The role of iodotrimethylsilane in the conjugate addition of butylcopper·lithium iodide to α-enones; silylation of an intermediate π-complex

Full text of DOI:10.1021/ja962122q

10904
J. Am. Chem. Soc. 1996, 118, 10904-10905
Table 1. LRPs for the Conjugate Addition of BuCu‚LiI to
2-Cyclohexenone (1) in the Presence of TMSIa
The Role of Iodotrimethylsilane in the Conjugate
Addition of Butylcopper‚Lithium Iodide to
r-Enones; Silylation of an Intermediate π-Complex
3 + 4
2
1
entry
reagent
timeb
(%)
(%) (%)
1
2
3
4
5
6
7
8
9
[BuCu‚LiI + TMSI] then 1 0.001 27 (>99:1)
5
4
6
8
2
3
3
9
64
59
35
29
54
45
34
23
Magnus Eriksson,* Anders Johansson, Martin Nilsson and
Thomas Olsson†
0.01
0.1
28 (>99:1)
50 (>99:1)
55 (98:2)
1.0
Department of Organic Chemistry
Chalmers UniVersity of Technology
S-412 96 Go¨teborg, Sweden
[BuCu‚LiI + 1] then TMSI 0.001 34 (93:7)
0.01
0.1
1.0
40 (93:7)
49 (93:7)
53 (92:8)
ReceiVed June 24, 1996
BuCu‚LiI then [1+TMSI]
0.001 56 (>99:1) <1 32
10
11
12
0.01
0.1
58 (>99:1)
56 (>99:1)
60 (>99:1)
2
4
7
30
31
21
The effect of TMSCl (chlorotrimethylsilane) on the rate as
well as the stereochemical outcome of conjugate additions of
organocuprates to R,â-unsaturated carbonyl compounds has been
studied by several groups.1 In previous work, we have
introduced iodotrimethylsilane2 (TMSI) as an efficient promoter
in conjugate additions of mono-organocopper compounds RCu‚
LiI to R-enones and -enoates.3 In this paper, we focus on the
effect of TMSI on the formation of TMS enol ethers in the early
stages of the reaction. It is shown by quenching the reactions
after short times that TMSI induces direct formation of the TMS
enol ether from a presumed mono-organocopper-enone π-com-
plex. We also report the activating effect of pyridine on the
conjugate addition of BuCu‚LiI in the absence of TMSI.
Conjugate addition of organocopper reagents in the presence
of TMSCl and TMSI has received considerable attention in
recent years. Besides the rate-accelerating effect generally
observed, the presence of TMSCl often leads to formation of
TMS enol ethers1a,b although exceptions have been noted.1e
Following the early observations by Normant et al.,4 Corey and
Boaz reported the dramatic effect of TMSCl on the stereochem-
istry in the conjugate addition of organocuprates to a bicyclic
γ-alkoxy enone.1c Based on these results, they proposed that
TMSCl traps an intermediate π-complex (d-π*)5 leading to a
silylated Cu(III) intermediate, which undergoes subsequent
reductive elimination.
1.0
a All reactions were run in THF at -78 °C. b Given in hours (h):
1.0 h ) 60 min, 0.1 h ) 6.0 min, 0.01 h ) 36 s, 0.001 h ) 4 s.
the ability to coordinate to the enone carbonyl oxygen. This
model suggested that the conjugate addition and the formation
of TMS enol ethers occurred in one step.
A fourth alternative was recently put forward by Bertz et al.
who proposed that the Cl of TMSCl attacks copper in the
organocuprate-enone π-complex to induce formation of the
product enolate via a tetracoordinate square-planar â-cuprio
intermediate.9 They investigated the conjugate addition of Bu2-
CuLi‚LiI to 2-cyclohexenone in the presence of excess TMSCl.
The important observation was that the TMS enol ether is
formed in a subsequent silylation step in Et2O as well as in
THF.
