Enantioselective 1,2-Anionotropic Rearrangement of Acylsilane through a Bisguanidinium Silicate Ion Pair

Article abstract of DOI:10.1021/jacs.7b13056

Highly enantioselective bisguanidinium-catalyzed tandem rearrangements of acylsilanes are reported. The acylsilanes were activated via an addition of fluoride on the silicon to form a penta-coordinate anionic silicate intermediate. The silicate then underwent alkyl or aryl group migration from the silicon atom to the neighboring carbonyl carbon atom (1,2-anionotropic rearrangement), followed by [1,2]-Brook rearrangement to provide the secondary alcohols in high yields with excellent enantioselectivities (up to 95% ee). The isolation of an α-silylcarbinol intermediate as well as DFT calculations revealed that the 1,2-anionotropic rearrangement occurred via a bisguanidinium silicate ion pair, which is the stereodetermining step. The chiral center formed is then retained without inversion through the subsequent [1,2]-Brook rearrangement. Crotyl acylsilanes were smoothly transformed into homoallylic linear crotyl alcohols with retention of E/Z geometry, and no branched alcohols were detected. This clearly suggested that the 1,2-anionotropic rearrangement occurred through a three-membered instead of a five-membered transition state.

Full text of DOI:10.1021/jacs.7b13056

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Article
Enantioselective 1,2-Anionotropic Rearrangement of
Acylsilane through Bisguanidinium Silicate Ion Pair
Weidi Cao, Davin Tan, Richmond Lee, and Choon-Hong Tan
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.7b13056 • Publication Date (Web): 11 Jan 2018
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Enantioselective 1,2-Anionotropic Rearrangement of Acylsilane
through Bisguanidinium Silicate Ion Pair
Weidi Cao,1 Davin Tan,1,2 Richmond Lee,2* Choon-Hong Tan1*
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1Division of Chemistry and Biological Chemistry, Nanyang Technological University, 21 Nanyang Link, Singapore 637371
2Division of Science and Math, Singapore University of Technology and Design, 8 Somapah Road, Singapore 487372
ABSTRACT: Highly enantioselective bisguanidinium-catalyzed tandem rearrangements of acylsilanes are reported. The acylsilanes
were activated via an addition of fluoride on the silicon to form a penta-coordinate anionic silicate intermediate. The silicate then
underwent alkyl or aryl group migration from the silicon atom to the neighboring carbonyl carbon atom (1,2-anionotropic rearrange-
ment), followed by [1,2]-Brook rearrangement to provide the secondary alcohols in high yields with excellent enantioselectivities (up
to 95% ee). The isolation of an α-silylcarbinol intermediate as well as DFT calculations revealed that the 1,2-anionotropic rearrange-
ment occurred via a bisguanidinium silicate ion-pair, which is the stereo-determining step. The chiral center formed is then retained
without inversion through the subsequent [1,2]-Brook rearrangement. Crotyl acylsilanes were smoothly transform into homoallylic
linear crotyl alcohols with retention of E/Z geometry and no branched alcohols were detected. This clearly suggested that the 1,2-
anionotropic rearrangement occurred through a three-membered instead of a five-membered transition state.
Ion-pairing catalysis,8 comprising of chiral cation working
■ INTRODUCTION
synergistically with metal-centered anions, has been reported
Hypervalent silicon have been widely applied to organic syn-
for several enantioselective transformations.9 Specifically, di-
thesis and catalysis due to its unique structure and reactivity.1
cationic bisguanidinium has been used to direct permanganate,
Penta- and hexa-coordinate silicon are known to be crucial in-
diphosphatobisperoxotungstate and dinuclear oxodiperoxomo-
termediates in many reactions. A representative reaction involv-
lybdosulfate anions in enantioselective oxohydroxylation and
ing pentavalent silicon intermediate is the Brook rearrange-
sulfoxidation reactions.9a-c Bisguanidinium silicates have also
ment.2 This process generally requires base and its putative re-
been proposed to be key intermediates in enantioselective alkyl-
action mechanism is an intramolecular anionic migration of the
ations using silylamide.9d In this study, we hypothesized that the
silyl group from carbon to oxygen. Acylsilanes are carbonyl de-
silicate intermediate derived from acylsilane can be mediated
rivatives and behave similarly to aldehydes or ketones and are
susceptible to nucleophilic additions.3 Addition of a nucleophile
to acylsilane, catalyzed with a chiral metal-complex, generates
an enantiopure a-silyl alkoxide, which is a precursor to Brook
rearrangement (Scheme 1). This is the most common strategy
towards catalytic enantioselective Brook rearrangements. For
example, Johnson4a reported a chiral (salen)-Al(OiPr) catalyzed
cyanation of acylsilanes and Marek4c reported a Zn-mediated
enantioselective alkynylation of acylsilanes. Both reactions are
followed by stereoselective Brook rearrangements. Alterna-
tively, the enantiopure α-silyl alkoxide can be generated
through hydride reduction of alkynoylsilane using stoichio-
metric chiral amide, as demonstrated by Takeda.4e Several other
chemoselective and diastereoselective variants of this nucleo-
philic addition strategy have also been reported.2d-e, 5
using a chiral cation to promote enantioselective 1,2-aniono-
tropic rearrangement and followed by stereoselective Brooks
rearrangement, lead to chiral secondary alcohols (Scheme 2).
