Iterative dianion relay along the ring: Formation of gem- Bis(trimethylsilyl) cyclopentenones from 2,5-Bis(trimethylsilyl) oxy-cyclopentadienyl dianions and acid chlorides

Article abstract of DOI:10.1002/chem.201100830

Dianionic relay linchpins: A new type of anion relay linchpin for migrating silyl groups was developed to form gem-bis(trimethylsilyl) cyclopentenones containing a stable enol moiety. The dianion was relayed iteratively along the Cp ring with the exocycli

Full text of DOI:10.1002/chem.201100830

COMMUNICATION
DOI: 10.1002/chem.201100830
Iterative Dianion Relay Along the Ring: Formation of gem-Bis(trimethylsilyl)
Cyclopentenones from 2,5-Bis(trimethylsilyl) Oxy-cyclopentadienyl Dianions
and Acid Chlorides
Heng Li,[a] Lantao Liu,[a] Zitao Wang,[a] Fei Zhao,[a] Shaoguang Zhang,[a]
Wen-Xiong Zhang,[a] and Zhenfeng Xi*[a, b]
Anionic migration of silyl groups has become one of the
most useful protocols for synthetic chemistry.[1–3] The intra-
molecular 1,n-anionic migration of a silyl group from a
carbon atom to an oxygen atom is generally referred to as
Brook rearrangement (Scheme 1) and the reverse process
(from an oxygen atom to a carbon atom) is called retro-
Brook rearrangement (or West rearrangement).[1,4–6] Both
the Brook rearrangement and the retro-Brook rearrange-
ment are currently widely applied in organic synthesis.[1,2]
As illustrated in Scheme 1, a recent yet very useful strategy
applying anionic migrations of silyl groups is the anion relay
chemistry (ARC) developed by Smith III et al.[7f,g,h,j,k] The
ARC, a multi-component linchpin protocol, has been dem-
onstrated to be useful for high-efficient and facile synthesis
of structurally complex scaffolds.[3] To further apply to syn-
thetic chemistry the useful protocol based on the anionic mi-
gration of silyl groups, the design and development of new
linchpins is currently of great demand and represents a
great challenge. In recent years, we have demonstrated that
the reaction of 1,4-dilithio-1,3-butadienes 1 with CO leads
to the formation of substituted oxy-cyclopentadienyl dianion
intermediates 2 (OCp dianions; Cp=cyclopentadienyl).[8]
Because of the concomitance of the Cp anion, the exocyclic
oxyanion, and those multi-reactive sites, the OCp dianions 2
are structurally very unique and can be used for novel reac-
Scheme 1. Modes of anionic migration of silyl groups. ASG=anion stabi-
lizing group, LP=linchpin.
tion chemistry. During the course of our continuous study
on their reaction chemistry, we realized that those OCp di-
A
Cp ring with the exocyclic oxyanion as the posthouse, was
observed the first time in anionic migration of silyl groups
(Scheme 1). Interesting and otherwise unavailable com-
pounds have been thus generated. Herein, we report our
preliminary results.
as a new type of dianionic relay linchpins. Iterative anion
relay, in which one silyl group was shifted twice along the
[a] H. Li, Dr. L. Liu, Z. Wang, F. Zhao, S. Zhang, Prof. Dr. W.-X. Zhang,
Prof. Dr. Z. Xi
1,4-Dilithio-1,4-bis(trimethylsilyl)-1,3-butadienes (dilithio
reagents) 1 can be readily generated in quantitative yields
from their corresponding 1,4-diiodobutadienes and tBuLi.[8b]
Treatment of dilithio reagents 1 with CO led to the forma-
tion of OCp dianions 2. When the reaction mixture contain-
ing 2a in diethyl ether was further treated with two equiva-
lents of ArCOCl possessing electron-donating groups on Ar,
such as 4-methylbenzoyl chloride, a double-acylation prod-
uct was obtained.[8b] However, surprisingly, when one equiv-
alent of PhCOCl was used, the 3-cyclopentenone derivative
5aa containing a stable enol moiety was obtained in 74%
Beijing National Laboratory for Molecular Sciences (BNLMS)
Key Laboratory of Bioorganic Chemistry and Molecular Engineering
of Ministry of Education, College of Chemistry
Peking University, Beijing 100871 (P.R. China)
Fax : (+86)10-62751708
E-mail: zfxi@pku.edu.cn
[b] Prof. Dr. Z. Xi
State Key Laboratory of Organometallic Chemistry
SIOC, CAS Shanghai 200032 (P.R. China)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201100830.
