Palladium(0)-catalyzed C(sp3)-Si bond formation: Via formal carbene insertion into a Si-H bond

Article abstract of DOI:10.1039/c8cc06768f

Pd(0)-Catalyzed formal carbene insertion into Si-H bonds has been achieved as an efficient method for C(sp³)-Si bond formation. The reaction, which uses readily available N-tosylhydrazones as the diazo precursors, is highly efficient and shows a wide substrate scope. Rh(ii) and Cu(i) salts, which are the widely used catalysts for carbene insertion reactions, have been proved to be ineffective for the current reaction. A Pd(ii) carbene migratory insertion/reductive elimination mechanism is proposed.

Full text of DOI:10.1039/c8cc06768f

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DOI: 10.1039/C8CC06768F
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Palladium(0)-Catalyzed C(sp3)-Si Bond Formation via Formal
Carbene Insertion into Si-H Bond†
Zhenxing Liu,a Jingfeng Huo,a Tianren Fu,a Haocheng Tan,a Fei Ye,a Mohammad Lokman Hossaina
Received 00th January 20xx,
Accepted 00th January 20xx
and Jianbo Wang ab
*
DOI: 10.1039/x0xx00000x
www.rsc.org/
Pd(0)-catalyzed formal carbene insertion into Si-H bonds have catalyzed C-H bonds insertion.7 It is worth mentioning that for those
been achieved as an efficient method for C(sp3)-Si bond formation.
The reaction, which uses readily available N-tosylhydrazones as
the diazo precursors, is highly efficient and shows wide substrate
scope. Rh(II) and Cu(I) salts, which are the widely used catalysts
for carbene insertion reactions, have been proved to be
ineffective for the current reaction. A Pd(II) carbene migratory
insertion/reductive elimination mechanism is proposed.
Organosilicon compounds play vital roles in various fields such as
organic synthesis, material sciences and life sciences.1 Therefore,
the methods for constructing C-Si bonds are highly demanded. For
the C(sp3)-Si bond formation, hydrosilylation of alkene represents
one of the most important methods, which has found applications
both in research laboratory and in industry (Scheme 1, a).2
However, this powerful method still suffers drawbacks of low
efficiency and poor regioselectivity with hindered alkenes.3 Other
effective way to construct C(sp3)-Si bonds includes the reaction of
organometallic species with silicon electrophiles.4 Besides, the
coupling of silicon nucleophiles (Zn and B-based silicon nucleophiles)
with alkyl electrophiles has been reported by Fu and Oestreich
(Scheme 1, b).5
Scheme 1Construction of C(sp3)-Si bond.
carbene Si-H bonds insertions, the relatively stable diazocarbonyl
compounds have been applied as the carbene precursor in most
cases. Thus, the carbene Si-H insertion method is limited to the
introduction of C-Si bond to the -position of an electron-
withdrawing group. The diazo substrates without an electron-
withdrawing substituent are unstable, but they can be generated in
situ from N-tosylhydrazones through Bamford-Stevens reaction.8
Therefore, N-tosylhydrazones have recently been extensively
explored in transition-metal-catalyzed carbene transfer reactions as
well as in cross-coupling reactions.9
On the other hand, transition-metal-catalyzed carbene insertion
into Si-H bonds represents a unique way for the C(sp3)-Si bond
formation (Scheme 1, c).6 A series of transition metals, including
Rh(II), Rh(I), Cu(II), Cu(I), Ir(III), Ag(I), Ru(II) and Fe(II), are effective
for this transformation. Rh(II) and Cu(I) salts are among the most
frequently used catalysts for this reaction. Mechanistic studies
indicate the Si-H insertion occurs through a concerted three-
membered cyclic transition state, similar to the Rh(II) or Cu(I)-
We have recently reported a Pd(0)-catalyzed formal carbene
insertion into Si-Si and Sn-Sn bonds with N-tosylhydrazones as the
carbene precursors.10 The reaction is proposed to follow a reaction
sequence consisting of oxidative addition of σ-bonds to Pd(0), Pd(II)
carbene formation, migratory insertion and finally reductive
elimination. As the continuation of our interest in this type of σ-
bond insertion reaction, herein we report our study on the Pd(0)-
catalyzed carbene insertion into Si-H bonds with N-tosylhydrazones
as the carbene precursors (Scheme 1, d).11 To the best of our
a. Beijing National Laboratory of Molecular Sciences (BNLMS), Key Laboratory of
Bioorganic Chemistry and Molecular Engineering of Ministry of Education,
College of Chemistry, Peking University, Beijing 100871, China. E-mail:
wangjb@pku.edu.cn
b.The State Key Laboratory of Organometallic Chemistry, Shanghai Institute of
Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
† Electronic supplementary information (ESI) available: Experimental details,
Characterization data. See DOI: 10.1039/x0xx00000x
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diaryl ketones could be used in the reaction and the corresponding
DOI: 10.1039/C8CC06768F
products were obtained in moderate to good yields (3n-r). Besides,
knowledge, this reaction represents the first example of formal Si-H
carbene insertion with palladium catalyst.