Scheme 1. Tandem nucleophilic addition/[1,2]-Brook rear-
rangement of acylsilane (previous works).
[1,2]-Brook
rearrangement
O
*
O
OSiR3
R''
O
R''-MLn*
products
SiR3
R'
SiR3
R'
SiR3
R'
R'
R''
α-silyl alkoxide
R''
Scheme 2. Tandem 1,2-anionotropic/[1,2]-Brook rearrange-
ment of acylsilane (current strategy).
*
*
R4N
R4N
O
1,2-anionotropic
rearrangement
O
*
O
R4N
SiR''R2
X- = F- or alkoxide
X
*
R'
SiR2X
R''
silicate
intermediate
R'
R'
SiR2X
SiR2X
Acylsilanes can also be activated via a nucleophilic attack on
the silicon to form a penta-coordinate anionic silicate interme-
diate (Scheme 2). The silicate can then undergo alkyl or aryl
group migration from the silicon atom to the neighboring car-
bonyl carbon atom (1,2-anionotropic rearrangement), followed
by [1,2]-Brook rearrangement to provide a secondary alcohol.
Brook6 and others7 reported this tandem rearrangement of
acylsilanes using alkoxide or fluoride salts. To the best of our
knowledge, the enantioselective catalytic variant of this reac-
tion, has not been realized.
R''
[1,2]-Brook
rearrangement
*
*
R4N
R4N
O
OH
R''
OSiR2X
R''
R'
R'
R'
R''
■ RESULTS AND DISCUSSION
Enantioselective 1,2-Anionotropic Rearrangement of
Acylsilane. In the initial study, acylsilane 1a was selected as
the model starting substrate. When 1a was used in the presence
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of CsF and bisguanidinium catalyst BG-tBu (5 mol %), no re-
Page 2 of 5
ing electronic or steric properties. The corresponding chiral se-
cond alcohols 3a-3k were furnished with good yields (69-93%)
and high enantioselectivities (84-95% ee).10 Substrates bearing
electron withdrawing groups on the migrating aryl group were
more reactive,11 presumably due to increased Lewis acidity of
silicon and facilitating the formation of the hypervalent silicate
intermediate. In the subsequent anionotropic shift, electron
withdrawing groups also stabilized the migratory aryl anion.
Furanyl group was well tolerated and provided the furanyl al-
cohol 3l in 69% yield with 84% ee. The substituents on benzyl
group of the acylsilane had little effect on the yields and enan-
tioselectivity (3m-3p).
1
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4
5
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action was observed (Table 1, entry 1; see SI, Table S1). Trace
amount of the desired product 3a was obtained, after 48 h, when
H2O was added as a proton source (entry 2). As a result, we
further probed the use of alcohols as the proton source, which
led to improve reactivities and enantioselectivities (entries 3-8).
The use of a bulky silyl alcohol iPr3SiOH was found to be the
best proton source (entry 8) and at this stage we were intrigued
by the influence of the proton source on enantioselectivity. We
initially suspected that the reaction might to be an enantioselec-
tive protonation reaction of the carbanion but further investiga-
tions refuted this hypothesis as a silylated alcohol intermediate
2a was isolated and spectroscopically identified. Various sol-
vents were screened and TBME was found to furnish the best
yield and enantioselectivity (entries 8-11). Lower reaction tem-
peratures led to improve enantioselectivities but at a cost, i.e.
longer reaction times and reduced yields (entries 12-14). In-
creasing the catalyst loading to 10 mol % and amount of CsF
gave the optimal reaction conditions (entry 15). By employing
a newly developed bisguanidinium catalyst BG-TMS, enanti-
oselectivity was further improved (entry 16).
