Borane-catalyzed selective hydrosilylation of internal ynamides leading to β-silyl (Z)-enamides

Article abstract of DOI:10.1021/acs.orglett.6b03485

We have developed a borane-catalyzed regioand stereoselective hydrosilylation of internal ynamides for the first time. The scope of ynamide substrates and silane reactants was broad under mild reaction conditions, affording synthetically versatile β-silyl (Z)-enamide products. The observed stereoselectivity was reasoned to be due to the β-silicon effect on a postulated ketene iminium intermediate.

Full text of DOI:10.1021/acs.orglett.6b03485

Letter
pubs.acs.org/OrgLett
Borane-Catalyzed Selective Hydrosilylation of Internal Ynamides
Leading to β‑Silyl (Z)‑Enamides
Youngchan Kim,†,‡,§ Ramesh B. Dateer,‡,†,§ and Sukbok Chang*,‡,†
†Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea
‡Center for Catalytic Hydrocarbon Functionalization, Institute for Basic Science (IBS), Daejeon 34141, Korea
S
* Supporting Information
ABSTRACT: We have developed a borane-catalyzed regio-
and stereoselective hydrosilylation of internal ynamides for the
first time. The scope of ynamide substrates and silane reactants
was broad under mild reaction conditions, affording syntheti-
cally versatile β-silyl (Z)-enamide products. The observed
stereoselectivity was reasoned to be due to the β-silicon effect
on a postulated ketene iminium intermediate.
metrical internal alkynes are especially challenging substrates. As
inylsilanes are versatile compounds that serve as an
1
a result, several approaches have been investigated to improve
the limitations:6 intramolecular hydrosilylation,7 the use of
polarized alkynes,8 or the presence of internal directing groups.9
Lewis acids have been shown to be effective for the
hydrosilylation of alkynes, wherein Lewis acidic metal species
are initially inserted into triple bonds and then transmetalation
by silanes is followed to afford vinylsilane products. For instance,
Molander and Yamamoto independently reported organo-
aluminum or yttrium-catalyzed hydrosilylation of alkynes.10
Although these procedures were successfully applied to internal
alkynes as well as terminal ones, there is room to improve the
regioselectivity. In addition, compatibility of labile functional
groups was rather insufficient mainly due to the acidic nature of
the metal species (Scheme 1a).11
Vimportant synthetic building unit.
In fact, they are
frequently utilized in a broad range of transformations, including
Tamao−Fleming oxidation, electrophilic substitution, and cross-
coupling reactions.2 Among various preparative methods for
vinylsilanes, hydrosilylation of alkynes is one of the most
straightforward, convenient, and atom-economical procedures.3
While transition-metal catalysts such as platinum, ruthenium,
rhodium, or iridium have been well studied for the hydro-
silylation of alkynes (Scheme 1a),4 control of regio- and/or
stereoselectivity is often problematic.5 In this context, unsym-
Scheme 1. Hydrosilylation of Unsymmetrical Internal Alkynes
We herein report the borane-catalyzed selective hydro-
silylation of ynamides for the first time (Scheme 1b). The
scope was found to be broad with high functional group tolerance
under mild conditions. Moreover, the reaction occurs with
excellent regio- and stereoselectivity to afford synthetically
valuable β-silyl (Z)-enamide products. Based on the mechanistic
studies, including computational calculations, the β-silicon effect
was hypothesized to be responsible for the observed excellent
stereoselectivity.
We commenced our study by monitoring a test reaction of a
representative ynamide 1a with diethylsilane (2.0 equiv) in the
presence of B(C6F5)3 catalyst (5 mol %) in chloroform-d (Table
1
1). The progress of hydrosilylation was checked by H NMR
spectroscopy. The hydrosilylation reaction proceeded with
moderate efficiency at room temperature to afford β-silyl (Z)-
enamide 2a (66% 1H NMR yield after 24 h, entry 1).
Received: November 21, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b03485
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
a
Table 1. Optimization of Reaction Conditions
Scheme 2. Substrate Scope of Ynamides
b
entry
B(C6F5)3 (mol %)
solvent
time (h)
yield (%)
c
1
5
5
3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
toluene-d8
THF-d8
24
6
66
94
2
3
d
6
96
4
24
24
24
24
NR
71
e
5
3
3
3
6
7
79
NR
a
Conditions: 1a (0.2 mmol), diethylsilane (2.0 equiv), and B(C6F5)3
b
catalyst in CDCl3 (0.8 mL). Determined by 1H NMR analysis of the
c
d
crude mixture (internal standard: mesitylene). At 25 °C. At 80 °C.
e
Diethylsilane (1.1 equiv).
