Highly regio- and stereoselective four-component iodoamination of Se-substituted allenes. An efficient synthesis of N-(3-organoseleno-2-iodo-2(Z)-propenyl) acetamides

Article abstract of DOI:10.1039/b300879g

Z-Selectivity was observed for iodohydroxylation of Se-substituted allenes with I₂ and H₂O, which is opposite to that of 1,2-allenyl sulfoxides. With n-hexane as the co-solvent Z-iodoamination leading to N-(3-organoseleno-2-iodo-2(Z)

Full text of DOI:10.1039/b300879g

Highly regio- and stereoselective four-component iodoamination of
Se-substituted allenes. an efficient synthesis of
N-(3-organoseleno-2-iodo-2(Z)-propenyl) acetamides†
Shengming Ma,*ab Xueshi Haoa and Xian Huanga
a Department of Chemistry, Zhejiang University, Hangzhou 310028, P. R. China
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, P. R. China. E-mail: masm@pub.sioc.ac.cn;
Fax: (+86)21-64166128
Received (in Corvallis, OR, USA) 22nd January 2003, Accepted 27th February 2003
First published as an Advance Article on the web 2nd April 2003
Z-Selectivity was observed for iodohydroxylation of Se-
substituted allenes with I2 and H2O, which is opposite to that
of 1,2-allenyl sulfoxides. With n-hexane as the co-solvent Z-
iodoamination leading to N-(3-organoseleno-2-iodo-2(Z)-
propenyl)acetamide was observed. A brief rational for the
stereoselectivity of this reaction is provided.
Allenes are useful intermediates for organic synthesis due to the
presence of unique cumulated CNC double bonds.1,2 In our
Scheme 1 Regio- and stereoselectivity of addition reaction involving
group, we have developed the coupling-cyclization of function-
alized allenes3 and the nucleophilic addition of electron-
deficient allenes.4 For addition reaction of allenes with two
different reagents, there would be problems of regio- and
stereoselectivity (Scheme 1).5 In order to make these method-
ologies synthetically attractive, it is desirable to address the
issue of selectivity in these reactions. In our previous studies,
we observed that (1) the regioselectivity of hydrohalogenation
reaction of electron-deficient allenes leading to b,g-unsaturated
functionalized alkenes can be controlled by the electronic effect
of the electron-withdrawing group;4 (2) the iodohydroxylation
reaction of 1,2-allene sulfoxides exhibits excellent regio- and E-
stereoselectivity.5 Here we wish to report the highly regio- and
stereoselective electrophilic addition reaction of Se-substituted
allenes with I2, H2O, and nitriles.
We started this research with the iodohydroxylation of
1,2-propadienyl phenyl selenide (1a) with I2 and H2O. Some
typical results are summarized in Table 1. From Table 1, it is
interesting to note that when the iodohydroxylation of 1a with
I2 and H2O was carried out under the same conditions employed
for 1,2-allenyl sulfoxides,5 the expected product 2a was isolated
in only 28% yield. However, it is interesting to observe that the
stereoselectivity is 12.5+1 with the Z-isomer being the major
product! This is completely opposite to the results for the
allenes.
corresponding sulfoxides5 (entry 1, Table 1). Interestingly,
when n-hexane was added to a mixture of MeCN and H2O as the
solvent, besides the formation of Z-2a, a new product that is N-
(2-iodo-3-phenylseleno-2(Z)-propenyl)acetamide Z-3a was
formed (entries 2–4, Table 1). When only 1 equiv of H2O was
added, the reaction at 25 °C afforded Z-3a highly ster-
eoselectively as the only product (entry 7, Table 1). In the
presence of 12 or 16 equiv of H2O, the stereoselectivity is lower
(entries 5 and 6, Table 1). The stereoselectivity, which is
opposite to that of 1,2-allenyl sulfoxides, was determined
unambiguously by X-ray diffraction study of Z-3a.6
A typical procedure is as follows: A solution of phenyl
1,2-propadienyl selenide (195 mg, 1 mmol) in 2 mL of MeCN
was added slowly (over 30 min) to a solution of iodine (507.6
mg, 2 mmol) in acetonitrile (3 mL) with n-hexane (5 mL) under
a N2 atmosphere. After being stirred at 25 °C for 9 hours, the
mixture was diluted with ether, then saturated aqueous solutions
of NaHCO3 and Na2S2O3 were added to the solution. The
mixture was extracted with ether (25 mL 3 3) and dried over
MgSO4. Evaporation and column chromatography on silica gel
(petroleum ether/ethyl acetate = 1+1) afforded Z-3a as a white
solid: m.p. 100–102 °C (CH2Cl2/n-hexane). Some typical
examples of the four-component reaction between 1-organose-
lenoallenes, nitriles, I2 and water are summarized in Table 2.
From the results in Table 2, following points are noteworthy: (1)
† Electronic supplementary information (ESI) available: experimental
section. See http://www.rsc.org/suppdata/cc/b3/b300879g/
Table 1 Addition reaction of 1a with I2 under different conditions
Entry
I2 (equiv)
Solvent
H2O (equiv) T (°C)
Time (h)
2a (%) (Z/E)c
3a (%) (Z/E)c
1a
2
3
4
5
2
2
2
2
2
2
2
MeCN+H2O (7+1)
MeCN+Ab = (1+1)
MeCN+A = (1+1)
MeCN+A = (1+1)
MeCN+A = (1+1)
MeCN+A = (1+1)
MeCN+A = (1+1)
—
8
4
21
25
25
25
25
25
25
10
28 (12.5+1)
27 (26+1)
18 (20+1)
22 (15+1)
63 (6.8+1)
60 (3.6+1)
0
0
12.5
12.5
11.5
10
11
17
15 (30+1)
36 (22+1)
44 (44+1)
0
3
16
12
1
6
7
0
64 (28+1)
a LiOAc·2H2O (2 equiv) was added. b A = n-Hexane. c Determined by 300 MHz 1H-NMR spectra of the crude product.
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CHEM. COMMUN., 2003, 1082–1083
This journal is © The Royal Society of Chemistry 2003

