Copper-Catalyzed Si-B Bond Activation in the Nucleophilic Substitution of Primary Aliphatic Triflates

Article abstract of DOI:10.1055/s-0035-1561407

A method for the nucleophilic displacement of the triflate leaving group attached to terminally functionalized alkyl groups with nucleophilic silicon is reported. Copper catalysis is used to release the silicon nucleophile from Suginome's Si-B reagent. Th

Full text of DOI:10.1055/s-0035-1561407

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©
Georg Thieme Verlag Stuttgart · New York
2016, 27, A–C
A
letter
Synlett
J. Scharfbier, M. Oestreich
Letter
Copper-Catalyzed Si–B Bond Activation in the Nucleophilic Substi-
tution of Primary Aliphatic Triflates
Jonas Scharfbier
cat. CuCN
Me2PhSiBpin
NaOt-Bu
Martin Oestreich*
FG
OTf
FG
SiMe2Ph
29–88% yield
8 examples)
high functional-group tolerance
FG = OTBDMS, Br, OTs, CO2R, CH=CH2, and C≡CH
Institut für Chemie, Technische Universität Berlin,
Straße des 17. Juni 115, 10623 Berlin, Germany
martin.oestreich@tu-berlin.de
THF
°C or r.t.
0
(
Received: 22.12.2015
Accepted after revision: 09.02.2016
Published online: 04.03.2016
Oestreich (2010/2013)
Shintani/Hayashi (2013)
CuX (catalytic)
Me2PhSiBpin (1)
DOI: 10.1055/s-0035-1561407; Art ID: st-2015-b0994-l
alkoxide
Abstract A method for the nucleophilic displacement of the triflate
leaving group attached to terminally functionalized alkyl groups with
nucleophilic silicon is reported. Copper catalysis is used to release the
silicon nucleophile from Suginome’s Si–B reagent. The functional group
tolerance is excellent, and halide leaving groups do also work with the
same protocol.
LG
SiMe2Ph
II
I
Shintani/Hayashi (2013)
CuX (catalytic)
Me2PhSiBpin (1)
alkoxide
LG
SiMe2Ph
Key words chemoselectivity, copper, nucleophilic substitution, sili-
con, transmetalation
III
this work
IV
The transmetalation of the Si–B interelement bond for
the catalytic formation of silicon nucleophiles has recently
CuX (catalytic)
Me PhSiBpin (1)
2
1
alkoxide
revolutionized synthetic silicon chemistry. Methods based
on copper have emerged as particularly broadly applicable.2
Alkyl
LG
Alkyl
SiMe2Ph
VI
V
The copper-based silicon nucleophile is usually generated
Scheme 1 Nucleophilic substitution of activated (allylic and benzylic)
and unactivated (aliphatic) C(sp )–X bonds (X = CN or Cl)
by σ-bond metathesis of the Si–B bond and the Cu–O bond
3
3
of an in situ generated copper(I) complex. With Sugi-
4
nome’s Me PhSiBpin (1) as the typical silicon source, sev-
2
eral fundamental Si–C bond-forming reactions were real-
While there are no examples for the case of silicon nuc-
leophiles, the analogous copper-catalyzed transformation
1,2
ized in racemic and asymmetric fashion. These include
,4-[
5–7]
and 1,2-addition as well as allylic substitution.[10–
8,9
with boron nucleophiles is now well established (LG = Cl,
13
1
1
2]
14
The displacement of a leaving group (LG) in the allylic
Br, I, and OTs). Moreover, the corresponding reduction
with Cu–H15 was also disclosed (LG = I and OTf). We here-
in report a new Si–C bond formation catalyzed by copper
that converts primary alkyl triflates and halides into func-
tionalized tetraorganosilanes.
16
position could be viewed as a nucleophilic substitution of
3
an activated C(sp )–LG bond with nucleophilic silicon (I →
11,12
II, Scheme 1, top).
A similar situation exists in benzylic
positions, but there is just one example with a phosphate
leaving group known to date (III → IV, Scheme 1, middle).12
Conversely, the related nucleophilic substitution of aliphat-
We commenced our study with a survey of leaving
groups, employing a straightforward catalytic setup (Table
1). Aliphatics 2a–f were reacted with silyl boronic ester 1 in
THF in the presence of catalytic amounts of CuCN and
NaOt-Bu as stoichiometric base. The reactions were started
at 0 °C, warmed to room temperature, and maintained at
this temperature for 16 hours. All substrates 2a–c with ha-
3
ic and as such unactivated C(sp )–LG bonds with silicon nu-
cleophiles is unprecedented (V → VI, Scheme 1, bottom).
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–C

