Showing papers by "Leo A. Paquette published in 2004"

Synthesis of Stereoisomeric Medium-Ring α,α‘-Dihydroxy Cycloalkanones

Abstract: The stereochemical course of the epoxidation of the silyl enol ethers of 2-tert-butyldimethylsilyloxycycloheptanone and -cyclooctanone has been investigated and shown to proceed exclusively anti to the existing α-substituent. 2-(Benzyloxy)cyclooctanone behaves similarly, and the presence of a transannular double bond does not alter the outcome. α-Ketol rearrangements are seen to operate during ensuing fluoride ion-induced removal of the silyl protecting groups in select examples. The preferred means for generating the cis isomers of the α,α‘-dihydroxy cycloalkanones involves methylenation of the monoprotected trans-dihydroxy ketones with the Nysted reagent, followed by oxidation and subsequent reduction with sodium borohydride. Ozonolysis and fluoride ion-induced desilylation complete the route.

Mono- and Bis-Acrolein Derivatives by Reliable and Efficient One-Step Methylenation of Aldehyde Precursors

Abstract: A series of aldehydes carrying different functional groups was transformed directly into the α-methylene derivatives. Dialdehydes behaved comparably at both active sites. When keto aldehydes are involved, excellent levelsof chemoselectivity are ob served, with the ketone substructures exhibiting no sign of reactivi ty.

C4′-Spiroalkylated Nucleosides Having Sulfur Incorporated at the Apex Position.

Abstract: Methodology based on the concept of thionium ion-initiated pinacolic ring expansion has been developed for accessing C4'-spirocyclic thionucleosides. The readily available racemic ketones 6 and 37 are conveniently resolved via their acetals with (R)-mandelic acid. Subsequent reactions beginning with utilization of the Pummerer rearrangement lend themselves to functionalization of the spirocyclic core and ultimately incorporation of the nucleosidic bases. Limitations to this strategy are pointed out. Acquisition of the alpha- and beta-isomers at C4' is equally facile. Absolute configurational assignments have been made possible by X-ray crystallography.

Synthesis of Stereoisomeric Medium‐Ring α,α′‐Dihydroxy Cycloalkanones.

Abstract: The stereochemical course of the epoxidation of the silyl enol ethers of 2-tert-butyldimethylsilyloxycycloheptanone and -cyclooctanone has been investigated and shown to proceed exclusively anti to the existing α-substituent. 2-(Benzyloxy)cyclooctanone behaves similarly, and the presence of a transannular double bond does not alter the outcome. α-Ketol rearrangements are seen to operate during ensuing fluoride ion-induced removal of the silyl protecting groups in select examples. The preferred means for generating the cis isomers of the α,α‘-dihydroxy cycloalkanones involves methylenation of the monoprotected trans-dihydroxy ketones with the Nysted reagent, followed by oxidation and subsequent reduction with sodium borohydride. Ozonolysis and fluoride ion-induced desilylation complete the route.

Conformational Restriction of Nucleosides by Spirocyclic Annulation at C4′ Including Synthesis of the Complementary Dideoxy and Didehydrodideoxy Analogues.

Abstract: The concept of spirocyclic restriction, when generically applied to nucleoside mimics, allows for the preparation of diastereomeric pairs carrying either a syn- or anti-oriented hydroxyl at C-5'. Reported herein are convenient synthetic routes to enantiomerically pure 1-oxaspiro[4.4]nonanes featuring fully dihydroxylated end products as well as congeners having dideoxy and didehydrodideoxy substitution patterns. Notable use is made of the capacity for introducing unsaturation in the furanose sector via phenylsulfenylation and the incorporation of uracil and thymine by way of their silylated derivatives under catalysis with stannic chloride.