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As benzylsilane, especially secondary benzylsilane, cannot be
easily accessed by hydrosilylation of alkenes or coupling reactions,
we chose N-tosylhydrazone 1d and commercially available
triethylsilane 2a as the substrates (Table 1).12 Upon some initial
experiments, we determined that 2 mol% Pd(PtBu3)2 with 3.0 equiv
N-tosylhydrazone derived from alkynyl ketone also worked well (3s).
It is noteworthy that the TIPS substituent is essential in this case,
otherwise the N-tosylhydrazone undergoes intramolecular
cyclization reaction. Apart from the preparation of benzylsilanes,
tetra-alkyl silanes could also be obtained with this reaction (3t-v).
o
LiOtBu in dioxane at 120 C as “standard” conditions, furnishing the
target compound 3d in 98% yield (Table 1, entry 1). The Pd(PtBu3)2
turned out to be necessary (Table 1, entry 2). Rh2(OAc)4, CuCl and
Cu(OTf)2, which are widely-used catalysts for carbene insertion into
Si-H bonds, failed to catalyse the current reaction (Table 1, entries
3-5). This indicates that the Pd(0)-catalyzed reaction is
mechanistically different from the classic Rh(II)- or Cu(I)-catalyzed
carbene Si-H bond insertion. Further experiments showed that
Pd(OAc)2 and Pd(PPh3)4 could not catalyse the reaction, while the
.
reaction with Pd2(dba)3/PtBu3 HBF4 gave the product in 40% yields
(Table 1, entries 6-8). This suggests the electron-rich phosphine
ligand is essential, presumably for the effective oxidative addition of
Si-H bond to Pd(0) (vide infra). It was also observed that high
temperature is beneficial for the insertion reaction as the yield
o
dropped to 78% when the reaction was carried out at 100 C (Table
1, entry 9).
Table 1 Investigation on the Reaction Parametersa
Entry Variation from the "standard" conditions
yieldb
98%
1
none
without Pd(PtBu3)2
2
trace
trace
trace
trace
trace
trace
3
4
5
6
7
8
with Rh2(OAc)4 (2 mol%), instead of Pd(PtBu3)2
with CuCl (5 mol%) instead of Pd(PtBu3)2
with Cu(OTf)2 (5 mol%) instead of Pd(PtBu3)2
with Pd(OAc)2 (5 mol%) instead of Pd(PtBu3)2
with Pd(PPh3)4 (5 mol%) instead of Pd(PtBu3)2
Scheme 2 Scope of the reaction with N-tosylhydrazones derived from
ketones. All the reactions were carried out in 0.3 mmol scale. All the yields
refer to the isolated products with silica gel column chromatography. aThe
yield in the bracket refer to a gram-scale reaction (1.08 g of 3c obtained).
.
with Pd2(dba)3 (2.5 mol%)/PtBu3 HBF4 (10 mol%)
instead of Pd(PtBu3)2
at 100 oC instead of 120 oC
40%
78%
The N-tosylhydrazones derived from aldehydes were then
examined. The reaction was found similarly efficient and the
substrate scope is wide (Scheme 3). For N-tosylhydrazones derived
from aromatic aldehydes, the yields ranged from moderate to good
(5a-i). Notably, NH2 group and Bpin could be tolerated (5b, 5f). The
reaction substrate could also be expanded to ferrocene-
carboxaldehyde and heteroaromatic aldehydes derived N-
tosylhydrazones (5j-l). N-Tosylhydrazones derived from alkynyl and
alkyl aldehydes also worked well (5m-q). Bis-N-tosylhydrazones
could also be used in the reaction, affording the corresponding bis-
silylation products in moderate yields (5r). Apart from triethylsilane,
9
aAll reactions were conducted in 0.1 mmol scale. bYields of isolated
products with silica gel column chromatography.
Next, we proceeded to explore the substrate scope of the
reaction. As shown in Scheme 2, a series of N-tosylhydrazones
worked well under the current conditions, affording the desired
products efficiently. For mono-substituted aromatic ketone derived
N-tosylhydrazones, the substrates bearing substituents on para-,
meta-, and ortho-positions with different electronic properties all
proceeded well in the reaction (3a-i). Interestingly, Bpin substituent dimethyl(phenyl)silane reacted similarly with N-tosylhydrazone 4e
and gave the product 5s in 71% yield.
could be tolerated under current conditions (3g). Substrates bearing
naphthyl-, indanyl- and sterically bulky isopropyl substituents also
reacted smoothly to give the corresponding products in good yields
(3j-l). Pyridine-containing N-tosylhydrazone was also a suitable
substrate for the reaction (3m). N-tosylhydrazone derived from
When Et2SiH2 was used as reactant, two C-Si bonds can be
formed in the reaction. As shown in Scheme 4, for the reactions of
N-tosylhydrazones derived from ketone and aldehyde with Et2SiH2
(2c), double Si-H insertion products could be afforded in low to
2 | J. Name., 2015, 00, 1-3
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Finally, we carried out the double Si-H insertionVsiesweAqrtuicelenOtinalilnlye
DOI: 10.1039/C8CC06768F
using two different N-tosylhydrazones in one pot manner, obtaining
the corresponding products (8a,b) in moderate yields (Scheme 5).