Importantly, the isolated product was determined to display
complete control of regio- and stereoselectivity as determined by
NMR spectroscopy (see the Supporting Information for details).
This result was significant in that while B(C6F5)3 was known to
catalyze hydrosilylation of unsaturated bonds such as olefins,
carbonyls, imines, carboxylic acids, and nitriles,12 only limited
examples of internal alkynes were known to undergo the borane-
catalyzed hydrosilylation.13 Therefore, we determined to
optimize the present hydrosilylation further by evaluating various
reaction parameters.
The hydrosilylation efficiency was significantly improved by
running the reaction at higher temperature even with lower
catalyst loading and in shorter time, and excellent product yield
was obtained in 6 h at 60 °C using 3 mol % of B(C6F5)3 catalyst
(entry 3). No reaction was observed in the absence of borane
species (entry 4). The product yield was slightly decreased with
the use of 1.1 equiv of silylating reagent (entry 5). Solvents other
than chloroform were less effective in the current hydrosilylation
of ynamide (entries 6 and 7).
With the above optimized reaction conditions in hand, we next
explored the scope of N-sulfonyl ynamides (Scheme 2).
Substrates bearing various para-substituents in the phenyl-
acetylenic moiety smoothly underwent the desired hydro-
silylation leading to the corresponding β-silyl (Z)-enamides in
high yields (2a−f), which displayed complete control of regio-
and stereoselectivity. Notably, the reaction efficiency was not
affected by the electronic variation, and substrates having either
electron-donating (Me or OMe) or -withdrawing substituents
(Cl or CF3) were hydrosilylated in good yields. The presence of
ortho substituents in the phenyl moiety of ynamides did not give
any detrimental effect on the desired reaction (2g and 2h).
Ynamide derivatives having naphthyl or alkenyl side chains were
also viable for the present hydrosilylation to furnish the
corresponding products (2i and 2j, respectively). In the latter
case, in particular, the olefinic double bond remained intact to
prove that the present hydrosilylation is highly chemoselective.
When alkyl ynamides were subjected to the standard
conditions, the desired hydrosilylation also took place smoothly
with complete control of regio- and stereoselectivity. For
instance, butyl-, cyclopropyl-, and cyclohexyl ynamides were all
reacted to afford the corresponding β-silyl (Z)-enamides in good
yields (2k−m). Replacement of the N-tosyl (Ts) group with the
N-mesyl (Ms) did not hamper the reactivity and selectivity (2n).
a
Conditions: substrate (0.2 mmol), silane (2.0 equiv), and B(C6F5)3
b
1
(3 mol %) in CHCl3 (0.8 mL) at 60 °C. Determined by H NMR
analysis of the crude mixture (internal standard: mesitylene). For 12 h
at 60 °C. For 0.5 h at 25 °C.
c
d
In addition, variation of N-substituents in substrates from N-
methyl to phenyl, cyclopropyl, n-pentyl, or cyclohexyl was
compatible with the present conditions to afford the
corresponding products in satisfactory yields (2o−r). The
structure of 2r was confirmed by X-ray crystallographic analysis.
On the other hand, the reaction of acetylenic terminal ynamides
and internal N-acyl ynamides was unsuccessful, and the desired
vinylsilanes were not obtained.
The scope of silanes was next briefly examined (Scheme 3).
Diphenylsilane, as another type of secondary hydrosilane in
addition to dietheylsilane, worked well in the current reactions,
still displaying excellent regio- and stereoselectivity (2s). Tertiary
silylating reagents such as dimethylphenylsilane, triethylsilane,
and benzyldimethylsilane were all efficient for the present
hydrosilylation (2s−v). However, the reaction with triisopro-
pylsilane or diethoxymethylsilane was ineffective even at elevated
temperature.
The synthetic utility of the present B(C6F5)3-catalyzed
hydrosilylation of ynamides was briefly examined. The reaction
procedure was convenient to carry out on a gram scale with
slightly lower loading of catalyst, still maintaining the high
efficiency and excellent selectivity (eq 1). In addition, the silyl
group in the obtained vinylsilane products was easily removed by
silver fluoride, affording synthetically versatile (E)-enamide 3
without scrambling the double bond (eq 2). The structure of 3
was confirmed by X-ray crystallographic analysis (see the
Supporting Information).
