Regio- and stereoselective hydroamidation of 1-alkynylphosphine sulfides catalyzed by cesium base

Article abstract of DOI:10.1021/ol8010979

(Chemical Equation Presented) Regio- and stereoselective hydroamidation of 1-alkynylphosphine sulfides proceeds in the presence of cesium carbonate to provide (E)-2-amino-1-thiophosphinyl-1-alkenes. Asymmetric hydrogenation of the adducts catalyzed by an

Full text of DOI:10.1021/ol8010979

ORGANIC
LETTERS
2008
Vol. 10, No. 14
3093-3095
Regio- and Stereoselective
Hydroamidation of 1-Alkynylphosphine
Sulfides Catalyzed by Cesium Base
Azusa Kondoh, Hideki Yorimitsu,* and Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto UniVersity,
Kyoto-daigaku Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
yori@orgrxn.mbox.media.kyoto-u.ac.jp; oshima@orgrxn.mbox.media.kyoto-u.ac.jp
Received May 13, 2008
ABSTRACT
Regio- and stereoselective hydroamidation of 1-alkynylphosphine sulfides proceeds in the presence of cesium carbonate to provide (E)-2-
amino-1-thiophosphinyl-1-alkenes. Asymmetric hydrogenation of the adducts catalyzed by an iridium complex followed by desulfidation yields
2-amino-1-phosphinoalkanes, which offers a new approach to chiral N,P-ligands that will potentially serve as ligands in asymmetric reactions.
Organophosphines play invaluable roles in organic synthesis,
especially as ligands for transition-metal catalysts. Develop-
ment of novel approaches to organophosphines is thus quite
important. We have been focusing on 1-alkynylphosphine
derivatives as precursors of new phosphines1 and reported
addition reactions of diphenylphosphine1a and thiols.1b
Considering the importance of bidentate aminophosphine
ligands in homogeneous transition-metal catalysis,2 we report
here cesium-catalyzed addition of amides or imides to
1-alkynylphosphine sulfides,3–5 directed toward the construc-
tion of vicinal N,P-frameworks.
Treatment of diphenyl(phenylethynyl)phosphine sulfide
(1a) with 2 equiv of N-benzyltosylamide (2a) in the presence
of a catalytic amount of cesium carbonate (10 mol %) in
DMSO for 11 h at 90 °C provided 1-(N-benzyl-N-tosyl-
amino)-2-diphenylthiophosphinyl-1-phenylethene (3a) in 84%
isolated yield with an E/Z ratio of 96/4 (Table 1, entry 1).
Recrystallization of the product allowed for the isolation of
the E isomer in 71% yield.6 Aprotic polar solvents, such as
DMSO, DMF, and NMP, are the solvents of choice. The
reactions in 1,4-dioxane (bp 100 °C), THF (bp 67 °C), and
toluene (bp 111 °C) at reflux afforded the product in
moderate yields. In protic solvents such as 2-propanol at
reflux, a trace amount of the product was obtained. Cesium
(1) (a) Kondoh, A.; Yorimitsu, H.; Oshima, K. J. Am. Chem. Soc. 2007,
129, 4099–4104. (b) Kondoh, A.; Yorimitsu, H.; Oshima, K. Org. Lett.
2007, 9, 1383–1385. (c) Kanemura, S.; Kondoh, A.; Yorimitsu, H.; Oshima,
K. Org. Lett. 2007, 9, 2031–2033. (d) Kondoh, A.; Yorimitsu, H.; Oshima,
K. J. Am. Chem. Soc. 2007, 129, 6996–6997.
(2) (a) Ro¨nnholm, P.; So¨dergren, M.; Hilmersson, G. Org. Lett. 2007,
9, 3781–3783. (b) Krauss, I. J.; Leighton, J. L Org. Lett. 2003, 5, 3201–
3203, and references cited therein. (c) Anderson, C.; Cubbon, R. J.; Harling,
J. D. Tetrahedron: Asymmetry 2001, 12, 923–935. (d) Ito, M.; Ikariya, T.
Chem. Commun. 2007, 5134–5142.
(4) For recent examples of intermolecular hydroamidation of alkynes,
see: (a) Yudha, S. S.; Kuninobu, Y.; Takai, K. Org. Lett. 2007, 9, 5609–
5611. (b) Goossen, L. J.; Rauhaus, J. E.; Deng, G. Angew. Chem., Int. Ed.
2005, 44, 4042–4045. (c) Kondo, T.; Tanaka, S.; Watanabe, Y. J. Chem.
Soc., Chem. Commun. 1995, 413–414.
(3) For recent reviews of catalytic hydroaminations and hydroamidations.
(a) Severin, R.; Doye, S. Chem. Soc. ReV. 2007, 36, 1407–1420. (b) Beller,
M.; Seayad, J.; Tillack, A.; Jiao, H. Angew. Chem., Int. Ed. 2004, 43, 3368–
3398. (c) Hong, S.; Marks, T. Acc. Chem. Res. 2004, 37, 673–686. (d)
Mu¨ller, T. E.; Beller, M. Chem. ReV. 1998, 98, 675–703. (e) Brunet, J. J.;
Neibecker, D. In Catalytic Heterofunctionalization; Togni, A., Gru¨tzmacher,
H., Eds.; Wiley-VCH: Weinheim, Germany, 2001; Chapter 4.
(5) For base-mediated additions of tosylamides to propiolates, see: (a)
Barbazanges, M.; Meyer, C.; Cossy, J. Org. Lett. 2007, 9, 3245–3248. (b)
Lee, E.; Kang, T. S.; Joo, B. J.; Tae, J. S.; Li, K. S.; Chung, C. K.
Tetrahedron Lett. 1995, 36, 417–420.
10.1021/ol8010979 CCC: $40.75
Published on Web 06/11/2008
2008 American Chemical Society