Scheme 5 Pd(0)-Catalyzed sequential cross-couplings of N-tosylhydrazones
with Et2SiH2.Reaction conditions for 1d, 2c with 1a or 4a: 1d (0.3 mmol), 2c
(0.45 mmol), Pd(PtBu3)2 (0.006+0.006 mmol, 2+2 mol%), LiOtBu (0.9+0.9
mmol, 3.0+3.0 equiv), 1a or 4a (0.45 mmol, 1.5 equiv), dioxane (4.0 mL), 120
oC for 4 h.
Based on the above results and our previous report,10 we have
proposed the reaction mechanism as shown in Scheme 6. The
catalytic cycle starts with the oxidative addition of Si-H bond to Pd(0)
A to generate Pd(II) species B.13 The Pd(II) species B then reacts
with the in-situ formed diazo substrate to generate Pd(II) carbene C.
Subsequently, there are two possible pathways: 1) the hydride may
migrate into carbenic carbon and to form D (path a); 2) or silyl
migratory insertion to give C (path b). Finally, reductive elimination
occurs to complete the catalytic cycle and give the insertion
products. Both paths are conceivable, further rigorous investigation
is required to unambiguously confirm the reaction mechanism.14
Scheme 3 Scope of the reaction with N-tosylhydrazones derived from
aldehydes. All the reactions were carried out in 0.3 mmol scale. All the yields
refer to the isolated products with silica gel column chromatography. aThe
amount of 4r is 0.15 mmol, others are the same as above.
moderate yields (7a-c). When bis-N-tosylhydrazones were used, 12-
membered silacycle could be obtained (7d). While the yield of
silacycle was poor, the reaction demonstrates the possibility to
access such type of silane compounds with this reaction.
Scheme 6 Proposed Reaction Mechanism
In summary, we have reported an efficient method for the C(sp3)-
Scheme 4 Pd(0)-Catalyzed cross-coupling of N-tosylhydrazones with Et2SiH2. Si bond formation. Compared with the classic transition-metal-
Reaction conditions for 1a, 4n, 4t with 2c: 1a, 4n or 4t (0.3 mmol), 2c (0.225
mmol), Pd(PtBu3)2 (0.006 mmol, 2 mol%), LiOtBu (0.9 mmol, 3.0 equiv),
dioxane (4.0 mL), 120 oC for 2 h. Reaction conditions for 6a with 2c: 6a (0.15
mmol), 2c (0.225 mmol), Pd(PtBu3)2 (0.006 mmol, 4 mol%), LiOtBu (0.9 mmol,
6.0 equiv), dioxane (4.0 mL), 120 oC for 2 h. All the yields refer to the
isolated products with silica gel column chromatography.
catalysed carbene Si-H insertions, the Pd(0)-catalysed reaction
expands the reaction scope for more general C(sp3)-Si bond
formations. Moreover, the Pd(0)-catalyzed formal Si-H bond
insertion is proposed to follow a stepwise mechanism involving
oxidative addition, carbene migratory insertion and resuctive
elimination, which is fundamentally different from the classic
carbene Si-H bond insertions. Further study toward
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Z. Liu, Q. Li, Y. Yang, X. Bi, Chem. Commun., 2017, 53, 2503; (b) E.-H.
enantioselective version of the reaction is currently under way in
our laboratory.
Wang, Y.-J. Ping, Z.-R. Li, H. Qin, Z.-J. Xu, C.-M. Che, OrgV. iLeewttA.r,t2ic0le1O8n, l2in0e,
DOI: 10.1039/C8CC06768F
4641.
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13 For related reports on oxidative addition of Si-H bonds to Pd(0), see: (a)
T. Hayashi, S. Hirate, K. Kitayama, H. Tsuji, A. Torii, Y. Uozumi, J. Org.
Chem., 2001, 66, 1441; (b) Y. Yamanoi, J. Org. Chem., 2005, 70, 9607.
14 For related reports on hydride and silicon migration of Pd carbene
species, see: (a) L. Zhou, Z. Liu, Y. Liu, Y. Zhang, J. Wang, Tetrahedron
2013, 69, 6083; (b) see ref. 10.
The project is supported by 973 Program (No. 2015CB856600) and
NSFC (Grant 21332002).
Notes and references
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11 While our work was undergoing, there were two recently reported Si-H
insertion examples utilizing hydrazones as carbene precursors. See: (a)
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DOI: 10.1039/C8CC06768F
Graphical Abstract
Pd(PtBu3)2(2 mol%)
SiEt3
R'
NNHTs
Et3SiH
+
LiOtBu (3.0 equiv)
dioxane, 120 oC
R
R
R'
(1.2 equiv)
41 examples
35-98%
Pd(0)-catalyzed formal carbene insertion into Si-H bonds have been achieved as an
efficient method for C(sp3)-Si bond formation.