Regio- and stereoselective hydrosilylation of 1,3-enynes catalyzed by palladium

Article abstract of DOI:10.1021/ol4001334

In the presence of Pd(0) and a phosphine, hydrosilylation of 1,3-enynes with Me₂SiHCl proceeds to yield dienylsilanes with the silicon function added to the internal alkyne carbon atom and with (E)-configuration of newly formed olefinic bond. The silanols isolated after hydrolysis of the primarily obtained products serve as precursors to conjugated dienes with different substitution patterns.

Full text of DOI:10.1021/ol4001334

ORGANIC
LETTERS
2013
Vol. 15, No. 7
1444–1447
Regio- and Stereoselective
Hydrosilylation of 1,3-Enynes
Catalyzed by Palladium
Hui Zhou and Christina Moberg*
Department of Chemistry, Organic Chemistry, School of Chemical Science and
Engineering, KTH Royal Institute of Technology, SE 100 44 Stockholm, Sweden
kimo@kth.se
Received January 16, 2013
ABSTRACT
In the presence of Pd(0) and a phosphine, hydrosilylation of 1,3-enynes with Me2SiHCl proceeds to yield dienylsilanes with the silicon function
added to the internal alkyne carbon atom and with (E)-configuration of newly formed olefinic bond. The silanols isolated after hydrolysis of the
primarily obtained products serve as precursors to conjugated dienes with different substitution patterns.
Hydrometalations transform alkynes to reactive vinyl-
metal or vinylmetalloid species, which are important build-
ing blocks in organic synthesis.1 Hydrosilylations of alkynes
areofparticularinterestsince theproductvinylsilaneshave
low toxicity, are easy to handle, and are tolerant to a wide
range of reaction conditions. Vinylsilanes with a siliconÀ
heteroatom bond are attractive reagents, which, for exam-
ple, can participate as reactive nucleophilic partners in
palladium-catalyzed cross-coupling reactions2 and be sub-
jected to TamaoÀFleming oxidations.3 The stereo- and
regiochemistry of the hydrosilane addition is a function of
the substrate, the catalyst, which most commonly is a
platinum, ruthenium, or cationic rhodium complex, and
to some extent the reaction conditions.4 Whereas terminal
alkynes under appropriate conditions react with high stereo-
and site selectivity, either in a syn or an anti fashion,
reactions with internal alkynes often result in mixtures of
products, unless a directing group5 is present in the substrate.
Hydrometalated 1,3-enynes are valuable precursors for
stereodefined 1,3-dienes. We are, however, aware of only a
few examples of hydrosilylations of this type of compounds.
Regio- and stereoselective platinum-catalyzed cis6 and
ruthenium-catalyzed trans7 hydrosilylations have been
used in natural product syntheses. Enynes with a terminal
triple bond have been shown to yield dienes with the silicon
function in terminal position,8 whereas an internal dienyne
gave a mixture of regioisomers.9 1,3-Enynes equipped with
a propargylic alcohol function were shown to be subject to
site-selective trans addition of triethylsilane in the presence
of a ruthenium complex, but enynes lacking alcohol func-
tion were resistant to the reaction.10 The most extensively
(5) (a) Trost, B. M.; Ball, Z. T.; Laemmerhold, K. M. J. Am. Chem.
Soc. 2005, 127, 10028–10038. (b) Kawasaki, Y.; Ishikawa, Y.; Igawa, K.;
Tomooka, K. J. Am. Chem. Soc. 2011, 133, 20712–20715.
(1) (a) Munslow, I. J. In Modern Reduction Methods; Andersson, P. G.,
Munslow, I. J., Eds.; Wiley-VCH: Weinheim, 2008; pp 363À385. (b) Trost,
B. M.; Ball, Z. T. Synthesis 2005, 853–887.
(2) (a) Hiyama, T. J. Organomet. Chem. 2002, 653, 58–61. (b)
Denmark, S. E.; Regens, C. S. Acc. Chem. Res. 2008, 41, 1486–1499.
(c) Nakao, Y.; Hiyama, T. Chem. Soc. Rev. 2011, 40, 4893–4901. (d)
Chang, W.-T. T.; Smith, R. C.; Regens, C. S.; Bailey, A. D.; Werner,
N. S.; Denmark, S. E. Org. React. 2011, 75, 213–745.
€
(6) Gallenkamp, D.; Furstner, A. J. Am. Chem. Soc. 2011, 133, 9232–
9235.
(7) Micoine, K.; Furstner, A. J. Am. Chem. Soc. 2010, 132, 14064–
14066.
€
ꢀ
(8) Bergueiro, J.; Montenegro, J.; Cambeiro, F.; Saa, C.; Lopez, S.
ꢀ
Chem.;Eur. J. 2012, 18, 4401–4410.
(9) Bergueiro, J.; Montenegro, J.; Cambeiro, F.; Saa, C.; Lopez, S.
ꢀ
ꢀ
(3) (a) Fleming, I.; Henning, R.; Plaut, H. J. Chem. Soc., Chem.
Commun. 1984, 29–31. (b) Tamao, K.; Ishida, N.; Tanaka, T.; Kumada,
M. Organometallics 1983, 2, 1694–1696.
Chem.;Eur. J. 2012, 18, 14100–14107.
€
(10) (a) Trost, B. M.; Ball, Z. T.; Joge, T. Angew. Chem., Int. Ed. 2003,
42, 3415–3418. (b) Trost, B. M.; Ball, Z. T. J. Am. Chem. Soc. 2005, 127,
17644–17655.
(4) Lim, D. S. W.; Anderson, E. A. Synthesis 2012, 44, 983–1010.
r
10.1021/ol4001334
Published on Web 03/07/2013
2013 American Chemical Society

