Silicon-tethered Heck reaction

Article abstract of DOI:10.1016/S0040-4039(00)01910-9

An approach to the synthesis of semicyclic dienes is described. The method employs a silicon-tethered version of the Heck reaction.

Full text of DOI:10.1016/S0040-4039(00)01910-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 203–206
Silicon-tethered Heck reaction
Anand Mayasundari and David G. J. Young*
Department of Chemistry, University of Tennessee, Knoxville, Knoxville, TN 37996, USA
Received 9 August 2000; revised 12 October 2000; accepted 13 October 2000
Abstract—An approach to the synthesis of semicyclic dienes is described. The method employs a silicon-tethered version of the
Heck reaction. © 2000 Elsevier Science Ltd. All rights reserved.
Curcusone A (1) has attracted interest from the anti-
cancer field due to its ability to enhance hyperthermic
oncotherapeutics in the Chinese hamster.1 As part of a
synthetic plan directed towards 1, 2 was envisioned as a
B-ring building block for the tricyclic nucleus (Scheme
1).2 At the onset of our studies, few approaches to the
substitution pattern of 2 had been described, which led
to the studies reported here.3
The first approach to 2 involved iodination of 3 to give
4 (Scheme 2).4 Application of Johnson’s modified Stille
conditions to 4 afforded 5 in low yield.5–7 It was
expected that 1,2-reduction of 5 would complete our
approach to 2; however, the standard reagents for
reduction (lithium aluminum hydride,8 diisobutylalu-
minum hydride,9 and sodium borohydride with or with-
out cerium trichloride10,11) failed to produce 2 in
meaningful yield.
Luche reduction of 4, which contains a stronger chelat-
ing group at C2, provided 6 in 95% yield (Scheme 3).
Attempts to couple 6 with vinyl organometallics were
problematic, but 2 could be obtained via the tert-
butyldimethylsilyl ether derived from 6.12
Due to the toxicity of the reagents in Scheme 3, our
attention turned to the silicon-based approach in
Scheme 4.13 The regiochemistry of alkenylation (8“9
Scheme 1. General synthetic approach to curcusone A.
Scheme 2. (a) I2, Pyr, CCl4; (b) Bu3SnCHꢀCH2, Pd(PhCN)2Cl2, CuI, Ph3As, NMP.
Scheme 3. (a) NaBH4, CeCl3·7H2O; (b) TBSCl, Imid.; (c) Bu3SnCHꢀCH2, Pd(PhCN)2Cl2, CuI, Ph3As, NMP; (d) Bu4NF.
Keywords: vinyl silanes; vinylation; dienes; palladium.
* Corresponding author.
0040-4039/01/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01910-9

204
A. Mayasundari, D. G. J. Young / Tetrahedron Letters 42 (2001) 203–206
Scheme 4.
Scheme 5. (a) Ph2(CH2ꢀCH)SiCl, DMAP; (b) (Ph3P)4Pd, Et3N, CH3CN; H2O (c) (Ph3P)4Pd, Et3N, CH3CN; CH3OH.
Scheme 6.
+10) was not a concern here since desilylation of either
heterocycle was expected to produce 11.14,15
The only acyclic case studied was 17 which produced a
2:1 E–Z mixture of dienes 18 and suggested the in-
volvement of an unstable vinyl palladate intermediate
(Scheme 6).
Substrates for the proposed Heck reaction were pre-
pared from the corresponding a-iodocycloalkenols
(Scheme 5).16,17 Treatment of 14 with 10 mol% of
tetrakis(triphenylphosphine)palladium(0) produced 15,
which contained the silicon analog of a hemiacetal.
Moreover, mixed acetals could be obtained from this
reaction by quenching with alcoholic solvents.
Methanol, for example, led to the isolation of 16 in
good yield. In practice, purification of acetals was
easier than hemiacetals, so products were generally
isolated as such.
As shown in Table 1, tetrakis(triphenylphosphine)-
palladium(0) faired better than palladium acetate or
dibenzylideneacetone. Decomposition of starting ma-
terial occurred at higher temperatures; thus lower tem-
peratures afforded higher yields. The runs in Table 1
employed 14 as the substrate and used a 10 mol%
catalyst loading.
Treatment of 8a–c with tetrakis(triphenylphosphine)-
palladium(0) afforded silylacetals 12a–c (Table 2). The
reaction gave good yields of small-ring compounds
(entry 1). b-Substitution on the alkene gave lower
yields, but was not detrimental (entry 2). The transfer
was less efficient in the seven-membered ring case (entry
3).
Table 1. Conversion of 14 to 15 in Et3N, CH3CN; H2O
Catalyst
Conditions
% 15
Pd(Ph3P)4
Pd(Ph3P)4
Pd2(dba)3(CHCl3)
Pd(dba)2
Pd(OAc)2, Ph3P
12 h, 50
12 h, rt
20 h, rt
48 h, 60
74 h, rt
61
89
39
30
35
A hypothetical mechanism is presented in Scheme 7.
Oxidative insertion of palladium into 8a affords 19.
This is followed by insertion of the silylethenyl group
into the palladiumꢁalkene bond of 19 to afford 20. A
b-silyl elimination step affords 21. The catalytic cycle is
completed via reductive elimination to produce 22 and
regenerate Pd(0).18
Table 2. Reaction of 8 with Pd(Ph3P)4, Et3N, CH3CN;
MeOH
In summary, a silicon-tethered version of the Heck
reaction has been developed. The reaction involves an
electrophilic silyl ether intermediate and a b-silyl elimi-
nation step. The reaction is useful for alkenylation of
five- and six-membered rings, but less efficient for
medium rings.19 Further studies will be reported in due
course.20
Entry c
Compound
n
X
% 12
1
2
3
8a
8b
8c
1
2
3
H
Me
H
86
57
46

