Abstract
Asymmetric processes, taking place via the intermediacy of chiral
oxonium ions arising from intramolecular haloetherification reactions
of chiral ene- and diene-acetals of optically pure C
2-symmetric
hydrobenzoine, have been developed. A novel, double intramolecular
haloetherification process was observed. The asymmetric reactions
developed in this effort were applied to the synthesis of several
natural products, including solenopsin A, (cis-6-methyltetrahydropyran-2-yl)acetic
acid, the pheromone of the wasp Paravespula
vulgaris, rubrenolide, rubrynolide, scyphostatin, cryptocaryone,
Sch 642305, and clavolonine. The strategies used in these syntheses
involved a new concept called ‘chiral auxiliary multiple-use
methodology’. In addition, intramolecular haloetherification
reactions of ene-acetals, derived from chiral optically pure norbornene
aldehydes and meso-diols, were applied
to asymmetric desymmetrization of meso-diols.
Finally, a new method for the resolution of racemic norbornene aldehydes,
utilizing chiral ene-acetal oxonium ion intermediates produced from
optically pure hydrobenzoin, was developed.
1 Introduction
2 Haloetherification of Ene-Acetals of Chiral Nonracemic Diols
2.1 Reactions of Ene-Acetals Leading to Asymmetric Synthesis of
1,4- and 1,5-Diols
2.2 Reactions of Ene-Ketals Containing Nucleophilic Functional
Groups
2.3 Applications to Natural Products Syntheses
2.3.1 Synthesis of the Wasp Paravespula
vulgaris Pheromone
3 Haloetherification of σ-Symmetric Diene-Acetals
3.1 Cyclic σ-Diene-Acetals
3.2 Double Iodoetherification Reactions of Acyclic Diene-Acetals
3.2.1 Acyclic Diene-Acetals
3.2.2 Acyclic Diene-Ketals
3.3 Natural Products Syntheses
3.3.1 Application of Double Intramolecular Haloetherification Reactions
of Acyclic Diene-Acetal to the Syntheses of Rubrenolide
and Rubrynolide
3.3.2 The Use of Cyclic Diene-Acetals
3.3.3 Chiral Auxiliary Multiple-Use Methodology as a New Concept
in Natural Products Synthesis
4 Reactions of the Ene-Acetals, Derived from Chiral Nonracemic
Ene-Aldehydes and a Non-Optically Active Diol
4.1 Asymmetric Desymmetrization of meso-1,2-Diols
4.2 Resolution of Racemic Norbornene Aldehydes
4.3 Asymmetric Desymmetrization of meso-1,3-
and -1,4-Diols
5 Conclusion
Key words
intramolecular reactions - acetals - asymmetric
synthesis - chiral auxiliaries - natural product
synthesis
