[Lewis acid]+[Co(CO)4]- complexes: A versatile class of catalysts for carbonylative ring expansion of epoxides and aziridines

Article abstract of DOI:10.1002/1521-3773(20020802)41:15<2781::AID-ANIE2781>3.0.CO;2-S

Efficient carbonyl insertion into C-O and C-N bonds using [Lewis acid]+[Co(CO)₄]^- complexes 1 and 2 gives regio- and stereoselective carbonylation of a variety of epoxides and aziridines to yield β-lactones and β-lactams, respectively. Both transformations are proposed to occur by the same mechanism, yielding products with inversion of configuration at the site of CO insertion.

Full text of DOI:10.1002/1521-3773(20020802)41:15<2781::AID-ANIE2781>3.0.CO;2-S

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Comprehensive Heterocyclic Chemistry II, Vol. 3 (Eds.: A. R.
Katrizky, C. W. Rees, E. F. V. Scriven), Pergamon, Oxford, 1996,
pp. 77 ± 220.
‡
À
[
Lewis Acid] [Co(CO) ] Complexes: A
4
Versatile Class of Catalysts for Carbonylative
Ring Expansion of Epoxides and Aziridines**
[
2ꢀ a) B. Iddon, Heterocycles 1985, 23, 417 ± 443; b) B. Iddon, R. I.
Ngochindo, Heterocycles 1994, 38, 2487 ± 2568; c) P. Merino, Prog.
Heterocycl. Chem. 1999, 11, 21 ± 42.
3ꢀ F. H. Pinkerton, S. F. Themes, J. Heterocycl. Chem. 1972, 9, 67 ± 72.
4ꢀ A. M. Roe, J. Chem. Soc. 1963, 2195 ± 2200.
Viswanath Mahadevan, Yutan D. Y. L. Getzler, and
Geoffrey W. Coates*
[
[
[
[
[
[
5ꢀ R. Gompper, E. Hoyer, H. Herlinger, Chem. Ber. 1959, 92, 550 ± 563.
6ꢀ E. Regel, K.-H. B¸chel, Liebigs Ann. Chem. 1977, 145 ± 148.
7ꢀ D. J. Hlasta, Org. Lett. 2001, 3, 157 ± 159.
8ꢀ a) L. S. Hegedus, Transition Metals in the Synthesis of Complex
Organic Molecules, University Science Books, Mill Valley, 1999; b) J.
Tsuji, Transition Metal Reagents and Catalysts, Wiley, Chichester,
Introduction of carbonyl functional groups by using tran-
sition-metal-catalyzed carbon monoxide (CO) insertion is a
synthetically useful transformation.[
1±3ꢀ
Application of this
methodology, in conjunction with readily available epoxide
[4ꢀ
and aziridine substrates provides facile access to b-lactones
and b-lactams,
2
000.
[5, 6ꢀ
useful precursors for organic synthesis as
[
9ꢀ a) M. Kosugi, M. Koshiba, A. Atoh, H. Sano, T. Migita, Bull. Chem.
Soc. Jpn. 1986, 59, 677 ± 679; b) T. Sakamoto, H. Nagata, Y. Kondo, M.
Shiraiwa, H. Yamanaka, Chem. Pharm. Bull. 1987, 35, 823 ± 828;
c) A. S. Bell, D. A. Roberts, K. S. Ruddock, Tetrahedron Lett. 1988, 39,
well as for the synthesis of polymers such as poly(3-
hydroxyalkanoates)[ and poly(b-peptides).
7ꢀ
[8, 9ꢀ
Few catalysts
are known to perform ring-expansive CO insertion into
5
1
013 ± 5016; d) D. A. Evans, T. Bach, Angew. Chem. 1993, 105, 1414 ±
415; Angew. Chem. Int. Ed. Engl. 1993, 32, 1326 ± 1327; e) J.
[10, 11, 12dꢀ
epoxides to give b-lactones.
Likewise, a limited
number of reagents[ and catalysts[12, 14, 15ꢀ are known to
carbonylate aziridines to yield b-lactams. Recently, regiose-
lective epoxide and aziridine carbonylation was achieved
13ꢀ
Ezquerra, C. Lamas, A. Pastor, J. L. GarcÌa-NavÌo, J. J. Vaquero,
Tetrahedron 1997, 53, 12755 ± 12764.
