Thiopyran route to polypropionates : simultaneous-two directional and enantiotopic group selective aldol reactions
Akinnusi, Olukayode T
The sequential aldol reactions of thiopyran derivatives 112 and 119 to rapidly generate hexapropionate building blocks in two carbon-carbon forming steps has been well studied within the Ward group. An extension of this strategy to generate non-racemic tetra- and hexapropionate fragments involved the use of non-racemic 119 which was obtained via resolution of the acid derivate 131. Part of the present work concerns the preparation of non-racemic 119 via enantioselective protonation of various thiopyran based ester derivatives. The trend observed in the ee obtained for the various ester derivatives is consistent with what has been previously observed by other groups. Section 2.3 discusses the use of β-ketocarbonyl analogues of thiopyranone in vinylogous aldol reactions. A β-ketocarbonyl analogue was prepared and shown to undergo stereoselective aldol reactions under previously established condtions. The stereoselectivities of the reactions were in all cases consistent with what has been previously observed for the aldol reactions of 112 and 119 within the group. Section 2.4 discusses the preparation of a meso dialdehyde derivative of thiopyranone (196) and it’s use in a simultaneouse two directional aldol reaction to generate a hexapropionate building block with six stereocenters in a one pot reaction. The meso adduct 202as generated was successfully desymmetrized via enantioselective enolization to afford an enantioenriched adduct with seven stereogenic centers. The meso dialdehyde 196 was also desymmetrized via an enantiotopic group selective aldol reaction promoted with (S)-proline. This reaction proceeds via a dynamic kinetic and thermodynamic resolution to afford a single stereoisomer. The enantioenriched aldol adduct was converted to a tetrapropionate unit and also demonstrated after derivatization to undergo a second aldol reaction affording a non-racemic hexapropionate synthon. This chemistry is discussed in section 2.5. Section 2.6 discuses the assignment of the relative and absolute configurations of the various aldol adducts via NMR and X-ray. To demonstrate the synthetic usefulness of this research, the hexapropionate synthon 202as was used as a template towards the confirmation or reassignment of the core spiroketal structure reported for enteridic acid.
DegreeDoctor of Philosophy (Ph.D.)
SupervisorWard, Dale E.
CommitteeReid, R. Stephen; Majewski, Marek
Copyright DateJune 2006