Direct alkynylation of bridgehead halides with silver acetylides and Towards the Total Synthesis of trans-Crotonin

Rebecca Pouwer (2007). Direct alkynylation of bridgehead halides with silver acetylides and Towards the Total Synthesis of trans-Crotonin PhD Thesis, School of Chemistry and Molecular Biosciences, The University of Queensland.

       
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Author Rebecca Pouwer
Thesis Title Direct alkynylation of bridgehead halides with silver acetylides and Towards the Total Synthesis of trans-Crotonin
School, Centre or Institute School of Chemistry and Molecular Biosciences
Institution The University of Queensland
Publication date 2007-09
Thesis type PhD Thesis
Supervisor Blanchfield, Joanne T.
Williams, Craig
Subjects 03 Chemical Sciences
Abstract/Summary Direct acetylenic carbon¬carbon bond formation at the bridgehead position of bicyclic cages is an area of synthetic methodology increasingly in demand, fuelled by the rapidly growing field of nanotechnology. Not surprisingly, however, this type of direct methodology is poorly represented in the chemical literature. Investigation was therefore initiated into developing selective bridgehead alkynylation methodology, with a wide range of functional group tolerance, utilising stable reagents. As a result, silver(I) acetylides were found to facilitate direct carbon-carbon bond formation at the bridgehead position of 1¬haloadamantanes, and in some instances related systems such as carborate anions and bicyclo[2.2.2]octanes. A range of aryl silver(I) acetylides were found to effect bridgehead alkynylation in 1iodoadamantane with yields ranging between 20–68%. Alkyl silver(I) acetylides reacted with 1iodoadamantane with yields ranging between 25–42% yield, and generally required high temperatures for reaction. Studies into the mechanism of this novel reaction have revealed both an ionic and a radical component to be active. A novel approach towards the total synthesis of the clerodane diterpenoid transCrotonin, and a number of structurally related compounds, is described. Rather than conform to the traditional synthetic strategies employed in the synthesis of clerodane diterpenoids, an innovative approach to the construction of the decalin core with a C12furan substituted C9 spiroȖlactone was developed employing a 6ʌ electrocyclisation reaction of Į2,4,6hexatrienyl Ȗbutyrolactones. These novel trienes were synthesized in good yield via a Sonogashira/partial hydrogenation protocol, and were found to cyclise in good to excellent yield under microwave irradiation. Furthermore, 2,4,6hexatrienyl substituted esters were synthesised in good to excellent yield via a novel vinyl telluriumtin exchange/Stille protocol. These novel trienes were found to cyclise in good to excellent yield under microwave irradiation. Manipulations of this core have led to the synthesis of an advanced intermediate in the total synthesis of epitransCrotonin. A Diels-Alder approach to the construction of the decalin core with a C12furan substituted C9 spiroȖlactone is also described.

 
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