[
[
10ꢀ a) S. Pivsa-Art, T. Satoh, Y. Kawamura, M. Miura, M. Nomura, Bull.
Chem. Soc. Jpn. 1998, 71, 467 ± 473; b) M. Ababri, F. Dehmel, P.
Knochel, Tetrahedron Lett. 1999, 40, 7449 ± 7453.
11ꢀ a) T. Fukuyama, N. Chatani, J. Tatsumi, F. Kakiuchi, S. Murai, J. Am.
Chem. Soc. 1998, 120, 11522 ± 11523; b) N. Chatani, T. Fukuyama, H.
Tatamidani, F. Kakiuchi, S. Murai, J. Org. Chem. 2000, 65, 4039 ± 4047.
12ꢀ K. L. Tan, R. G. Bergman, J. A. Ellman, J. Am. Chem. Soc. 2001, 123,
using a catalyst system consisting of a mixture of [PPNꢀ-
[12dꢀ
[
Co(CO) ꢀ and BF ¥ Et O (PPN ˆ Ph PˆNˆPPh ).
How-
4
3
2
3
3
ever, most of these catalysts require long reaction times, high
temperatures, high catalyst loading, and/or external additives.
There is continuing motivation for developing fast, single-
component catalysts; ideally a single catalyst would efficiently
carbonylate both epoxides and aziridines. Herein, we report a
well-defined [Cp Ti(thf) ꢀ[Co(CO) ꢀ catalyst (1; Cp ˆ
[
[
2
685 ± 2686.
13ꢀ It is well known that iridium complexes react with a variety of alkynes
to form iridacyclopentadiene complexes; see: a) G. J. Leigh, R. L.
Richards in Comprehensive Organometallic Chemistry, Vol. 5 (Eds.:
G. Wilkinson, F. G. A. Stone, E. W. Abel), Pergamon, Oxford, 1982,
pp. 541 ± 628; b) J. D. Atwood in Comprehensive Organometallic
Chemistry II, Vol. 8 (Eds.: E. W. Abel, F. G. A. Stone, G. Wilkinson),
Pergamon, Oxford, 1995, pp. 303 ± 417.
14ꢀ Examples of silylative dimerization of aromatic aldehydes catalyzed
by transition-metal complexes: a) E. Frainnet, R. Bourhis, F. Simonin,
F. Moulines, J. Organomet. Chem. 1976, 105, 17 ± 31; b) H. Shimada, J.-
P. Q¸, H. Matsuzaka, Y. Ishii, M. Hidai, Chem. Lett. 1995, 671 ± 672.
2
2
4
[16ꢀ
C H ),
readily synthesized from commercially available
5
5
[
Cp Ti(CO) ꢀ and [Co (CO) ꢀ, is efficient for carbonylation of
2 2 2 8
both epoxide and aziridine substrates. During the course of
this work we discovered that the discrete catalyst [(sal-
[
[11, 17ꢀ
ph)Al(thf) ꢀ[Co(CO) ꢀ (2),
is also active for regioselec-
2
4
tive aziridine carbonylation (Scheme 1).
À
The [Co(CO)4ꢀ ion is the putative active species for CO
2 8
We also have found that [Co (CO) ꢀ catalyzes the silylative dimeriza-
tion of aromatic aldehydes: c) S. Murai, T. Kato, N. Sonoda,
unpublished data.
[1, 11, 12aꢀ
insertion reactions that use [Co (CO) ꢀ as the catalyst.
2
8
Based on this postulate, a variety of [cationꢀ[Co(CO) ꢀ
4
18ꢀ
[11ꢀ
[
15ꢀ Many examples of carbopalladation to CÀO double bonds have been
complexes[ were previously screened
for CO insertion
reported; see: I. P. Beletskaya, A. V. Cheprakov, Chem. Rev. 2000,
1
into propylene oxide. Complexes 1 and 2 are efficient catalysts
for the carbonylation of a variety of both epoxides and
aziridines.
