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

4.2 – Carbasugar synthesis
4.2 Synthesis of a Carbasugar Analogue
Ph
O
N
OMe
102b
Ph
HO
HO
OH
OH
OH
275
Stereochemistry:
Relative set by anti-addition
Absolute set by chosen auxilliary
(sugar shown is L )
Scheme 4.10 – a family of possible analogues
The intention of this synthesis is to achieve the complete stereoselective oxygenation
of an adduct produced by the methods outlined in the previous chapters. The most
suitable aromatic derivatives are the anisoles since these are already partially
oxygenated and dearomatisation gives enol ethers. Whilst enol ethers are versatile in
their own right, they readily yield ketones, opening up a plethora of chemistry,
furthermore, adduct 102b can be hydrolysed to an enone (section 3.2), a motif which
has often been used in making cyclitols. In light of this, and that the yields for addition
are slightly higher, the 4-methoxy oxazoline derivative 102b will be used in the initial
synthetic work. Since 275 contains densely packed hydrophilic and hydrophobic
portions its biological activity might be of interest. Furthermore a synthesis including
the isopropyl group might be seen as a guide for future work whilst we learn about the
behaviour of the pendent oxazolinyl group.
Since this synthesis is intended to exemplify the synthetic utility of the oxazoline
chemistry, it is hoped that this substituent may prove useful in two ways; by enhancing
stereoselectivity by hindering one face of the carbocycle, and providing a useful
chromophore for reaction monitoring and purification.
4.2.1 Synthetic strategy
We are afforded the luxury of planning a forward synthesis based upon chemistry we
are most confident will work since all diastereoisomers of 275 are possible synthetic
targets. This is outlined below, with a brief rational of reagents suitable for substratebased
stereoselectivity, much of which is based around the axial position of the
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