Conjugate Addition of Perfluoroarenes to α,β-Unsaturated Carbonyls Enabled by an Alkoxide-Hydrosilane System: Implication of a Radical Pathway

Article abstract of DOI:10.1021/jacs.8b05744

Conjugate addition of organometallic reagents to α,β-unsaturated carbonyls is a key strategy for the construction of carbon-carbon bond in organic synthesis. Although direct C-H addition to unsaturated bonds via transition metal catalysis is explored in recent years, electron-deficient arenes that do not bear directing groups continue to be challenging. Herein we disclose the first example of a conjugate addition of perfluoroarenes to α,β-unsaturated carbonyls enabled by an alkoxide-hydrosilane system. The reaction is convenient to carry out at room temperature over a broad range of substrates and reactants to furnish synthetically versatile products in high to excellent yields. Mechanistic experiments in combination with computational studies suggest that a radical pathway is most likely operative in this transformation. The hypervalent silicate and silanide species, which are relevant to the proposed mechanism, were observed experimentally by NMR and single crystal X-ray diffraction analyses.

Full text of DOI:10.1021/jacs.8b05744

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Article
Conjugate Addition of Perfluoroarenes to #,#-Unsaturated Carbonyls Enabled
by an Alkoxide-Hydrosilane System: Implication of a Radical Pathway
Weilong Xie, Sung-Woo Park, Hoimin Jung, Dongwook Kim, Mu-Hyun Baik, and Sukbok Chang
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.8b05744 • Publication Date (Web): 10 Jul 2018
Downloaded from http://pubs.acs.org on July 10, 2018
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Journal of the American Chemical Society
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Conjugate Addition of Perfluoroarenes to α,β-Unsaturated Car-
bonyls Enabled by an Alkoxide-Hydrosilane System: Implication
of a Radical Pathway
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Weilong Xie,†,‡ SungꢀWoo Park,†,‡ Hoimin Jung,‡,† Dongwook Kim,†,‡ MuꢀHyun Baik,†,‡,* and Sukbok Chang†,‡,*
†Center for Catalytic Hydrocarbon Functionalizations, Institute for Basic Science (IBS), Daejeon 34141, Republic of Korea
‡Department of Chemistry, Korea Advanced Institute of Science & Technology (KAIST), Daejeon 34141, Republic of Korea
KEYWORDS: conjugate addition • perfluoroarenes • sodium tertꢀbutoxide • hydrosilanes • radical pathway
ABSTRACT: Conjugate addition of organometallic reagents to α,βꢀunsaturated carbonyls is a key strategy for the construction of
carbonꢀcarbon bond in organic synthesis. Although direct C–H addition to unsaturated bonds via transition metal catalysis is exꢀ
plored in recent years, electronꢀdeficient arenes that do not bear directing groups continue to be challenging. Herein we disclose the
first example of a conjugate addition of perfluoroarenes to α,βꢀunsaturated carbonyls enabled by an alkoxideꢀhydrosilane system.
The reaction is convenient to carry out at room temperature over a broad range of substrates and reactants to furnish synthetically
versatile products in high to excellent yields. Mechanistic experiments in combination with computational studies suggest that a
radical pathway is most likely operative in this transformation. The hypervalent silicate and silanide species, which are relevant to
the proposed mechanism, were observed experimentally by NMR and single crystal Xꢀray diffraction analyses.
ꢀ INTRODUCTION
plied for nonꢀdirected C–H addition, electronꢀdeficient arenes
continue to be a problematic class of substrates even for preꢀ
cious metal catalysts at elevated temperatures (90 ~ 120 oC).9
Construction of a carbonꢀcarbon bond via a conjugate addition
of organometallic reagents to α,βꢀunsaturated carbonyls is a
wellꢀestablished methodology in organic synthesis (Scheme
1a).1 An array of organometallic reagents, including organoꢀ
magnesiums (commonly referred to as Grignard reagents),2
organolithiums,3 and organozincs4 either in the presence or
absence of copper catalysts are employed in these reactions.
Unfortunately, special precautions such as low temperature
(i.e., –78 oC) and inert atmosphere are often required for stabiꢀ
lizing the highly reactive organometallic reagents to attain
satisfactory yields and/or selectivity. In this context, transition
metal catalyst systems based on rhodium, also palladium, coꢀ
balt or copper, in combination with organoboron reagents
emerged as promising alternatives in the last decades.5 Alkyl
radical species generated in situ via several photoredox sysꢀ
tems have also been utilized for the conjugate addition reacꢀ
tions.6
Scheme 1. Conjugate Addition of Perfluoroarenes
More recently, a strategy towards the direct C–H addition of
hydrocarbons to α,βꢀunsaturated carbonyls has been of great
interest, as it may offer a more straightforward alternative to
the conventional approaches that rely on preactivated reaꢀ
gents.7 In this context, metal catalysts again proved important
for progress, mainly enabling a chelationꢀassisted C–H bond
activation.8 The scope of substrates amenable to these efficient
methods has been extended to some extent, but remains a chalꢀ
lenge in part due to the required presence of directing groups.9
While some transition metal systems were successfully apꢀ
Perfluoroarenes are an important class of molecules that are
utilized widely in drugs, agrochemicals, functional materials
such as liquid crystals (LCs), organic lightꢀemitting diodes
(OLEDs), and electron transport materials owing to the unique
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property of the fluorine group.10 Thus, a mild, efficient and
While examining various combinations of alkoxides and hyꢀ
3
4
5
6
7
8
9
selective method for the facile functionalization of perꢀ
fluoroarenes is highly sought after. Recently, transition metal
catalysts, including palladium, nickel, copper and gold, have
been successfully employed for this purpose.11 Curiously, the
conjugate addition of perfluoroarenes is an underexplored
mechanistic possibility. For instance, Zhao et al. reported a
rhodium catalyst for the conjugate addition of perfluoroarenes
drosilanes, we realized that an alkoxideꢀsilane was previously
employed for the reduction of unsaturated bonds.16 Therefore,
we were concerned initially that a simple reduction product
(2a’) may also be formed in addition to the desired conjugaꢀ
tion product (3a). No desired product was formed in the abꢀ
sence of hydrosilane (entry 1), and significantly tertiary
silanes such as Et3SiH, PhMe2SiH, or Ph2MeSiH were ineffecꢀ
tive (entries 2–4). In contrast, the use of secondary hyꢀ
drosilanes such as Et2SiH2 furnished the desired product in
moderate yield (entry 5). Solvents other than THF gave low
product yields (entries 5–10).
o
to acryl esters at 120 C.9b Mainly because perfluoroarenes
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ligate to transition metals leading to relatively strong σꢀbonds
(M–C6F5),12 harsh reaction conditions are accordingly required
to achieve the subsequent transmetalations efficiently.
