S.Handa, C.J.Rose / Tetrahedron Letters 45 (2004) 8643–8645
8645
conditions, however, failed to give any of the anticipated
products resulting from 1,2-imino migration. Only the
directly reduced products 13b–15b (isolated, after reac-
tion with NaBH4, as the corresponding salicylalde-
hyde-derived benzyl amines) were formed in these
reactions. Any 3-exo-trig cyclisation of the radicals gen-
erated from the selenides 13a and 14a would produce the
same azacyclopropyl carbinyl radical intermediate,
which would be expected to give the same reaction prod-
ucts in either case. The absence of any product 13b from
the reaction of 14a (and of 14b from 13a) therefore indi-
cates that the 3-exo-trig cyclisation step is not occurring
in either of these reactions and suggests that the pres-
ence of an a-carboxyl ester may be necessary to facilitate
azacyclopropyl formation. The influence of imine polari-
sation in radical cyclisation reactions has been docu-
mented.14,15 Thus, nucleophilic alkyl radicals have a
strong preference for attack on the electrophilic imine
C-atom and consequently there are only a few reports
of alkyl radical addition onto the electronegative
N-atom of imines.15 The failure of both 13a and 14a
to undergo 3-exo-trig cyclisation onto the imine N-atom
suggests that the electron withdrawing ester group in 9a,
9b and 12 may be necessary to activate the imine to
attack at the ÔwrongÕ end.
presented here do not let us distinguish between these
two possibilities.
In summary we have begun to discover some of the
factors that are important for a successful free radical-
mediated 1,2-imino migration. We are currently investi-
gating this intriguing transformation for the synthesis of
b-amino acid derivatives.
Acknowledgements
The authors thank the EPSRC and AstraZeneca Charn-
wood for a CNA award.
References and notes
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The absence of any 1,2-imino migration products from
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