Double-activation method

The first synthesis of enterobactin, a microbial chelator and transporter of environmental iron, was accomplished by the coupling of three protected L-serine units and macrocyclization by the double activation method. 

The l ,J -DBFOX/Ph-transition metal aqua complex catalysts should be suitable for the further applications to conjugate addition reactions of carbon nucleophiles [90-92]. What we challenged is the double activation method as a new methodology of catalyzed asymmetric reactions. Therein donor and acceptor molecules are both activated by achiral Lewis amines and chiral Lewis acids, respectively the chiral Lewis acid catalysts used in this reaction are J ,J -DBFOX/Ph-transition metal aqua complexes. 

We employed malononitrile and l-crotonoyl-3,5-dimethylpyrazole as donor and acceptor molecules, respectively. We have found that this reaction at room temperature in chloroform can be effectively catalyzed by the J ,J -DBFOX/Ph-nick-el(II) and -zinc(II) complexes in the absence of Lewis bases leading to l-(4,4-dicya-no-3-methylbutanoyl)-3,5-dimethylpyrazole in a good chemical yield and enantio-selectivity (Scheme 7.47). However, copper(II), iron(II), and titanium complexes were not effective at all, either the catalytic activity or the enantioselectivity being not sufficient. With the J ,J -DBFOX/Ph-nickel(II) aqua complex in hand as the most reactive catalyst, we then investigated the double activation method by using this catalyst. 

Macrolactonization of CD-hydroxyl-acid using 2,2 -dipyridyl disulfide. Also known as Corey-Nicolaou double activation method. 

Method 2. Corey s double activation method for lactone formation is patterned after Mukaiyama s procedure for peptide formation and involves refluxing a solution of the 2-pyridinethiol ester of a hydroxy acid in a high-boiling solvent for a prolonged period of time.6... 

This double activation method has been successfully used in numerous syntheses of complex natural products [7]. Plata and Kallmerten [16] claimed that this procedure was the most reliable one examined for effecting macrocyclization in the synthesis of the naturally occuring antibiotic ( + )-18-deoxynargenicin (18). 

Corey, E. J., Brunelle, D. J. New Reagents for Conversion of Hydroxy-Acids to Macrolactones by Double Activation Method. Tetrahedron Lett. 1976, 17, 3409-3412. 

Itoh, K. and Kanemasa, S. (2002) Enantioselective Michael additions of nitromethane by a catal3ftic double activation method using chiral Lewis acid and chiral atitine catalysts. Journal of the American Chemical Society, 124, 13394—13395 Itoh, K., Oderaotoshi, Y. and Kanemasa, S. (2003) Enantioselective Michael addition reactions of malononitrile catalysed by chiral Lewis acid and achiral antine catalysts. Tetrahedron Asymmetry, 14, 635 39. 

The double activation method has been used for synthesis of the natural macrolidc (4) from Cciilia/oxporiiiin reci/ei. ... 

Some new methods for the formation of macrolides have also come to light. An alternative double activation method is the reaction between the usual hydroxy-acid precursors and NN-dimethylformamide dineopentylacetal, affording intermediates of type (113) which cyclize as shown.Yields for n = 10—16 are in the range 40—50%, the remainder of the substrate ending up as cyclic oligomers. Trost and Verhoeven have developed a route to macrolides in which the ring-closure step is a C—C bond formation by intramolecular attack of an ester enolate on a 7r-allyl-palladium complex (viz. 114) prepared from an allylic acetate and Pd(PPh3)4. ... 

Cyanuric chloride can be used to lactonise o)-hydroxy-acids in yields that are comparable with the various double-activation methods. The reagent is very cheap, and the reactions can be carried out using only moderately high dilutions (10 mMol of acid in 100 ml of acetone). An alternative double-activation method... 

Alternatives to the established double activation method for the lactonization of >-hydroxy-acids via 2-pyridyl thioesters are use of the more reactive 4-(2-amino-6-methyl)pyrimidyl analogues " or mixtures of 2-chloro-6-methyl-l,3-diphenylpyridinium tetrafluoroborate, 2,6-dimethylpyridine, and benzyl-triethylammonium chloride in refluxing 1,2-dichloroethane. ... 

Chen F-X, Zhou H, Liu X, Qin B, Feng X, Zhang G, Jiang Y (2004) Enantioselective cyanosilylation of ketones by a catalytic double-activation method with an aluminum complex and an N-oxide. Chem Eur J 10 4790-4797... 

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