Stoltz, Grubbs et al. recently disclosed a novel and elegant
strategy for the C–H silylation of heteroarenes employing
KOtBu as a catalyst.13 A plausible mechanism was proposed
where either trialkylsilyl radicals or pentavalent silicates are
involved.13c,d Interestingly, electronꢀrich silicates were reportꢀ
ed to undergo a singleꢀelectron transfer (SET) pathway to
form radical species.13g,14 Given that perfluoroarenes exhibit
high electron affinities,10b,i,15 we envisioned that an alkoxideꢀ
hydrosilane system could enable an electron transfer to perꢀ
fluoroarene to generate an aryl radical anion that may subseꢀ
quently add to α,βꢀunsaturated carbonyls, possibly in a selecꢀ
tive manner. In fact, alkoxideꢀhydrosilane systems were utiꢀ
lized effectively in the C–X bond cleavage (X = O or S),13e,f
C(sp)–H bond silylation13b and carbonyl reduction reactions.16
The alkoxideꢀhydrosilane system has attracted much attention
because it can provide notable advantages over transition metꢀ
alꢀbased procedures, such as practicability, sustainability and
cost effectiveness. However, mechanistic details are not
straightforward in the most known reactions mediated by
alkoxideꢀhydrosilanes.13 Moreover, the isolation of mechanisꢀ
tically relevant intermediates (i.e., ionic and/or radical silyl
species) has remained elusive thus far.
Herein, we report the first example of a C–H conjugate addiꢀ
tion of perfluoroarenes to α,βꢀunsaturated carbonyls enabled
by an alkoxideꢀhydrosilane system. The reaction was convenꢀ
ient to carry out under mild conditions (room temperature)
over a broad range of substrates and reactants to furnish synꢀ
thetically valuable products in high to excellent yields. Mechꢀ
anistic studies revealed that a radical pathway is most likely
involved based on the EPR and radical scavenger experiments.
An in situ formed compound of sodium silanide was characꢀ
terized by a single crystal Xꢀray diffraction study and its
mechanistic role was contextualized.
Table 1. Optimization for Conjugate Additiona
Yield(%)b
Conversion
Entry
Base
Silane
Solvent
(%)b
3a
<1
<1
<1
3
2a’
<1
<1
<1
<1
<1
<1
<1
11
7
1
NaOtBu
NaOtBu
NaOtBu
‒
THF
THF
37
55
2
Et3SiH
3
PhMe2SiH
Ph2MeSiH
Et2SiH2
THF
62
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
4
THF
88
5
THF
90
68
12
49
38
29
<1
<1
78
91
67
<1
56
<1
18
<1
<1
20
50
<1
6
Et2SiH2
1,4ꢀdioxane
Et2O
89
7
Et2SiH2
88
8
Et2SiH2
toluene
pentane
1,2ꢀDCE
THF
70
9
Et2SiH2
57
10
11
12
13
14
15
16
17
18
19
20c
21d
22e
23f
Et2SiH2
31
6
tBu2SiH2
PhMeSiH2
Ph2SiH2
Ph(Mes)SiH2
(Mes)2SiH2
PhSiH3
33
<1
<1
<1
<1
<1
7
THF
>99
>99
>99
81
THF
THF
THF
THF
>99
>99
82
ꢀ RESULTS AND DISCUSSIONS
LiOtBu
KOtBu
NaOMe
NaOtBu
NaOtBu
NaOtBu
NaOH
Ph2SiH2
Ph2SiH2
Ph2SiH2
Ph2SiH2
Ph2SiH2
Ph2SiH2
Ph2SiH2
THF
<1
6
THF
Reaction Optimization. Inspired by the singleꢀelectron
transfer (SET) pathways of the alkoxideꢀsilane systems,13,14 we
initially hypothesized that electronꢀdeficient perfluoroarenes
might be a plausible reagent to form an aryl radical anion that
may react with α,βꢀunsaturated carbonyls to enable the desired
conjugate addition. Based on this proposal, we commenced
THF
>99
52
<1
29
8
THF
THF
>99
>99
>99
THF
<1
<1
our study by allowing
a
model substrate, 2,3,5,6ꢀ
tetrafluoroanisole (1a), to react with tertꢀbutyl benzylidenecyꢀ
anoacetate (2a, 1.0 equiv), a representative α,βꢀunsaturated
carbonyl compound (Table 1).
THF
aReaction conditions: 1a (0.2 mmol), 2a (1.0 equiv), base (2.0
o
equiv) and silane (1.0 equiv) in THF (0.5 mL) at 25 C for 12
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b
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h. Conversions of 2a and crude NMR yields were obtained
zenes afforded the desired products in moderate yields (3j–3k),
and that having more than one reactive C–H bonds showed
reaction at the more acidic position. 1,3ꢀDifluorobenzene proꢀ
vided the desired product (3l) in low yield (10%) that was
slightly improved when using NaOCMe2Et instead of NaOtBu.
1ꢀChloroꢀ2,4ꢀdifluorobenzene and 3,5ꢀdifluoropyridine unꢀ
derwent the desired conjugate addition in varied yields (3m–
3n) while monofluorobenzene did not react (3o).
after aqueous workup. c0.5 Equiv of NaOtBu. 1.0 Equiv of
d
NaOtBu. e1.5 Equiv of NaOtBu. f25 or 60 oC.
5
6
7
8
The reduction product 2a’ was formed in certain solvents (enꢀ
tries 8–10), but remained a minor side product, in general. A
subsequent study on the effect of secondary hydrosilanes for
improving the reaction efficiency disclosed some interesting
t
9
aspects. For instance, while Bu2SiH2 was totally ineffective
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Table 3. Scope of α,β-Unsaturated Carbonyl Compoundsa
(entry 11), the use of PhMeSiH2 or Ph2SiH2 gave higher yields
(entries 12–13). Hydrosilanes bearing a sterically bulky Mes
moiety (Mes = 2,4,6ꢀtrimethylphenyl) were much less effecꢀ
tive (entries 14–15). Primary hydrosilane PhSiH3 displayed
lower efficiency (entry 16). In addition, both counter cations
and alkoxides were found to have dramatic effects: Na+ > K+ >
Li+ (entries 13 and 17–18); tBuO– > MeO– (entries 13 and 19).
