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

3.1 – Oxazoline synthesis
O
Ar
OH
i) SOCl 2
ii)
HN
O
Ar
N
86%
H 2 SO 4 , Et 2 O
rt, 16 hr
O
Ar
N
75%
Ar =
NC
122
Scheme 3.5 – acid catalysed rearrangement of benzoyl aziridines
The aziridine nitrogen is unable to fully participate in the stabilising n N →π * C–O
interaction since it is constrained in a three membered ring. This is seen in a crystal
structure obtained by Lectka and co-workers in which the aziridine C–N bonds are 68°
out of the C=O plane, and longer than other secondary amines. 121 Therefore the partly
pyramidal acyl aziridines have reactivity akin to amines, and it is postulated by Lectka
that the nitrogen basicity drives the rearrangement. This has been borne out by his
studies which show that the rearrangement takes place in the presence of azaphilic
Lewis acids (Cu II , Sn II , Zn II ) but not oxophilic ones (Yb III , Ti IV , Sb V , Al III , 122 BF 122 3 ).
Another, and perhaps the main, impetus for the rearrangement would be the
developing n N →π* C–O interaction in the transition state, which no doubt explains why
the reverse reaction is not observed.
Ar
N
O
Cu(OTf) 2
THF
Ph
Ph
Cu(OTf) 2
O N
N
O N
THF
Ar
Ph O
Ph
76-89%
169 4 examples 171 172
M
N
O
Ar
170
Scheme 3.6 – acid catalysed rearrangement of aziridines 121
In this work, Leckta synthesises a number of cis-substituted oxazolines 169, and
transition state calculations suggest a heterolytic process via cation 170 rather than a
concerted mechanism favoured by other authors. 120 Under these conditions, optically
pure aziridine 171 rearranges to give the known oxazoline 172 with complete regioand
stereoselectivity; the regioselectivity is consistent with formation of the more
stable cation, whilst the stereoselectivity is attributed to the formation of tight ion
pairs. No yield is given for this final reaction in either the text or supporting
information.
98