Synthesis And Hetero-Diels-Alder Reation Of Dendralenes

Abstract

Dendralenes are a family of cross-conjugated hydrocarbons that are garnering significant interest due to their potential to undergo diene-transmissive (DT) Diels-Alder (DA) sequences hence rapidly generate fused polycycles. However, despite the boom in publications of dendralenes, most of the published dendralenic studies are limited to carbo-dienophiles and the practical access to higher dendralenes is limited. Described herein are projects addressing these two aspects. This thesis depicts the contributions we made in hetero-Diels-Alder reactions of [3]dendralenes and general synthesis methods towards [4]dendralenes.

Chapter 1 focuses on an general introduction to Chapters 2 to 4.

Chapter 2 describes the first enantioselective oxa-Diels-Alder reactions between substituted and unsubstituted [3]dendralenes with phenylglyoxal to construct dihydropyran motifs with a palladium(II) cationic catalyst. This method also shows divergent regioselectivity for different substituted [3]dendralenes. Performing this process in a diene-transmissive sequence reveals a rapid, step- and atom-economic method to obtain either hydroisochromene or regioisometic hydropyranopyran polycycles from [3]dendralenes. The removal of the phenylglyoxal-derived benzoyl group from oxa-Diels-Alder reaction adduct accomplishes an enantioselective formal [4+2]cycloaddtion of CO2 to dendralenes.

Chapter 3 explores the aza-Diels-Alder reactions of substituted [3]dendralenes. A variety of imines are found to react well with substituted [3]dendralenes in this process and regioselectivity is witnessed. A curious E/Z isomerisation of the non-reacting olefin form the dendralenes reveals the step-wise cycloaddition mechanism. The aza-Diels-Alder adducts are shown to react with different carbo-dienophiles to form hydroisoquinoline heterocycles, which are the central skeletons of a variety of natural products and bioactive compounds.

Chapter 4 investigates a general synthesis of substituted [4]dendralenes involving two-fold Suzuki-Miyaura cross-coupling of a 2-butyne-1,4-diol derivative with an alkenyl boronic ester. This method enables a significant extension of available substitution patterns of [4]dendralenes. By changing the Pd(0) source and ligands, the first catalyst-controlled formation of both E- and Z-diastereomers at the internal olefins of [4]dendralenes is accomplished. The first site selective [4+2] cycloaddition to [4]dendralenes has also been achieved.

Chapter 5 summarises the work described in this thesis and discusses possible future work. Show more