B
Synlett
J. Scharfbier, M. Oestreich
Letter
lide leaving groups showed conversions depending on their
leaving group ability (entries 1–3). Yields of 3, however,
were significantly lower than conversions of 2, indicating
other competing pathways such as elimination. Tosylate 2d
did not react, but triflate 2e afforded 3 in high yield at full
conversion (entries 4 and 5). Phosphate 2f was in turn inert
under these reactions conditions (entry 6).
full consumption of 2e (entries 4 and 5); often-used
NaOMe led to decomposition (entry 6). A control experi-
1
ment in the absence of CuCN demonstrated not only the
chemical instability of triflate 2e toward NaOt-Bu but also
the ability of NaOt-Bu to promote this reaction alone (entry
17
7). The catalyst loading had little or no effect, and results
with 1.0 and 10 mol% of CuCN were in the same range as
with 5.0 mol%.
With a reliable procedure at hand,18 we evaluated the
scope of the method (Scheme 2). All triflates were freshly
prepared by standard protocols (see the Supporting Infor-
mation for characterization data) and immediately used.
Our model compound afforded 88% isolated yield (2e → 3),
and the same yield was obtained for a substrate containing
a TBDMS-protected hydroxy group (4e → 11). Substrates
with potential leaving groups at the other terminus of the
alkyl chain reacted in decent yields of 65% and 68% (5e → 12
and 6e → 13). An ester group was also tolerated (7e → 14),
and the same applied to unsaturation in the form of C–C
multiple bonds (8e–10e → 15–17). The moderate yield of
Table 1 Survey of Leaving Groups
CuCN (5.0 mol%)
Me2PhSiBpin (1, 1.5 equiv)
NaOt-Bu (1.5 equiv)
n-Hept
LG
n-Hept
SiMe2Ph
THF
2a–f
3
0
°C to r.t.
16 h
Entry
Substrate
Leaving group
Conv. of 2 (%)a Yield of 3 (%)b
1
2
3
4
5
6
2a
2b
2c
2d
2e
2f
Cl
23
45
16
28
55
–
Br
I
>99
n.r.c
40% for 15 is the result of its difficult purification, and the
OTs
OTf
poor yield of 29% for 17 remains unexplained.
>99
92
–
n.r.c
CuCN (5.0 mol%)
Me2PhSiBpin (1, 1.5 equiv)
NaOt-Bu (1.5 equiv)
OP(O)(OEt)
2
a
Determined by GLC analysis with tetracosane as internal standard.
Determined by calibrated GLC analysis with tetracosane as internal stan-
b
R
OTf
R
SiMe2Ph
dard.
THF
0 °C (to r.t.)
c
2e and 4e–10e
3 and 11–17
No reaction.
We continued with triflate 2e for further optimization
Table 2). A closer look at the reaction time showed that full
conversion is already reached at 0 °C within 1 hour, but the
reaction rate decreased substantially at lower temperatures
entries 1–3). Other tert-butoxides, such as LiOt-Bu and
TBDMSO
SiMe2Ph
SiMe2Ph
(
3
(from 2e): 88%
(0 °C, 2 h)
11 (from 4e): 87%
(0 °C, 3 h)
Br
SiMe2Ph
TsO
SiMe2Ph
(
1
1
2 (from 5e): 65%
13 (from 6e): 68%
KOt-Bu, were less effective, furnishing 3 in lower yields at
(0 °C, 2 h)
(0 °C, 2 h)
EtO2C
SiMe2Ph
4 (from 7e): 77%
(0 °C to r.t., 7 h)
SiMe2Ph
15 (from 8e): 40%
(0 °C to r.t., 18 h)
Table 2 Screening of Temperature and Base in the Nucleophilic Substi-
tution of n-Octyl Trifluoromethanesulfonate (2e)a
Ph
SiMe2Ph
16 (from 9e): 75%
0 °C to r.t., 16 h)
SiMe2Ph
17 (from 10e): 29%
(0 °C to r.t., 18 h)
Entry
Base
Temp (°C) Time (h) Conversion of Yield of
b c
2
e (%)
3 (%)
(
1
2
3
4
5
NaOt-Bu
0
–25
–50
0
1
1
1
1
1
2
3
>99
56
92
52
26
83
63
14
12
Scheme 2 Scope of the copper-catalyzed nucleophilic substitution of
functionalized alkyl triflates
NaOt-Bu
NaOt-Bu
LiOt-Bu
KOt-Bu
32
>99
>99
>99
>99
To summarize, we developed the displacement of unac-
3
0
tivated C(sp )–LG bonds (LG = Cl, Br, I, and OTf) with the sil-
6
NaOMe
NaOt-Bu
0
icon nucleophile released from an Si–B reagent by copper
catalysis. The reaction works best with the triflate leaving
group, and various functionalized primary alkyl triflates
were converted into the corresponding tetraorganosilanes
in good to high isolated yields. Extension of this methodolo-
7d
0
a
Reactions were performed using CuCN (0.012 mmol), 1 (0.38 mmol, 1.5
equiv), and the indicated base (0.38 mmol, 1.5 equiv) in THF (1 mL) at the
indicated temperature for 1 or 2 h.
b
Determined by GLC analysis with tetracosane as internal standard.
19
c
gy to secondary alkyl electrophiles and its mechanistic
Determined by calibrated GLC analysis with tetracosane as internal stan-
dard.
analysis (ionic or radical)1
4,16
will be reported in due course.
d
Without CuCN.
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–C

