This paper presents a new approach to linear aminopolyhydroxylated structures, based on the rapid assembly of a highly functionalized heterotricyclic system and its cleavage. The complex tricyclic structure is obtained by a sequence of two mild tandem reactions: the first involves a base-promoted nitroaldol-intramolecular cyclization between an activated primary nitroalkane and an aldehyde bearing a leaving group on the alpha-carbon atom to give 4-hydroxy-2-isoxazolines-2-oxides. In the second tandem process, the 4-hydroxy group was used as an anchor to link an olefinic residue (either an allyl group or a vinylsilane), which then gave rise to a spontaneous intramolecular cycloaddition with the nitrone moiety of the 2-isoxazoline-2-oxide to afford a complex tricyclic structure, These two tandem processes could be condensed into a single three-component domino reaction, which starting from the three acyclic substrates realizes a big jump in molecular complexity through the selective formation of five new bonds and four new chiral centers all concerted as a dynamic continuum in which every event depends on all the others, The second part of this project dealt with the cleavage of the tricyclic structure to unmask the target linear compounds, The richness of functionalities that were selectively installed on the tricyclic structures was screened for possible cleavages. Methods to reduce the exocyclic ester group, hydrogenolyse the bicyclic nitroso acetal, and hydroxydesylilate the cyclic silyl ether were found. In addition, during the early attempts of linearization of the tricyclic compounds, unexpected clean fragmentations of the products were observed, some of them affording synthetically useful new products. An array of interesting linear aminopolyhydroxylated structures was obtained by the combination of one or two cleavage steps from the tricycle, with overall very good acyclic selectivity, efficiency, and atom economy.
Righi, P., Marotta, E., Rosini, G. (1998). Linear aminopolyhydroxylated structures through rapid domino assembly of a highly functionalized heterotricyclic system and its selective cleavage. CHEMISTRY-A EUROPEAN JOURNAL, 4(12), 2501-2512 [10.1002/(SICI)1521-3765(19981204)4:12<2501::AID-CHEM2501>3.3.CO;2-9].
Linear aminopolyhydroxylated structures through rapid domino assembly of a highly functionalized heterotricyclic system and its selective cleavage
Righi, P;Marotta, E;Rosini, G
1998
Abstract
This paper presents a new approach to linear aminopolyhydroxylated structures, based on the rapid assembly of a highly functionalized heterotricyclic system and its cleavage. The complex tricyclic structure is obtained by a sequence of two mild tandem reactions: the first involves a base-promoted nitroaldol-intramolecular cyclization between an activated primary nitroalkane and an aldehyde bearing a leaving group on the alpha-carbon atom to give 4-hydroxy-2-isoxazolines-2-oxides. In the second tandem process, the 4-hydroxy group was used as an anchor to link an olefinic residue (either an allyl group or a vinylsilane), which then gave rise to a spontaneous intramolecular cycloaddition with the nitrone moiety of the 2-isoxazoline-2-oxide to afford a complex tricyclic structure, These two tandem processes could be condensed into a single three-component domino reaction, which starting from the three acyclic substrates realizes a big jump in molecular complexity through the selective formation of five new bonds and four new chiral centers all concerted as a dynamic continuum in which every event depends on all the others, The second part of this project dealt with the cleavage of the tricyclic structure to unmask the target linear compounds, The richness of functionalities that were selectively installed on the tricyclic structures was screened for possible cleavages. Methods to reduce the exocyclic ester group, hydrogenolyse the bicyclic nitroso acetal, and hydroxydesylilate the cyclic silyl ether were found. In addition, during the early attempts of linearization of the tricyclic compounds, unexpected clean fragmentations of the products were observed, some of them affording synthetically useful new products. An array of interesting linear aminopolyhydroxylated structures was obtained by the combination of one or two cleavage steps from the tricycle, with overall very good acyclic selectivity, efficiency, and atom economy.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
