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

3.1 – Oxazoline synthesis
3.1.4.b Method B: ring expansion of benzoyl aziridines
Ph
Ph
Ph
Ph
O
Cl
HN
173
Ph
O
N
Ph
SiO 2 , CH 2 Cl 2
O
N
R
Et 2 O, petrol,
Et 3 N, -10 °C
R
R
100 101
e.r. >95:5
Entry R 100 / % SiO 2 t 101 / % d.r.
a H 84 “excess” 18 hr 94 64 >99:1
b 4-OMe 89 “excess” 8 d 58 99:1
c 4-OMe 89 10 x wt 7 hr 80 >95:5
d 3-OMe 87 10 x wt 16 hr 85 >95:5
Table 3.3 – synthesis of oxazolines via aziridines (Route B)
Aziridines 100 were made under low solubility conditions to precipitate the
triethylammonium salt to minimise chloride attack of the aziridine ring. 129 Initial
studies of the aziridine rearrangement made it clear that “excess” silica was not
sufficient for the reaction and known quantities were used. Parallel experiments
showed that phenyl aziridine 100a rearranged approximately twice as quickly as paraanisoyl
aziridine 100b, in disagreement with the observations of Lectka (section
3.1.1.b) but consistent with later results. The transformation of aziridine 100b was
also attempted in the presence of sodium iodide in acetone, 120 but no oxazoline was
detected after 10 days. This is consistent with the findings of Meyers, who postulated
that iodide only catalysed the rearrangement of electron-deficient arylaziridines. 122
Whilst HPLC analysis of the product oxazolines showed them to be optically pure,
some epimeric oxazoline was isolated (entry b) and characterised by comparison with
known sample. Further studies in the group showed that under identical conditions
syn-aziridine 180 gave a 2:1 cis:trans mixture (Scheme 3.12), 130 not dissimilar to the
observations of Aggarwal who found a similar cis-aziridine rearranged in a 3:1
trans:cis ratio, also on silica. 123 A stereoselective reaction is consistent with the
cationic mechanism proposed by Lectka (vide supra).
104