Finally, the amount of NaOtBu was critical with 2 equiv of
alkoxide being optimal (entries 13 and 20–22).
F
F
O
Ph2SiH2 (1.0 equiv)
NaOtBu (2.0 equiv)
F
=
tBuO
O
OtBu
R1
MeO
+
F
R1
THF, RT, 12 h
F
R2
R2
F
F
OMe
1a
2
4
F
Me
MeO
MeO
Me2N
CN
CO2tBu
CN
CN
CO2tBu
CN
CO2tBu
CO2tBu
MeO
4a, 83%
4b, 84%
4c, 63%
4d, 71%
Si(iPr)3
O
N
Ph
Ph
CO2tBu
CN
CO2tBu
CN
CO2tBu
CN
CO2tBu
Table 2. Scope of Fluoroarenesa
CN
O
Ph2SiH2 (1.0 equiv)
NaOtBu (2.0 equiv)
O
4g, 73%
OtBu
4e, 71%
4f, 67%
4h, 78%
=
OtBu
Fn
Fn
Ph
+
THF, RT, 12 h
Ph
CN
F
CN
O
Me3Si
1
2a
B
3 (d.r. 1)
CN
CO2tBu
CN
CO2tBu
CN
CO2tBu
O
CN
F
F
F
F
F
F
F
F
CO2tBu
MeO
tBuO
(iPr)3Si
O
N
4i, 80%
4j, 52%
4k, 31%,
(50%)b
4l, 89%
F
F
F
F
F
F
F
F
3a, 81%
3b, 76%
3c, 88%
3d, 77%
CN
CO2tBu
CN
CO2tBu
CN
CO2tBu
CO2tBu
CO2tBu
F
F
F
F
F
F
F
F
F
F
F
S
O
Ph
4
4p, 71%
4m, 87%
4n, 63%
4o, 57%
F
F
F
F
Me CO2tBu
CN
CO2tBu
Ph
CN
CO2tBu
3e, 72%
3f, 79%
3g, 68%
3h, 73%
Ph
CN
F
F
F
F
F
F
F
4q, 58%
4r, 10%
4s, 72%
4t, <1%
F
F
aReaction conditions: 2,3,5,6ꢀtetrafluoroanisole (0.2 mmol),
F
F
F
α,βꢀunsaturated carbonyl compounds (1.0 equiv), NaOtBu (2.0
3l, 10%
(21%)b
3j, 56%
3i, 72%
3k, 63%
o
equiv) and Ph2SiH2 (1.0 equiv) in THF (0.5 mL) at 25 C for
F
Cl
F
F
12 h; isolated product yields. b3.0 Equiv of NaOtBu was used.
N
F
F
The scope of the Michael acceptors, i.e. the α,βꢀunsaturated
carbonyls (all are in Eꢀform except for the formation of prodꢀ
uct 4q obtained from Zꢀolefin), was investigated against
2,3,5,6ꢀtetrafluoroanisole (1a) at room temperature (Table 3).
tertꢀButyl benzylidenecyanoacetate derivatives having methyl,
(bis)methoxy, and dimethylammino substituents at the phenyl
moiety underwent the conjugate reaction with 1a smoothly in
good product yields (4a–4d). Functional groups such as siꢀ
lyloxy and pyridinyl were compatible with the current condiꢀ
tions (4e–4f). Modification of the aryl moiety to include biꢀ
phenyl, naphthyl, and pyrenyl groups also gives the desired
products without difficulty (4g–4j). While boronic ester was
found to be less tolerant (4k), other functional groups includꢀ
ing silyl and vinyl groups were completely compatible with
the present conditions (4l–4m). Michael acceptors having hetꢀ
erocycles such as thiophene or furan instead of phenyl also
underwent the desired reaction (4n–4o). Importantly, the presꢀ
ence of cyano or ester groups in the Michael acceptors was not
3n, 41%b
3m, 74%
3o, <1%
aReaction conditions: fluoroarenes (0.2 mmol), tertꢀbutyl benꢀ
zylidenecyanoacetate (1.0 equiv), NaOtBu (2.0 equiv) and
Ph2SiH2 (1.0 equiv) in THF (0.5 mL) at 25 oC for 12 h; isolatꢀ
ed product yields. bNaOCMe2Et was used as a base.
Scope of Perfluroroarenes and Michael Acceptors. With
the optimized reaction conditions in hand, we proceeded to
evaluate the scope of perfluoroarene substrates engaging a
model reactant 2a (Table 2). Tetrafluorobenzenes with methꢀ
oxy or tertꢀbutoxy substituent at the 4ꢀposition underwent the
desired reaction smoothly (3a–3b). Substrates bearing a silyl
or amino group were compatible with the present conditions to
afford the corresponding products in high yields (3c–3d). Tetꢀ
rafluorobenzenes having phenyl, alkyl, or alkenyl substituents
underwent the Michael addition also efficiently (3e–3g). Two
isomeric products were obtained in similar efficiency from the
individual isomeric tertaflurobenzenes (3h–3i). Trifluorobenꢀ
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required as demonstrated in the formation of products 4p and
catalyzed by TsOH affording 5 (75%), which was subsequentꢀ
3
4
5
6
7
8
9
4q. In contrast, a (hetero)aryl moiety was found to be essential
as seen in the poor product yield from an alkylꢀsubstituted
Michael acceptor (4r). Notably, a conjugated dienyl carbonyl
underwent the reaction in a selective manner with good yield
(4s). On the other hand, a reaction of 1a with tertꢀbutyl cinꢀ
namate without bearing an αꢀsubstituent did not furnish the
desired Michael addition product (4t).