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Table 1. Formation of gem-bis(trimethylsilyl) cyclopentenones containing
a stable enol moiety from electron-withdrawing ArCOCl.
Entry
ArCOCl
Product
Yield [%][a]
1
74
Figure 1. ORTEP drawing of 5aa with 30% thermal ellipsoids. Hydrogen
7a
5aa
À
atoms are omitted for clarity. Selected bond lengths [ꢁ]: C1 C2 1.498(7),
À
À
À
À
À
C1 C5 1.474(6), C2 C3 1.550(6), C3 C4 1.324(6), C4 C5 1.451(6), C5
À
À
À
À
C11 1.339(6), C1 O2 1.271(5), C11 O1 1.364(5), C2 Si1 1.929(3), C2
Si1#1 1.929(3).
2
80
The skeleton of stable enols 5aa–5ae represents a new type
among the reported structures.[9] We believe that this trans-
formation process is unprecedented and should be of mech-
anistic significance.
7b
5ab
To obtain more evidence for the understanding of the re-
action mechanism, we used more acid chlorides with diversi-
fied substituents on the Ar group. The results are listed in
Table 2. When we used 2,4,6-trichlorobenzoyl chloride to
react with 2a in diethyl ether solvent, another unexpected
type of product 6af was obtained in 70% yield of the isolat-
ed product upon hydrolysis of the reaction mixture with
water (Table 2, entry 1). This is a cyclopentadiene derivative,
again with the shift of one SiMe3 group. Obviously, this
product is structurally very different from products 5. We
then used 2,4,6-trichlorobenzoyl chloride, 2,6-dichlorobenzo-
yl chloride and 2,4,6-trimethylbenzoyl chloride to react with
2a–2d, respectively. The type 6 products were also obtained
generally in good yields. The structure of 6ag was confirmed
by single crystal X-ray structural analysis (see the Support-
ing Information). It was interesting to observe the formation
of by-products 5bf, 5cf, and 5ch (Table 2, entries 4–6). With
the enlargement of the alkyl group R, the yield of byprod-
ucts of the type 5 increased (Table 2, entries 1, 4, and 5).
The different aggregation pattern among 2a (Me), 2b (nPr),
and 2c (n-Hex) is proposed to be the major reason for such
a difference.[10]
3
84
7c
7d
7e
5ac
5ad
5ae
4
65
5
66
[a] Yield of isolated product.
yield of the isolated product upon hydrolysis of the reaction
mixture (Table 1, entry 1). No double-acylation product was
obtained even when two equivalents of PhCOCl were used.
The X-ray structural analysis of 5aa revealed clearly that
two trimethylsilyl groups were attached on the same carbon
atom (Figure 1). With this result in hand, we were curious
about the influence of the electronic effect of the Ar group
on this reaction. Thus, ArCOCl moieties containing elec-
tron-withdrawing groups were tested. Stable enol derivatives
5ab–5ae as the sole products were obtained in good to ex-
cellent yields of the isolated product (Table 1, entries 2–5).
