Iron-catalyzed olefin carbometalation [15]

Full text of DOI:10.1021/ja983066r

978
J. Am. Chem. Soc. 2000, 122, 978-979
Scheme 1
Iron-Catalyzed Olefin Carbometalation
Masaharu Nakamura, Atsushi Hirai, and Eiichi Nakamura*
Department of Chemistry, The UniVersity of Tokyo
Hongo, Bunkyo-ku, 113-0033, Japan
ReceiVed August 26, 1998
Among various transition metals, iron is nontoxic, cheap, and
hence of great potential synthetic use. We report herein the first
use of iron complexes as catalysts for olefin carbometalation and
for an asymmetric organometallic reaction. The reaction adds to
the repertoire of iron-catalyzed organometallic reactions, of which
only a few examples have thus far been reported;1 no effective
chiral ligand system for alkyliron species has been previously
developed. We have been studying the carbometalation of olefins
for their stereochemistry2,3 and for the possibility of using them
in new reactions, such as an olefinic analogues of the aldol
reaction.4 Here we describe the iron catalysis in the olefin
carbometalation as exemplified by the addition of Grignard and
organozinc reagents to cyclopropenone acetal 1 (Scheme 1) and
bicyclic olefins 4 and 5 (eqs 1 and 2). A new ternary catalytic
system, consisting of iron, chiral diphosphine, and diamine, has
been developed for catalytic enantioselective carbometalation with
dialkylzinc reagents. The present reaction allows the use of
functionalized alkyl, vinyl, and aryl organometallics, thus broad-
ening the scope of nucleophiles to be used for olefin carbometa-
lation reactions.5,6
The reaction of a Grignard reagent was investigated first.
Uncatalyzed reaction in THF did not take place at low temper-
atures and gave a complex mixture at higher temperatures (up to
65 °C). Among various transition metal complexes examined,
some metal complexes of Groups 6, 8, and 9 were found to
catalyze the reaction to a varying extent,7 and FeCl3 (3-5 mol
%) was the most effective. Poor catalytic activity was found for
nickel catalysts.5 Addition of a THF solution of FeCl3 to a mixture
of 1 and a Grignard reagent (1.2-1.5 equiv) kept between -78
and -45 °C immediately afforded a dark brown solution and after
0.5-5 h gave the desired 2-substituted cyclopropanone acetal 3
upon aqueous quenching. The reactions of phenyl, vinyl, and alkyl
Grignard reagents under these conditions afforded the substituted
cyclopropanone acetal 3 in good to excellent yields (entries 1-4
in Table 1). Notably, the reaction of the Grignard reagent
possessing â-hydrogen atoms took place in good yield. For
instance, 2-phenylethylmagnesium bromide (entry 4) afforded the
desired carbometalation product in high yield. Styrene and 1,4-
diphenylbutane (â-elimination and oxidative coupling products
in the initial transformation of Fe(III) to Fe(I))8 were formed in
a few percent yields, and there was no trace of unsubstituted
cyclopropanone acetal 3 (R1, R2 ) H), which could have formed
if metal hydride species had been generated in situ.9
The intermediate 2 can be trapped with carbon electrophiles
(entries 8-11). The reaction with trans-cinnamyl bromide under
iron catalysis took place exclusively in an SN2 manner with
conservation of the olefin geometry.10 The stereochemistry of the
trapping was exclusively (>97%) cis, as determined by NOE
experiment as well as by comparison with authentic samples.2
Organozinc reagents also took part in the iron-catalyzed
reaction under similar conditions. The reaction with diethylzinc
and dipentylzinc at -25 °C proceeded under the iron catalysis
conditions to give 3 with R1 ) C2H5, R2 ) H and 3 with R1 )
C5H11, R2 ) H in 73% and 91% yields, respectively (entries 5
and 6). The advantage of organozinc reagent rests on the tolerance
of the electrophilic center in the nucleophile,11 and zinc homoeno-
late12 of isopropyl propionate smoothly reacted with 1 through a
transition metal homoenolate species13 (entry 7).
The iron catalysis also operates in alkylative ring-opening
reactions of oxabicyclo olefins14 4 and 5, as shown in eqs 1 and
2. The addition of PhMgBr to 4, thus, took place at ambient
temperature in the presence of 10 mol % of FeCl3 to give
cyclohexenol 6 selectively in 62% yield. The Diels-Alder product
of furan and CPA (5) also takes part in the reaction to give the
bicyclic hexenol 7 in 55% yield.