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Synlett
J. Scharfbier, M. Oestreich
Letter
Acknowledgment
(10) Delvos, L. B.; Oestreich, M. Chim. Oggi 2013, 31, 74.
(11) (a) Vyas, D. J.; Oestreich, M. Angew. Chem. Int. Ed. 2010, 49,
M.O. is indebted to the Einstein Foundation (Berlin) for an endowed
professorship.
8513. (b) Delvos, L. B.; Vyas, D. J.; Oestreich, M. Angew. Chem. Int.
Ed. 2013, 52, 4650. (c) Hazra, C. K.; Irran, E.; Oestreich, M. Eur. J.
Org. Chem. 2013, 4903. (d) Delvos, L. B.; Hensel, A.; Oestreich, M.
Synthesis 2014, 46, 2957. (e) Delvos, L. B.; Oestreich, M. Synthesis
Supporting Information
2015, 47, 924.
(
(
12) Takeda, M.; Shintani, R.; Hayashi, T. J. Org. Chem. 2013, 78, 5007.
13) Cid, J.; Gulyás, H.; Carbó, J. J.; Fernández, E. Chem. Soc. Rev. 2012,
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1561407.
S
u
p
p
ortioIgnfrm oaitn
S
u
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p
ortioIgnfrm oaitn
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18) Copper-Catalyzed Nucleophilic Substitution of Functional-
4
ized Alkyl Triflates; General Procedure
A flame-dried Schlenk tube was charged with CuCN (1.1 mg, 5.0
mol%) and NaOt-Bu (36 mg, 1.5 equiv); when required,
tetracosane was added as internal standard at this stage. THF
was added (0.25 M), and the resulting solution was cooled to
(
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0
(
°C. After 10 min, 1 (98 mg, 1.5 equiv) and the indicated triflate
0.25 mmol) were successively added. The purple solution was
maintained at 0 °C or room temperature for the indicated time
monitoring by GLC analysis). The reaction was then diluted
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(
with MTBE (5 mL) and filtered through a short plug of silica gel,
followed by rinsing with MTBE (2 × 5 mL). The solvents were
evaporated under reduced pressure, and the crude material was
purified by flash chromatography on silica gel with the indi-
cated solvents as eluent (see the Supporting Information for
details). The tetraorganosilanes were obtained as colorless oils.
19) The current procedure was not applicable to secondary alkyl
bromides, iodides, and triflates as a result of facile elimination.
High and moderate conversion was obtained for bromides and
iodides, respectively, but only traces of the desired tetraorga-
nosilanes were detected by GLC analysis; triflates were gener-
ally too labile.
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©
Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–C