Addition of allylindium reagents to α- iminotrifluoroethylphosphonates: Synthesis of CF3-containing α-aminoalkylphosphonates

Article abstract of DOI:10.1080/00397910802431156

Treatment of α-iminotrifluoroethylphosphonates with allylindium reagents in the presence of acetic acid afforded the corresponding CF3 -containing α-aminoalkylphosphonates in high yields (83-97%) under mild conditions. Copyright Taylor & Francis Group, LL

Full text of DOI:10.1080/00397910802431156

Synthetic Communications1, 39: 792–798, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802431156
Addition of Allylindium Reagents to
a-Iminotrifluoroethylphosphonates: Synthesis
of CF3-Containing a-Aminoalkylphosphonates
Ki Hyung Suh and Dae Young Kim
Department of Chemistry, Soonchunhyang University, Asan,
Chungnam, Korea
Abstract: Treatment of a-iminotrifluoroethylphosphonates with allylindium
reagents in the presence of acetic acid afforded the corresponding CF3 -containing
a-aminoalkylphosphonates in high yields (83–97%) under mild conditions.
Keywords: Allylation, a-aminoalkylphosphonates, a-iminotrifluoroethylphospho-
nates, indium
a-Aminoalkylphosphonates have received an increasing amount of atten-
tion in medicinal and synthetic organic chemistry because they are impor-
tant surrogates for a-amino carboxylic acids.[1] These compounds can be
potent antibacterial agents, enzyme inhibitors,[2] antibiotics and pharma-
cological agents,[3] herbicides,[4] and haptens of catalytic antibodies.[5]
Introduction of fluorine atoms into biologically active compounds often
leads to improvement of their biological characteristics because of the
unique properties of the fluorine atom.[6] Recently, Osipov and cowor-
kers have reported the allylation of a-iminotrifluoroethylphosphonates
using Grignard reagents to afforded a-trifluoromethyl-a-aminophospho-
nates, which are the phosphorus analogs of a-trifluoromethyl-substituted
a-amino acids.[7] Allylindium reagents have emerged as particularly mild
Received May 7, 2008.
Address correspondence to Dae Young Kim, Department of Chemistry,
Soonchunhyang University, Asan, Chungnam 336-745, Korea. E-mail:
dyoung@sch.ac.kr
792

CF3-Containing a-Aminoalkylphosphonates
793
organometallic reagents, and indium-mediated Barbier type reactions of
a variety of functional groups have been reported.[8]
As part of research program related to the development of synthetic
methods for the preparation a-functionalized phosphonates,[9] we
reported the synthesis of tertiary a-hydroxy alkylphosphonates by the
addition of allylindium reagents to acylphonates.[10] In this article, we
report the synthesis of a-trifluoromethyl-a-aminophosphonates through
indium-mediated allyation of iminophosphonates.
To determine suitable reaction conditions for the addition of allylin-
dium reagents to an a-iminophosphonates, the a-iminophosphonate
1a was prepared through reaction of imidoyl chloride and triethyl
phosphite.[7,11] When phosphonate 1a was treated with allyl bromide
(2a) and indium metal in water, in mixtures of water and an organic
cosolvent, or in THF, the desired a-aminophosphonate 3a was isolated
in moderate to low yield. In the presence of acetic acid as additive in
THF, the desired a-aminophosphonate 3a was obtained in high yield
after 2 h at room temperature (Table 1). Addition of acetic acid as an
additive increased the yield and accelerated the reaction rate.[10,11]
Effect of N-protecting groups of phosphonates 1 was studied in THF,
and the results are shown in Table 1 (entries 1–3). N-o-Methoxyphenyl
a-iminophosphonate 1a exhibited the highest yield.
As shown in Table 2, high yields of the allyl adducts also were
obtained with several other allylic bromides under these reaction condi-
tions. Indium-mediated allylation reaction of a-iminotrifluoroethylpho-
sphonate 1a showed excellent regioselectivity when cinnamyl (2c),
crotyl (2d), or c,c-dimethyl allyl bromide (2f) was used (Table 2, entries
3, 4, and 6). The c-allyation products were obtained exclusively, and no
a-products were observed. These results are in accord with the previously
Table 1. Effect of N-protecting groups of a-iminophosphonates 1
Entry
1, R
Time (h)
Yield (%)
1
2
3
1a, o-OMe,Ph (OMP)
1b, Benzoyl
1c, Cbz
2
2
3
91
80
62

