Silver-catalyzed hydroamination of siloxy alkynes

Article abstract of DOI:10.1002/anie.200601276

(Chemical Equation Presented) New catalytic process: The silver-catalyzed hydroamination of siloxy alkynes with secondary amides furnishes silyl ketene aminals with high efficiency and excellent diastereoselectivity (see scheme), including some that are unavailable by conventional silylation methods. The reaction comprises a fast and reversible silver-alkyne complexation, followed by a rate-determining C-N bond-forming step.

Full text of DOI:10.1002/anie.200601276

Angewandte
Chemie
example of hydroamination of electron-rich alkynes by using
a silver-based catalyst that enables syn-selective addition of
secondary amides and carbamates to furnish the correspond-
ing silyl ketene aminals with high efficiency and excellent
diastereoselectivity. Our mechanistic studies demonstrate
that the reaction proceeds by a fast and reversible silver–
À
alkyne complexation,followed by a rate-determining C
N
bond-forming step,which provides an important mechanistic
platform for further development of d10 catalysts for alkyne
and alkene hydroamination.
During our continuing investigation of the development
À
À
of new catalytic C C and C X bond-forming reactions with
electron-rich alkynes,[6] we discovered that treatment of siloxy
alkyne 1 (TIPS = iPr3Si) with carbamate 2 in the presence of
either a silver- or a gold-based catalyst resulted in the
formation of silyl ketene aminal 3 (Table 1). Initial inves-
Table 1: Hydroamination of siloxy alkynes: catalyst evaluation.
Entry
Catalyst
Catalyst loading
Reaction time
Yield [%][a]
1
2
3
4
5
6
7
8
AuCl
5 mol%
5 mol%
5 mol%
1 mol%
0.3 mol%
5 mol%
5 mol%
5 mol%
1.5 h
30 min
30 min
30min
2 h
3 h
3 h
3 h
51
75
AuCl3
AgNTf2
AgNTf2
AgNTf2
HNTf2
PdCl2
91 (82[b])
95 (86[b])
81
Hydroamination
<5
<5[c]
40[c]
PtCl2
DOI: 10.1002/anie.200601276
[a] Determined by NMR integration with respect to an internal standard.
[b] Yield of isolated product (reaction giving best yield highlighted in
bold). [c] The reaction was conducted in toluene at 808C.
Silver-Catalyzed Hydroamination of Siloxy
Alkynes**
Jianwei Sun and Sergey A. Kozmin*
tigations revealed that the use of AgNTf2 (Tf = CF3SO2)
proved to be superior to that of AuCl and AuCl3 (Table 1,
entries 1–3).[7] This finding is especially noteworthy as silver-
based catalysts have not been used extensively for the
hydroamination of alkynes and alkenes.[8] The hydroamina-
tion product, 3,was obtained in 86% yield after 30 min at
room temperature by using only 1 mol% of AgNTf2 (Table 1,
entry 4). The catalyst loading could be further decreased to
0.3 mol% without significant loss of efficiency (Table 1,
Transition-metal-catalyzed hydroamination of alkynes has
[1]
À
emerged as a valuable method for C N bond formation.
While significant progress in this area has been made,[2]
several important limitations remain to be addressed. The
majority of the previously developed catalytic processes
employ highly nucleophilic primary amines that afford the
corresponding imines as a result of tautomerization of the
initially produced enamides.[3–5] We describe herein the first
entry 5). Furthermore,subjecting the reactants to HNTf
2
(5 mol%) produced only a trace of enol silane 3,which
ruled out a possible involvement of the conjugate Brønsted
acid in the alkyne activation (Table 1,entry 6). Interestingly,
PdCl2 and PtCl2 proved to be much less effective at catalyzing
this reaction (Table 1,entries 7 and 8).
Having established a standard reaction protocol,we
examined the scope of this catalytic process. The reaction of
either 5- or 4-substituted oxazolidinones, 4 and 6,with siloxy
alkyne 1 afforded the desired products, 5 and 7,respectively
(Table 2,entries 1 and 2). Hydroamination of 1 with secon-
dary amide 8 afforded silyl ketene aminal 9 with good
efficiency (Table 2,entry 3),thus demonstrating that the
[*] J. Sun, Prof. Dr. S. A. Kozmin
Department of Chemistry
University of Chicago
5735 South Ellis Avenue, Chicago, IL 60637 (USA)
Fax: (+1)773-702-0805
E-mail: skozmin@uchicago.edu
[**] This work was supported by the NSF CAREER (CHE-0447751).
S.A.K. thanks the Sloan Foundation, the Dreyfus Foundation,
Amgen, and GlaxoSmithKline for additional funding.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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Communications
