Showing papers by "Leo A. Paquette published in 2003"
TL;DR: The convergent, stereocontrolled synthesis of enantiopure stereoisomeric 9,10-cyclic acetals, whose designed role was to serve as potential precursors to Taxol, is reported and isomerization was sufficiently rapid that oxygenation at C2 was now precluded.
Abstract: The convergent, stereocontrolled synthesis of enantiopure stereoisomeric 9,10-cyclic acetals, whose designed role was to serve as potential precursors to Taxol, is reported. These advanced intermediates are multiply functionalized and carry a bridgehead α-ketol array which was key to isomerization into the proper framework. In agreement with relative strain energy values obtained by MM3 calculations, a dichotomy was observed between these two families. While the trans-fused acetals failed to undergo bridge migration, their cis counterparts did so efficiently. In fact, isomerization was sufficiently rapid that oxygenation at C2 was now precluded. The operation of several unusual transannular hydride shifts is also detailed.
33 citations
TL;DR: Methodology based on the concept of thionium ion-initiated pinacolic ring expansion has been developed for accessing C4'-spirocyclic thionucleosides and absolute configurational assignments have been made possible by X-ray crystallography.
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.
26 citations
Book•
01 Jan 2003
TL;DR: In this paper, the authors present a review of organic synthesis procedures featuring Chiral, Non-Racemic Reagent Preparation, and a Reagent Formula Index, with a discussion of the most relevant papers.
Abstract: Preface. Introduction. Recent Review Articles and Monographs. Organic Synthesis Procedures Featuring Chiral, Non-Racemic Reagent Preparation. List of Contributors. Reagent Formula Index. Subject Index.
21 citations
TL;DR: 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.
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.
21 citations
TL;DR: The feasibility of the title reaction has been pursued for the purpose of advancing a concise total synthesis of Taxol as discussed by the authors, and the reaction sequence associated with arrival at taxane 18 is short (15 steps from a d-camphor derivative) and notably efficient.
Abstract: The feasibility of the title reaction has been pursued for the purpose of advancing a concise total synthesis of Taxol. Of the two closely related series examined, the first featured an exo-methylene group at C4. The second consisted of an α-epoxide at that site. Strikingly, the olefinic construct proved inert to attempted α-ketol rearrangement. In contrast, the oxiranyl derivative isomerized smoothly. The reaction sequence associated with arrival at taxane 18 is short (15 steps from a d-camphor derivative) and notably efficient. The thermodynamic issues that are raised by this investigation have been clarified by an assessment of molecular mechanics-derived (MM3) steric energy calculations.
14 citations
TL;DR: Tangential features of the route outlined herein include specific rearrangement reactions and a retro-aldol cleavage of ring A that provides for the convenient implementation of additional hydroxyl groups ultimately conducive to intramolecular S(N)2 reaction.
Abstract: An oxetane D-ring has been fused to the framework of the highly functionalized taxane 2. The synthetic route is based on a trimethylsilyl triflate-promoted epoxide-opening step, followed by stereocontrolled, regioreversed oxirane formation and reductive transposition of this intermediate with bis(cyclopentadienyl)titanium(III) chloride. This last key step provides for the convenient implementation of additional hydroxyl groups ultimately conducive to intramolecular SN2 reaction. Tangential features of the route outlined herein include specific rearrangement reactions and a retro-aldol cleavage of ring A.
13 citations
TL;DR: The rho value for the composite aromatic derivatives (R = p-XC(6)H(4)-) differs from that of the aliphatic series, although both are negative because electron-donating groups accelerate the reaction.
6 citations
TL;DR: In this paper, the convergent, stereocontrolled synthesis of enantiopure stereoisomeric 9,10-cyclic acetals, whose designed role was to serve as potential precursors to Taxol, is reported.
Abstract: The convergent, stereocontrolled synthesis of enantiopure stereoisomeric 9,10-cyclic acetals, whose designed role was to serve as potential precursors to Taxol, is reported. These advanced intermediates are multiply functionalized and carry a bridgehead α-ketol array which was key to isomerization into the proper framework. In agreement with relative strain energy values obtained by MM3 calculations, a dichotomy was observed between these two families. While the trans-fused acetals failed to undergo bridge migration, their cis counterparts did so efficiently. In fact, isomerization was sufficiently rapid that oxygenation at C2 was now precluded. The operation of several unusual transannular hydride shifts is also detailed.
1 citations
TL;DR: The feasibility of the title reaction has been pursued for the purpose of advancing a concise total synthesis of Taxol as mentioned in this paper, and the reaction sequence associated with arrival at taxane 18 is short (15 steps from a d-camphor derivative) and notably efficient.
Abstract: The feasibility of the title reaction has been pursued for the purpose of advancing a concise total synthesis of Taxol. Of the two closely related series examined, the first featured an exo-methylene group at C4. The second consisted of an α-epoxide at that site. Strikingly, the olefinic construct proved inert to attempted α-ketol rearrangement. In contrast, the oxiranyl derivative isomerized smoothly. The reaction sequence associated with arrival at taxane 18 is short (15 steps from a d-camphor derivative) and notably efficient. The thermodynamic issues that are raised by this investigation have been clarified by an assessment of molecular mechanics-derived (MM3) steric energy calculations.
TL;DR: In this paper, the kinetic responses of nine compounds of type 6 to ring-closing metathesis as promoted by 2 to give the identical product 7 were described and subjected to Hammett analysis.
Abstract: This report details the kinetic responses of nine compounds of type 6 to ring-closing metathesis as promoted by 2 to give the identical product 7. The experimental observations have been subjected to Hammett analysis. The ρ value for the composite aromatic derivatives (R = p-XC6H4−) differs from that of the aliphatic series, although both are negative because electron-donating groups accelerate the reaction.
TL;DR: In this paper, an oxetane D-ring has been fused to the framework of the highly functionalized taxane 2 and a synthetic route is based on a trimethylsilyl triflate-promoted epoxide-opening step, followed by stereocontrolled, regioreversed oxirane formation and reductive transposition of this intermediate with bis(cyclopentadienyl)titanium(III) chloride.
Abstract: An oxetane D-ring has been fused to the framework of the highly functionalized taxane 2. The synthetic route is based on a trimethylsilyl triflate-promoted epoxide-opening step, followed by stereocontrolled, regioreversed oxirane formation and reductive transposition of this intermediate with bis(cyclopentadienyl)titanium(III) chloride. This last key step provides for the convenient implementation of additional hydroxyl groups ultimately conducive to intramolecular SN2 reaction. Tangential features of the route outlined herein include specific rearrangement reactions and a retro-aldol cleavage of ring A.