Table 1. Hydroamidation of 1-Alkynylphosphine Sulfides
Other nitrogen nucleophiles were examined. Imides were
suitable nucleophiles for this addition reaction (eqs 2 and
3). Interestingly, the stereoselectivity was completely con-
trolled when imides were used. In addition, succinimide (2f)
could react with sterically hindered tert-butyl-substituted
substrate, with which N-benzyltosylamide (2a) could not
react, and the corresponding adduct was obtained in good
yield. The addition of 2-pyrrolidinone also proceeded, albeit
with lower stereoselectivity (eq 4). Acyclic amides such as
N-benzylacetamide did not react at all.
entry
1
1
R1
2
R2
3
yield (%) E/Z
1a Ph
2a Bna
3aa
84
71b
74
83
82c
89
88
92
70
97
15
23
96/4
100/0
97/3
95/5
95/5
>99/1
>99/1
87/13
2
3
4
5
6
7
8
9
1b 4-Ac-C6H4
1c 4-MeO2C-C6H4 2a Bn
1d 4-MeO-C6H4
1e 2-pyridyl
1f
1g n-C6H13
1h c-C6H11
1a Ph
2a Bn
3ba
3ca
3da
3ea
3fa
2a Bn
2a Bn
2a Bn
2a Bn
2a Bn
2b n-C4H9 3ab
2c c-C6H11 3ac
2d
H
3ga′
3ha′
96/4
92/8
>99/1
10 1a Ph
11 1a Ph
H
3ad
a Bn ) C6H5CH2. b After recrystallization. c Performed for 24 h.
carbonate is the most effective base. The uses of potassium
carbonate and sodium carbonate led to lower yields. When
organic bases such as DBU and DABCO were used, no
reaction occurred.
Various combinations of 1-alkynylphosphine sulfides and
amides were examined under the optimized reaction condi-
tions (Table 1). A variety of functional groups, such as keto,
ester, methoxy, and pyridyl groups, were compatible under
the reaction conditions (entries 2-5). The reaction of
ethynyldiphenylphosphine sulfide (1f) also proceeded smoothly
with perfect stereoselectivity (entry 6). However, the reac-
tions of sterically demanding o-methoxyphenyl- and tert-
butyl-substituted substrates did not take place. The additions
to primary and secondary alkyl-substituted 1-alkynylphos-
phine sulfides also proceeded, although migration of the
carbon-carbon double bond occurred to afford 3ga′ and 3ha′
exclusively (entries 7 and 8). The scope of sulfonamides was
investigated (entries 9-11). The addition of primary alkyl-
substituted tosylamides proceeded in high yields (entries 1
and 9). However, additions of secondary alkyl-substituted
tosylamide 2c and tosylamide (2d) provided the correspond-
ing products in low yields (entries 10 and 11), and no reaction
occurred when N-phenyltosylamide and N-tert-butyltosyl-
amide were used. The reaction of N-benzyl-10-camphorsul-
fonylamide proceeded smoothly (eq 1).
The amidation was applicable to intramolecular cycliza-
tions. When 1-alkynylphosphine sulfide 4a which has a
tosylamido group was treated with cesium carbonate at
ambient temperature, the cyclization proceeded smoothly (eq
5). In the case of eq 6, where tetramethylene-tethered 4b
was used as a substrate, the migration of the C-C double
bond of the product occurred.
(6) The X-ray crystallographic analysis of 3ca verified the E stereo-
chemistry of the major isomers. See the Supporting Information.
(7) For recent reviews, see: (a) Ka¨llstro¨m, K.; Munslow, I.; Andersson,
P. G. Chem. -Eur. J. 2006, 12, 3194–3200. (b) Cui, X.; Burgess, K. Chem.
ReV. 2005, 105, 3272–3296.
(8) (a) Togni, A.; Breutel, C.; Schnyder, A.; Spindler, F.; Landert, H.;
Tajani, A. J. Am. Chem. Soc. 1994, 116, 4062–4066. (b) Togni, A. Angew.
Chem., Int. Ed. 1996, 35, 1475–1477.
We envisioned that the enantioselective hydrogenation of
the adducts would offer a new approach to chiral bidentate
3094
Org. Lett., Vol. 10, No. 14, 2008

