Manganese-catalyzed synthesis of hydantoin derivatives from terminal alkynes and isocyanates

Article abstract of DOI:10.1246/cl.2008.740

Hydantoin derivatives were obtained by the reactions of terminal alkynes with isocyanates in the presence of a catalytic amount of a manganese complex, MnBr(CO)₅. This reaction also proceeded using a rhenium complex, Re₂(CO)₁₀, or an iron complex, Fe(CO)₅, as a catalyst. Copyright

Full text of DOI:10.1246/cl.2008.740

740
Chemistry Letters Vol.37, No.7 (2008)
Manganese-catalyzed Synthesis of Hydantoin Derivatives from Terminal Alkynes and Isocyanates
Yoichiro Kuninobu,Ã Kou Kikuchi, and Kazuhiko TakaiÃ
Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University,
Tsushima, Okayama 700-8530
(Received April 24, 2008; CL-080429; E-mail: kuninobu@cc.okayama-u.ac.jp, ktakai@cc.okayama-u.ac.jp)
Hydantoin derivatives were obtained by the reactions of ter-
minal alkynes with isocyanates in the presence of a catalytic
amount of a manganese complex, MnBr(CO)5. This reaction
also proceeded using a rhenium complex, Re2(CO)10, or an iron
complex, Fe(CO)5, as a catalyst.
Table 1. Reactions between several terminal alkynes 1 and
phenyl isocyanate (2a)a
Ph
R
N
MnBr(CO)5 (5.0 mol %)
O
+
R
Ph N C O
Dioxane, 150 °C, 24 h
N
O
Ph
1
2a
3
Yield/%b
R
Entry
Hydantoin derivatives have been used in a wide number
of applications, such as bioactive compounds1 and amino acids
synthesis.2 There have been many approaches to the synthesis
of hydantoin derivatives including the Urech method,3
the Bucherer–Bergs type reaction,4 and transformations via
intramolecular cyclization.5 Metal-promoted preparations of
hydantoins have also been reported; iron-,6 lead-,7 and sodium-
mediated8 reactions, and ruthenium-9 and palladium-catalyzed10
reactions. Recently, fourth-row-transition-metal-catalyzed reac-
tions have received much attention because they are abundant
and cheap compared to fifth- or sixth-row transition metals.
However, examples of fourth-row-transition-metal-catalyzed
syntheses of hydantoin derivatives are still rare. We will report
herein the manganese-catalyzed construction of hydantoin
frameworks from terminal alkynes and isocyanates.
p-MeOC6H4
p-MeC6H4
p-CF3C6H4
p-ClC6H4
77 (82)
79 (85)
93 (95)
88 (90)
89 (89)
1
2
3
4
5
1b
1c
1d
1e
1f
3b
3c
3d
3e
3f
p-BrC6H4
6c
7c
1g
1h
3g
3h
65 (70)
32 (40)
n-C10H21
PhCH2OCH2
c-C6H11
8c
9
15 (22)
89 (90)
1i
1j
3i
3j
a1 (1.0 equiv); 2a (2.2 equiv). bIsolated yield. The yield determined
by 1H NMR is reported in parentheses. 2a (2.0 equiv).
c
Treatment of phenylalkyne 1a with phenyl isocyanate (2a)
in the presence of a catalytic amount of a manganese complex,
MnBr(CO)5, in dioxane at 150 ꢀC for 24 h in a sealed tube
gave hydantoin derivative 3a in 91% yield stereoselectively
(eq 1).11–13 We also found that a catalytic amount of a rhenium
complex, Re2(CO)10 (2.5 mol %), or an iron complex, Fe(CO)5
(5.0 mol %),14 promoted the formation of hydantoin derivative
3a under the same reaction conditions in 55% and 75% yields,
respectively.
toin derivatives under the conditions. The iron complex,
Fe(CO)5, promoted the reactions; however, the yields of hydan-
toins 3b–3j were moderate (See the Supporting Information,
Table S1).16 In the case of Re2(CO)10, the yields of 3b–3j
decreased considerably (See the Supporting Information,
Table S1).16
Treatment of an aryl isocyanate bearing an electron-donat-
ing group, 2b or 2c, with phenylacetylene (1a) produced hydan-
toins 3k and 3l in 93% and 91% yields, respectively (Table 2,
Entries 1 and 2). An aryl isocyanate having an electron-donating
group, 2d, gave hydantoin 3m in 94% yield (Table 2, Entry 3).
A secondary alkyl isocyanate 2e provided hydantoin derivative
3n in good yield (Table 2, Entry 4). Although Re2(CO)10 and
Fe(CO)5 promoted the reactions, the yields of hydantoins 3k–
Ph
N
MnBr(CO)5
(5.0 mol %)
Ph
O
+
Ph
2a
(2.2 equiv)
N C O
Ph
1a
(1.0 equiv)
(1)
N
Dioxane
150 °C, 24 h
O
Ph
3a 91%
Terminal aromatic alkynes having an electron-donating
group at the para position, 1b and 1c, gave hydantoin derivatives
3b and 3c in 77% and 79% yields, respectively (Table 1, Entries
1 and 2). By using an alkyne bearing an electron-withdrawing
group, 1d, the yield was improved and hydantoin 3d was
obtained in 93% yield (Table 1, Entry 3). Aryl alkynes with a
halogen atom at the para position, 1e and 1f, produced hydan-
toins 3e and 3f in good yields without loss of the halogen
atom (Table 1, Entries 4 and 5). By the reaction of enyne 1g with
phenyl isocyanate (2a), hydantoin 3g was also produced in mod-
erate yield (Table 1, Entry 6). Terminal alkynes having primary
alkyl groups, 1h–1j, afforded hydantoins 3h and 3i in low yields
(Table 1, Entries 7 and 8). In contrast, the reaction of secondary
alkyl alkyne 1j afforded hydantoin 3j in 89% yield (Table 1,
Entry 9). Internal alkynes, on the other hand, did not give hydan-
Table 2. Reactions between terminal alkyne 1a and several
isocyanates 2a
R
Ph
N
MnBr(CO)5 (5.0 mol %)
O
+
Ph
R
N C O
N
Dioxane, 150 °C, 24 h
1a
2
O
R
3
Entry
R
Yield/%b
1
2
3
4
p-MeOC6H4
p-MeC6H4
p-CF3C6H4
c-C6H11
2b
2c
2d
2e
3k
3l
3m
3n
93 (95)
91 (94)
94 (95)
84 (90)
a1a (1.0 equiv); 2 (2.2 equiv). bIsolated yield. The yield determined
by 1H NMR is reported in parentheses.
Copyright Ó 2008 The Chemical Society of Japan