(1) Davies, S. G. Organotransition Metal ChemistrysApplication to
Organic Synthesis; Pergamon Press: Oxford, 1982. Pearson, A. J. In
ComprehensiVe Organometallic Chemistry; Wilkinson, G., Stone, F. G. A.,
Abel, E. W., Eds.; Pergamon Press: Oxford, 1982; Vol. 8, p 939.
(2) (a) Nakamura, E.; Isaka, M.; Matsuzawa, S. J. Am. Chem. Soc. 1988,
110, 1297-1298. (b) Nakamura, E.; Kubota, K.; Isaka, M. J. Org. Chem.
1992, 57, 5809-5819. (c) Kubota, K.; Nakamura, M.; Isaka, M.; Nakamura,
E. J. Am. Chem. Soc. 1993, 115, 5867-5368. (d) Nakamura, M.; Arai, M.;
Nakamura, E. J. Am. Chem. Soc. 1995, 117, 1179-1180.
(3) Hoveyda, A. H.; Heron, N. M. In ComprehensiVe Asymmetric Catalysis;
Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999; p
431.
(4) (a) Nakamura, E.; Kubota, K. J. Org. Chem. 1997, 62, 792-793. (b)
Nakamura, E.; Kubota, K.; Sakata. G. J. Am. Chem. Soc. 1997, 119, 5457-
5458. (c) Kubota, K.; Nakamura, E. Angew. Chem., Int. Ed. Engl. 1997, 36,
2491-2493. (d) Nakamura, E.; Kubota, K. Tetrahedron Lett. 1997, 38, 7099-
7102. (e) Nakamura, E.; Sakata, G.; Kubota, K. Tetrahedron Lett. 1998, 39,
2157-2159.
(5) Marek, I. J. Chem. Soc., Perkin Trans. 1 1999, 535-544. Kondakov,
D. Y.; Negishi, E.-i. J. Am. Chem. Soc. 1996, 118, 1577-1578. Kondakov,
D. Y.; Negishi, E.-i. J. Am. Chem. Soc. 1995, 117, 10771-10772. Klein, S.;
Marek, I.; Poisson, J.-F.; Normant, J.-F, J. Am. Chem. Soc. 1995, 117, 8853-
8854.
(6) Gomez-Bengoa, E.; Heron, N. M.; Didiuk, M. T.; Luchaco, C. A.;
Hoveyda, A. H. J. Am. Chem. Soc. 1998, 120, 7649-7650. Yanagisawa, A.;
Habaue, S.; Yamamoto, H. J. Am. Chem. Soc. 1989, 111, 366-368.
(7) In the presence of 3 mol % of a transition metal complex, the addition
of C6H5MgBr to 1 took place at -45 °C for 2 h in 30% (FeCl3), 20% (Fe-
(acac)3), 16% (CoCl2), 16% (CrCl2), 8% (CoCl(PPh3)3), 7% (CoCl2(PPh3)2,
and 4% yields (CrCl3). FeCl2, RuCl3, Ru(acac)3, RhCl(PPh3)3, and Cr(acac)3
afforded 3 in less than 2% yield under the same conditions.
(8) Cf.: Tamura M.; Kochi, J. K. J. Am. Chem. Soc. 1971, 93, 1487-
1489. Neumann, S. M.; Kochi, J. K. J. Org. Chem. 1975, 40, 599-606. Smith,
R. S.; Kochi, J. K. J. Org. Chem. 1976, 41, 502-509.
(9) Kochi, J. K. Organometallic Mechanisms and Catalysis; Academic
Press: New York, 1978; p 246.
(10) Yanagisawa, A.; Nomura, N.; Yamamoto H. Synlett 1991, 513-514.
Sekiya, K.; Nakamura, E. Tetrahedron Lett. 1988, 40, 5155-5156.
(11) Nakamura, E. Synlett 1991, 539. Nakamura, M.; Nakamura, E. J. Synth.
Org. Chem., Jpn. 1998, 56, 632-644.
(12) Nakamura, E.; Aoki, S.; Sekiya, K.; Oshino, H.; Kuwajima, I. J. Am.
Chem. Soc. 1987, 109, 8056-8066.
(13) Cf.: Aoki, S.; Fujimura, T.; Nakamura, E.; Kuwajima, I. J. Am. Chem.
