Twiddle, Steven John Robert (2005) The Stereoselective synthesis of polyene natural products. Doctoral thesis, Durham University.
A strategy for the stereocontrolled synthesis of polyene units was developed which centred around the chemistry of the vinyl boronate ester 4,4,6-trimethyl-2-vinyl-l,3,2- dioxaborinane 123. Reaction conditions have been developed to allow the Heck coupling of 123 with a range of aryl and alkenyl electrophiles. The reaction is promoted by cationic palladium species which can be generated through the addition of metal salts to the reaction mixture. Conversely conditions have also been developed which allows 123 to react exclusively at the boron functionality along the Suzuki-Miyaura pathway, the syntheses of a range of styrene and diene systems being demonstrated. Vinyl boronate 123 demonstrates complete chemoselectivity which is controlled by the reaction conditions employed. The alkenyl boronate esters, products of the Heck coupling of 123, can be converted to alkenyl iodides to produce the E- or Z-isomer with extremely high geometrical purity. This is done through an iododeboronation reaction involving ICI and NaOMe where the order of reagent addition determines the stereochemical outcome. Presented within is a detailed insight into the mechanistic intricacies of the transformations and the use of alternative and novel reagents such as pyridine-ICl for stereoselective iodo- and chlorodeboronation reactions is also demonstrated. This strategy was successfully applied to the syntheses of 1,6-diphenyl-1,3,5- . hexatrienes of varying alkene geometries 205-207, which were prepared from just iodobenzene and vinyl boronate 123 using those three key reactions. The use of this strategy also went some way to preparing the tetraene-containing natural product ixoric acid 124, although a total synthesis was not achieved during these studies. Research towards the first total synthesis of the natural product viridenomycin 125 was also conducted, especially towards the cyclopentenol core 246. An advanced intermediate cyclopentenone 248, was prepared from readily available starting materials along a succinct synthetic pathway to provide 248 in a good yield whilst expressing high diastereo- and enantioselectivity. Thus, a route was demonstrated which appears superior to those already existing in the literature.
|Item Type:||Thesis (Doctoral)|
|Award:||Doctor of Philosophy|
|Copyright:||Copyright of this thesis is held by the author|
|Deposited On:||09 Sep 2011 09:54|