Chemistry Letters Vol.37, No.7 (2008)
741
Financial support by a Grant-in-Aid for Scientific Research
on Priority Areas from MEXT and for Young Scientists (B)
(No. 18750088) from JSPS is acknowledgment.
R
H
R'
N
O
MnI
R
R
MnIII
H
N
R'
R'
N
C O
R'
O
R'
H MnIII
N
References and Notes
O
R'
R'
R
HN
1
a) F. L. Wessels, T. J. Schwan, S. F. Pong, J. Pharm. Sci. 1980,
69, 1102. b) A. G. Caldwell, C. J. Harris, R. Stepney, N.
Wittaker, J. Chem. Soc., Parkin Trans. 1 1980, 495. c) N.
Mehta, C. A. Risinger Dinguid, F. E. Soroko, J. Med. Chem.
1981, 24, 465. d) P. F. Kador, J. H. Kinoshita, N. E. Sharpless,
J. Med. Chem. 1985, 28, 841. e) W. J. Brouillette, V. P.
Jestkov, M. L. Brown, M. S. Akhtar, T. M. DeLorey, G. B.
Brown, J. Med. Chem. 1994, 37, 3289. f) T. Mizuno, T. Kino,
T. Ito, T. Miyata, Synth. Commun. 2000, 30, 1675.
a) E. Ware, Chem. Rev. 1950, 46, 403. b) C. A. Lopez, G. G.
Trigo, Adv. Heterocycl. Chem. 1985, 38, 177. c) S. G. Burton,
R. A. Dorrington, Tetrahedron: Asymmetry 2004, 15, 2737.
F. Urech, Justus Liebigs Ann. Chem. 1873, 165, 99.
a) H. T. Bucherer, W. J. Steiner, J. Prakt. Chem. 1934, 140,
291. b) H. T. Bucherer, V. A. Lieb, J. Prakt. Chem. 1934,
141, 5.
R'
R
N
MnI
O
O
H
N
C O
H
R'
III N
N
Mn
O
R
R
O
O
MnI
N
N
R'
R'
O
Scheme 1. Proposed mechanism for the formation of hydantoin
derivatives.
2
3n with the two catalysts were lower than those with MnBr(CO)5
(See the Supporting Information, Table S2).16 However, primary
and tertiary alkyl isocyanates (2-phenylethyl isocyanate, octa-
decyl isocyanate, and 1-adamantyl isocyanate) did not provide
the corresponding hydantoin derivative because of the trimeriza-
tion of the isocyanates under the reaction conditions. The forma-
tion of hydantoin derivative did not proceed using trimethylsilyl
isocyanate and tosyl isocyanate.
To elucidate the reaction mechanism, we carried out the re-
action of 4 in the presence of a manganese catalyst, MnBr(CO)5,
at 150 ꢀC for 24 h (eq 2). As a result, hydantoin 3l was obtained
quantitatively. This result suggests that hydantoin 3l was formed
via the formation of 4.
3
4
5
a) M. M. Sim, A. Ganesan, J. Org. Chem. 1997, 62, 3230.
b) I. Belai, Tetrahedron Lett. 2003, 44, 7475. c) A. Volonterio,
M. Zanda, Tetrahedron Lett. 2003, 44, 8549. d) P. M.
Fresneda, M. Castaneda, M. A. Sanz, P. Molina, Tetrahedron
Lett. 2004, 45, 1655. e) A. Alizadeh, E. Sheikhi, Tetrahedron
Lett. 2007, 48, 4887.
6
a) Y. Ohshiro, K. Kinugasa, T. Minami, T. Agawa, J. Org.
Chem. 1970, 35, 2136. b) A. Baba, Y. Ohshiro, T. Agawa,
J. Organomet. Chem. 1975, 87, 247.
7
8
9
A. G. Davies, R. J. Puddephatt, J. Chem. Soc. C 1968, 317.
S. F. A. Kettle, et al., J. Chem. Soc. 1965, 5737.
