M. Benamer et al. / Tetrahedron Letters 51 (2010) 645–648
647
Ph
Ph
(4 equiv.)
Al
O
P
O
P
Ph
Ph
N
NH
Ph
b)
H3C
Ph
(de = 80% )
AcNH
H3C
(-)- 4a
5
Ph
a)
c), d)
O
PhCHO
Ph
(+)-10
( ee = 78% )
O
P
NaNH2
e)
Ph
H3C
NH2
P OMe
H3C
Ph
(+)- 3
(+)- 9
(ee = 94%)
Scheme 2. Reagents and conditions: (a) TiCl4, CH2Cl2, 0 °C to rt, 1 h; (b) toluene, 0 °C to rt, 1 h; (c) aq 3 M HCl in MeOH (1:5), 0 °C to rt, 1.5 h; (d) Ac2O, CH2Cl2, iPr2NEt, 0 °C to
rt, 1 h; (e) NaNH2, THF, À45 °C, 1 h.
Ph
Si face
addition
H
O
P
O
P
H
N
N
H
Al
Ph
Scheme 3. Proposed model for the alkynylation of phosphinoylimine.
reacted with dimethyl aluminum phenylacetylide18 to give opti-
Acknowledgment
cally active 519 as a mixture of two diastereomers in a 90:10 ratio
(Scheme 2). The separation of the diastereomers was not attempted
and the mixture was submitted to the cleavage of the chiral auxil-
iary. Treatment of 5 with HCl in MeOH, was followed by Ac2O treat-
ment and allowed the isolation of methylphosphinate (+)-920 and
The authors would like to thank ‘Groupe Saidal’ (Alger) for
financial support.
References and notes
N-acetyl propargylamine (+)-10.21 The [ D value of 1021 was con-
a]
1. Bloch, R. Chem. Rev. 1998, 98, 1407–1438.
sistent with diastereomeric excess (80%) of the alkynylation and
the enantiomeric purity of the chiral auxiliary, its sign allowed
the determination of the absolute configuration of 10 as R.6 The
model we proposed for the alkynylation of N-p-tolylsulfinylimines
can also be applied here.6 This model (Scheme 3) was based on the
necessity to use 4 equiv of organometallic reagent to attain a rea-
sonable reaction time, it was then proposed that two molecules of
the organoaluminum are complexed to the imine: one at the nitro-
gen and the other at the oxygen of the phosphoryl. The antiperipla-
nar disposition of these groups resulting from these complexations
and the addition on the less-hindered face could explain the config-
uration of the major propargylamide 5.
Eventually, it was demonstrated that the chiral auxiliary can be
recovered (Scheme 2). Methylphosphinate (+)-9 was obtained
through inversion of configuration at phosphorus from the acidic
cleavage of 5. Furthermore, treatment of (+)-9 with NaNH2 led to
phosphinamide (+)-3, resulting in a second inversion of configura-
tion, in fair yield (31%) but without loss of enantiomeric purity
(ee = 94% from chiral HPLC).
2. Morton, D.; Stockman, R. A. Tetrahedron 2006, 62, 8869–8905.
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In conclusion, we have shown that chiral phosphinoylimines
are good substrates for the addition of aluminum acetylides giving
rise to propargylamines in good chemical yields and enantiomeric
excesses. The chiral inductor can be recovered without loss of opti-
cal purity.