B
DOI: 10.1021/acs.orglett.6b03485
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
energy barriers differ 3.1 kcal/mol between anti-addition (10.8
kcal/mol) and syn-addition (13.9 kcal/mol, Figure 1). This
difference in the free energy barriers (ΔΔG⧧) is in reasonably
good agreement with the experimental results, suggesting that
the anti-addition path will be predominant.
Scheme 3. Substrate Scope of Silanes
a
Conditions: 1a (0.2 mmol), silane (2.0 equiv), and B(C6F5)3 (3 mol
b
%) in CHCl3 (0.8 mL) at 60 °C. Determined by 1H NMR analysis of
the crude mixture (internal standard: mesitylene). At 80 °C for 12 h.
c
Figure 1. Relative energetics in the product-determining transition
states [values in the parentheses are the relative free energies in kcal/
mol; color code: H (white), B (pink), C (gray), N (purple), O (red), F
(green), Si (gold), and S (yellow)].
Analysis of the geometry-optimized structure of ketene
iminium species provided an additional insight into the reason
for the observed stereoselectivity (Figure 2). The difference in
We wondered about the rationale on the observed regio- and
stereoselectivity in the present borane-catalyzed hydrosilyation
of ynamides. In accordance with the precedents to form a borane-
silane adduct I in situ,14 the first step is believed to be a selective
addition of ynamide to the silylium species, leading to ketene
iminium species II (Scheme 4).15 A subsequent hydride attack to
Scheme 4. Mode of the Present Hydrosilylation of Ynamides
Figure 2. (a) Geometry-optimized structure of ketene iminium species
and (b) schematic presentation of β-silicon effect.
dihedral angles between Si−C(1)−C(2) and C(3)−C(1)−C(2)
was determined to be 18°. This geometrical bias can be attributed
to the β-silicon effect to overlap the C(1)−Si and empty p-orbital
of a carbocationic C(2) atom.16 This alignment will accordingly
decrease the dihedral angle of Si−C(1)−C(2) relative to that of
C(3)−C(1)−C(2),17 thus favoring the borohydride attack to
ketene iminium species via the sterically more accessible anti-
addition path.
In conclusion, the B(C6F5)3-catalyzed highly regio- and
stereoselective hydrosilylation of ynamides has been developed
to deliver synthetically versatile β-silyl (Z)-enamide products.
The scope of ynamides and silanes was broad, and the reaction
proceeds efficiently under mild and convenient conditions. The
observed stereoselectivity was rationalized to result from a β-
silicon effect of a postulated ketene iminium intermediate.
the assumed intermediate II by borohydride III can proceed via
two paths: (a) to the opposite side from the silyl group or (b) to
the same side relative to the silyl moiety. While experimental
results showed the exclusive formation of β-silyl (Z)-enamide
products indicating the preference of path (a), computational
calculations on this process were performed.
Calculations based on the density functional theory (DFT)
showed that in a reaction of the presupposed ketene iminium
intermediate (INT) with borohydride the solution-phase free
C
DOI: 10.1021/acs.orglett.6b03485
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.6b03485.
■
S
Complete experimental details and relevant spectra for all
important compounds (PDF)
Crystallographic data for 2r (CIF)
(8) (a) Ding, S.; Song, L.-J.; Wang, Y.; Zhang, X.; Chung, L. W.; Wu, Y.-
D.; Sun, J. Angew. Chem., Int. Ed. 2015, 54, 5632. (b) Hamze, A.; Provot,
O.; Alami, M.; Brion, J.-D. Org. Lett. 2005, 7, 5625. (c) Song, L.-J.; Ding,
S.; Wang, Y.; Zhang, X.; Wu, Y.-D.; Sun, J. J. Org. Chem. 2016, 81, 6157.
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Crystallographic data for 3 (CIF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: sbchang@kaist.ac.kr.
ORCID
Sukbok Chang: 0000-0001-9069-0946
Author Contributions
§Y.K. and R.B.D. contributed equally.
́
Organometallics 1995, 14, 4570. (c) Perez, M.; Hounjet, L. J.; Caputo,
Notes
C. B.; Dobrovetsky, R.; Stephan, D. W. J. Am. Chem. Soc. 2013, 135,
18308. (d) Sudo, T.; Asao, N.; Gevorgyan, V.; Yamamoto, Y. J. Org.
Chem. 1999, 64, 2494. (e) Sudo, T.; Asao, N.; Yamamoto, Y. J. Org.
Chem. 2000, 65, 8919.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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This research was supported by the Institute for Basic Science
(IBS-R010-D1). We thank Dr. Hyun-Ji Song (Center for
Catalytic Hydrocarbon Functionalization, Institute for Basic
Science) for helpful discussions.
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