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Table 2. Enantioselective 1,2-Anionotropic Rearrangement
of Aryl Acylsilane.a
BG-TMS (10 mol %)
CsF (4.0 equiv.)
O
OH
1 M TBAF
THF, rt
R
R
3
Si
iPr3SiOH (2.0 equiv.)
Ar
Ar
1
TBME, - 50 o
C
OH
OH
Me OH
Me
3a
3c
3b
78% yield, 93% ee
OH
83% yield, 90% ee
OH
93% yield, 92% ee
OH
Table 1. Optimization of the Reaction Conditions.a
MeO
Me
3d
80% yield, 90% ee
OH
3e
3f
BG (5 mol %)
CsF (1.0 equiv.)
O
OH
OSiMe2OR''
Me
1 M TBAF
THF, rt
77% yield, 95% ee
73% yield, 88% ee
Ph
3a
Ph
Si
Bn
1a
Me
Ph
Ph
R''OH (2.0 equiv.)
solvent, temp.
OH
OH
Ph
2a
R
N
R
N
R =
Ph
Ph
Ph
3g
3i
3h
R'
nBu
F
MeO
Br
75% yield, 90% ee
74% yield, 90% ee
84% yield, 90% ee
N
N
N
R
N
R
Ph
OH
OH
OH
R'
BG-tBu R' = tBu
BG-TMS R' = TMS
2Cl
3j
3k
3l
O
Cl
entry
R²OH
solvent
T/oC time
(h)
rt
rt
yield
(%)b
ee
74% yield, 85% ee
77% yield, 89% ee
69% yield, 84% ee
(%)c
F
Me
OMe
OH
OH
OH
1
2
-
TBME
TBME
48
48
NRd
-
-
H2O
trace
3m
3n
80% yield, 89% ee
3o
81% yield, 91% ee
80% yield, 90% ee
3
4
MeOH
TBME
TBME
TBME
TBME
rt
rt
48
12
1
80
87
76
77
81
93
87
86
88
91
93
51
89
83
15
21
40
49
53
55
51
9
OH
tBuOH
3p
5
Me3SiOH
Et3SiOH
rt
73% yield, 95% ee
a Reactions were carried out with BG-TMS (10 mol %), CsF (0.4 mmol,
4.0 equiv.), 1 (0.10 mmol), iPr3SiOH (0.2 mmol, 2.0 equiv.) in TBME (0.5
mL) at -50 oC. b Isolated yields of 3. c Determined by chiral HPLC.
6
rt
1
7
tBuMe2SiOH TBME
rt
1
8
iPr3SiOH
iPr3SiOH
iPr3SiOH
iPr3SiOH
iPr3SiOH
iPr3SiOH
iPr3SiOH
iPr3SiOH
iPr3SiOH
TBME
Et2O
rt
1
9
rt
2
Scheme 3. Enantioselective 1,2-anionotropic rearrangement
of allyl and crotyl acylsilanes.
10
11
12
13
14
15e
16f
DCM
rt
1
BG-tBu (10 mol %)
CsF (4.0 equiv.)
a)
OH
O
Toluene
TBME
TBME
TBME
TBME
TBME
rt
1
26
69
81
89
87
90
1 M TBAF
THF, rt
Bn
Si
Bn
1q
iPr3SiOH (2 equiv.)
0
4
3q 87% yield
TBME, -70 o
C
87% ee
-40
-50
-50
-50
14
72
36
48
b)
OH
BG-tBu (10 mol %)
CsF (4.0 equiv.)
O
1 M TBAF
THF, rt
Bn
Si
Bn
iPr3SiOH (2 equiv.)