studied substrates are silicon-substituted butenynes;11
other examples are rare.12 The desired dienylsilanes have
instead commonly been prepared by indirect methods,
such as silylation of dienylmagnesium compounds,13 ring-
opening of silylated sulfolenes,14 electrophilic addition to
bissilylated 2-butynes,15 HornerÀEmmons reaction of the
anion of silylated 2-propenylphosphonate,16 and Suzuki
coupling of an R-iodo vinylsilane.17
Intrigued by the lack of more general studies, we decided
to investigate hydrosilylations of variously substituted 1,3-
enynes, thereby getting access to less substituted 1,3-dienes
than obtained via our previous silaborations of the same
substrates.18 Addition of diphenylsilane to (Z)-non-2-en-
4-yne (2a) and (Z)-5-phenyl-2-en-4-yne(2b) inthe presence
of Pd(dba)2 and PCy3 was first attempted.19 We were
pleased to note that addition to the alkyne function oc-
curred with high regioselectivity to yield the products of
pure cis-addition (Scheme 1), as evidenced by NOE (see the
Supporting Information). In the absence of phosphine
ligand, low yields of products were obtained (7% from 2a).
Table S1). However, improved results were observed in the
presence of Pd(0) catalysts obtained by in situ reduction of
Pd(II). Thus, Pd(acac)2 was reduced with DIBAL-H in the
presence of a phosphine prior to the addition of enyne and
silane. After completed reaction, water and pyridine were
added, which resulted in hydrolysis to the desired silanol. In
order to find the most suitable reaction conditions, various
ligands were screened in the reaction with enyne 2c (Table 1,
entries 1À5) . Use of triphenylphosphine and diphenylcy-
clohexylphosphine resulted in poor yields, most likely due to
inefficient oxidative addition of the silane to Pd(0) (Table 1,
entries 1 and 2). Highest site selectivity, in combination with
a high yield, was observed with electron-rich PEt3 (Table 1,
entry 4). A temperature of 80 °C was required, as lower
temperature resulted in lower yields (Table 1, entries 6À8).
Table 1. Screening of Reaction Conditions for Hydrosilylation
of 2c
Scheme 1. Palladium-Catalyzed Addition of Diphenylsilane to
1,3-Enynes
entry
temp (°C)
ligand
yielda (%)
3c:4cb
1
2
3
4
5
6
7
8
80
80
80
80
80
20
40
60
PPh3
PPh2Cy
PCy3
PEt3
10
15
92
90
61
14
50
72
87:13
84:16
84:16
93:7
After these preliminary attempts, we turned our atten-
tion to heterosubstituted silanes, which are crucial as
nucleophilic partners in palladium-catalyzed cross-coupling
reactions.20 The conditions which proved to be successful
for additions described in Scheme 1 unfortunately resulted
in no or unsatisfactory yields of products when diphenylsi-
lane was exchanged for chlorodimethylsilane, even at ele-
vated temperature (80 °C, see the Supporting Information,
SPhos
PEt3
75:25
93:7
PEt3
93:7
PEt3
93:7
a Isolated yield. b Determined by 1H NMR analysis of crude reaction
mixture.
The high preference for formation of the product with
the silicon function at the internal position is probably a
result of electronic factors and can be explained by the
preference for addition of palladium to the allylic position,
assuming that the reaction proceeds via the ChalkÀHarrod
mechanism, which involves oxidative addition21 of the
silane to the zerovalent metal center followed by insertion
of the olefin into the MÀH bond.22 Equally high site selec-
tivity was observed in platinum-catalyzed hydrosilylations
of conjugated ynones.23
(11) (a) Kusumoto, T.; Hiyama, T. Chem. Lett. 1985, 1405–1408. (b)
Kusumoto, T.; Ando, K.; Hiyama, T. Bull. Chem. Soc. Jpn. 1992, 65,
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Chem. Lett. 1997, 623–624. (d) Maruyama, Y.; Yoshiuchi, K.; Ozawa, F.
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J. 1996, 28, 513–519. (b) Sanda, F.; Murata, J.; Endo, T. J. Polym. Sci.,
Part A: Polym. Chem. 1998, 36, 2037–2042. (c) Junker, C. S.; Welker,
M. E.; Day, C. S. J. Org. Chem. 2010, 75, 8155–8165.
(14) Chou, T.-s.; Tso, H.-H.; Tao, Y.-T.; Lin, L. C. J. Org. Chem.
1987, 52, 244–246.
(15) Pornet, J. J. Organomet. Chem. 1988, 340, 273–282.
(16) Christov, V. C. Phosphorus, Sulfur, Silicon 1998, 132, 79–83.
(17) Frank, S. A.; Chen, H.; Kunz, R. K.; Schnaderbeck, M. J.;
Roush, W. R. Org. Lett. 2000, 2, 2691–2694.
(21) The formation of a palladium hydride by oxidative addition of
silanes has been demonstrated; see: Boyle, R. C.; Mague, J. T.; Fink,
M. J. J. Am. Chem. Soc. 2003, 125, 3228–3229.
(18) Zhou, H.; Moberg, C. J. Am. Chem. Soc. 2012, 134, 15992–
15999.
(19) Pd2(dba)3 CHCl3/PCy3 has previously been used for the hydro-
silylation af alkynes; see: Motoda, D.; Shinokubo, H.; Oshima, K.
Synlett 2002, 1529–1531.
(22) Chalk, A. J.; Harrod, J. F. J. Am. Chem. Soc. 1965, 87, 16–21.
(23) (a) Rooke, D. A.; Ferreira, E. M. J. Am. Chem. Soc. 2010, 132,
11926–11928. (b) Rooke, D. A.; Ferreira, E. M. Angew. Chem., Int. Ed.
2012, 51, 3225–3230. (c) Sumida, Y.; Kato, T.; Yoshida, S.; Hosoya, T.
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(24) A decrease in catalyst loading from 5 to 1 mol % resulted in a
decreased yield (70% instead of 90% for the reaction in entry 1) under
otherwise identical conditions.
Org. Lett., Vol. 15, No. 7, 2013
1445