The above transformations leading to the type 5 products
and the type 6 products were both intriguing. We set our
mind on making clear this novel transformation by isolating
the intermediates. First, we successfully isolated the inter-
mediates from the reaction mixture between the OCp di-
anions 2 with acid chlorides. As given in Scheme 2, when
the OCp dianion 2a was treated with 2,4,6-trichlorobenzoyl
chloride, the O-acylated intermediate 3af was obtained in
65% yield of the isolated product. In a similar manner, 3ag
was obtained in 70% yield of the isolated product.
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Formation of gem-Bis(trimethylsilyl) Cyclopentenones through Anion Relay Chemistry
COMMUNICATION
Table 2. Formation of gem-bis(trimethylsilyl) cyclopentadienes from
bulky ArCOCl.
Table 2. (Continued)
Entry Dilithio
reagent
ArCOCl
Product
Yield
[%][a]
48
22
6ch
5ch
6
1c
7h
Entry Dilithio
reagent
ArCOCl
Product
Yield
[%][a]
1
2
3
4
1a
1a
1a
70
77
77
62
12
7
7 f
62
7 f
6af
6ag
6ah
1d
[a] Yield of isolated product.
6df
7g
7h
7 f
1b
6bf
5bf
Scheme 2. Isolation and trapping experiments of the O-acylated inter-
mediates. Ar=2,4,6-trichlorophenyl.
5
7 f
43
26
Recrystallization of 3af with 1 equivalent of N,N,N’,N’-
tetramethylethylenediamine (TMEDA) from Et2O/hexane
(1:1) mixed solvent afforded the single crystals 3af-
TMEDA, whose structure was successfully determined by
single-crystal X-ray structural analysis (Figure 2). The struc-
ture of 3af-TMEDA is a monomeric CpLi compound in
which the distances between the lithium and the carbons of
1c
6cf
5cf
Cp ring range from 2.352 ꢁ to 2.588 ꢁ.[11] The Li1 C1
À
bond length (2.352 ꢁ) is significantly shorter than Li1-C2-5
(2.455-2.588 ꢁ), owing to the coordination of the oxygen in
the carbonyl group. Hydrolysis of the isolated intermediates
3af and 3ag with water afforded their corresponding prod-
uct 6af and 6ag in quantitative yields. These results demon-
strated that compounds 6 must be formed upon protonation
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Z. Xi et al.
Figure 3. ORTEP drawing of 4af-TMEDA with 10% thermal ellipsoids.
À
Hydrogen atoms are omitted for clarity. Selected bond lengths [ꢁ]: C1
Figure 2. ORTEP drawing of 3af-TMEDA with 30% thermal ellipsoids.
À
À
À
À
C2 1.500(7), C1 C5 1.561(8), C2 C3 1.502(7), C2 C6 1.440(7), C3 C4
À
Hydrogen atoms are omitted for clarity. Selected bond lengths [ꢁ]: C1
À
À
À
À
1.384(7), C4 C5 1.556(7), C1 O1 1.258(7), C6 O2 1.297(7), O1 Li1
À
À
À
À
C2 1.421(5), C1 C5 1.407(5), C2 C3 1.440(5), C3 C4 1.399(5), C4 C5
À
1.922(11), O2 Li1 1.946(10).
À
À
À
À
1.459(5), C1 Li1 2.352(8), C2 Li1 2.488(8), C3 Li1 2.586(9), C4 Li1
À
À
À
2.588(9), C5 Li1 2.455(8). C1 O2 1.458(4), Li1 O1 2.250(8).
ture of 4af-TMEDA was determined by single-crystal X-ray
structural analysis (Figure 3). It features a monomeric che-
late enolate lithium structure.[13] Two nitrogen atoms of
TMEDA and two oxygen atoms form the tetrahedral coor-
dination geometry around Li1. The coordination of one de-
localized -OC3O- unit with one negative charge (analogous
to the acetylacetonate ligand) to the Li center leads to the
formation of the six-membered ring. Hydrolysis of the iso-
lated intermediate 4af led to its corresponding product 5af
in a quantitative yield.
of 3. The protonated intermediate 8 is proposed to undergo
a fast[1,3] sigmatropic silyl shift due to the suitable configura-
tion for s-p hyperconjugation.[12] This hypothesis was further
supported by the formation of 9. The X-ray structure of 9
revealed that the second acyl group is attached to the C3 of
the cyclopentadienyl ring (see the Supporting Information).
