A Unified Approach to Carbocyclic Frameworks: DTDA Sequences in Total Synthesis

Abstract

[3]Dendralene is a small π-­rich hydrocarbon that is capable of taking part in a wide range of chemical reactions, not least of which is the diene transmissive Diels–Alder (DTDA) reaction sequence. Unfortunately, the synthesis of this molecule relies on highly toxic and commercially unavailable intermediates, namely chloroprene. Chapter 1 of this thesis details a new synthetic approach to [3]dendralene via a double cross coupling reaction beginning with 1,1-­‐‑ dichloroethylene and vinyl magnesium bromide. This work was extended to the synthesis of a variety of symmetrically substituted [3]dendralenes.

Chapter 2 details the exploration of the Diels–Alder reactivity of [3]dendralene. While there has been some experimental work examining [3]dendralene in DTDA sequences, these have tended to focus on symmetrical and highly reactive dienophiles. This chapter describes the use of unsymmetrical dienophiles, which are either cyclic or acyclic in nature. This enables the synthesis of a range of polycyclic frameworks in just two steps. Through this methodology, the synthesis of bicyclic, linear tricyclic, angular tricyclic and angular tetracyclic structures is possible.

The angular tetracyclic framework mentioned above is present in a number of natural products, including marine sponge derived compounds xestoquinone and halenaquinone. Chapter 3 presents a comprehensive review into previous syntheses of these two natural products as well as briefly examining work towards related natural products.

Finally, Chapter 4 details our attempts to apply a DTDA reaction sequence beginning with [3]dendralene to the total synthesis of the natural product xestoquinone. [3]dendralene was reacted sequentially with two carbocyclic dienophiles before a series of functional group manipulations led to an advanced precursor of the targeted natural product.