00, 3009 ± 3066.
16ꢀ J. F. Hartwig, J. Am. Chem. Soc. 1996, 118, 7010 ± 7011.
8
17ꢀ A similar reaction is known for the case of [Co (CO) ꢀ; see: A. J.
[
[
2
Chalk, J. F. Harrod, J. Am. Chem. Soc. 1967, 89, 1640 ± 1647.
18ꢀ A 1-methyl-3-(dimethylsilyl)imidazol-2-ylidene may be involved as a
key intermediate in the present reaction; see: S. Sol e¬ , H. Gornitzka,
O. Guerret, G. Bertrand, J. Am. Chem. Soc. 1998, 120, 9100 ± 9101.
Catalyst 1 (5 mol%) regioselectively carbonylates a variety
of epoxides under mild conditions and in high yields.
Propylene oxide is converted into b-butyrolactone in 95%
yield in 4 h at 608C; the carbonylation is highly regioselective
producing exclusively the 4-methyloxetan-2-one isomer (Ta-
[
ble 1, entry 1). Carbonylation of propylene oxide was not
observed with other potential catalysts[
18, 19ꢀ
under a variety of
[
*ꢀ Prof. Dr. G. W. Coates, Dr. V. Mahadevan, Y. D. Y. L. Getzler
Department of Chemistry and Chemical Biology
Baker Laboratory, Cornell University
Ithaca, New York 14853-1301 (USA)
Fax : (‡1)607-255-4137
E-mail: gc39@cornell.edu
[
**ꢀ G.W.C. gratefully acknowledges a Packard Foundation Fellowship in
Science and Engineering, an Arnold and Mabel Beckman Foundation
Young Investigator Award, and an NSF CAREER Award. V.M. was
supported by the Cornell Center for Materials Research.
Supporting information for this article is available on the WWW under
http://www.angewandte.org or from the author.
Angew. Chem. Int. Ed. 2002, 41, No. 15
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Table 1. Carbonylation of epoxides to b-lactones using 1.[aꢀ
conditions, which included changes in catalyst loading (2-
0 mol%), temperature (50 ± 1008C), and reaction time (12±
48 h). (R)-Propylene oxide is converted into (R)-b-butyrolac-
tone in 95% yield with >99% retention of configuration
1
Entry Substrate
Temp Time Products
Yield
[%ꢀ[
bꢀ
[
8Cꢀ
[hꢀ
4
(
Table 1, entry 2), consistent with the high regioselectivity
1
60
60
95
observed for CO insertion. Retention of stereochemistry
allows the synthesis of enantiomerically enriched b-lactones
from readily available chiral epoxides.[ Compound 1 also
catalyzes the transformation of 1,2-epoxybutane to 4-ethyl-
oxetan-2-one (Table 1, entry 3). Functional epoxides such as
20ꢀ
2
4
95[cꢀ
1,2-epoxy-5-hexene (Table 1, entry 4) and epichlorohydrin
(
Table 1, entry 5) are carbonylated to the corresponding
3
4
5
60
60
60
4
4
5
99
90
60
lactones. The hindered substrate isobutylene oxide reacts to
generate a mixture of isomeric lactones in a 4:1 ratio with
9
0% overall yield (Table 1, entry 6).
Catalyst 1 also carbonylates cis- and trans-2,3-epoxybutanes
regioselectively to trans- and cis-lactones, respectively, in high
yield and with inversion of configuration (Table 1, entries 7
and 8). The cis- and trans-lactone products were individually
identified by comparing C NMR spectroscopic data with
those reported,[
1
3
21, 22ꢀ
as well as, by pyrolysis; thermal syn de-
carboxylation of the lactones generates alkenes with retention
of stereochemistry.[ Comparison of the resulting alkenes
with authentic cis- and trans-2-butene samples using H NMR
6
7
8
50
60
60
3
10
10
90
99
75
23ꢀ
1
spectroscopy allowed identification of the parent lac-
tones.[
24, 25ꢀ
Both 1 and 2 are capable of carbonylating aziridines to
generate b-lactams, although they exhibit interesting differ-
ences in reactivity. Catalyst 1 carbonylates 1-benzyl-2-methyl
aziridine in 90% yield compared to 50% obtained with 2
under similar conditions (Table 2, entry 1). However, in both
cases, CO insertion occurs selectively at the least hindered
ring CÀN bond. Catalyst 1 also carbonylates 7-benzyl-7-
[
aꢀ 5 mol% catalyst 1 (0.2m in DME), 6200 kPa (900 psi) CO, 1.92 mmol
1
epoxide. [bꢀ Yields determined by H NMR spectroscopy. [cꢀ > 99% (R)-
b-Butyrolactone.