N,P-ligands. However, the enantioselective hydrogenation
was not trivial because the adducts are regarded as the
sterically demanding and doubly heteroatom-substituted
unusual alkenes. After extensive screening of the reaction
conditions, we finally found that a combination of a cationic
iridium complex7 and ligand 78 catalyzed the desired reaction
with high enantioselectivity (Scheme 1).9 The hydrogenation
Scheme 2. Desulfidation with Tris(trimethylsilyl)silane
Scheme 1. Iridium-Catalyzed Enantioselective Hydrogenation
In particular, the optically active phosphine 6a-S would be
useful as a ligand after further modifications.
In conclusion, we have found that the cesium-catalyzed
hydroamidation of 1-alkynylphosphine sulfides proceeds in
good yields with high regio- and stereoselectivities. In light
of the importance of organophosphorus compounds, the
products and their derivatives can be useful in organic
synthesis. In addition, we have demonstrated that the iridium-
catalyzed enantioselective hydrogenation of the adducts
afforded optically active phosphine sulfides. The protocol,
the sequential hydroamidation/hydrogenation, offers an
alternative to the conventional approach to chiral 2-amino-
1-phosphinoalkanes.
of 3aa in the presence of catalytic amounts of [IrCl(cod)]2,
AgBF4, and 7 under 0.1 MPa of hydrogen in boiling ethanol
provided 6a in excellent yield (93%) with 97% ee. The
hydrogenation of 3af was less enantioselective (89% ee), yet
high enough to potentially allow for improving the optical
purity by recrystallization.
Some of the phosphine sulfides thus synthesized were
subjected to radical desulfidation conditions10 to provide the
corresponding trivalent phosphines in high yields (Scheme 2).
Acknowledgment. This work was supported by Grants-
in-Aid for Scientific Research and GCOE Research from
MEXT and JSPS. A.K. acknowledges JSPS for financial
support.
(9) When (R)-BINAP was used as a ligand instead of 7, 91% ee of 6a
was obtained in 82% yield. However, (R)-BINAP was less effective for
the enantioselective hydrogenation of 3af to provide 6b in 99% yield with
15% ee.
Supporting Information Available: Experimental pro-
cedure and characterization data. This material is available
free of charge via the Internet at http://pubs.acs.org.
(10) Romeo, R.; Wozniak, L. A.; Chatgilialoglu, C. Tetrahedron Lett.
2000, 41, 9899–9902.
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