ly cyclized to furnish a sixꢀmembered tetrahydroquinoline
derivative 6 (82%) via a B(C6F5)3ꢀcatalyzed silylative reducꢀ
tion of nitrile, which was recently developed in our research
group,17 and then followed by an intramolecular nucleophilic
ipsoꢀsubstitution (Scheme 2b).10k In addition, a product 3m
was easily converted to its carboxylic acid 7 (91%) via a tanꢀ
dem process of decarboxylation of ester and hydrolysis of
nitrile. A FriedelꢀCrafts cyclization of 7 was found to be facile
by the action of chlorosulfonic acid to form an indanone deꢀ
rivative 8 (87%), the structure of which was confirmed by an
Xꢀray crystallographic analysis. Reductive bromination of 8
took place quantitatively to give 9 (Scheme 2c). Finally, a
synthetic route to a bioactive compound was preliminarily
examined on the basis of the currently developed approach
(Scheme 2d). 3,3ꢀDiphenylpropanal 10 could be readily obꢀ
tained in 70% yield (4 steps; see the SI for details) starting
from 1ꢀchloroꢀ2,4ꢀdifluorobenzene (1m). Reductive amination
of 10 with a substituted piperidine compound afforded 11 in
high yield, a fluoroꢀsubstituted analogue of CCR5 receptor
antagonist.18
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
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47
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58
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60
Scheme 2. Synthetic Applications of Obtained Products
a) Gram-scale reaction
NaOtBu (2.0 equiv)
F
Ph
O
O
Cl
Ph2SiH2 (1.0 equiv)
THF, 0 oC - RT, 20 h
Cl
OtBu
OtBu
+
Ph
F
CN
2a
10 mmol
CN
F
F
1m
10 mmol
3m
(82%, 3.10 g)
b) Six-membered ring formation
NaOtBu (2.0 equiv)
Ph2SiH2 (1.0 equiv)
F
Ph
F
O
O
F
F
OtBu
+
Ph
OtBu
THF, 0 oC - RT, 20 h
CN
CN
2a
10 mmol
F
F
1k
3k
(84%, 3.04 g)
10 mmol
CN
F
F
F
H
1) 10 mol% TsOH,
toluene, reflux, 2 h
2) DMF, reflux, 2 h
1) 3 mol% B(C6F5)3, Et2SiH2,
CDCl3, RT, 12 h
2) NaH, THF, 60 oC, 20 h
N
ꢀ MECHANISTIC STUDIES
F
A number of alkoxideꢀhydrosilane systems were previously
utilized to mediate different reactions, including carbonyl reꢀ
duction, C–X bond cleavage (X = O, S), and C–H bond silylaꢀ
tion.13,14,16 Various mechanisms were proposed to rationalize
these alkoxide/silaneꢀbased transformations. For instance,
Stoltz, Grubbs and coꢀworkers suggested that trialkylsilyl radꢀ
icals and/or pentavalent silicates play a key role in the C–H
silylation on the basis of experimental and computational studꢀ
ies.13c,d Despite this notable advance, more mechanistic data
are needed to better understand the alkoxideꢀhydrosilane sysꢀ
tems and establish it as a general platform in organic synthesis.
In the current conjugate addition of perfluoroarenes to α,βꢀ
unsaturated carbonyls, a series of mechanistic experiments
were performed with the hope to identify common features
and highlight the differences to the originally proposed behavꢀ
ior of the alkoxideꢀhydrosilane system. The impact of radical
scavengers on the reaction progress was first examined
(Scheme 3a). Galvinoxyl (Gal) showed an apparent inhibition
of the reaction, and no desired product was obtained when 3
equiv of Gal was added. With 2,6ꢀdiꢀtertꢀbutylꢀ1,4ꢀ
benzoquinone (BQ), known as an effective silyl radical trapꢀ
ping reagent,19 the reaction was also largely suppressed. It was
previously shown that the homolytic cleavage of a carbon–
sulfur bond is accompanied in a radical pathway.20,13f In this
context, when tetrafluorobenzene bearing an arylthiol substitꢀ
uent (1p) was subjected to the standard conditions, we obꢀ
tained not only the desired product 12 (48%) but also observed
its dethiolated derivative 3h (12%) along with pꢀtoluenethiol
13 by a GCꢀMS analysis (Scheme 3b). When an isolated comꢀ
pound 12 was subjected to the current alkoxideꢀhydrosilane
system, the C–S bond of 12 was found to be significantly
cleaved (see the SI for details). Likewise, an alkyl bromide
bond was cleaved, and anthracene was partially reduced under
the current reaction conditions (see the SI for details). In addiꢀ
tion, a sharp EPR signal was detected from the reaction mixꢀ
F
Ph
6 (82%)
5 (75%)
c) Five-membered ring formation
NaOtBu (2.0 equiv)
Ph2SiH2 (1.0 equiv)
OtBu
THF, 0 oC - RT, 20 h
F
Ph
F
O
O
Cl
Cl
OtBu
+
Ph
F
F
CN
CN
2a
1m
3m (82%)
1) 10 mol% TsOH
reflux, 2 h
F
Ph
O
Cl
F
F
2) DMF, reflux, 2 h
Chlorosulfonic acid
CH2Cl2, 0 oC - RT, 1 h
OH
3) AcOH/H2SO4/H2O
reflux, 30 h
7 (91%)
F
8 (87%)
Cl
Cl
F
F
PPh3 HBr
DMSO, 80 oC, 20 h
9 (99%)
X-ray of 8
Br
d) Synthesis of bioactive compound derivative
O
N
O
Cl
F
HN
4 steps
Cl
NaBH(OAc)3, RT, 12 h
F
F
F
1m
10 (70%)
N
N
Ph
Ph
N
N
O
F
O
F
11 (90%)
CCR5 receptor antagonist
Cl
SO2Me
Synthetic Applications. The synthetic utility of this novel
methodology was briefly examined, as summarize in Scheme
2. First, a gram scale reaction of 1ꢀchloroꢀ2,4ꢀdifluorobenzene
(1m) with 2a (1.0 equiv) afforded the desired product 3m in
82% yield (3.10 g, Scheme 2a). Similarly, 1,2,4ꢀ
trifluorobenzene (1k) efficiently underwent the conjugate adꢀ
dition to afford 3k (84%, 3.04 g). Decarboxylation of 3k was
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ture (Scheme 3c), which strongly suggests that radical species
with only 17% yield of the presumed silicate species (see the
SI for details). Considering that the pentavalent silicate species
tend to adopt the trigonalꢀbipyramidal geometries, they can
undergo a facile and rapid intramolecular permutation between
substituents via Berry pseudorotation, thus, making a precise
are formed. Based on the above preliminary mechanistic data,
we concluded that the present alkoxide/hydrosilaneꢀmediated
conjugate addition of perfluoroarenes to α,βꢀunsaturated carꢀ
bonyls proceeds via a radical pathway.