Table 2 Reaction of 1,2-propadienyl organoselenides with nitriles and I2
H2O
(equiv) (h)
Time
Yield of 3 Z/E ratio
(%)
Entry
R
RA
of 3a
1
2
3
4
5
6
7
8
9
C6H5
C6H5
Me
n-Pr
Me
Me
Me
Me
Me
1
1
1
0
1
1
1
1
0
10.5
10
14.5
21
11.5
12
10
9.5
11.5
59 (3a)
46 (3b)
62 (3c)
45 (3c)
60 (3d)
51 (3e)
54 (3f)
51 (3g)
23 (3g)
418+1
421+1
422+1
421+1
443+1
465+1
426+1
419+1
430+1
p-CH3C6H4
p-CH3C6H4
o-CH3C6H4
p-BrC6H4
p-ClC6H4
p-CH3OC6H4 Me
p-CH3OC6H4 Me
Scheme 3
a Determined by 300 MHz 1H NMR spectra of the crude product.
Natural Science Foundation of China, Cheung Kong Scholars
Programme and Zhejiang University.
for the substrates studied, the yields are moderate; (2) The yield
in the absence of water is lower.
Z-3a is a useful synthetic intermediate. Its reduction of the
carbonyl group in 3a with DIBAL in toluene afforded N-(3A-
phenylseleno-2-iodo-(2E)-propenyl) N-ethyl amine (Z-8a) in
79% yield, while upon its treatment with NaH, the reaction
afforded 2-methyl-5-(phenylselenomethyl)oxazole (9a) in 96%
yield (Scheme 2).7
Notes and References
1 (a) The Chemistry of the Allenes, ed. S. R. Landor, Academic Press, New
York, 1982; Vols. 1–3; (b) The Chemistry of Ketenes, Allenes and
Related Compounds, ed. S. Patai, Wiley: New York, 1980; Vols. 1 and
2; (c) L. Brandsma and H. D. Verkruijsee, Synthesis of Acetylenes,
Allenes and Cumulenes, Elsevier, New York, 1980; (d) C. Bruneau and
P. H. Dixneuf, Compr. Org. Funct. Group Transform, 1995, 1, 953; (e)
J. A. Marshall, Chem. Rev, 1996, 96, 31; (f) H. F. Schuster and G. M.
Coppola, Allene in Organic Synthesis, Wiley, New York, 1984; (g) D. R.
Taylor, Chem. Rev., 1967, 67, 317; (h) M. Aso and K. Kanematsu, Trends
Org. Chem., 1995, 5, 157; (i) R. Zimmer, Synthesis, 1993, 2, 165.
2 For recent reviews, see: (a) R. Zimmer, C. U. Dinesh, E. NanDanan and
F. Khan, Chem. Rev., 2000, 100, 3067; (b) A. S. K. Hashmi, Angew.
Chem. Int. Ed., 2000, 39, 3590; (c) X. Lu, C. Zhang and Z. Xu, Acc.
Chem. Res., 2001, 34, 535.
3 For some of our recent work, see: (a) S. Ma and S. Zhao, J. Am. Chem.
Soc., 2001, 123, 5578; (b) S. Ma and S. Wu, Chem. Commun., 2001, 441;
(c) S. Ma and S. Wu, Tetrahedron Lett., 2001, 42, 4075; (d) S. Ma, Z. Shi
and Z. S. Wu, Tetrahedron:Asymmetry, 2001, 12, 193; (e) S. Ma and Z.
Shi, Chem. Commun., 2002, 540; (f) S. Ma, N. Jiao, S. Zhao and H. Hou,
J. Org. Chem., 2002, 67, 2837; (g) S. Ma, D. Duan and Y. Wang, J.
Comb. Chem., 2002, 4, 239; (h) S. Ma and Z. Yu, Angew. Chem. Int. Ed.,
2002, 41, 1775.4.
4 (a) S. Ma, Z. Shi and L. Li, J. Org. Chem., 1998, 63, 4522; (b) S. Ma and
Q. Wei, J. Org. Chem., 1999, 64, 1026; (c) S. Ma, L. Li and H. Xie, J.
Org. Chem., 1999, 64, 5325; (d) S. Ma and Q. Wei, Eur. J. Org. Chem.,
2000, 10, 1939; (e) S. Ma and L. Li, Synlett, 2001, 8, 1206; (f) S. Ma, L.
