pyrene-4,5-oxide a 40-fold difference between the rates of hydration for the +) and (-) enantiomers was observed in vitro (Armstrong et al., 1980). Mono-substituted epoxides (such as 1,2-epoxyhexane and its geometrical isomer. 

Under the usual conditions (THF or liquid ammonia as solvent), mono-substituted epoxides are attacked on the methylene carbon atom. The stereochemistry of the ring opening of vidnally di-substituted epoxides (e.g., epoxycyclohexane) is in accordance with an SN2-mechanism. 

Doubly substituted analogues of TS-1 have also been reported. Trong et al. (130) synthesized bifunctional molecular sieves with titanium and various trivalent ions, for example, Ti-MFI that also contained, Al, or Ga. Tin and vanadium have also been incorporated into the titanium silicalite structure (33,131) by a primary synthesis method. The incorporation of a second metal changes the redox properties of the materials as well as their morphology. Incorporation of tin into titanium silicalite improved the epoxidation selectivity of the catalyst compared with that of (mono-substituted) TS-1. 

Epoxides are alkylating agents in vivo being able to react with different nucleophihc centres of cellular macromolecules including proteins and DNA. DNA adducts in turn have shown considerable association with carcinogenic processes (Hemminki 1993, Hemminki et al. 1994). The specific DNA adducts induced by some mono-substituted epoxides were recently reviewed by Koskinen and PlnA (2000). In the rat, 600 ppm vaporised styrene inhaled for 12 h per day, 4 days per week for 4 weeks caused a severe outer hair cell loss and an increase of cytoplasmic vesiculation and vacuohsation, and abnormal mitochondria with disrupted cristae and formation of membrane-bound spherical bodies in the outer hair cells in the organ of Corti (Makitie et al. 2002). 

The epoxidation reaction works with many alkenes, but it is slow with mono-substituted (terminal) alkenes. Why do terminal alkenes react more slowly with peroxycarboxylic acids The reaction rate (Chapter 7, Section 7.11) of two alkenes can be examined in order to determine if one is a stronger Lewis base. As a rule, the alkene best able to donate electrons should undergo epoxidation faster if the Lewis acid-base analogy is correct. Alkyl groups are electron releasing, and more alkyl substituents on a C=C unit lead to greater electron density in the 7i-bond, which makes that alkene a stronger Lewis base. 

Koskinen M, Pina K (2000) Specific DNA adducts induced by some mono-substituted epoxides in vitro and in vivo. Chem Biol Interact 129(3) 209-229... 

The highest stereoselectivities are reached with disubstituted (Z) -alkenes (with ee-values up to 99%) as well as trisubstituted alkenes, whereas mono-substituted olefins are poorer substrates. Concerning the mechanism of the Jacobsen epoxidation (see Ref. [21]), asymmetric epoxidation of non-activated olefins can be performed with numerous other transition-metal catalysts [22]. 

Full mechanistic details of asymmetric epoxidation (AE) reactions can be found in a comprehensive review. The features of the transition state which leads to high enantioselectivities over such a wide range of allyl functions have been intensively studied, but it is arguably more instructive from a practical point of view to indicate the behaviour of some commonly encoim-tered substrates with this catalyst. Tri- and tetra-substituted allylic alcohols with their electron-rich double bonds react rapidly, even at -35 °C. 3-( )-Monosubstituted allylic alcohols also react rapidly (1-4 h, as in Protocol 1) while other mono-substitution patterns dramatically slow down the reaction (10-50 h), necessitating the use of cryostatic cooling units. These reactivity patterns are summarised in Scheme 1.2. 

One of the most significant discoveries in asymmetric catalysis is without question Jacobsen s kinetic resolution reaction of racemic mono-substituted epoxides with water [131] and other nucleophUes [32,131,132]. The Co-salen complex 142 provides reliable access to a wide range of terminal epoxides in exceptionally high optical purities (> 99 % ee), as well as the corresponding... 

In general, mono-substituted oxiranes (Fig. 1, Table 1) have been hydrolyzed by fungal and mammalian epoxide hydrolases with low to moderate enantioselectivity so far. It was only recently that red yeasts were identified as the biocatalysts of choice for these substrates. 

Small mono-substituted oxiranes bearing a halogen atom in its side chain such as compounds 1.2 and 1.3 have been hydrolyzed by mammalian and yeast epoxide hydrolases with very low enantioselectivity (E = 3 and 5.5, respectively). More recently, three red yeasts and one bacterial strain (Chryseomonas luteola [107]) have been reported to trans-... 

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