6
7
8
Scheme 3. Preliminary Mechanistic Studies
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 1. NMR spectra of silole (14) at 213 K [29Si{1H} NMR:
1
Figure 1aꢀi, H NMR: Figure 1bꢀi], variableꢀtemperature (VT)
Next, we attempted to identify a plausible activation mode of
hydrosilanes in interaction with sodium tertꢀbutoxide. As exꢀ
plained above, the reaction efficiency was found to be closely
connected to the structure of hydrosilanes and alkoxides examꢀ
ined (Table 1). Because of the vacant 3d orbitals available on
the silicon atom, hypervalent silicates are commonly proposed
to form in situ upon interaction with ligands such as fluoride
or oxygen or nitrogenꢀcontaining Lewis bases.21 Whereas a
number of organosilicates are characterized by NMR and/or
Xꢀray analyses,22 no compelling spectroscopic analysis has
been reported in case of a tertꢀbutoxideꢀhydrosilane sysꢀ
tem.13c,d,g Stoltz and Grubbs et al. used in situ ATRꢀFTIR specꢀ
troscopy to trace the activation mode of Si–H bond in their C–
H silylation reactions under the KOtBuꢀEt3SiH system.13c
In our current system, when Ph2SiH2 was treated with NaOtꢀ
Bu at 213 K, a new resonance peak appeared at δ = –82.2 ppm
in 29Si NMR, which can be attributed to hypervalent silicon
NMR spectra for the interaction of silole (14) with NaOtBu
(213 to 293 K) [29Si{1H} NMR: Figure 1aꢀii ~ 1aꢀiv, 1H NMR:
Figure 1bꢀii ~ 1bꢀvi].
spectroscopic observation of the silicates a difficult task.22a
The poor conversion of Ph2SiH2 to its silicates as seen above
was another critical issue in an attempt to isolate any mechaꢀ
nistically relevant silyl species. On the other hand, it is well
known that silole rings have the C–Si–C angle at around 90o,23
thereby likely positioning the silole rings of their resultant
silicate species at the axial and equatorial positions. Conseꢀ
quently, this geometric arrangement will allow the presumed
siloleꢀderived pentavalent silicates to have only two isomers
(Figure 1, 15-I and 15-II). Moreover, these putative silole
silicates are expected to be stabilized by the delocalization of
the negative charge over the silole ring, thus making the specꢀ
troscopic characterization more convenient when compared to
1
species. However, five new Si–H peaks appeared in H NMR
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the fluxional behavior of Ph2SiH2 that was employed in the
current conjugate addition.
Figure 2. Xꢀray structure of 16 with minor parts of disordered
solvent omitted for clarity. Selected bond lengths (Å) and anꢀ
gles (deg): Si1−Si2, 2.337(2); Si2−Na3, 3.090(2); C2−Si1−C4,
89.8(2); C2−Si1−Si2, 115.57(15); C4−Si1−Si2, 117.06(16);
Si1−Si2−Na, 127.96(8).
Thus, we prepared a silole 14 in 4 steps24 and treated it with
NaOtBu (1.0 equiv) at 213 K. As anticipated, a silicate species
was observed to form, evidenced by an upfield shifted 29Si{1H}
NMR signal at δ = –124.1 ppm [t, J(H,Si) = 210.5 Hz],22
which was distinctive to the signature of 14, which appeared at
–42.8 ppm [t, J(H,Si) = 209.2 Hz] (Figure 1aꢀi and 1aꢀii).
In the same line, 1H NMR spectroscopy showed that the resꢀ
onance peak of Si–H of 14 [δ = 4.70 (s, 2H)] was shifted
downfield to δ = 5.27 (s, 2H) upon treatment with NaOtBu
(Figure 1bꢀi and 1bꢀii). Furthermore, the silole arene C–H
peaks of the putative silicates were shifted upfield, implying
that the negative charge of the silole silicate is delocalized
over the arene rings, as predicted. Two new proton peaks were
observed in the tertꢀbutyl region of the presumed silicates
(shown in the inset of Figure 1bꢀii), suggesting the existence
of two silicate isomers in the 14ꢀNaOtBu system. We also
performed variableꢀtemperature (VT) NMR experiments to
monitor the interaction behavior of silole with NaOtBu. The
Si–H peak of the assumed silicates became broadended from a
sharp singlet upon a gradual increase of temperature from 213
to 293 K (Figure 1bꢀii ~ 1bꢀvi), indicating that the silicate is in
fast equilibrium with the individual silole and NaOtBu at highꢀ
er temperatures. This interpretation was further substantiated
by the silicon peak becoming similarly broadened at higher
temperatures likely for the same reason.25
Encouraged by the aforementioned spectroscopic observaꢀ
tions of the putative hypervalent silicates of silole (14), we
attempted to isolate this mechanistically relevant silyl species.
When silole 14 was treated with NaOtBu (1.0 equiv) in anhyꢀ
drous THF/1,4ꢀdioxane, the initially colorless solution slowly
turned yellow over time, and an airꢀ and moistureꢀsensitive
yellow solid (16) was isolated in 30% after one day (50% after
2 days, Scheme 4a). 29Si{1H} NMR spectrum displayed two
silicon peaks at δ = –28.6 ppm (doublet, JSiꢀH = 180.1 Hz) and
at δ = –71.5 ppm (singlet). In addition, a sharp peak was obꢀ
served in 23Na NMR at δ = 1.74 ppm. Pleasingly, we were able
to obtain the solid state structure of 16 by Xꢀray crystalloꢀ
graphic analysis to reveal a sodium silanide species with two
silole moieties forming a new Si–Si bond (Figure 2). The bond
length of Si1–Si2 is 2.337(2) Å, being slightly shorter than the
known value (~2.36 Å) of a reported disilicate,22c and the bond
angles of C2–Si1–Si2 and C4–Si1–Si2 are 115.57(15)o and
117.06(16)o, respectively. A sodium cation is ionꢀpaired to the
anionic silicon center with 3.090(2) Å, being slightly longer
than the reported one (3.02 Å) for the trimethoxyhypersilaꢀ
nide.26 To our best knowledge, silanide 16 represents the first
silyl species isolated from the alkoxide/hydrosilane systems.