No silyl shift took place when the C3 was captured.
As mentioned above, the aggregation pattern of organo-
lithium compounds remarkably influences the formation of
products 5. We then dissolved compound 3af in tetrahydro-
furan (THF) because THF is known to be able to de-aggre-
gate organolithium compounds and trigger the Brook rear-
rangement.[7g] The THF solution was kept at room tempera-
ture and monitored by NMR spectroscopy (Scheme 3). In-
terestingly, the in situ recorded NMR spectra clearly demon-
strated that compound 3af slowly transformed into the
different compound 4af within three days (see the Support-
ing Information for detailed NMR spectra). Recrystalliza-
tion of 4af with 1 equivalent of TMEDA from diethyl ether
afforded the suitable single crystals 4af-TMEDA. The struc-
Inspired by the above mentioned THF-promoted transfor-
mation, we applied this experimental protocol to more sub-
strates, which are shown in Table 2. Products 5af, 5ag, and
5cf were obtained as sole products in good yields (Figure 4).
Figure 4. Formation of gem-bis(trimethylsilyl) cyclopentenones contain-
ing a stable enol moiety from bulky ArCOCl in THF.
A proposed mechanism for the formation of 5 is given in
Scheme 4. First, the oxyanion of 2 was trapped by acid chlo-
ride and formed the Cp anion species 3. Next, sequential
acyl migration of 3 led to 10. After Brook rearrangement,
the anion was relayed back to the Cp with the help of silyl
migration for the first time generating 11, as the resonance
form of 12, which was stabilized by a-effect of silyl group.[14]
Finally, the retro-Brook rearrangement occurred along with
Scheme 3. Observation of the novel transformation in THF and isolation
of the chelate enolate lithium intermediates. Ar=2,4,6-trichlorophenyl.
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Formation of gem-Bis(trimethylsilyl) Cyclopentenones through Anion Relay Chemistry
COMMUNICATION
[5] a) J. L. Speier, J. Am. Chem. Soc. 1952, 74, 1003–1010; b) R. West,
R. Lowe, H. F. Steward, A. Wright, J. Am. Chem. Soc. 1971, 93,
282–283.
[6] a) B. M. Comanita, S. Woo, A. G. Fallis, Tetrahedron Lett. 1999, 40,
5283–5289; b) H. Taguchi, K. Takami, A. Tsubouchi, T. Takeda, Tet-
rahedron Lett. 2004, 45, 429–432.
[7] a) I. Matsuda, S. Murata, Y. Ishii, J. Chem. Soc. Perkin Trans. 1
1979, 26–30; b) L. F. Tietze, H. Geissler, J. A. Gewart, U. Jakobi,
Synlett 1994, 511–512; c) H. Shinokubo, K. Miura, K. Oshima, K.
Utimoto, Tetrahedron 1996, 52, 503–514; d) W. H. Moser, K. E.
Endsley, J. T. Colyer, Org. Lett. 2000, 2, 717–719; e) W. H. Moser, J.
Zhang, C. S. Lecher, T. L. Frazier, M. Pink, Org. Lett. 2002, 4, 1981–
1984; f) A. B. Smith III, M. O. Duffey, Synlett 2004, 1363–1366;
g) A. B. Smith III, M. Xian, J. Am. Chem. Soc. 2006, 128, 66–67;
h) A. B. Smith III, M. Xian, W.-S. Kim, D.-S. Kim, J. Am. Chem.
Soc. 2006, 128, 12368–12369; i) N. O. Devarie-Baez, B. J. Shuhler, H.