Li, Q. Wei, X. Xie, G. Wang, Z. Shi and J. Zhang, Pure. Appl. Chem.,
2000, 72, 1739; (g) S. Ma, H. Xie, G. Wang, J. Zhang and Z. Shi,
Synthesis, 2001, 5, 713; (h) S. Ma, S. Yin, L. Li and F. Tao, Org. Lett.,
2002, 4, 505.
Scheme 2
It can be assumed that the lone electron pair of selenium atom
would interact with I2 to form a molecular complex.8 Intra-
molecular electrophilic addition of I2 with the CNC bond remote
from the Se group would form intermediate Z-4a. The strong
soft Lewis acid and base interaction between the positively
charged iodine atom and Se9 may be responsible for the
stereoselectivity of this reaction. Upon hydrolysis, the reaction
affords Z-2a. Its reaction with MeCN leads to intermediate Z-
5a, which would produce Z-3a after hydrolysis (Scheme 3).
In conclusion, we have developed a highly regio- and
stereoselective four-component iodoamination reaction of
1,2-allenyl selenides with I2, H2O, and nitriles. The Z-
stereoselectivity for this reaction may be controlled by the soft
Lewis base and acid interaction between the selenium atom and
the positively charged iodine atom.8 The regioselectivity in this
reaction may be controlled by the steric and electronic effects of
the Se-containing groups. Although the precise origin of the
stereoselectivity observed during this transformation requires
more investigation this reaction may open up new area for the
control of selectivity in addition reactions of allenes. The scope
of this reaction, the real nature of the Z-stereoselectivity, and the
synthetic application of these reactions are currently being
carried out in our laboratory.
5 S. Ma, Q. Wei and H. Wang, Org. Lett., 2000, 2, 3893.
6 Crystal Data for Z-3a: C11H12INOSe, Mw = 380.08, monoclinic, Space
group P2(1)/c, Mo-Ka, final R indices [I > 2 s(I)] R1 = 0.0355, wR2
=
0.0696, a = 10.9005(10), b = 13.2791(12), c = 9.8573(9), Å, b (2)°, V
= 1300.8(2), Å3, T = 20.0 °C, Z = 4, Reflections collected/Total
7761/Unique 3019 (Rint = 0.0719), No Observation (I > 2.00s(I)) 1845,
Parameter 154. CCDC 186925. See http://www.rsc.org/suppdata/cc/b3/
b300879g/ for crystallographic data in .cif or other electronic format.
7 (a) K. M. Short and C. B. Ziegler, Jr, Tetrahedron Lett., 1993, 34, 71; (b)
C. Giuseppe, C. Corrado and G. Mario, J. Chem. Soc. Perkin. Trans. I,
1984, 255.
8 W. Nakanishi, Y. Yamamoto, Y. Kusuyama, Y. Ikeda and H. Iwamura,
Chem. Lett., 1983, 675; S. M. Godfrey, C. A. McAuliffe, R. G. Pritchard
and S. Sarwar, J. Chem. Soc., Dalton Trans., 1997, 1031.
9 T. H. Lowry and K. S. Richardson, Mechanism and Theory in Organic
Chemistry, 3rd Edn., Harper & Row, Publishers, Inc., New York, 1987, p.
319.
Financial support from the Major State Basic Research
Development Program (Grant No. G2000077500), National
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