RESUMO
A new approach to the tetracycline core structure is presented. The pivotal intermediate is identified as macrocycle III. The two interior bonds (C4a-C12a and C5a-C11a) are to be constructed through sequential transannular Michael additions (III-II) and compression-promoted transannular isoxazole alkylations from intermediate II.
Assuntos
Antibacterianos/síntese química , Produtos Biológicos/síntese química , Isoxazóis/química , Tetraciclina/síntese química , Alquilação , Antibacterianos/química , Antibacterianos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Ciclização , Estrutura Molecular , Tetraciclina/química , Tetraciclina/farmacologiaRESUMO
We document a copper-catalyzed, enantioselective, conjugate addition involving the direct use of a terminal acetylene, which undergoes in situ metalation. The addition reactions of phenylacetylene to Meldrum's acid derived acceptors take place in aqueous media, without recourse to inert atmosphere. The success of the enantioselective process was enabled by the use of a new class of conveniently accessed P,N-ligands, which we have termed PINAP. These modular ligands are responsive to numerous electronic and steric modifications that permit optimization of the reaction.
RESUMO
[reaction: see text] The conjugate addition of in situ generated zinc alkynylides is reported. The use of chiral, ephedrine derived acceptors provides access to enantiomerically enriched beta-alkynyl acids in good yields.
RESUMO
[reaction: see text] The enantioselective conjugate addition reaction of Et(2)Zn to Meldrum's acid derived acceptors, mediated by a catalyst formed from Cu(O(2)CCF(3))(2) and a phosphoramidite ligand, is reported. Adducts are obtained in useful yields and up to 94% ee.
RESUMO
We document that alkynyl copper reagents generated under aqueous conditions from terminal acetylenes, catalytic Cu(OAc)2, and sodium ascorbate undergo additions to Meldrum's acid-derived Michael acceptors at room temperature (Scheme 1). The additions are not only novel, but also constitute the first example of the conjugate addition reaction of an acetylide catalytic in copper.