Although mechanistic details on the formation of silanide 16
are not fully elucidated at the moment, recent studies showed
that alkali metalꢀalkoxides can serve as an electron donor in
tBuOꢀmediated arylation of arenes with aryl halides.27 In addiꢀ
tion, pentavalent silicates were shown to undergo a singleꢀ
electron transfer (SET) to produce radical species.14 On the
other hand, hydrosilanes are known to accept an electron into
vacant d orbitals to form silyl radicals.28 Moreover, it was reꢀ
ported previously that a Si–Si bond can be formed via a reꢀ
combination of two silyl radical species.29 Based on our above
mechanistic studies and literature precedents,13,14,27ꢀ29 we proꢀ
pose a plausible pathway for the formation of silanide 16, as
illustrated in Scheme 4b. First, silole 14 interacts with NaOtBu
to form hypervalent silicates (15), the two isomeric structures
of which are shown in Figure 1. The release of the
[Na(H)OtBu]• radical species (17) will lead to a silole radical
18, which can dimerize to give 19 that being a precursor of 16.
Considering that silanides are versatile and synthetically useꢀ
ful moieties in organic chemistry and that they are prepared
mainly from the reduction of silicon halides or disilanes with
alkali metals,30 this unexpected result in our current procedure
suggests that this new methodology may serve as an alternaꢀ
tive route to silanides. Significantly, the silole 14 was also
shown to mediate the desired conjugate addition between 1a
and 2a, although the efficiency became expectedly lower
when compared to Ph2SiH2 (Scheme 5a). More importantly,
the isolated sodium silanide 16 enabled the desired conjugate
addition albeit in only 25% NMR yield, which could be a bit
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 4. Formation of Sodium Silanide
t
improved to 51% by adding BuOH (no desired product was
formed in the absence of 16). We rationalized this result by
assuming that while silanide 16 can serve as a precursor of a
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silyl radical species 18 under the reaction conditions although
this process is not fully understood at the moment. Since the
reaction efficiency with 16 was improved by the presence of
tBuOH (Scheme 5b), a dianionic silicate 20 is proposed to
form more effectively via a disilane 19 with NaOtBu to generꢀ
ate 21 that is assumed to be a precursor of 18.
electron transfer (SET),13g and trisubstituted silyl radicals may
2
3
4
5
6
7
lead a radical chain pathway.13c
Starting with the fluorobenzene substrate 1, a singleꢀelectron
transfer (SET) from [Ph2Si(H)OtBu]–•Na+ 22, an analogue of
21, to substrate 1 was modeled. The barrier of this electron
transfer event was estimated using the computed energies of
the reactant and product states and employing the Marcus theꢀ
ory.13g,37 These calculations suggested a free energy barrier for
the electron transfer to be only 4.8 kcal/mol. Thus, the aryl
radial anion intermediate 23 may be generated readily, as illusꢀ
trated in Scheme 6b. This radical anion intermediate 23 can
attack the Michael acceptor to generate an intermediate 24
practically in a barrierless fashion to form the C–C bond, as
our calculations found a transition state 23-TS that is only 0.6
kcal/mol higher in energy than 23. Next, the pentavalent siliꢀ
cate species (25) can abstract an ipsoꢀhydrogen atom to evolve
H2 and afford the conjugate addition adduct 26 with a barrier
of 26.5 kcal/mol, as shown in Scheme 6d (see the SI for deꢀ
tails). The resulting radical species [Ph2Si(H)OtBu]–• (22) may
participate in the next singleꢀelectron transfer process.
8
9
Scheme 5. Silanide Mediated Conjugate Addition
a) Silole mediated conjugate addition
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
F
Ph
O
OMe
14 (1.0 equiv)
F
O
OtBu
F
F
F
F
NaOtBu (2.0 equiv)
+
Ph
OtBu
CN
THF, 25 oC, 12 h
MeO
F
CN
2a
F
1a
3a
Yield: 57% (with 14)
91% (with Ph2SiH2)
b) Silanide mediated conjugate addition
F
F
Ph
O
OMe
O
F
MeO
OtBu
+
F
F
F
Additive (0.5 equiv)
Ph
OtBu
+
NaOtBu (1.0 equiv)
THF, 25 oC, 12 h
CN
Si
F
CN
F
OtBu
tBuO
1a
2a
3a
Alternatively, a mechanism similar to what was proposed by
Stoltz, Grubbs et al. for the BuOKꢀEt3SiHꢀmediated C–H
16
16 + tBuOH
tBuOH
<1
Additive
Yield of 3a (%)
None
<1
t
25
51
silyation13c,d may be operative. Accordingly, the conjugate
addition may involve an arylsilane species as a key intermediꢀ
ate, as highlighted in Scheme 6c and marked Path 2 in
Scheme 6d. This mechanism starts with a diphenylhydrosilyl
radical [Ph2(H)Si•] that reacts with fluorobenzene traversing
the transition state 1-TS with barrier of 14.9 kcal/mol. The
ipsoꢀhydrogen of the radical adduct (27) may be detached by
silicate 25 with a barrier of 4.1 kcal/mol to furnish a silylbenꢀ
zene species 28. This intermediate 28 may then be activated
by tBuO– anion to transiently form a pentacoordinated species
29, which will then lead to an aryl anion (30) with a negligible
barrier of 3.4 kcal/mol upon cleavage of the C–Si bond. In this
pathway, the Michael addition is proposed to occur via the
aryl anion species (see the SI for full energy profiles).
c) Proposed homolysis mechanism for 16
2-
Si
Si
+ 2 NaOtBu
- 2 NaOtBu
Si
Si
tBuOH
- NaOtBu
H
OtBu
H
H
H
+
tBuO
2 Na
H
Na
Si
Si
20
19
16 (Without Solvent)
H
Homolysis
+ 2 NaOtBu
- 2 NaOtBu
Si
2
2
Na
Si
OtBu
H
18
21
Unfortunately, it is not possible to use these computed proꢀ
files to definitively conclude which of these two possible and
plausible pathways are operative. The first pathway involves a
singleꢀelectron transfer (SET), which is reasoned to occur
readily upon collision of the reactants due to the low barrier
for the key electron transfer event. The ipsoꢀhydrogen abstracꢀ
tion, however, requires a barrier of 26.5 kcal/mol, which is a
bit too high to explain the reaction at ambient conditions. But,
since the SET is likely irreversible with the back transfer being
associated with a much higher barrier, it can be argued that
Path 1 will be followed once the radical anion is produced.