azabicyclo[4.1.0ꢀheptane in 80% yield compared to <5%
Table 2. Carbonylation of aziridines to b-lactams using 1 and 2.[aꢀ
Entry
1
Substrate
Catalyst
Temp [8Cꢀ
Time [hꢀ
Products
Yield [%ꢀ[bꢀ
1
2
60
60
6
6
90
50
2
1
2
80
80
18
18
80
< 5
3
4
1
2
90
90
6
6
35
99
1
60
5
95
1
[
aꢀ 5 mol% catalyst (0.2 m in DME), 6200 kPa (900 psi) CO, 1.92 mmol aziridine; TBS ˆ tert-butyldimethylsilyl, Ts ˆ tosyl. [bꢀ Yields determined by H NMR
spectroscopy.
2782
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yield obtained with 2 (Table 2, entry 2). Both 1 and 2 show
unprecedented activity in carbonylating the electron deficient
ly carbonylate a variety of epoxides and aziridines under mild
conditions. Carbonylation of (R)-propylene oxide can be
carried efficiently on a multigram scale. Between 1 and 2, a
variety of epoxides and aziridines are efficiently carbonylated
in high yield and selectivity with intriguing differences in
reactivity. Further, we propose the insertion of CO into both
epoxides and aziridines proceeds through a similar mecha-
nism, which generates b-lactone and b-lactam products with
inversion at the site of nucleophilic attack.
1-tosyl-2-methylaziridine substrate. However, 2 gives much
higher lactam yields (99%) than 1 (35%) (Table 2, entry 3),
which is important because of the availability of enantiomeri-
cally-pure N-tosyl aziridines.[
26, 27ꢀ
Finally, 1 reacts with cis-1-
benzyl-2-(tert-butyldimethylsilyloxymethyl)-3-methyl aziri-
dine to predominantly yield the trans-lactone with high
selectivity for CO insertion at the (Me)CÀN bond of the
aziridine (Table 2, entry 4). Relative to previously reported
systems, 1 and 2 react faster, under milder conditions to
generate lactams in higher yield and selectivity. However, the
differences in reactivity between 1 and 2 are not understood at
the current time.
Received: March 4, 2002 [Z18813ꢀ
[
[
[
1ꢀ J. P. Collman, L. S. Hegedus, J. R. Norton, R. G. Finke, Principles and
Applications of Organotransition Metal Chemistry, 2nd ed., University
Science Books, Sausalito, 1987.
2ꢀ R. F. Heck in Organic Synthesis via Metal Carbonyls, Vol. 1 (Eds.: I.
Wender, P. Pino), Interscience Publishers, New York, 1968, pp. 373 ±
We propose the carbonylations of both epoxides and
aziridines proceed through a unifying mechanism involving
À
a backside nucleophilic attack by the [Co(CO)4ꢀ ion at the
4
04.
least-substituted carbon center (Scheme 1). The role of the
cationic Lewis acid counterpart is to bind and activate the
substrate.[11ꢀ Insertion of CO followed by ring-closure results
in lactone and lactam products, with inversion of configura-
tion at the site of attack. Discrete catalysts such as 1 and 2 will
allow the elucidation of the mechanism of CO insertion into
these substrates.
3ꢀ L. S. Hegedus, Transition Metals in the Synthesis of Complex Organic
Molecules, University Science Books, Mill Valley, 1994.
[4ꢀ H. W. Yang, D. Romo, Tetrahedron 1999, 55, 6403 ± 6434.