yields of cis-addition products with the silyl function at the
internal position, and with retained configuration of the
original olefinic bond, were obtained (Table 2, entries 1À8).
A substrate with a terminal olefin was unreactive (Table 2,
entry 10), and enynes with a silicon substituent or a hetero-
atom in propargylic position resulted in complex mixtures
(Table 2, entries 9, 12À13). However, enyne 2o, with a
heteroatom in a position more remote from the alkyne
function, was smoothly transformed tothe desiredproduct
(Table 2, entry 14). Reaction of an enyne with terminal
alkyne function resulted in a moderate yield of an adduct
with opposite site selectivity (Table 2, entry 11); this mode
of addition is that commonly observed with terminal
alkynes. No allene derivatives were observed in any of
the reaction mixtures.
Table 2. Palladium-Catalyzed Hydrosilylation of Various 1,3-
Enynes to Silanols with Dimethylchlorosilane
The vinylsilanols obtained proved to serve as versatile
nucleophiles in palladium-catalyzed cross-couplings.2b As
expected, reaction with iodoarenes in the presence of Pd-
(PPh3)4 mediated by Ag2O25 gave high yields of coupling
products (Scheme 2).
Scheme 2. Ag2O-Mediated Cross-Coupling
In our previous studies, we showed that the type of
product obtained from palladium-catalyzed cross-cou-
pling of 1,1-disubstituted 2-dienylsilanols was dependent
on the activator used.16 Whereas Ag2O-mediated coupling
afforded 1,3-dienes, like in the above examples, coupling
performed in the presence of base gave 1,2-dienes. We were
thereforesurprisedtonotethat, underthesameconditions,
the present substrates resulted in clean conversion to 1,3-
dienes (Table 3). The use of bases with sodium as counter-
ion resulted in no or low yields (Table 3, entries 1, 3À5),
even under microwave conditions (Table 3, entry 2), while
those with potassium as counterion gave higher yields
(Table 3, entries 6À9).26
Finally, treatment of vinylsilane 3 with tetrabutylam-
monium fluoride resulted in desilylation (Scheme 3). The
a Isolated yield. b Determined by 1H NMR analysis of crude reaction
mixture. c Replacement of Pd(acac)2 by Pd(OAc)2 gave identical results.
d 0.15 mmol enyne was used. From a reaction using 1.5 mmol of enyne,
94% product was isolated. e No reaction.
(25) Weibel, J.-M.; Blanc, A.; Pale, P. Chem. Rev. 2008, 108, 3149–
3173.
(26) A similar difference in reactivity was previously observed for
coupling with aryl chlorides; see: Denmark, S. E.; Kallemeyn, J. M.
J. Am. Chem. Soc. 2006, 128, 15958–15959.
(27) (a) Lu, G.-P.; Voigtritter, K. R.; Cai, C.; Lipshutz, B. H. J. Org.
Chem. 2012, 77, 3700–3703. (b) Semba, K.; Fujihara, T.; Xu, T.; Terao,
J.; Tsuji, Y. Adv. Synth. Catal. 2012, 354, 1542–1550.
The optimized conditions were applied to hydrosilylations
of a variety of enynes (Table 2).24 From most reactions, high
1446
Org. Lett., Vol. 15, No. 7, 2013