We have previously reported the isolation of TMS enol ethers
in high yields from conjugate additions of RCu‚LiI compounds
to R-enones in the presence of TMSI,10 and we recently extended
the scope of this protocol to include conjugate addition of copper
acetylides.11 However, so far we have made no special attempts
to determine if the TMS enol ether is the initial product from
the conjugate addition at low temperature or if it is formed in
a subsequent silylation step. To address this problem, we have
studied the reaction between BuCu‚LiI, TMSI and 2-cyclohex-
enone (1) in dilute (0.05 M) THF solution.12
By quenching the reactions at low temperature after increasing
time intervals, it is possible to monitor the buildup of product,
either as the conjugate adduct 3-butylcyclohexanone (2) or the
TMS enol ether 3-butyl-1-((trimethylsilyl)oxy)cyclohexene (3),
as well as the disappearance of the starting material. Using
the concept of logarithmic reactivity profiles (LRPs), recently
introduced in organocopper chemistry by Bertz et al.,9,13 we
have performed three different sets of reactions in the presence
of TMSI. They differ in the order of addition of 1 and TMSI
to BuCu‚LiI. These results are summarized in Table 1.
When 1 was added to a mixture of BuCu‚LiI and TMSI at
-78 °C, a considerable amount of TMS enol ether 3 was formed
already after 0.001 h, and it gradually increased with time
(entries 1-4). Traces of the regioisomeric TMS enol ether
5-butyl-1-((trimethylsilyl)oxy)cyclohexene (4) were also ob-
served. However, one reaction mixture was stirred for 10 h at
-78 °C before the reaction was quenched to give a 75% yield
of 3 and 4 with an isomer ratio of 85:15. Apparently, TMSI
can promote some isomerization of the TMS enol ethers over
an extended time even at -78 °C.
Kuwajima and Nakamura have suggested that TMSCl func-
tions as a Lewis acid toward the R-enone prior to addition of
the copper reagent6 to explain the stereochemical changes in
the conjugate addition of dibutylcuprates to 2- and 5-substituted
2-cyclohexenones in the absence or presence of the additive.
A third possibility involves the interaction between TMSCl
and the diorganocuprate prior to reaction with the enone as
observed by Lindstedt et al.7 using 13C NMR. On the basis of
7
changes in the Li and 35Cl NMR spectra of organocuprates
and organocuprate-TMSCl mixtures, Lipshutz et al.8 proposed
that the Cl of TMSCl coordinates Li+ in the organocuprate
thereby increasing the electrophilic character of the silicon and
† Astra Ha¨ssle AB, S-431 83 Mo¨lndal, Sweden
(1) (a) Nakamura, E.; Matsuzawa, S.; Horiguchi, Y.; Kuwajima, I.
Tetrahedron Lett. 1986, 27, 4029. (b) Johnson, C. R.; Marren, T. J.
Tetrahedron Lett. 1987, 28, 27. (c) Corey, E. J.; Boaz, N. W. Tetrahedron
Lett. 1985, 26, 6015. (d) Ibid. 1985, 26, 6019. (e) Alexakis, A.; Berlan, J.;
Besace, Y. Tetrahedron Lett. 1986, 27, 1047.
(2) (a) Jung, M. E.; Martinelli, M. J. in Encyclopedia of Reagents for
Organic Synthesis;Paquette, L., Ed.; Wiley: New York, 1995; Vol 4, p
2854. (b) Olah, G. A.; Prakash, G. K.; Krishnamurti, R. AdV. Silicon Chem.
1991, 1, 1.
(3) (a) Bergdahl, M.; Lindstedt, E.-L.; Nilsson, M.; Olsson, T. Tetrahe-
dron 1989, 44, 535. (b) Bergdahl, M.; Nilsson, M.; Olsson, T.; Stern, K.
Tetrahedron 1991, 47, 9691. (c) Eriksson, M.; Hjelmencrantz, A.; Nilsson,
M.; Olsson, T. Tetrahedron 1995, 46, 12631.
(4) (a) Chuit, C.; Foulon, J. P.; Normant, J.-F. Tetrahedron 1980, 36,
2305. (b) Ibid. 1981, 37, 1385.
(5) Corey, E. J.; Boaz, N. W. Tetrahedron Lett. 1984, 25, 3063.
(6) Horiguchi, Y.; Komatsu, M.; Kuwajima, I. Tetrahedron Lett. 1989,
30, 7087.
(7) Lindstedt, E.-L.; Nilsson, M.; Olsson, T. J. Organometal. Chem. 1987,
334, 255.
(8) Lipshutz, B. H.; Dimock, S. H.; James, B. J. Am. Chem. Soc. 1993,
115, 9283.
(9) Bertz, S. H.; Miao, G.; Rossiter, B. R.; Snyder, J. P. J. Am. Chem.
Soc. 1995, 117, 11023.
