The double [3 + 2] photocycloaddition reaction.

Abstract

A remarkable double [3 + 2] photocycloaddition reaction that results in the formation of fenestrane 2 from aromatic acetal 1 is reported. During the formation of 2, four carbon-carbon bonds, five new rings, and seven new stereocenters are created in a one-pot process. The reaction occurs in a sequential manner from the linear meta photocycloadduct 3, while the angular meta photocycloadduct 4 undergoes an alternative fragmentation-translocation photoreaction to afford angular tricycle 6.

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The Double [3+2]
Photocycloaddition Reaction




Jason A. Woolford













Submitted to the University of Sussex in part fulfilment of the requirements of the degree of
Doctor of Philosophy, September 2010

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Declaration

I hereby declare that this thesis has not been submitted in whole or in part form for the award of
another degree.

Signed


Jason Antony Woolford

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UNIVERSITY OF SUSSEX
JASON ANTONY WOOLFORD
DOCTOR OF PHILOSOPHY OF CHEMISTRY
THE DOUBLE [3+2] PHOTOCYCLOADDITION REACTION
SUMMARY

One of a synthetic organic chemists‟ greatest challenges is to create step-efficient routes toward
compounds with high molecular complexity. Therefore, reactions such as the meta
photocycloaddition of an olefin to a benzene derivative, which provide more than one bond in a
single step are of significant importance. It this remarkable reaction three new σ bonds, three
new rings and up to six new stereocenters are formed simultaneously. Additional complexity
can be added by tethering the two reacting partners together and this form of the reaction has
found many uses in natural product synthesis.

In this work a remarkable double [3+2] photocycloaddition reaction is reported that results in
the formation of a complex cis, cis, cis, trans-[5, 5, 5, 5] fenestrane derivative from a simple flat
aromatic acetal with two branching alkenes. During this dramatic transformation four carbon-
carbon bonds, five new rings and seven new stereocenters are created in a single one-pot
process using only UV light. The reaction occurs in a sequential manner from the linear meta
photocycloadduct, via a secondary [3+2] addition of the alkene across the cyclopropane of the
adduct. In addition, an angular meta photocycloadduct also produced in the initial addition step,
undergoes an alternative fragmentation-translocation photoreaction to afford a silphinene-like
angular tricyclic compound.

In this work the investigation of this newly discovered process is discussed via the synthesis and
subsequent irradiation of a series of photosubstrates containing different functional groups in
the arene-alkene tether. In addition, attempts toward the synthesis of alternative structures using
the same double [3+2] photocycloaddition are reported.

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Contents

Acknowledgments
Abstract
Abbreviations
1 Introduction and background 1
1.1 The Step economy 1
1.2 The arene-alkene meta photocycloaddition 4
1.2.1 Introduction: photocycloaddition of an alkene to a benzene
derivative 4
1.2.2 Mechanism of the meta photocycloaddition reaction 10
1.2.3 Regio- and stereoselectivity issues 13
1.2.4 The importance of tether length 18
1.2.5 Reactions of meta photocycloadducts and their use in natural
product synthesis 20
1.3 Previous Penkett group studies: Palladium catalysed reactions of
meta photocycloadducts 26
2 Discovery of the double [3+2] photocycloaddition 30
2.1 Introduction: Original aim 30
2.2 Preliminary studies 32
2.3 Discovery of the double [3+2] photocycloaddition and structural
elucidation 40
3 A brief discussion on fenestranes 47
3.1 Introduction 47
3.2 Synthesis of fenestranes 49
3.3 Naturally occurring fenestranes 53
4 Investigation of the double [3+2] photocycloaddition reaction for the
synthesis of fenestranes 56