[
[
5ꢀ K. Khumtaveeporn, H. Alper, Acc. Chem. Res. 1995, 28, 414 ± 422.
6ꢀ P. A. Magriotis, Angew. Chem. 2001, 113, 4507 ± 4509; Angew. Chem.
Int. Ed. 2001, 40, 4377 ± 4379.
[7ꢀ H. M. M¸ller, D. Seebach, Angew. Chem. 1993, 105, 483 ± 509; Angew.
Chem. Int. Ed. Engl. 1993, 32, 477 ± 502.
[
8ꢀ a) D. Seebach, M. Overhand, F. N. M. Kuhnle, B. Martinoni, L.
Oberer, U. Hommel, H. Widmer, Helv. Chim. Acta 1996, 79, 913 ± 941;
b) R. P. Cheng, S. H. Gellman, W. F. DeGrado, Chem. Rev. 2001, 101,
In summary, the discrete catalysts [Cp Ti(thf) ꢀ[Co(CO) ꢀ
2
2
4
(
1) and [(salph)Al(thf) ꢀ[Co(CO) ꢀ (2) are shown to efficient-
2
4
3
219 ± 3232; c) J. J. Cheng, T. J. De-
ming, J. Am. Chem. Soc. 2001, 123,
457 ± 9458.
LnM
X
Co(CO)4
R2
9
[
9ꢀ For the direct copolymerization of
CO with aziridines and epoxides,
respectively, see: a) L. Jia, E. Ding,
W. R. Anderson, Chem. Commun.
X
R1
R1
R2
X = NR, O
2
001, 1436 ± 1437; b) M. Allmending-
er, R. Eberhardt, G. Luinstra, B.
Rieger, J. Am. Chem. Soc. 2002, 124,
5
[
646 ± 5647. See also references [10ꢀ,
11ꢀ, and [12dꢀ for prior reports of
CO/epoxide copolymerization.
O
LnM
X
Co(CO)3
LnM] [Co(CO)4] -
+
[
[
[
10ꢀ E. Drent, E. Kragtwijk (Shell Inter-
nationale Research B. V. Maatschap-
pij, Neth.), EP 577206, 1994 [Chem.
Abstr. 1994, 120, 191517cꢀ.
11ꢀ Y. D. Y. L. Getzler, V. Mahadevan, E.
Lobkovsky, G. W. Coates, J. Am.
Chem. Soc. 2002, 124, 1174 ± 1175,
and references therein.
R1
R2
O
X
CO
O
[12ꢀ For Co-catalyzed aziridine carbonyla-
tions, see: a) M. E. Piotti, H. Alper, J.
Am. Chem. Soc. 1996, 118, 111 ± 116;
b) P. Davoli, I. Moretti, F. Prati, H.
Alper, J. Org. Chem. 1999, 64, 518 ±
R1
R2
LnM
X
Co(CO)4
R1
R2
5
21; c) P. Davoli, F. Prati, Hetero-
cycles 2000, 53, 2379 ± 2389; d) J. T.
Lee, P. J. Thomas, H. Alper, J. Org.
Chem. 2001, 66, 5424 ± 5426.
[
13ꢀ a) W. Chamchaang, A. R. Pinhas,
Chem. Commun. 1988, 710 ± 711;
b) W. Chamchaang, A. R. Pinhas, J.
Org. Chem. 1990, 55, 2943 ± 2950;
c) S. V. Ley, B. Middleton, Chem.
Commun. 1998, 1995 ± 1996.
[Co(CO)4] -
O
O
O
Co(CO)4] -
[
N
N
LnM] [Co(CO)4] -
+
Ti+
Al+
[
=
tBu
O
O
tBu
tBu
O
tBu
[14ꢀ For Rh-catalyzed aziridine carbony-
lations, see: a) H. Alper, F. Urso,
D. J. H. Smith, J. Am. Chem. Soc.
1983, 105, 6737 ± 6738; D. Roberto,
1
2
Scheme 1. Proposed catalytic cycle for epoxide and aziridine carbonylation.
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COMMUNICATIONS
an indispensable strategy in synthetic chemistry.[ Since the
1ꢀ
H. Alper, Organometallics 1984, 3, 1767 ± 1769; for enantiospecific
carbonylation, see: b) S. Calet, F. Urso, H. Alper, J. Am. Chem. Soc.