Table 2: Ag-catalyzed hydroamination: nucleophile scope.[a]
Table 3: Ag-catalyzed hydroamination: alkyne scope.
Yield [%][b]
72
Entry
1
Alkyne
Product
Yield [%][a]
Entry
1
Nucleophile
Product
86
2
3
86
71
2
3
81
76
4
5
80
86
4
5
73
45
[a] General reaction protocol: siloxy alkyne (0.40 mmol) and amide
(0.36 mmol) were dissolved in CH2Cl2 (5 mL) and treated with AgNTf2
(0.0036 mmol) at 208C. The resulting solution was stirred for 30 min,
then treated with one drop of Et3N. The solvent was removed under
reduced pressure and the crude product was purified by flash
chromatography on silica gel. [b] Yield of isolated spectroscopically
pure products that were fully characterized by NMR and IR spectros-
copies and mass spectrometry.
[a] Refers to yields of isolated spectroscopically pure products that were
fully characterized by NMR and IR spectroscopies and mass spectrom-
etry.
high syn selectivity,we carried out a series of kinetic studies of
the reaction of alkyne 1 with carbamate 2 in the presence of
AgNTf2 at À208C. We found that the reaction was first-order
with respect to both carbamate 2 and the silver catalyst,and
zero-order with respect to alkyne 1,thus providing the
empirical rate law: r= kobs[AgNTf2][2],in which kobs = 1.52 ”
10À2 mÀ1 sÀ1.[9] Furthermore,using deuterated oxazolidinone 2,
we found no primary deuterium isotope effect (kH/kD = 1.03).
We propose that the reaction begins with a fast and
reversible complexation between 1 and AgNTf2 to give silver–
alkyne complex A (Scheme 1),which is supported by our
previous stoichiometric studies.[6b] At high concentrations of
alkyne,the catalyst is saturated with the alkyne and the
equilibrium favors intermediate A,which explains why the
reaction is zero-order with respect to the alkyne. The alkyne
activation is followed by the rate-determining step,which
entails the addition of the carbamate 2 to the silver–alkyne
complex A. We believe that this reaction proceeds via a six-
membered chelated transition state, B,which explains the
high syn selectivity of the hydroamination process.[10] Subse-
quent release of the proton from intermediate C,followed by
protodemetallation of the alkenyl–silver compound D affords
the observed product, 3,and regenerates the silver catalyst.
The proposed rate-determining step is fully consistent with
the absence of any primary deuterium isotope effect.
reaction is not limited to the use of cyclic carbamates.
Furthermore,lactams 10 and 12 were used to produce the
corresponding enol silanes, 11 and 13 (Table 2,entries 4 and
5),thus illustrating the ability of this method to produce silyl
ketene aminals that would not be available by using conven-
tional silylation methods due to the problems associated with
chemoselective generation of the required enols or enolates.
We next examined the scope of siloxy alkyne substitution
(Table 3). Subjecting arene- or alkene-conjugated alkynes, 14
and 16,to the standard reaction conditions with carbamate 2
afforded the corresponding ketene aminals, 15 and 17,
respectively (Table 3,entries 1 and 2). Hydroamination of
diyne 18 proceeded to give enyne 19 with complete chemo-
and diastereoselectivity (Table 3,entry 3). Other alkyl-sub-
stituted alkynes, 20 and 22,gave the expected hydroamination
products, 21 and 23 (Table 3,entries 4 and 5). The lower
efficiency of the reaction in entry 5 of Table 3 is attributed to
the significant increase in the steric bulk in direct proximity to
the reaction site. While the current protocol is highly effective
for hydroamination of a wide range of siloxy alkynes,
ynamides and simple internal alkynes proved to be unreactive
under its conditions.
To gain further insight into the mechanism of the Ag-
catalyzed hydroamination and the nature of the observed
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hydroamination of electron-rich alkynes with either secon-
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efficient method for the synthesis of a range of synthetically
useful silyl ketene aminals and provides an important
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Received: March 31,2006
Published online: June 29,2006
Keywords: alkynes · homogeneous catalysis · hydroamination ·
.
silver
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