A. Mayasundari, D. G. J. Young / Tetrahedron Letters 42 (2001) 203–206
205
Scheme 7. Proposed catalytic cycle.
Acknowledgements
1643. (c) Koot, W.-J.; VanGinkel, R.; Kranenburg, M.;
Hiemstra, H.; Louwrier, S.; Moolenaar, M. J.; Speck-
camp, W. N. Tetrahedron Lett. 1991, 32, 401.
Support provided by the University of Tennessee,
Knoxville is gratefully acknowledged.
15. Karabelas, K.; Hallberg, A. J. Org. Chem. 1988, 53, 4909.
16. Sieburth, S.; Fensterbank, L. J. Org. Chem. 1992, 57,
5279.
17. Dieck, H. A.; Heck, R. F. J. Org. Chem. 1975, 40, 1083.
18. It was suggested by a reviewer that oxidative insertion of
palladium into the siliconꢁcarbon bond of 19 could pro-
duce 23, which could reductively eliminate to afford 21.
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6.26 (dd, 1H), 5.32 (d, 1H), 4.99 (d, 1H), 2.51 (m, 2H),
1
2.32 (m, 2H), 1.65 (m, 4H). For 6: H NMR (CDCl3, 250
MHz) l 6.57 (t, 1H, J=7.0 Hz), 4.40 (d, 1H, J=7.0 Hz),
2.29–2.15 (m, 1H), 2.03–1.89 (m, 2H), 1.76–1.49 (m,
5H), 0.91 (s, 9H), 0.15 (s, 3H), 0.08 (s, 3H); HRMS (EI)
calcd for C9H16IOSi (M+−C4H9) m/z 295.0015, found
1
m/z 295.0024. For 7: H NMR (CDCl3, 250 MHz) l 6.60
(t, 1H, J=7.1 Hz), 4.31 (t, 1H, J=5.1 Hz), 2.36 (d, 1H,
J=5.0 Hz), 2.21–1.47 (m, 8H); HRMS (EI) calcd for
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pound 8a: H NMR (CDCl3, 250 MHz) l 7.74–7.71 (m,
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6.37–6.27 (m, 2H), 5.98 (dd, 1H, J=20.1, 3.9 Hz),
4.93–4.88 (m, 1H), 2.54–2.39 (m, 1H), 2.27–2.06 (m,
2H), 1.98–1.52 (m, 1H); HRMS (EI) calcd for
C19H19IOSi (M+) m/z 418.025, found m/z 418.029. For
8b: 1H NMR (CDCl3, 250 MHz) l 7.76–7.73 (m, 4H),
7.48–7.31 (m, 6H), 6.66 (dd, 1H, J=20.2, 14.4 Hz), 6.23
(dd, 1H, J=14.8, 3.8 Hz), 5.97 (dd, 1H, J=20.2, 3.8
Hz), 4.50 (s, 1H), 2.30–1.96 (m, 2H), 1.91 (s, 3H),
1.83–1.72 (m, 3H), 1.65–1.57 (m, 1H); HRMS (EI) calcd
for C21H23IOSi (M+) m/z 446.0563, found m/z 446.0553.
For 8c: 1H NMR (CDCl3, 250 MHz) l 7.76–7.71 (m,
4H), 7.51–7.32 (m, 6H), 6.70–6.56 (m), 6.34 (dd, 1H,
J=14.8, 3.9 Hz), 5.98 (dd, 1H, J=20.1, 3.9 Hz), 4.63–
4.60 (m, 1H), 2.38–2.25 (m, 1H), 2.06–1.94 (m, 1H),
1.81–1.48 (m, 5H); HRMS (EI) calcd for C21H23IOSi
(M+) m/z 446.0563, found m/z 446.0548. For 12a: 1H
NMR (CDCl3, 250 MHz) l 7.74–7.60 (m, 4H), 7.46–7.27