(10) Bergdahl, M.; Eriksson, M.; Nilsson, M.; Olsson, T. J. Org. Chem.
1993, 58, 7238. Idem. J. Org. Chem. 1994, 59, 7184 (correction).
(11) Eriksson, M.; Iliefski, T.; Nilsson, M.; Olsson, T. Submitted.
(12) The preparative procedure uses more concentrated reaction mixtures
(ca. 0.2-0.3 M) and a slight excess of reagent. See ref 10 for a representative
procedure.
(13) Bertz, S. H.; Miao, G.; Eriksson, M. J. Chem. Soc., Chem. Commun.
1996, 815.
S0002-7863(96)02122-1 CCC: $12.00 © 1996 American Chemical Society

Communications to the Editor
J. Am. Chem. Soc., Vol. 118, No. 44, 1996 10905
In the second LRP, TMSI was added to a mixture of BuCu‚
LiI and 1 at -78 °C (entries 5-8). The ratio (ca. 93:7) of the
TMS enol ethers 3 and 4 is similar for all reaction times, which
may suggest some isomerization under the reaction conditions.
Addition of a mixture of TMSI and 1 to BuCu‚LiI (entries
9-12) led to the immediate formation of the TMS enol ether 3
in good yield14 together with minor amounts of 2. It appears
as the premixing of TMSI and 1 before addition to BuCu‚LiI
gives the highest yields of 3 after 0.001 and 0.01 h at -78 °C.
For control purposes and as a blank experiment, BuCu‚LiI
was reacted with 1 in the absence of TMSI. Addition of 1 to
BuCu‚LiI in THF at -78 °C immediately gave greenish-yellow
suspensions15 which indicates formation of a π-complex.16,15
Quenching these reactions with aqueous sodium hydrogen
carbonate after 0.001, 0.01, or 0.1 h returned the starting enone,15
whereas the 1.0 h reaction gave 4% of 2 along with recovered
1. In strong contrast, quenching a 0.1 h reaction only 0.001 h
after addition of 3 equiv of pyridine gave 20% of 2. This shows
that pyridine can have an activating effect also on the conjugate
addition of BuCu‚LiI as has been recently shown for organo-
cuprates.13 When triethylamine was used instead of pyridine,
only 3% of 2 was observed.
All reactions that contained TMSI were quenched at -78 °C
by addition of 3 equiv of Et3N followed by 6 mL of aqueous
saturated sodium hydrogen carbonate after 0.001 h. In addition
to 3, a minor amount of 2 was observed in almost all reactions
involving TMSI, and it also seemed to increase slightly with
time.17 Control experiments where pure 3 in THF was subjected
to the quench conditions gave 85% of recovered TMS enol ether
and 4% of 2 formed from hydrolysis of 3, presumably by HI
from hydrolyzed TMSI. The conjugate adduct 3-butylcyclo-
hexanone (2) was stable under the quench conditions.
The rate of silylation of an enolate in Et2O and THF/Et2O
by TMSI was investigated. Conjugate addition of BuCu‚LiI to
1 in pure THF at -78 °C was slow18 and gave rise to complex
reaction mixtures already at -50 °C. We therefore prepared
the enolate in Et2O at 0.2 M19 and diluted the mixture with
THF to 0.05 M. Addition of TMSI to such an enolate at -78
°C followed by the usual quench with Et3N and NaHCO3 after
0.001 h and 0.01 h gave 6 and 24% of 3, respectively. The
corresponding experiments in pure diethyl ether gave <1% of
3. Consequently, most of the 3 observed in THF using BuCu‚
LiI in the presence of TMSI is formed directly from the
conjugate addition and not as a result of a subsequent silylation
of an intermediate enolate.
For comparison with BuCu‚LiI/TMSI, we investigated the
conjugate addition of Bu2CuLi‚LiI/TMSI to 2-cyclohexenone
at 0.05 M in THF. Addition of TMSI to a mixture of Bu2-
CuLi‚LiI and 1 gave 80 and 79% of 3 after 0.001 and 0.01 h,
respectively. In contrast, quenching a 0.001 h reaction without
TMSI with NaHCO3 gave only 9% of 2 which clearly
demonstrates the activating effect of TMSI. More importantly,
also in the Bu2CuLi‚LiI case is the silylation of an enolate at
-78 °C by TMSI too slow to account for the amount of 3
observed.
