LETTER
Alkylation of Asymmetric Phosphonamidates
511
(Scheme 6). The assigned structure for 9 was subsequent-
ly confirmed by X-ray crystallography. A mechanism for
the formation of compound 9 is proposed below
(Scheme 6).
H
H
H
P
P
H
O
O
O
O
R
N
R
N
B
A
H
Scheme 4
Ph2C
Ph3C
Ph2C
P
P
P
N
O
N
O
ingly however, when 3b was treated with 1.5 equivalents
of base and electrophile (MeI, BnBr and allylbromide) in
the presence of DMPU, we obtained compounds 8a–c as
the products. This was accompanied by the observation
that the anions derived from 3b in the absence of DMPU
are yellow-orange, whereas in the presence of DMPU the
anions are intensely orange-red. The intense colour of the
anion can presumably be attributed to strong delocalisa-
tion. Therefore, we infer that compounds 8a–c are ob-
tained directly from the quenching of the anion located at
the corresponding nitrogen side chain, and not through a
secondary migration of the electrophile. In other words, in
the presence of DMPU, either 1b is directly deprotonated
at the nitrogen side chain position, or the carbanion at the
position α to the phosphorus atom is formed but is trans-
muted to the one at the nitrogen side chain position
through a proton transfer. At any rate, the reaction of the
anion with the electrophiles is considerably faster under
these conditions. The exception arose when TMSCl was
used as an elelctrophile. In this reaction, there was no ev-
idence of incorporation of a TMS group on the nitrogen
side-chain by crude NMR. Instead, only α-silylphosphon-
amidate 7b was obtained. Furthermore, the reaction was
relatively sluggish affording a considerable quantity of
unreacted starting material. Both of these observations
suggest that the transmutation of the carbanion may be a
reversible process. With bulkier electrophiles, such as
TMSCl, the quenching of the anion at the more sterically
hindered nitrogen side chain position is disfavoured and
hence only α-silylphosphonamidates were obtained
(Scheme 5).
N
O
O
O
O
red anion
3c
H
Ph2HC
Ph2HC
Ph2C
work up
H
P
P
P
N
O
N
O
N
O
O
O
O
9
Scheme 6
In summary, DMPU has a significant influence on the
deprotonation of 3b,c by chelation to the metal (lithium)
cation and generating ‘naked’ carbanions, which are not
stable and either undergo a reversible proton shift (for 3b)
or an irreversible skeletal rearrangement (for 3c). The re-
sulting anions obtained in both cases are stabilized
through delocalisation. In contrast, carbanions derived
from 3a are stable in the presence of DMPU because seg-
regation of metal (lithium) cation from the carbanion is
not thermodynamically feasible.
Acknowledgement
We would like to thank the EPSRC (Grant GR/L70066) for a
project studentship (CLJ) and the Garlick Scholarship Foundation
(administered through King’s College London Association) for a
studentship (H.-W. Yu). We are grateful to Dr. Jon W. Steed
(King’s College London) and Dr. Andrew White (Imperical Col-
lege, London) for X-ray crystal structure determination.
E
Ph2C
E
Ph2HC
Ph2HC
References
a
P
P
P
N
O
N
O
N
O
+
(1) (a) Gréguen, C.; O’Brien, P.; Powell, H. R.; Raithby, P. R.;
Warren, S. J. Chem. Soc., Perkin Trans. 1 1998, 3405.
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(3) (a) Hanessian, S.; Bennani, Y. L. Tetrahedron Lett. 1990, 31,
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(4) Afarinkia, K.; Angell, R.; Jones, C. L.; Lowman, J.
Tetrahedron Lett. 2001, 42, 743.
O
O
O
8a R = Me 30%
8b R = CH2CH=CH2 36%
8c R = CH2Ph 38%
7b R = SiMe3
3b
Scheme 5 Reagents and conditions: a) LDA, –78 °C, toluene,
DMPU, E+.
When 3c was treated with LDA in the presence of DMPU,
we obtained an unexpected result. Surprisingly, the anion
derived from 3c in the absence of DMPU is yellow-or-
ange, whereas in the presence of DMPU, the anion is in-
tensely purple-red. The presence of electrophiles had no
influence on the course of reaction and we obtained the
same product regardless of the electrophile used. We sub-
sequently isolated this product and identified it as 9
(5) Typical Experimental Procedure: LDA (3.37 mL, 6.82
mmol) was added to a stirred solution of 3-
(diphenylmethyl)-2-propyl-1,3,2-oxazaphosphorinane 2-
Synlett 2003, No. 4, 509–512 ISSN 0936-5214 © Thieme Stuttgart · New York