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(CH ꢀCH)MgBr (2 equiv.)
6 ꢁꢁꢁꢁ2ꢁꢁꢁꢁꢁꢁꢁꢁꢁꢁꢁꢁꢁꢁꢁꢂ 2
(0.01 mol%) Pd(Ph P) 64%
3
4
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206
A. Mayasundari, D. G. J. Young / Tetrahedron Letters 42 (2001) 203–206
(m, 6H), 6.47 (dd, 1H, J=17.6, 10.9 Hz), 5.91 (s, 1H),
15: 1H NMR (CDCl3, 250 MHz) l 7.75–7.61 (m, 4H),
7.47–7.28 (m, 6H), 6.29 (dd, 1H, J=17.7, 11.0 Hz), 5.90
(m, 1H), 5.24 (d, 1H, J=17.6 Hz), 4.97 (d, 1H, J=11.0
Hz), 4.73 (t, 1H, J=3.0 Hz), 2.91 (s, 1H), 2.27–1.87 (m,
4H), 1.67–1.50 (m, 2H); 13C NMR (CDCl3, 62.9 MHz) l
138.1, 137.2, 134.7, 134.2, 132.1, 130.2, 127.8, 127.7,
111.5, 64.5, 31.7, 25.8, 16.8. For 16: 1H NMR (CDCl3,
250 MHz) l 7.76–7.61 (m, 4H), 7.52–7.27 (m, 6H), 6.32
(dd, 1H, J=17.7, 11.0 Hz), 5.93 (m, 1H), 5.28 (d, 1H,
J=17.7 Hz), 5.00 (d, 1H, J=11.0 Hz), 4.69 (t, 1H,
J=3.0 Hz), 3.64 (s, 3H), 2.31–1.95 (m, 4H), 1.66–1.44
(m, 2H); HRMS (EI) calcd for C21H24O2Si (M+) m/z
5.39 (d, 1H, J=17.6 Hz), 5.21–5.09 (m, 2H), 3.60 (s,
3H), 2.60–2.48 (m, 1H), 2.37–1.91 (m, 3H); HRMS (EI)
calcd for C20H22O2Si (M+) m/z 322.1389, found m/z
1
322.1393. For 12b: H NMR (CDCl3, 250 MHz) l 7.80–
7.63 (m, 4H), 7.52–7.24 (m, 6H), 6.40 (dd, 1H, J=17.7,
11.0 Hz), 5.26 (d, 1H, J=17.7 Hz), 5.04 (d, 1H, J=11.0
Hz), 4.69 (t, 1H, J=3.0 Hz), 3.54 (s, 3H), 2.31–1.95 (m,
1
4H), 1.82 (s, 3H), 1.66–1.44 (m, 2H). For 12c: H NMR
(CDCl3, 250 MHz) l 7.69–7.59 (m, 4H), 7.51–7.28 (m,
6H), 6.22 (dd, 1H, J=17.5, 10.9 Hz), 5.96 (m, 1H),
4.94–4.77 (m, 3H), 3.52 (s, 3H), 2.70–2.58 (m, 1H),
2.33–2.06 (m, 2H, 1.96–1.66 (m, 3H), 1.55–1.34 (m, 2H);
HRMS (EI) calcd for C22H26O2Si (M+) m/z 350.1702,
found m/z 350.1711. For 14: 1H NMR (CDCl3, 250
MHz) l 7.74–7.70 (m, 4H), 7.48–7.29 (m, 6H), 6.62 (dd,
1H, J=20.3, 14.9 Hz), 6.52 (t, 1H, J=3.9 Hz), 6.32 (dd,
1H, J=14.9, 3.7 Hz), 5.96 (dd, 1H, J=20.4, 3.9 Hz),
4.37 (s, 1H), 2.21–1.74 (m, 5H), 1.64–1.56 (m, 1H). For
1
336.1546, found m/z 336.1559. For 17: H NMR (CDCl3,
250 MHz) l 7.68–7.63 (m, 4H), 7.54–7.25 (m, 11H), 6.94
(s, 1H), 6.51 (dd, 1H, J=20.1, 14.8 Hz), 6.28 (dd, 1H,
J=14.8, J=4.0 Hz), 5.94 (dd, 1H, J=20.1, 4.0 Hz),
4.35 (q, 1H, J=6.0 Hz), 1.43 (d, 3H, J=6.0 Hz); HRMS
(EI) calcd for C24H23IOSi (M+) m/z 482.0563, found m/z
482.0552.
.
.