Soc. 1988, 110, 3296-3298. Fujimura, T.; Aoki, S.; Nakamura, E. J. Org.
Chem. 1991, 56, 2810-2821.
(14) Lautens, M.; Ma, S. J. Org. Chem. 1996, 61, 7246-7247.
10.1021/ja983066r CCC: $19.00 © 2000 American Chemical Society
Published on Web 01/25/2000

Communications to the Editor
J. Am. Chem. Soc., Vol. 122, No. 5, 2000 979
Table 1. Iron-Catalyzed Carbometalation of Cyclopropenone
Acetal, Forming 3 (Scheme 1, Top)a
Table 2. Enantioselective Carbozincation Reaction (Scheme 1,
Bottom)a
3
entry
R2Zn
ligandb
cosolvent
yield (%)c
ee (%)d
organometallics,
62e
64g
88e
73
92(R)
90(R)
89(R)
85(R)
71(R)
79(R)
0(-)
2(R)
13(S)
35(R)
entry
R1-metal
R2 b
yield (%)c
1
2f
3
4
5
Pr2Zn
Et2Zn
Et2Zn
Et2Zn
Pr2Zn
Et2Zn
Et2Zn
Et2Zn
Et2Zn
Et2Zn
A
A
A
A
B
B
B
C
D
E
THP
THP
THP
THF
THF
THF
THF
THF
THF
THF
1
2
3
4
5
6
7
8
9
C6H5MgBr
CH2dCHMgBr
CH3MgBr
H
H
H
H
H
H
H
96
75
66
85
73
91
76
85e
75e
90e
56f
82g
78g
69
C6H5CH2CH2MgCl
6
(C2H5)2Znd
7h
8
(C5H11)2Znd
55
73
4
(iPrOCOCH2CH2)2Zn
C6H5MgBr
9
10
CH2dCHCH2
(E)-C6H5CHdCHCH2
CH3
C6H5MgBr
C6H5MgBr
C6H5MgBr
10
11
a The reaction were carried out in a manner described in footnote
16. b A, [(R)-p-Tol-BINAP]: (R)-2,2′-bis[bis(4-methylphenyl)phos-
phino]-1,1′-binaphthyl. B, [(R)-BINAP]: (R)-2,2′-bis(diphenylphos-
phino)-1,1′binaphthyl. C, [(R)-(S)-BPPFA]: (R)-N,N-dimethyl-1-[(S)-
1′,2-bis(diphenylphosphino)ferrocenyl]ethylamine. D, [(S,S)-BPPM]:
(2S,4S)-tert-butyl 4-(diphenylphosphino)-2-(diphenylphosphinomethyl)-
1-pyrrolidinecarboxylate. E, [(R)-(S)-PPFA]: (R)-N,N-dimethyl-1-[(S)-
2-(diphenylphosphino)ferrocenyl]ethylamine. TMEDA (2.0-3.0 equiv
for dialkylzinc) was also added unless otherwise noted. c GLC yield
otherwise noted. d Absolute configuration, which was determined by
correlation to a known compound2d for the propyl product or by
inference for the ethyl product, is shown in the parentheses. e NMR
yield. f Large scale experiment. g Isolated yield. h TMEDA was absent.
CH(C6H5)OH
a The reactions were carried out in THF or THF/toluene at -78 to
-25 °C for 0.5-5 h in the presence of 3-5 mol % of FeCl3. b Saturated
aqueous NH4Cl was used as electrophile (entries 1-7). Allyl bromide,
(E)-cinnamyl chloride, methyl iodide, and benzaldehyde (2-3 equiv)
were used as electrophile for entries 8-11, respectively. c Yield based
on pure isolated material. d Purchased as 1.0 M toluene solution from
Tri Chemical Laboratory Inc. e Diastereomeric ratio was determined
as >97:3 by H NMR. f A 1:1 diastereomer mixture for the benzylic
1
chiral center.