Scheme 1
5
3
7
2
6
lated product.20 However, we found that Bu2CuLi‚LiI/TMSI
as well as Bu2CuLi‚LiI/6TMSCl and 1 in Et2O did afford mainly
nonsilylated product (2), in consonance with their results. In
two recent studies, it is proposed that nucleophilic attack of
TMSCl9 or solvent (Me2O)21 on an organocuprate-olefin
π-complex gives a tetracoordinated square planar â-cuprio
intermediate with a low energy barrier toward reductive
elimination to product. A corresponding scenario may explain
the activating effect of pyridine on the BuCu‚LiI reactions in
the absence of TMSI but cannot (i.e., via 6) explain the large
amounts of 3 formed at short reaction times in the BuCu‚LiI/
TMSI or the Bu2CuLi‚LiI/TMSI system.
What then, is the role of TMSI in the BuCu‚LiI reactions?
As depicted in Scheme 1, two pathways to the TMS enol ether
3 are conceivable: (i) a process where TMSI silylates a
π-complex leading to direct formation of the TMS enol ether
or (ii) silylation of an intermediate enolate from conjugate
addition of RCu‚LiI.
We propose that the powerful silylating agent TMSI22 can
directly silylate an intermediate π-complex 5 to give 3 and that
this is the major pathway in THF (Scheme 1). The results are
thus consistent with a mechanism analogous to the one proposed
by Corey and Boaz for organocuprates and TMSCl.1c They
stated, “It is likely that the trapping occurs at the π-complex
stage since its steady-state concentration is doubtless much
greater than that of the copper(III) â-adduct”. The ratios of 3
to 2 from Table 1 suggest that the amount of 3 formed by the
proposed mechanism varies from ca 80% (entry 1) up to almost
quantitative (entry 9).
In conclusion, we have shown that iodotrimethylsilane in
combination with BuCu‚LiI or Bu2CuLi‚LiI in THF leads to
direct formation of TMS enol ethers from a presumed organo-
copper-enone π-complex. The present results thus appear to
rule out significant amounts of an enolate 7 as a viable
intermediate on the reaction pathway. On the other hand, they
do not allow the discrimination between an R-cuprio ketone3c,11
or a silylated â-cuprio intermediate.1c,21
Acknowledgment. We are grateful to the Carl Trygger Foundation
and Astra Ha¨ssle AB for financial support of this work and to Astra
Ha¨ssle AB for generous gift of chemicals. We thank Dr. Steven Bertz
for helpful comments and the suggestion that we investigate the possible
activating effect of pyridine in our system.
The predominant formation of 3 from Bu2CuLi‚LiI/TMSI and
1 in THF differs from the results of Bertz et al.9 for the Bu2-
CuLi‚LiI/6TMSCl system in THF which gave mainly nonsily-
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(14) The fact that the yield of 3 does not significantly increase after the
initial 4 s could indicate that a complex between TMSI and the carbonyl
oxygen of the enone is an important event in the rate-determining step.
See also ref 6.
(15) Vellekoop, A. S.; Smith, R. A. J. J. Am. Chem. Soc. 1994, 116,
2902.
(16) (a) Christenson, B.; Olsson, T.; Ullenius, C. Tetrahedron 1989, 45,
523. (b) Bertz, S. H.; Smith, R. A. J. J. Am. Chem. Soc. 1989, 111, 8276.
(17) The small but increasing amounts of 2 in the reaction mixtures may
be due to cleavage of 3 by TMSI. See: Jung, M. E.; Lyster, M. A. J. Org.
Chem. 1977, 42, 3761.
(18) Bertz, S. H.; Dabbagh, G. Tetrahedron 1989, 45, 425.
(19) House, H. O.; Fischer, W. F., Jr., J. Org. Chem. 1968, 33, 949.
JA962122Q
(20) It was reported9 that with 6 equiv of TMSCl in THF, approximately
a quarter of the product could be attributed to silylation of a cuprate-
enone π-complex. Most recent results show that Bu2CuLi‚LiI in THF with
1 or 2 equiv of TMSCl give mainly TMS enol ether. Private communication
with Dr. Steven Bertz.
(21) Snyder, J. P. J. Am. Chem. Soc. 1995, 117, 11025.
(22) (a) Hergott, H. H.; Simchen, G. Liebigs Ann. Chem. 1980, 1718.
(b) Miller, R. D.; McKean, D. R. Synthesis 1979, 730.