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

Chapter 3 – Oxazoline synthesis & removal
HO
Ph
Ph
OH
Ph
Ph Ph
Ph
Ph
NH
O
H
N
O
NH
Ph
i) MeSO 2 Cl, Et 3 N
ii) NaOH, MeOH,
H 2 O, Δ 4 hr
O
N
H
N
O
N
168
53%
Scheme 3.3 – cyclisation of amides by mesylation 119
Activation has also been achieved by Du and co-workers, by mesylation before
cyclisation under strongly basic conditions (Scheme 3.3). Although an extra step is
required in the isolation of the mesylate, shorter reaction times and cheaper reagents
somewhat offset this practicality. 119 Whilst the synthesis of bis-oxazoline ligand 168
proceeds in lower yield than the Linclau method, each cyclisation effectively takes
place in 70-75% yield. In light of its simplicity it is somewhat surprising that this
method has not been used more widely; given that the diastereoselectivity is not
reported it is unclear how general this method is.
3.1.1.b Acyl aziridines
Ph
Ph
Ph
O
Ph
N
100a
Ph
SiO 2 , CH 2 Cl 2
O N
Ph
101a
94%
> 99:1 dr
> 99:1 er
64
Scheme 3.4 – silica catalysed rearrangement of benzoyl aziridines
Diphenyl oxazoline 101a was first synthesised by Purewal 63 and Cabedo 64 by the
rearrangement of benzoyl aziridine 100a on silica, with only a single stereoisomer
isolated. Although this was unexpected at the time, there is significant precedent for
the ring expansion of acyl aziridines catalysed by iodide, 120 heat, 120 Lewis acid, 121
aqueous acid, 122 and silica, 123 although the stereochemical outcome of the reaction had
not generally been studied.
97