[2ꢀ
pioneering work of Wilke and co-workers, nickel complexes
1
989, 111, 931 ± 934.
have been widely utilized as efficient catalysts for CÀC-bond
[
15ꢀ For Pd-catalyzed aziridine carbonylations, see: a) H. Alper, N. Hamel,
Tetrahedron Lett. 1987, 28, 3237 ± 3240; b) G. W. Spears, K. Nakanishi,
Y. Ohfune, Synlett 1991, 91 ± 92; c) D. Tanner, P. Somfai, Bioorg. Med.
Chem. Lett. 1993, 3, 2415 ± 2418.
16ꢀ Compound 1 was first synthesized by Merola and co-workers, see:
a) J. S. Merola, K. S. Campo, R. A. Gentile, Inorg. Chem. 1989, 28,
formations.[ Intramolecular variants such as the [4‡2ꢀ cyclo-
3ꢀ
[4ꢀ
addition reaction of 1,w-dienynes [Eq. (1)ꢀ, cyclization of
[5ꢀ
[6ꢀ
1,w-bis(enones),
w-dienyl aldehydes,
and w-alkynyl
enones [Eq. (2)ꢀ are all useful methods for the synthesis of
rather complex cyclic molecules of physiological interest.[
[
[7ꢀ
8ꢀ
2
950 ± 2954; b) J. S. Merola, K. S. Campo, R. A. Gentile, M. A.
Modrick, Inorg. Chim. Acta 1989, 165, 87 ± 90.
[
[
[
17ꢀ salph ˆ N,N'-bis(3,5-di-tert-butylsalicylidene)phenylenediamine. Cat-
alyst 2 is highly active for epoxide carbonylation (ref. [11ꢀ).
Ni (cat.)
18ꢀ Complexes screened for activity included Na[Co(CO)
CO) ꢀ, [nBu Nꢀ[Co(CO) ꢀ, and [Cp Coꢀ[Co(CO) ꢀ.
19ꢀ During the screening phase, Na[Co(CO) ꢀ (2mol%, 16 h, 80 8C,
900 kPa (1000 psi) CO, triglyme) reacted with propylene oxide to
4
ꢀ, [Ph
4
Pꢀ[Co-
(1)
(
4
4
4
2
4
R
R
R
R
4
6
give a mixture of products, yielding mostly acetone (6%) and poly(b-
hydroxybutyrate) (40%).
O
O
Ni (cat.)
R2' Zn
[
20ꢀ M. Tokunaga, J. F. Larrow, F. Kakiuchi, E. N. Jacobsen, Science 1997,
(2)
R'
2
77, 936 ± 938.
21ꢀ S. C. Casegreen, S. G. Davies, C. J. R. Hedgecock, Synlett 1991, 779 ±
80.
[
7
[
[
22ꢀ A. Griesbeck, D. Seebach, Helv. Chim. Acta 1987, 70, 1320 ± 1325.
23ꢀ a) D. S. Noyce, E. H. Banitt, J. Org. Chem. 1966, 31, 4043 ± 4047; b) W.
Adam, J. Baeza, J. Liu, J. Am. Chem. Soc. 1972, 94, 2000 ± 2006.
24ꢀ Alper and co-workers have reported the retention of stereochemistry
in the carbonylation of 2,3-epoxybutanes (ref. [12dꢀ), which is in
variance with our results. As the result of a typographical error
We report herein the four-component reaction of dime-
thylzinc, carbonyl compounds (aldehydes, ketones), and
dienes and alkynes of 1,w-dienylalkynes 1 in the presence of
[
a catalytic amount of [Ni(acac) ꢀ (acac ˆ acetylacetonato) at
2
room temperature to provide alkylidene cyclopentanes 2a,b
(
personal communication, P. Dervan) in the literature upon which
these assignments were based (ref. [25ꢀ), we propose that the
PPNꢀ[Co(CO) ꢀ/BF ¥ OEt system in fact proceeds with inversion
of stereochemistry, as well.