G. Suss-Fink, F. Schmidt, G. Herrmann, Chem. Ber. 1987, 120,
¨
1451.
Ph
Ph
HN
N
MnBr(CO)5 (5.0 mol %)
(2)
O
O
10 M. Beller, M. Eckert, W. A. Moradi, H. Neumann, Angew.
Chem., Int. Ed. 1999, 38, 1454.
N
N
Dioxane, 150 °C, 24 h
O
O
11 The structure of 3a was determined by a comparison with the
reported data in ref 6a, and by X-ray single-crystal structure
analysis.
12 Investigation of temperature in the reaction between phenyl-
acetylene (1a) (1.0 equiv) and p-methoxyphenyl isocyanate
(2b) (2.0 equiv): 50 ꢀC, 0%; 80 ꢀC, 30%; 100 ꢀC, 45%;
115 ꢀC, 59%; 135 ꢀC, 62%; 150 ꢀC, 75%.
13 An iron complex, Fe(acac)3 (5.0 mol %), provided hydantoin
derivative 3a in 8% yield. Only a trace amount of hydantoin
3a was obtained in the presence of a ruthenium complex,
Ru3(CO)12 or RuH2(CO)(PPh3)3. The reaction did not proceed
using ReBr(CO)5, [ReBr(CO)3(thf)]2, FeCl3, and RhCl3.
14 In a reported paper (ref 6), the formation reaction of hydantoins
proceeded stoichiometrically using an iron complex, Fe(CO)5.
However, as a result of our investigation, the iron complex
promoted the reaction catalytically.
15 Another reaction mechanism can be considered: (1) the forma-
tion of a manganese–alkylidene intermediate; (2) nucleophilic
addition of isocyanate to the intermediate; (3) addition of
another isocyanate; (4) addition of a manganese–carbon bond
of the alkenylmanganese moiety; (5) isomerization of an
olefinic moiety.
4
3l >99%
Judging from the result in eq 2 and the geometry of the olefin
moiety of the products, we propose the following mechanism for
the hydantoin synthesis (Scheme 1):15 (1) oxidative addition of a
terminal alkyne to a manganese center; (2) insertion of an iso-
cyanate into the manganese–carbon bond of the manganese ace-
tylide; (3) insertion of another isocyanate into the manganese–
nitrogen bond of the manganese amide intermediate; (4) reduc-
tive elimination and intramolecular cyclization.
By the treatment of hydantoin 3o with cerium ammonium
nitrate (CAN) at 25 ꢀC for 24 h, oxidative carbon–carbon double
bond cleavage took place, and imidazolidinetrione 5 was ob-
tained in 89% yield (eq 3). In this reaction, benzaldehyde was
obtained as a side product.
Ph
N
Ph
N
Ph
CAN (8.0 equiv)
O
O
O
(3)
CH3CN / H2O (2:1)
N
N
O
Ph
25 °C, 24 h
O
Ph
5 89%
3o
In summary, we have succeeded in MnBr(CO)5-catalyzed
synthesis of hydantoin derivatives from terminal alkynes and
isocyanates. The reaction proceeds with a catalytic amount
of a fourth-row-transition-metal complex, and has wide applica-
bility.
16 Supporting Information is available electronically on the
CSJ-Journal Web site, http://www.csj.jp/journals/chem-lett/
index.html.
Published on the web (Advance View) June 7, 2008; doi:10.1246/cl.2008.740