3r
TBME, -50 o
C
1r
81% yield, Z:E = 92:8
Z:E = 92:8
Z: 86% ee, E: 89% ee
c)
BG-tBu (10 mol %)
CsF (4.0 equiv.)
a Unless otherwise noted, reactions were carried out with BG-tBu (5 mol
%), CsF (0.1 mmol, 1.0 equiv.), 1a (0.10 mmol), ROH (0.2 mmol, 2.0
equiv.) in solvent (0.5 mL) at indicated temperature, rt = room tempera-
ture. b Isolated yield of 3a. c Determined by HPLC using chiral OD-H col-
umn. d NR = No reaction. e BG-tBu (10 mol%) and CsF (4.0 equiv.) were
used. f BG-TMS (10 mol %) and CsF (4.0 equiv.) were used.
OH
O
1 M TBAF
Bn
Si
Bn
1r
Z:E = 15:85
iPr3SiOH (2 equiv.)
THF, rt
TBME, -50 o
C
3r
83% yield,Z:E = 15:85
Z: 86% ee, E: 89% ee
Intermolecular asymmetric allylation of carbonyl compounds
or imine using silane reagents typically requires activation of
the silane reagent with Lewis bases or the electrophiles with
Lewis acids.12 For this intramolecular rearrangement, allyl
acylsilane 1q could smoothly transform into allylic alcohol 3q
(Scheme 3a). Fortuitously, (Z)-homoallylic linear crotyl alcohol
Using the optimized reaction condition, a series of aryl sub-
stituted acylsilanes were investigated (Table 2). The reaction
tolerated migrating aryl groups bearing substituents with vary-
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form two nearly iso-energetic intermediates: ring closure to give a
siloxirane intermediate intE (ΔG = -15.3 kcal/mol),15 and O
···H
3r was obtained from (Z)-crotyl acylsilane 1r using this proto-
1
2
3
4
5
6
7
8
̄
col (Scheme 3b). We initially predicted that a branched alco-
hol13 would be derived through a five-membered ring transition
state but retention of stereochemistry clearly suggested that the
1,2-anionotropic rearrangement proceeded through a three-
membered transition state instead (Scheme 3c). We also ex-
plored the use of vinyl acylsilanes, and only trace product was
achieved under the optimized conditions (Table 1, entry 13; see
SI for details). Further investigations are required to determine
if other mediator besides fluoride could facilitate this sluggish
migratory process.
bound intD (ΔG = -15.5 kcal/mol). Direct proton transfer from
intD between the alkoxyl group and Me3SiOH affords α-silyl-
carbinol 4. Tandem Brook rearrangement and protonation through
transition state TSE (ΔG‡ = +6.5 kcal/mol) leads to a pentavalent
precursor intF, which upon facile fluoride dissociation generates
silylated allylic alcohol 2q. It is thus interesting to observe that ion
pair catalysis can work synergistically with hydrogen bonding and
this will have significant implication in the understanding and de-
sign of ion pair-mediated reactions.
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[BGsF]
■
MECHANISTIC STUDIES
[BGsF]
BGs[Cl]2
CsF
R3SiOH
O
O
O
Identification of Reaction Intermediates. In order to fully un-
Bn
H
F
Si
Bn
F
Si
R3SiOH
R = Me
O
Si
Bn
derstand this tandem 1,2-anionotropic/Brook rearrangement, it was
indispensable to verify the enantio-determining step. Fortunately,
we were able to isolate α-silyl carbinol 4 and delighted to find it to
be in high enantiopurity (Scheme 4a). When treated with TBAF
solution, 4 underwent the [1,2]-Brook rearrangement with com-
plete conversion to allylic alcohol 3q without diminished enanti-
opurity (Scheme 4b).4d,14 Similarly, when silylated allylic alcohol
2q was treated with TBAF solution, allylic alcohol 3q was obtained
while retaining both its enantiopurity and absolute configuration
(Scheme 4c). These experiments indicated that the 1,2-anionotropic
rearrangement to be the enantio-determining step and was indirect
evidence for the presence of a tight bisguanidinium silicate ion pair
(Scheme 2). We also found that the amount of CsF used had no
effect on enantioselectivity but had a positive correlation to the re-
activity (Scheme 5).