Despite numerous reports on the metal/ligand systems in
transition metal catalysis, nothing has been known about the effect
of chiral ligand on the alkyliron species. Exploration of enanti-
oselective reaction led to a new ternary catalytic system, iron/
chiral chelate diphosphine/diamine15 for the reaction of zinc
reagent (bottom of Scheme 1). As shown in Table 2, addition of
dialkylzinc to CPA proceeded with 89-92% ee in the presence
of (R)-p-Tol-BINAP16 (7.5 mol %), FeCl3 (5 mol %), and
N,N,N′,N′-tetramethylethylenediamine (TMEDA, 2.5 equiv for
organozinc reagent) in toluene/tetrahydropyran (THP) solution
(entries 1-3).17 Enantioselectivity was significantly reduced by
the use of THF instead of THP as cosolvent (entry 2 vs 4). Despite
only small structural difference, BINAP ligand showed signifi-
cantly lower enantioselectivity (entries 4 and 6).
Thus, in the absence of TMEDA, the FeCl3-catalyzed reaction
of Et2Zn with 1 in the presence of (R)-BINAP (7.5 mol %)15 gave
a racemic mixture (Table 2, entry 7).
Various chiral phosphine ligands were examined for the
enantioselective carbozincation and found to be much less
effective than p-Tol-BINAP and BINAP.18 The reaction also took
place smoothly with bidentate phosphines other than BINAP, but
with much lower selectivities (e.g., C, (R)-(S)-BPPFA, entry 8,
and D, (S,S)-BPPM, entry 9). In addition, the reaction rate
depended on the phosphine structure; thus, the reaction was faster
with a bidentate phosphine than with a monodentate one (e.g.,
E, (R)-(S)-PPFA, with which the reaction was extremely sluggish
(4% yield, entry 10)).
In summary, we found that iron catalysts are effective for
promotion of olefin carbometalation. The new (soft) phosphine/
(hard) diamine ligand system for the iron/zinc bimetallic reagent
provides a prospect for further development of enantioselective
synthetic transformations using iron as catalyst.
Although TMEDA (>2.0 equiv for Et2Zn) slowed the reaction,
its presence was essential for the enantioselective carbometalation.
(15) A tridentate amine, N,N,N′,N”,N”-pentamethyldiethylenetriamine,
exerted the same effects. Interestingly enough, monodentate amines (triethyl-
N,N-methylpyrroridine and N-methylmorphorine) produced a racemic product.
(16) Takaya, H.; Mashima, K.; Koyano, K.; Yagi, M.; Kumobayashi, H.;
Taketori, T.; Akutagawa, S.; Noyori, R. J. Org. Chem. 1986, 51, 629-635.
Miyashita, A.; Yasuda, A.; Takaya, H.; Toriumi, K.; Ito, T.; Souchi, T.; Noyori,
R. J. Am. Chem. Soc. 1980, 102, 7932-7934.
(17) To a mixture of (R)-p-Tol-BINAP (0.102 g, 0.15 mmol) and 1.0-M
toluene solution of Et2Zn (4.0 mL, 4.0 mmol) was added dropwise a 0.1-M
THP solution of FeCl3 (1.0 mL, 0.1 mmol) and TMEDA (1.51 mL, 10.0 mmol)
at 25 °C. After being stirred for 10 min at 25 °C, the reaction mixture was
diluted with toluene (8.2 mL). A solution of CPA (1, 0.28 mL, 2.0 mmol) in
toluene (5 mL) was added over 2 h. The reaction mixture was stirred for 6
days at 0 °C and at 10 °C for 1 day and then quenched with saturated NH4Cl.
Purification with silica gel chromatography and bulb-to-bulb distillation (130-
140 °C/15-20 mmHg) afforded pure 2-ethylcyclopropanone acetal 3 (R1 )
Et, R2 ) H) (0.219 g, 64% yield). Chiral GLC analysis showed that the (R)-
product was obtained as a major enantiomer with 90% ee. In a smaller scale
(0.4 mmol) experiment, the carbozincation product was obtained in 88% yield
with 89% ee (Table 2, entry 3).
Acknowledgment. We thank Prof. K. Mashima at the University of
Osaka for helpful discussions. A.H. thanks the Japan Society for
Promotion of Science for a scholarship. This work is supported by
Monbusho, Grant-in-Aid for Scientific Research on Priority Area (No.
403-11166220, “Molecular Physical Chemistry”).
Supporting Information Available: Experimental and characteriza-
tion details (PDF). This material is available free of charge via the Internet
at http://pubs.acs.org.
JA983066R
(18) Chiral ligands such as (-)-sparteine, PyBOX, bis-oxazoline (BOX),
DIOP, and CHIRAPHOS were ineffective either to promote the reaction or
to effect enantioselective reaction.