Linear aminopolyhydroxylated structures through rapid domino assembly of ahighly functionalized heterotricyclic system and its selective cleavage

This paper presents a new approach to linear aminopolyhydroxylated structur es, based on the rapid assembly of a highly functionalized heterotricyclic system and its cleavage. The complex tricyclic structure is obtained by a s equence of two mild tandem reactions: the first involves a base-promoted ni troaldol-intramolecular cyclization between an activated primary nitroalkan e 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-hydr oxy group was used as an anchor to link an olefinic residue (either an ally l group or a vinylsilane), which then gave rise to a spontaneous intramolec ular cycloaddition with the nitrone moiety of the 2-isoxazoline-2-oxide to afford a complex tricyclic structure, These two tandem processes could be c ondensed into a single three-component domino reaction, which starting from the three acyclic substrates realizes a big jump in molecular complexity t hrough the selective formation of five new bonds and four new chiral center s 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 th e cyclic silyl ether were found. In addition, during the early attempts of linearization of the tricyclic compounds, unexpected clean fragmentations o f the products were observed, some of them affording synthetically useful n ew products. An array of interesting linear aminopolyhydroxylated structure s was obtained by the combination of one or two cleavage steps from the tri cycle, with overall very good acyclic selectivity, efficiency, and atom eco nomy.