Wang, M. Xian, Org. Lett. 2007, 9, 4655–4658; j) A. B. Smith III,
W.-S. Kim, W. M. Wuest, Angew. Chem. 2008, 120, 7190–7194;
Angew. Chem. Int. Ed. 2008, 47, 7082–7086; k) A. B. Smith III,
W. M. Wuest, Chem. Commun. 2008, 5883–5895.
Scheme 4. Proposed mechanism for the formation of gem-bis(trimethyl-
silyl) cyclopentenones containing a stable enol moiety.
[8] a) Q. Song, J. Chen, X. Jin, Z. Xi, J. Am. Chem. Soc. 2001, 123,
10419–10420; b) L. Liu, W.-X. Zhang, C. Wang, C. Y. Wang, Z. Xi,
Angew. Chem. 2009, 121, 8255–8258; Angew. Chem. Int. Ed. 2009,
48, 8111–8114; c) Z. Xi, Acc. Chem. Res. 2010, 43, 1342–1351.
[9] Formation of stable enols: a) H. Hart, Chem. Rev. 1979, 79, 515–
528; b) B. Capon, B.-Z. Guo, F. C. Kwok, A. K. Siddhanta, C.
Zucco, Acc. Chem. Res. 1988, 21, 135–140; c) Z. Rappoport, S. E.
Biali, Acc. Chem. Res. 1988, 21, 442; d) K. W. Kramarz, R. Elsen-
berg, Organometallics 1992, 11, 1997–1999; e) A. M. Polozov, O. N.
Kataeva, I. A. Litvinov, J. Org. Chem. 1994, 59, 1572–1573; f) Q.
Hu, C. Wang, D. Li, Z. Xi, Org. Biomol. Chem. 2007, 5, 2114–2118;
g) D. M. Chenoweth, K. Chenoweth, W. A. Goddard III, J. Org.
Chem. 2008, 73, 6853–6856; h) H. Li, W. Li, Z. Li, Chem. Commun.
2009, 3264–3266.
silyl migration for the second time and the oxyanion was re-
generated forming 13 or 4.
In summary, we have developed a novel dianionic relay
linchpin. Key intermediates were obtained to confirm the
proposed process, in which the anion was relayed iteratively
along the Cp ring with the exocyclic oxyanion as the post-
house.
Acknowledgements
[10] V. H. Gessner, C. Dschlein, C. Strohmann, Chem. Eur. J. 2009, 15,
3320–3334.
This work was supported by the Natural Science Foundation of China
and the Major State Basic Research Development Program
(2011CB808705).
[11] a) A. Sekiguchi, Y. Sugai, K. Ebata, C. Kabuto, H. Sakurai, J. Am.
Chem. Soc. 1993, 115, 1144–1146; b) F. Zaegel, J. C. Gallucci, P.
Meunier, B. Gautheron, M. R. Sivik, L. A. Paquette, J. Am. Chem.
Soc. 1994, 116, 6466–6467; c) P. Jutzi, N. Burford, Chem. Rev. 1999,
99, 969–990; d) U. Siemeling, Chem. Rev. 2000, 100, 1495–1526;
e) G. Fraenkel, X. Chen, A. Chow, J. C. Gallucci, H. Liu, J. Org.
Chem. 2005, 70, 9131–9138; f) J. Paradies, G. Erker, R. Frçhlich,
Angew. Chem. 2006, 118, 3150–3153; Angew. Chem. Int. Ed. 2006,
45, 3079–3082.
Keywords: anion relay chemistry
ligands dilithio reagents silyl groups
intermediates
·
cyclopentadienyl
·
·
·
reactive
[12] a) H. Kwart, J. Slutsky, J. Am. Chem. Soc. 1972, 94, 2515–2516; b) J.
