A Route to Carbasugar Analogues - Jonathan Clayden - The ...

Chapter 1: Introduction
diastereomeric excess; this is believed to be formed due to the disruption of chelate 14,
allowing the diastereomeric product to be formed.
The methoxy group serves two purposes; firstly an ortho-substituent is essential to
desymmetrise the enolate intermediate, and secondly it participates in the internal
chelate 14. This was demonstrated by replacement of the methoxy group with a
methyl one, giving the thermodynamic diastereomer related to diene 16. The
replacement of the prolinol methoxy has minimal effect, showing that it plays no
significant role. 11 Reduction products 15 and 16 are amenable to a wide range of
functional group manipulations; the diene portion may be further reduced or
functionalised, whilst removal of the auxiliary permits facile lactonisation.
Pioneering work on the asymmetric Birch reduction of aromatic heterocycles has also
been performed in the laboratories of Donohoe, however this is outside of the scope of
this survey. 12
1.3 Nucleophilic Dearomatisation without Heavy Metals
Unlike the electrophilic Birch reduction, nucleophilic dearomatisation permits the
concomitant nucleophilic and electrophilic functionalisation of an aromatic system,
allowing two stereocentres to be formed in a single reaction. The methods presented
below generally employ strong π-acceptors to lower the energy of the benzene LUMO;
however the functional groups which promote the addition are often prone to reaction
themselves which is minimised by judicious choice of reaction conditions, or by the
use of steric bulk to protect the functional groups.
The reactions often suffer from rearomatisation of reaction intermediates, poor
chemoselectivity and poor regioselectivity during either the nucleophilic or
electrophilic functionalisation. The first section presents some examples of the
dearomatisation of benzenoid rings, the next explores Meyers’ dearomatisation of
naphthyloxazolines, before catalytic methods for dearomatisation are briefly discussed.
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