794
K. H. Suh and D. Y. Kim
Table 2. Addition of allylindium reagents of a-iminotriflouroethylphosphate 1a
Entry
1
Allyl bromide 2
Product 3
Yielda (%)
91
2
94
97
3b
4b
93
5
91
(Continued )

CF3-Containing a-Aminoalkylphosphonates
Table 2. Continued
795
Entry
6
Allyl bromide 2
Product 3
Yielda (%)
83
aYields are isolated yields.
bOnly c-allylation product was obtained.
known regioselectivity observed for the indium-mediated allylation
reaction.[11]
In summary, we have accomplished the efficient synthesis of a-
trifluoromethyl-a-aminoalkylphosphonates from a-iminotrifluoroethyl-
phosphonate in high yield through an indium-mediated allylation.
The process works well with several different allylic bromides. Current
efforts are focused on developing synthetic applications and asymme-
tric versions of the allylation of a-iminotrifluoroethylphosphonates.
TYPICAL PROCEDURE FOR THE ALLYLATION OF
a-IMINOPHOSPHONATES
A solution of iminophosphonate (1a, 101 mg, 0.3 mmol) in THF (0.5 mL)
and acetic acid (17.2 mL, 0.3 mmol) were added successively to a stirred
suspension of indium (103 mg, 0.9 mmol) and allyl bromide (2a,
108 mg, 0.9 mmol) in THF (2 mL) at room temperature. The reaction
mixture was stirred for 2 h, quenched by the addition of saturated aqu-
eous NH4Cl (2 mL), and extracted with ethyl ether (2 ꢀ 20 mL). The com-
bined organic layers were washed with saturated NaHCO3 and brine,
dried over MgSO4, and concentrated in vacuo. The resulting residue
was purified by column chromatography to afford the a-aminophos-
1
phonate 3a (104 mg, 91%). H NMR (CDCl3, 200 MHz) 1.22 (t, 6H,
J ¼ 6.0 Hz), 2.91–3.02 (m, 2H), 3.86 (s, 3H), 4.07–4.34 (m, 4H), 5.00 (d,
1H, J ¼ 12.0 Hz), 5.22 (d, 1H, J ¼ 12.0 Hz), 5.77–5.94 (m, 1H), 6.76–6.87
(m, 3H), 7.30 (m, 1H); 13C NMR (CDCl3, 50 MHz) 15.97 (d, J ¼ 5.3 Hz),
35.41, 55.48, 63.56 (dq, J ¼ 26.6 Hz, J ¼ 153.5 Hz), 63.46 (d, J ¼ 7.6 Hz),
63.26 (d, J ¼ 7.9 Hz), 109.87, 117.86, 119.66, 120.11, 120.45, 125.32 (dq,
J ¼ 10.0 Hz, J ¼ 286.4 Hz), 130.85 (d, J ¼ 5.0 Hz), 133.31 (d, J ¼ 5.8 Hz),
149.03; 31P NMR (CDCl3, 121 MHz) 19.5; 19F NMR (CDCl3,
282 MHz) 68.4; MS (EI) 381 (Mþ, 13), 340 (20), 244 (100), 202 (55).

796
K. H. Suh and D. Y. Kim
ACKNOWLEDGMENT
This research was supported by a Korea Research Foundation Grant
from the Korean government (KRF-2006-521-C00099).
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