This reasoning is consistent with our experimental results
summarized in Table 2, where the fluoroarene substrates beꢀ
come more reactive when they have multiple fluorine substituꢀ
ents. The fluorine atoms decrease the LUMO level of arene
substrates with concomitant increase of electron acceptability,
thereby making the key SET event more feasible.
ꢀ COMPUTATIONAL STUDIES
We sought to understand the mechanism by constructing a
computer model based on density functional theory (DFT)31
considering two mechanistic scenarios illustrated in Scheme 6.
The B3LYPꢀD332 functional with 6ꢀ31G**33 basis set was
used for the geometry optimizations and the energies were reꢀ
evaluated with a larger basis set, ccꢀpVTZ(ꢀf),34 and solvation
energies for THF (ε = 7.6) were obtained from a continuum
model,35 following a modeling protocol that were used in nuꢀ
merous previous studies.
The first mechanistic scenario marked as Path 1 in Scheme
6a invokes a singleꢀelectron transfer (SET) event to produce a
radical anion, whereas in Path 2 a radicalꢀionic process is
proposed to furnish an aryl anion. In both pathways, the reacꢀ
tive intermediates can act as nucleophiles to attack the α,βꢀ
unsaturated carbonyls to form the desired products. In Scheme
5c, employing the silole substrate as a mechanistic probe, we
suggested that a silyl radical species (18) can participate in the
conjugate addition reaction. In the real system where Ph2SiH2
is used, it is reasonable to propose that an analogous radical
anion (22) or a diphenylhydrosilyl radical [Ph2(H)Si•] species
is generated in situ.36 The radical anion may undergo a singleꢀ
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Scheme 6. Proposed Mechanistic Pathways and Computational Studies
O
4
5
6
7
8
9
a
Ph
OtBu
H
SET pathway
CN
–
Fn
[Ph2Si(H)OtBu]-
Path 1
Path 2
Na
Radical anion
CN
H
22
Ph2SiH2
+
O
Fn
Fn
NaOtBu
OtBu
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Si(H)Ph2
Ph
products
Ionic pathway
Radical pathway
Ionic pathway
Fn
Fn
H2
Aryl anion
Silylated intermediate
b
c
Path 1
Path 2
F
F
G
H
G
H
OMe
(kcal/mol)
(kcal/mol)
Si
F
F
Ph
Ph
1-TS
(14.85)
1-SET
(4.78)
27-TS
(10.37)
1
(0.00)
23-TS
(–7.36)
27
(6.27)
OMe
F
F
23
(–7.96)
F
F
H
24
(–9.13)
H
1
OMe
F
F
F
Ph O–
OtBu
(0.00)
F
F
F
H
Si
F
Ph
F
OMe
Ph
Ph
F
H
F
F
F
F
OMe
Si
OMe
–
F
F
F
F
CN
Ph
MeO
F
F
F
H
28
(–24.94)
H
d
Path 1
Path 2
O
Ph
Si
F
F
Ph O–
OtBu
Ph
H
Ph O–
Ph
H
F
F
NaOtBu
F
OtBu
F
F
CN
F
MeO
F
F
OtBu
[Ph2Si(H2)OtBu]-
Na
+
CN
CN
MeO
F
F
F
F
25
F
F
OMe
24
OMe
[Ph2Si(H)OtBu]-
26
OtBu
Na
(22)
Na
30
Ph
aqueous
workup
28
Ph Si
+ H2
H
F
F
F
F
tBuO–
t
Ph S
i(H)O
Bu
2
Product
OMe
29
Whereas Path 1 is plausible and is supported by experiꢀ
mental data, the alternative Path 2 cannot be ruled out at the
present stage because the barriers in each of the proposed steps
are low and consistent with a facile reaction under the present
conditions. The highest barrier in this pathway is 14.9
kcal/mol and is associated with the initial silyl radical
[Ph2(H)Si•] attack on the fluorobenzene substrate. Considering
the fact that we could not isolate or detect a silylaryl species
(e.g. 28),38 an essential intermediate according to the Path 2,
more definitive experimental evidence will be needed to supꢀ
port this pathway. Taken together, the EPR, radical scavenger
experiments, and DFT calculations suggest that a radical
pathway is mainly operative in the current reaction system
while we cannot fully exclude other possibilities of ionic or
neutral paths at the present stage.13c,d
ꢀ CONCLUSION
We have developed for the first time a procedure for the conꢀ
jugate addition of perfluoroarenes to α,βꢀunsaturated carbonyls
by a system of NaOtBuꢀhydrosilanes. The reaction is convenꢀ
ient to carry out at room temperature over a broad range of
substrates and reactants to furnish synthetically useful prodꢀ
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lective conjugate addition of Grignard reagents on 3ꢀboronyl unsatuꢀ
ucts in high to excellent yields. Mechanistic studies suggested
rated esters and thioesters. J. Am. Chem. Soc. 2010, 132, 5544. (d)
Hatano, M.; Mizuno, M.; Ishihara, K. Regioselective 1,4ꢀ and 1,6ꢀ
conjugate additions of Grignard reagentꢀderived organozinc(II)ates to
polyconjugated esters. Org. Lett. 2016, 18, 4462.
that a singleꢀelectron transfer (SET) process is most likely
involved on the basis of EPR and radical scavenger experiꢀ
ments. Significantly, key hypervalent silicates were observed
by NMR and a silanide species could be characterized by an
Xꢀray crystallographic analysis, representing the first example
of a mechanistically relevant silyl species from the alkoxideꢀ
hydrosilane systems. Computational studies also support our
proposal of radical intermediacy, but an alternative radicalꢀ
ionic pathway proposed for the related silylation intermediacy
could not be ruled out at the moment. This transition metalꢀ
free method should be useful for various applications in synꢀ
thetic and medicinal chemistry as a practical tool for forming
carbonꢀcarbon bonds of fluoroarenes.
(3) For selected references on organolithiums, see: (a) Corey, E. J.;
Naef, R.; Hannon, F. J. Enantioselective conjugate addition of rationꢀ
ally designed chiral cuprate reagents to 2ꢀcycloalkenones. J. Am.
Chem. Soc. 1986, 108, 7114. (b) Plunian, B. Directed conjugate addiꢀ
tion of organolithium reagents to α,βꢀunsaturated carboxylic acids.