SiR3
1q
ΔG = 0.0 kcal/mol
intB
-5.0
intA
-2.6
[BGsF]
[BGsF]
O
[BGsF]
O
O
H
O
Bn
Bn
Bn
H
O
F
Si
H
O
F
Si
Si
SiR3
F
SiR3
SiR3
TSB-3m
intD
-15.5
6.6
intC
-5.4
Proton transfer
[BGsF]
F
[BGsF]
O
H
Bn
O
H
SiR3
O
Bn
Si
H
O
F
Si
O
Si
O
Bn
SiR3
R3Si
TSE
+ BGs[F]2
-8.8
intE
-15.3
Brook rearrangement
and deprotonation
4
-20.5
Scheme 4. Investigation of the enantio-determining step.
Siloxirane intermediate
BG-tBu (10 mol %)
a)
O
OH
Bn
SiMe2OSiiPr3
4, 87% ee
OSiMe2OSiiPr3
CsF (4.0 equiv.)
iPr3SiOH (2 equiv.)
TBME, -70 oC
[BGsF]
SiR3
[BGsF]
Bn
Si
Bn
1q
Bn
O
F
O
Bn
O
F
O
Si
Si
Si
O
2q
Bn
+ BGs[F]2
2q
H
O
H
b)
c)
R3Si
intF
90% yield, 4:2q = 1:4
R3Si
OH
OH
1 M TBAF
THF, rt
-48.8
Bn
TSF
-40.7
-51.6
Bn
SiMe2OSiiPr3
100% conversion
4, 87% ee
3q, 87% ee
Figure 1. Proposed hydrogen bonding-assisted tandem 1,2-an-
ionotropic rearrangement. Values in kcal/mol are calculated
solution free energies of minimum and TS electronic structures
optimized at B3LYP-B3/def2TZVP/SMD//B3LYP/6-31+G(d)
level of theory (see SI on DFT methods).
OSiMe2OSiiPr3
OH
1 M TBAF
THF, rt
Bn
Bn
3q, 87% ee
2q
100% conversion
Scheme 5. The role of fluoride.
■
CONCLUSIONS
BG-tBu (5 mol %)
CsF (x equiv.)
OH
O
In summary, the first catalytic asymmetric tandem 1,2-aniono-
1 M TBAF
THF, rt
tropic/Brook arrangements of acylsilane furnishing highly enantio-
enriched secondary alcohols has been described. Isolation of reac-
tion intermediates such as α-silyl carbinol 4 and silylated allylic
alcohol 2q, coupled with theoretical calculations, a bisguanidinium
hypervalent silicate ion pair was proposed to be the key intermedi-
ate for the stereo-determining 1,2-anionotropic rearrangement. In
addition, experimental and computational results suggested that the
1,2-anionotropic rearrangement proceeded through a three-mem-
bered ring transition state. This new synthetic strategy in ion pair-
ing catalysis is important to expand the repertoire of reactions for
acylsilanes. This also points to the future use of chiral cations as an
approach to mediate reactions containing silicates as intermediates.
3q
Bn
x = 0; 24 h, NR
x = 0.1, 4 h, 91% yield, 49% ee
x = 1, 0.5 h, 93% yield, 48% ee
Si
Bn iPr3SiOH (2 equiv.)
TBME, rt
1q
Theoretical Modelling Studies. Protic additives like alcohol are
important to the reaction, with the bulky silyl alcohol having sig-
nificant effect on enantioselectivity (Table 1, entries 2-5). Further-
more, the isolation of α-silyl carbinol 4 and silylated allylic alcohol
2q as reaction intermediates (Scheme 4) serve to suggest R3SiOH
as an important mediator early in the reaction. It is proposed that
once halide exchange occurs with the original bisguanidinium chlo-
ride catalyst, a pentavalent silyl complex intA is formed (Figure 1;
BGs is truncated version of BG-tBu). Our DFT model predicts that
Me3SiOH is able to stabilize intA by 2.4 kcal/mol through non-
covalent hydrogen bonding to the F-Si bond generating intB (See
SI for DFT methods and detailed discussion). A low energy barrier
involving three-membered transition state TSB-3m (ΔG‡ = +11.6
kcal/mol) was found to be more energetically plausible over a five-
membered ring transition state for the anionotropic rearrangement
process (See SI). Subsequently the α-silylalkoxide intC is able to
ASSOCIATED CONTENT
Supporting Information
Experimental procedures and compound characterization data.
This material is available free of charge via the internet at
http://pubs.acs.org.