(
(
X ˆ C(CO Et) ) and their heterocyclic analogues 2c ± e
2
2
X ˆ O, NTs) in good yields and with excellent stereoselec-
[
4
3
2
tivity (Table 1). This four-component reaction may be re-
garded as an extended version of the reactions portrayed in
Equation (1) (a two-component coupling of a diene and an
alkyne) and in Equation (2) (a three-component coupling of
organozinc, alkyne, and enone).
[
[
25ꢀ P. B. Dervan, C. R. Jones, J. Org. Chem. 1979, 44, 2116 ± 2123.
26ꢀ H. M. I. Osborn, J. Sweeney, Tetrahedron: Asymmetry 1997, 8, 1693 ±
1
715.
[
27ꢀ D. Tanner, Angew. Chem. 1994, 106, 625 ± 646; Angew. Chem. Int. Ed.
Engl. 1994, 33, 599 ± 619.
The scope of the present reaction was examined with
various 1,w-dienynes 1a ± e (1.0 mmol) in the presence of a
catalytic amount of [Ni(acac) ꢀ (0.1 mmol), an aldehyde or
2
ketone (2.0 mmol), and dimethylzinc (2.4 mmol) in dry THF
at room temperature under nitrogen. All the 1,w-dienynes
Remarkably High 1,5-Diastereoselectivity in a
Nickel-Catalyzed Conjugate Addition of
1
a ± e were so reactive that almost all the reactions were
1
complete within 1 h at room temperature, irrespective of R
Me Zn and Carbonyl Compounds to 1,w-
2
and X of 1 and of the carbonyl compounds (Table 1). The
Dienynes with Through-Space Coupling**
conjugate addition of [Me Znꢀ and of the carbonyl compound
2
to 1,w-dienynes 1 occurs at the terminal positions of the
alkyne and the diene moieties, respectively; the through-
space interactions of the alkyne and diene groups ensure CÀC
Akihiro Ezoe, Masanari Kimura,* Takahiro Inoue,
Masahiko Mori, and Yoshinao Tamaru*
coupling at the internal positions. Terminal alkyne 1a
provided 2a in moderate yield (Table 1, entry 1), whereas
internal alkynes 1b ± e general gave more satisfactory results
Carbon ± carbon-bond formation is the most important and
fundamental process in organic synthesis. In particular, the
coupling reaction of unsaturated CÀC bonds mediated by low-
(
Table 1, entries 2± 11). Especially rewarding here is that the
,w-dienynes tethered by a nitrogen (1c) or an oxygen (1d,e)
valent transition metals is a rapidly growing field and is now
1
reacted with similar ease and furnished pyrrolidine and
tetrahydrofuran derivatives, respectively, in reasonable yields.
Bulky substituents around the carbonyl group either retard
the reaction (Table 1, entry 10) or cause a decrease in yield
(Table 1, entry 11). The reaction displayed a remarkably high
level of stereoselectivity (>97%, in most cases) between the
cycloalkane methine and the OH-bearing carbon centers as
well as excellent stereoselectivity (100%) with respect to the
exocyclic tri- and tetrasubstituted double bonds.[
[
*ꢀ Dr. M. Kimura, Prof. Dr. Y. Tamaru, A. Ezoe, T. Inoue, M. Mori
Department of Applied Chemistry
Faculty of Engineering, Nagasaki University
1
-14 Bunkyo-machi, Nagasaki 852-8521 (Japan)
Fax : (‡81)95-847-9008
E-mail: masanari@net.nagasaki-u.ac.jp, tamaru@net.nagasaki-u.ac.jp
[
**ꢀ We thank Y. Ohhama (NMR Facility) for technical assistance.
Financial support by the Ministry of Education, Culture, Sports,
Science, and Technology, Japanese Government, is gratefully ac-
knowledged.
9ꢀ
The structures of 2 were tentatively assigned by analogy
with the structure of piperidine derivative 4, which was
Supporting information for this article is available on the WWW under
http://www.angewandte.org or from the author.
2784
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
1433-7851/02/4115-2784 $ 20.00+.50/0
Angew. Chem. Int. Ed. 2002, 41, No. 15