Chem. Commun. 1998, 0, 81. (c) Izumiseki, A.; Yamamoto, H. Selecꢀ
tive Michael reaction controlled by supersilyl protecting group. Anꢀ
gew. Chem., Int. Ed. 2015, 54, 8697. (d) Chepyshev, S. V.; Lujanꢀ
Montelongo, J. A.; Chao, A.; Fleming, F. F. Alkenyl isocyanide conꢀ
jugate additions: a rapid route to γ‐carbolines. Angew. Chem., Int. Ed.
2017, 56, 4310.
(4) For selected references on organozincs, see: (a) Wilsily, A.; Lou,
T.; Fillion, E. Enantioselective copperꢀcatalyzed conjugate addition of
dimethylzinc to 5ꢀ(1ꢀarylalkylidene) meldrum’s acids. Synthesis 2009,
2066. (b) Palais, L.; Babel, L.; Quintard, A.; Belot, S.; Alexakis, A.
Copperꢀcatalyzed enantioselective 1,4ꢀaddition to α,βꢀunsaturated
aldehydes. Org. Lett. 2010, 12, 1988. (c) Endo, K.; Ogawa, M.; Shiꢀ
bata, T. Multinuclear catalyst for copper‐catalyzed asymmetric conjuꢀ
gate addition of organozinc reagents. Angew. Chem., Int. Ed. 2010, 49,
2410.
(5) (a) Takaya, Y.; Ogasawara, M.; Hayashi, T.; Sakai, M.; Miyaura,
N. Rhodiumꢀcatalyzed asymmetric 1,4ꢀaddition of arylꢀ and alkenylꢀ
boronic acids to enones. J. Am. Chem. Soc. 1998, 120, 5579. (b)
Nishikata, T.; Yamamoto, Y.; Miyaura, N. Conjugate addition of aryl
boronic acids to enones catalyzed by cationic palladium(II)ꢀ
phosphane complexes. Angew. Chem., Int. Ed. 2003, 42, 2768. (c)
Takatsu, K.; Shintani, R.; Hayashi, T. Copper‐catalyzed 1,4‐addition
of organoboronates to alkylidene cyanoacetates: mechanistic insight
and application to asymmetric catalysis. Angew. Chem., Int. Ed. 2011,
50, 5548. (d) Yoshida, M.; Ohmiya, H.; Sawamura, M. Enantioselecꢀ
tive conjugate addition of alkylboranes catalyzed by a copper–Nꢀ
heterocyclic carbene complex. J. Am. Chem. Soc. 2012, 134, 11896.
(e) Wu, C.; Yue, G.; Nielsen, C. D.ꢀT.; Xu, K.; Hirao, H.; Zhou, J.
Asymmetric conjugate addition of organoboron reagents to common
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ꢀ ASSOCIATED CONTENT
Supporting Information
Experimental procedures, characterization data, spectroscopic
data, crystallographic data, Cartesian coordinates of all computed
structures and energy components. The Supporting Information is
available free of charge on the ACS Publications website at DOI:
ꢀ
AUTHOR INFORMATION
Corresponding Authors
*mbaik2805@kaist.ac.kr
*sbchang@kaist.ac.kr
ORCID
MuꢀHyun Baik: 0000ꢀ0002ꢀ8832ꢀ8187
Sukbok Chang: 0000ꢀ0001ꢀ9069ꢀ0946
Notes
The authors declare no competing financial interest.
ꢀ
ACKNOWLEDGEMENTS
This research was supported by the Institute for Basic Science
(IBSꢀR010ꢀD1) in Korea. Single crystal Xꢀray diffraction experiꢀ
ments with synchrotron radiation were performed at the BL2Dꢀ
SMC in Pohang Accelerator Laboratory.
ꢀ
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(24) Tanabe, M.; Iwase, S.; Takahashi, A.; Osakada, K. Tetramer
and polymer of 2,7ꢀdialkoxyꢀ9Hꢀ9ꢀsilafluorene composed of Si backꢀ
bone and πꢀstacked biphenylene groups. Chem. Lett. 2016, 45, 394.
(25) A similar behavior of broadening 29Si NMR signals in silicate
species over temperatures was reported by Lammertsma, K. et al.: see
the [Ref. 22a].
(35) (a) Marten, B.; Kim, K.; Cortis, C.; Friesner, R. A.; Murphy, R.
B.; Ringnalda, M. N.; Sitkoff, D.; Honig, B. New model for calculaꢀ
tion of solvation free energies: correction of selfꢀconsistent reaction
field continuum dielectric theory for shortꢀrange hydrogenꢀbonding
effects. J. Phys. Chem. 1996, 100, 11775. (b) Edinger, S. R.; Cortis,
C.; Shenkin, P. S.; Friesner, R. A. Solvation free energies of peptides:ꢁ
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calculations. J. Phys. Chem. B 1999, 103, 3057.
(36) The formation of the radical anion 22 from tBuO– and
[Ph2(H)Si•] intermediate was calculated to be energetically feasible
with –27.1 kcal/mol free energy (see the SI for details).
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(37) (a) Marcus, R. A. On the theory of oxidationꢀreduction reacꢀ
tions involving electron transfer. I. J. Chem. Phys. 1956, 24, 966. (b)
Marcus, R. A. Electron transfer reactions in chemistry: Theory and
experiment (Nobel lecture). Angew. Chem., Int. Ed. 1993, 32, 1111. (c)
Nelsen, S. F.; Blackstock, S. C.; Kim, Y. Estimation of inner shell
Marcus terms for amino nitrogen compounds by molecular orbital
calculations. J. Am. Chem. Soc. 1987, 109, 677.
(38) When a silylated intermediate 28 was separately prepared and
allowed to react with α,βꢀunsaturated carbonyl compound (2a) in the
presence of NaOtBu (1.0 equiv), an addition product 3a was obtained
in 81% after 12 h at room temperature (see the SI for details).
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O
R1
O
OtBu
R1
H
OtBu
R2
RT, 12 h
> 30 Examples, Scalable
Conjugate Addition
H
Ph2SiH2
+
NaOtBu
Fn
R2
Fn
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(R1= Aryl, Alkenyl; R2 = CN, CO2tBu)
Synthetically Versatile Products
Fn
Two Pathways
Radical Intermediacy (EPR)
Silicates Observed (NMR)
Silanide Isolated (X-ray)
Computations
[Si]
Fn
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