Nucleophiles epoxides ring opening with

In addition, the GMA/EDMA copolymer proved to serve as a basic unit for the fabrication of highly permeable bioreactors in capillary format. Trypsin immobilization after epoxide ring opening with diethylamine and attachment of glutaraldehyde is mentioned as the probably most prominent example [64], The immobilization of trypsin was also carried out using another class of reactive monolithic methacrylate polymer, which is based on 2-vinyl-4,4-dimethylazlactone, acrylamide, and ethylene dimethacrylate [65]. In contrast to GMA/EDMA, trypsin can directly be immobilized onto this kind of monolith, as the 2-vinyl-4,4-dimethylazlactone moieties smoothly react with weak nucleophils even at room temperature. 

The [Mn(salen)]-catalyzed epoxidation of chromene derivatives was discovered to occur with exceptional enantioselectivity [74]. Chromene derivatives bearing 2,2-disubstitution appear to combine all the important substrate characteristics required for a highly enantioselective epoxidation. The synthetic utility of the enantioenriched epoxychroman products is increased by the predictable regio- and stereochemical outcome of epoxide ring opening with a variety of nucleophiles. These two features were highlighted in the synthesis of the selective potassium channel activator BRL 55834 [78]. Catalyst loadings as low as... 

Racemic epoxide 40 was first transformed into p-dimethylamino alcohol 41 by nucleophilic epoxide ring opening. Treatment of this racemic mixture (1.0 mol equiv.) with ( + )-DIPT (1.2 mol equiv.),Ti(OPr-i)4 (2.0 mol equiv.), and t-BuOOH (0.6 mol equiv.) allowed to obtain N-oxide 42 and to recover the unreacted (,S)-enantiomer of 41 in 56% yield and 92% e.e. Standard manipulations of this material including /V-methylation, epoxide formation, and addition of isopropylamine, gave ( )-43. 

Functional groups were selectively introduced at the C-2 position of isophorone via epoxide ring-opening with several nucleophiles obtained from active methylene groups. Different behavior was observed depending on the reaction conditions and the nature of nucleophilic agents [68]. The best experimental systems involved... 

MECHANISM 14.5 EPOXIDE RING OPENING WITH A STRONG NUCLEOPHILE... 

The fact that a strong base can be used to pull an H off an 5/7-hybridized carbon is another wrinkle that will be explored in upcoming activities. As a preview, note that the resulting acetylide anion is a carbon nucleophile that can be combined with carbon electrophiles to make a wide range of carbon-carbon bonds. The only example of this we have discussed so far is nucleophilic epoxide ring opening. 

Epoxides provide another useful a -synthon. Nucleophilic ring opening with dianions of carboxylic acids (P.L. Creger, 1972) leads to y-hydroxy carboxylic acids or y-lactones. Addition of imidoester anions to epoxides yields y-hydroxyaldehyde derivatives after reduction (H.W. Adickes, 1969). 

The experimental observations combine with the principles of nucleophilic substi tution to give the picture of epoxide ring opening shown m Figure 16 5 The nucleophile attacks the less crowded carbon from the side opposite the carbon-oxygen bond Bond... 

Primary cycloaUphatic amines react with phosgene to form isocyanates. Reaction of isocyanates with primary and secondary amines forms ureas. Dehydration of ureas or dehydrosulfuri2ation of thioureas results in carhodiimides. The nucleophilicity that deterrnines rapid amine reactivity with acid chlorides and isocyanates also promotes epoxide ring opening to form hydroxyalkyl- and dihydroxyalkylaniines. Michael addition to acrylonitrile yields stable cyanoethylcycloalkylarnines. 

Epoxidation of the simplest allylic alcohol, allyl alcohol 7, is achieved in 88-92% ee with yields of 50-60% using diisopropyl tartrate as ligand. In situ derivatization of the product glycidol 8 via esterification, sulfonylation, or ring opening with nucleophile is an attractive alternative to isolating glycidol. 

Ring-opening with heteroatomic nucleophiles is certainly among the most thoroughly studied behavior of epoxides, and this reaction continues to be a versatile workhorse of synthetic utility. This is exemplified in the recent literature by the examples of the p-cyclodextrin-catalyzed aminolysis of simple epoxides by aniline derivatives (i.e., 53 - 54) <00SL339> and the synthesis of oxa-azacrown ethers through the treatment of Ws-epoxides 55 with diamines 56. Yields in the latter synthesis are sensitive to the size of the macrocycle and substitution on the bis-epoxide <00TL1019>. 

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