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(6) (a) Brook, A. G. J. Org. Chem. 1960, 25, 1072; (b) Brook, A. G.;
AUTHOR INFORMATION
Corresponding Author
Schwartz, N. V. J. Org. Chem. 1962, 27, 2311; (c) Brook, A. G.;
Vandersar, T. J. D.; Limburg, W. Can. J. Chem. 1978, 56, 2758.
1
2
3
4
5
6
7
8
9
(7) (a) Zilch, H.; Tacke, R. J. Organomet. Chem., 1986, 316, 243; (b)
Page, P. C. B.; Rosenthal, S.; Williams, R. V. Tetrahedron Lett.
1987, 28, 4455; (c) Morihata, K.; Horiuchi, Y.; Taniguchi, M.;
Oshima, K.; Utimoto, K. Tetrahedron Letters, 1995, 36, 5555.
richmond_lee@sutd.edu.sg
choonhong@ntu.edu.sg
ORCID
Richmond Lee: 0000-0003-1264-4914
Choon-Hong Tan: 0000-0003-3190-7855
(8) (a) Hashimoto, T.; Maruoka K. Chem. Rev. 2007, 107, 5656; (b)
Mahlau, M.; List, B. Angew. Chem. Int. Ed. 2013, 52, 518; (c)
Brak, K.; Jacobsen, E. N. Angew. Chem. Int. Ed. 2013, 52, 534;
(d) Shirakawa, S.; Maruoka, K. Angew. Chem., Int. Ed. 2013, 52,
4312.
Notes
The authors declare no competing financial interest.
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(9) (a) Wang, C.; Zong, L.; Tan, C.-H. J. Am. Chem. Soc. 2015, 137,
10677; (b) Ye, X.; Moeljadi, A. M. P.; Chin, K. F.; Hirao, H.;
Zong, L.; Tan, C.-H. Angew. Chem., Int. Ed. 2016, 55, 7101; (c)
Zong, L.; Wang, C.; Moeljadi, A. M. P.; Ye, X.; Ganguly, R.; Li,
Y.; Hirao, H.; Tan, C.-H. Nat. Commun. 2016, 7, 13455; (d) Teng,
B.; Chen, W.; Dong, S.; Kee, C. W.; Gandamana, D. A.; Zong,
L.; Tan, C.-H. J. Am. Chem. Soc. 2016, 138, 9935; (e) Zong, L.;
Tan, C.-H. Acc. Chem. Res. 2017, 50, 842.
ACKNOWLEDGMENT
We gratefully acknowledge Nanyang Technological University
(M4011633) and Singapore University of Technology and Design
for financial support.
REFERENCES
(10) The absolute configuration of 3a-q was identified by comparing
(1) (a) Chuit, C.; Corriu, R. J. P.; Reye, C.; Young, J. C. Chem. Rev.
1993, 93, 1371; (b) Holmes, R. R. Chem. Rev. 1996, 96, 927; (c)
Rendler, S.; Oestreich, M. Synthesis 2005, 1727; (d) Voronkov,
M. G.; Trofimova, O. M.; Bolgova, Y. I.; Chernov, N. F. Russ.
Chem. Rev. 2007, 76, 825; (e) Benaglia, M.; Guizzetti, S.;
Pignataro, L. Coord. Chem. Rev. 2008, 252, 492; (f) Kost, D.; Ka-
likhman, I. Acc. Chem. Res. 2009, 42, 303.
to previous report. See supporting information for details.
(11) For example, the reactivity of 3i exceeds 3h, the two substrates
completely converted in 36 h and 72 h, respectively. See SI for
details.
(12) Kennedy, J. W. J.; Hall, D. G. Angew. Chem. Int. Ed. 2003, 42,
4732.
(2) (a) Brook, A. G. J. Am. Chem. Soc. 1958, 80, 1886; (b) Brook, A.
G.; Warner, C. M.; Mcgriskin, M. E. J. Am. Chem. Soc. 1959, 81,
981; (c) Brook, A. G. Acc. Chem. Res. 1974, 7, 77; (d) Moser, W.
H. Tetrahedron 2001, 57, 2065; (e) Sasaki, M.; Takeda, K. Brook
Rearrangement. In Molecular Rearrangements in Organic Syn-
thesis, Rojas, C. M. ed.; Wiley: Hoboken, 2015; pp 151.