Slutsky, H. Kwart, J. Am. Chem. Soc. 1973, 95, 8678–8685; c) S. Pro-
feta, R. J. Unwalla, F. K. Cartledge, J. Org. Chem. 1986, 51, 1884–
1885; d) T. Yamabe, K. Nakamura, Y. Shiota, K. Yoshizawa, S. Ka-
wauchi, M. Ishikawa, J. Am. Chem. Soc. 1997, 119, 807–815;
e) L. C. Zhang, C. Kabuto, M. Kira, J. Am. Chem. Soc. 1999, 121,
2925–2926; f) M. Takahashi, J. Phys. Chem. A 2005, 109, 11902–
11906.
[13] a) P. G. Williard, J. M. Salvino, Tetrahedron Lett. 1985, 26, 3931–
3934; b) R. Amstutz, J. D. Dunitz, T. Laube, W. B. Schweizer, D.
Seebach, Chem. Ber. 1986, 119, 434–443; c) R. A. Wanat, D. B.
Collum, G. Van Duyne, J. Clardy, R. T. DePue, J. Am. Chem. Soc.
1986, 108, 3415–3422; d) D. Seebach, Angew. Chem. 1988, 100,
1685–1715; Angew. Chem. Int. Ed. Engl. 1988, 27, 1624–1654.
[14] a) F. C. Whitmore, L. H. Sommer, J. Am. Chem. Soc. 1946, 68, 481–
484; b) L. H. Sommer, D. L. Bailey, W. A. Strong, F. C. Whitmore, J.
Am. Chem. Soc. 1946, 68, 1881–1883; c) D. J. Peterson, J. Org.
Chem. 1968, 33, 780–784; d) A. C. Hopkinson, M. H. Lien, J. Org.
Chem. 1981, 46, 998–1003; e) K. Itami, K. Mitsudo, J. Yoshida, Tet-
rahedron Lett. 1999, 40, 5533–5536.
[1] W. H. Moser, Tetrahedron 2001, 57, 2065–2084.
[2] a) K. Takeda, D. Nakane, M. Takeda, Org. Lett. 2000, 2, 1903–1905;
b) K. Takeda, Y. Sawada, K. Sumi, Org. Lett. 2002, 4, 1031–1033;
c) Y. Mi, J. V. Schreiber, E. J. Corey, J. Am. Chem. Soc. 2002, 124,
11290–11291; d) R. Unger, T. Cohen, I. Marek, Org. Lett. 2005, 7,
5313–5316; e) R. Unger, T. Cohen, I. Marek, Eur. J. Org. Chem.
2009, 1749–1756; f) T. Murai, R. Hori, Bull. Chem. Soc. Jpn. 2010,
83, 52–57.
[3] a) K. J. Hale, M. G. Hummersone, G. S. Bhatia, Org. Lett. 2000, 2,
2189–2192; b) A. B. Smith III, V. A. Doughty, Q. Lin, L. Zhuang,
M. D. McBriar, A. M. Boldi, W. H. Moser, N. Murase, K. Nakayama,
M. Sobukawa, Angew. Chem. 2001, 113, 197–201; Angew. Chem.
Int. Ed. 2001, 40, 191–195; c) A. B. Smith III, Q. Lin, V. A. Doughty,
L. Zhuang, M. D. McBriar, J. K. Kerns, C. S. Brook, N. Murase, K.
Nakayama, Angew. Chem. 2001, 113, 202–205; Angew. Chem. Int.
Ed. 2001, 40, 196–199; d) A. B. Smith III, M. A. Foley, S. Dong, A.
Orbin, J. Org. Chem. 2009, 74, 5987–6001.
[4] a) A. G. Brook, J. Am. Chem. Soc. 1958, 80, 1886–1889; b) A. G.
Brook, Acc. Chem. Res. 1974, 7, 77–84; c) M. Lautens, P. H. M. De-
langhe, J. B. Goh, C. H. Zhang, J. Org. Chem. 1995, 60, 4213–4227.
Received: March 18, 2011
Published online: May 25, 2011
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