Table 3. Base-Mediated Cross-Coupling
Scheme 3. Fluoride-Mediated Protiodesilylation
to 1,4-disubstituted and 1,2,4-trisubstituted 1,3-enynes,
conveniently accessible via Sonogashira coupling of term-
inal alkynes and vinyl halides,29 to yield dienylsilanols with
the silicon function at the internal position. Palladium-cata-
lyzed coupling of the products with iodoarenes, using
Ag2O as well as base, resulted in stereo- and regiochemi-
cally defined 1,3-dienes, whereas desilylation with tetrabu-
tylammonium fluoride resulted in overall cis-hydrogenation
of the triple bond.
a Isolated yield. b No reaction. c Reaction conditions: microwave,
100 °C, 2 h.
(Z)-configuration of the newly formed olefinic bond in 6b
1
was confirmed by comparison of its H NMR spectrum
Acknowledgment. We thank Dr. Zoltan Szabo, Depart-
ment of Chemistry, KTH, for making the NOE measure-
ments. Financial support from the Carl Trygger Founda-
tion for Scientific Research and the Swedish Research
Council is gratefully acknowledged.
with those previously published for the same compound27
and the configuration of the remaining compounds by
their 1H coupling constants. The overall process con-
stitutes a convenient method for the semihydrogenation
of 1,3-enynes, occurring without EÀZ isomerization and
over-reduction, which are commonly encountered pro-
blems in this type of reductions.28
Supporting Information Available. Experimental pro-
cedures, compound characterization data, and spectra.
This material is available free of charge via the Internet at
http://pubs.acs.org.
In summary, we have demonstrated that dimethyl-
chlorosilane undergoes palladium-catalyzed cis-addition
(28) For a recently reported selective process, see ref 23b.
(29) Negishi, E.-i.; Anastasia, L. Chem. Rev. 2003, 103, 1979–2017.
The authors declare no competing financial interest.
Org. Lett., Vol. 15, No. 7, 2013
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