(13) In previous reports, asymmetric crotylation addition of cro-
tylsilanes to carbonyl compounds generally occurred at the γ-po-
sition of the silicon atom and gave branch syn or anti alcohols.
For selected examples: (a) Denmark, S. E.; Fu, J. J. Am. Chem.
Soc. 2001, 123, 9488; (b) Hackman, B. M.; Lombardi, P. J.;
Leighton, J. L. Org. Lett. 2004, 6, 4375; (c) Kim, H.; Ho, S.;
Leighton, J. L. J. Am. Chem. Soc. 2011, 133, 6517; (d) Suen, L.
M.; Steigerwald, M. L.; Leighton, J. L. Chem. Sci., 2013, 4, 2413;
(e) Huang, Y.; Yang, L.; Shao, P.; Zhao. Y. Chem. Sci., 2013, 4,
3275.
(3) (a) Ricci, A.; Degl’Innocenti, A. Synthesis 1989, 647; (b) Page, P.
C. B.; Klair, S. S.; Rosenthal, S. Chem. Soc. Rev. 1990, 19, 147;
(c) Cirillo, P. F.; Panek, J. S. Org. Prep. Proced. Int., 1992, 24,
553; (d) Bonini, B. F.; Comes-Franchini, M.; Fochi, M.; Maz-
zanti, G.; Ricci, A. J. Organomet. Chem. 1998, 567, 181; (e)
Zhang, H.-J.; Priebbenow, D. L.; Bolm, C. Chem. Soc. Rev. 2013,
42, 8540.
(14) The Brook rearrangement is a stereospecific process following a
retentive course for α-silyl alkyl alcohols. (a) Hudrlik, P. F.; Hudr-
lik, A. M.; Kulkarni, A. K. J. Am. Chem. Soc. 1982, 104, 6809;
(b) Simov, B. P.; Wuggenig, F.; Mereiter, K.; Andres, H.; France,
J.; Schnelli, P.; Hammerschmidt, F. J. Am. Chem. Soc. 2005, 127,
13934.
(4) (a) Nicewicz, D. A.; Yates, C. M.; Johnson, J. S. Angew. Chem.
Int. Ed. 2004, 43, 2652; (b) Nicewicz, D. A.; Yates, C. M.; John-
son, J. S. J. Org. Chem. 2004, 69, 6548; (c) Smirnov, P.; Mathew,
J.; Nijs, A.; Katan, E.; Karni, M.; Bolm, C.; Apeloig, Y.; Marek,
I. Angew. Chem. Int. Ed. 2013, 52, 13717; (d) Unger, R.; Weisser,
F.; Chinkov, N.; Stanger, A. Cohen, T.; Marek, I. Org. Lett., 2009,
11,1853. (e) Sasaki, M.; Kondo, Y.; Kawahata, M.; Yamaguchi,
K.; Takeda, K. Angew. Chem., Int. Ed. 2011, 50, 6375.
(15) (a) Becerra, R.; Cannady, J. P.; Walsh, R. J. Phys. Chem. A 1999,
103, 4457; (b) Becerra, R.; Cannady, J. P.; Walsh, R. Phys. Chem.
Chem. Phys. 2001, 3, 2343; (c) Ishida, S.; Iwamoto, T.; Kira, M.
Organometallics 2010, 29, 5526.
(5) (a) Reynolds, T. E.; Bharadwaj, A. R.; Scheidt, K. A. J. Am.
Chem. Soc. 2006, 128, 15382; (b) Lettan II, R. B.; Woodward, C.
C.; Scheidt, K. A. Angew. Chem. Int. Ed. 2008, 47, 2294; (c) Nice-
wicz, D. A.; Johnson, J. S. J. Am. Chem. Soc. 2005, 127, 6170.
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BG-TMS or BG-tBu
(10 mol%)
CsF (4.0 equiv.)
O
OH
1 M TBAF
THF, rt
Si
R2
R1 R2
18 examples
up to 93% yield, 95% ee
R1
iPr3SiOH (2.0 equiv.)
TBME, -50 or -70 o
C
R1 = Ar, allyl
R2 = CH2Ar
O
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7
8
9
R2 SiMe2F
R1
R
R
R'
R =
Ph
Ph
Ph
Ph
N
N
N
N
N
N
R
R'
R
BG-tBu R' = tBu
BG-TMS R' = TMS
bisguanidinium silicate
ion pair
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