Type II Anion Relay Chemistry: Conformational Constraints to Achieve Effective [1,5]-Vinyl Brook Rearrangements

Article abstract of DOI:10.1021/jacs.7b04149

The design, synthesis, and evaluation of bifunctional linchpins, conformationally anchored on six-membered rings to achieve efficient [1,5]-Brook rearrangements involving vinyl silanes have been achieved. The restrained linchpins were subsequently exploit

Full text of DOI:10.1021/jacs.7b04149

Article
pubs.acs.org/JACS
Type II Anion Relay Chemistry: Conformational Constraints To
Achieve Effective [1,5]-Vinyl Brook Rearrangements
Qi Liu,† Yu Chen,‡ Xiao Zhang,‡ K. N. Houk,§ Yong Liang,*,‡ and Amos B. Smith, III*,†
†Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
‡State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing
210023, China
§Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, United States
S
* Supporting Information
ABSTRACT: The design, synthesis, and evaluation of bifunctional
linchpins, conformationally anchored on six-membered rings to
achieve efficient [1,5]-Brook rearrangements involving vinyl silanes
have been achieved. The restrained linchpins were subsequently
exploited in type II anion relay chemistry (ARC) to permit both
alkylations and Pd-mediated cross-coupling reactions (CCR) of sp2 stabilized carbanions. DFT calculations were then employed
to understand the mechanism and reactivity trends of [1,4]- and [1,5]-vinyl Brook rearrangements to provide insight on the role
of the required copper reagent and the substrate geometry.
Following the success of the ARC tactic exploiting the
dithiane as an sp3 carbon ASG, several linchpins were
subsequently designed, synthesized, and validated to exploit
sp2-hybridized carbons in [1,4]-Brook rearrangements. Anions
derived from furans,12 arenes, and olefins were employed.13
During this study, the stability of the sp2 carbanion derived
from arenes and olefins during the reversible O to C(sp2)
Brook rearrangement, not surprisingly, proved less favorable
compared to the C(sp3) dithiane stabilized carbanions. To
augment the sp2 based ARC tactic, we introduced a
stabilization factor, via the formation of an organocuprate.13,14
The latter permitted the successful validation of vinyl silanes
bearing β or γ electrophilic carbonyl sites for type II ARC
transformations based on [1,4]-Brook rearrangements.13
During these earlier studies, we recognized however that
the Brook rearrangement was quite sensitive to the specific
location of the silyl group on the double bond. The
conditions that proved effective for linchpin 10 (1.2 equiv of
n-BuLi and CuI; Scheme 2) did not permit facile [1,4]-silyl
migration with linchpin 12. In this case, 2 equiv of both n-
INTRODUCTION
■
In 2005, we defined a new platform for the construction of
molecular complexity termed anion relay chemistry (ARC;
Scheme 1).1 Critical to the success of this tactic is the ability
Scheme 1. Anion Relay Chemistry: Type I and Type II
to migrate charge in a controlled manner from an oxygen to
a carbon atom, bearing an anion stabilizing group (ASG),
during a reversible Brook rearrangement.2
Scheme 2. Type II ARC with [1,4]-Brook Rearrangement
The dithiane group, introduced by Corey and Seebach3 for
umpolung reactions and subsequently exploited by the
Schaumann4 and Tietze5 groups for what we now view as
early versions of the ARC tactic, has proven to be an
excellent ASG for both type I and type II ARC trans-
formations involving [1,4]-Brook rearrangements.6 Indeed, by
employing a series of diverse dithiane ARC linchpins, a
number of architecturally complex targets have been achieved,
as demonstrated in synthetic ventures toward spirastrellolide
E,7 (−)-secu’amamine A,8 rhizopodin,9 enigmazole A,10 and
most recently mandelalide A.11
Received: April 24, 2017
© XXXX American Chemical Society
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BuLi and CuI were required to complete the 1,4-silyl C(sp2)
to O migration over the course of a 2 h period at room
temperature (Scheme 2).13 At the time, it was not clear why
a second equivalent of n-BuLi and CuI significantly improved
the [1,4]-vinyl Brook rearrangement of 12.
Table 1. Three-Component Coupling of Linchpin 14 via
ARC/Alkylation
Recognizing that [1,5]-Brook rearrangements with vinyl
linchpins, and in particular linchpins with terminal olefins
held considerable promise for the construction of molecular
complexity, we began to investigate an ARC tactic based on
[1,5]-silyl C(sp2) to O migrations (Figure 1).15 We reasoned
a
Conditions 1: (a) 2.0 equiv of n-BuLi, Et2O, −78 °C; (b) 2.0 equiv of
b
CuBr·DMS, HMPA/THF (1:1), rt; then (c) and (d). Conditions 2:
(a) 1.1 equiv of n-BuLi, THF, −78 °C; (b) 2.0 equiv of CuBr·DMS,
1.0 equiv of t-BuOK, HMPA, rt; then (c) and (d).
Figure 1. Previous and present work: union reaction exploiting
[1,5]-Brook rearrangements.
Table 2. Three-Component Coupling of Linchpin 14 via
ARC/CCR
that anchoring the requisite ARC functionality on a phenyl or
cyclohexyl ring in a 1,2 fashion would limit bond rotation
and thereby potentially enhance the [1,5]-Brook rearrange-
ment.
RESULTS AND DISCUSSION
■
To initiate this study, we prepared phenyl linchpin 14 via
Negishi cross coupling of (1-trimethylsilyl)-vinyl zinc with 2-
bromo-benzaldehyde (see Supporting Information). Our
initial conditions for the [1,5]-Brook rearrangement were
derived from our previous work involving [1,4]-silyl C(sp2)
to O migration,13 as well as from earlier observations of the
Takeda16 and Song groups.17 Specifically, after addition of 2
equiv of n-BuLi to aldehyde 14, the resulting lithium alkoxide
was added into a suspension of CuBr·DMS in HMPA and
THF (1:1) via cannula to trigger the Brook rearrangement,
presumably permitting the formation of a vinyl-cuprate.
Importantly, we subsequently discovered that in place of
adding 2 equiv of the required nucleophile, an additive (i.e.,
1 equiv of a tert-butoxide salt) could be employed to achieve
similar results, thus eliminating the need for 2 equiv of the
potentially valuable nucleophile. The vinyl-cuprate was then
subjected to alkylation with a variety of electrophiles to
furnish three-component adducts in modest to good yields
(Table 1).
The organocuprate generated from the [1,5]-Brook
rearrangement was next evaluated for cross coupling with
various electrophilic partners, employing Pd(PPh3)4 as the
catalyst (Table 2). Both electron-deficient and -rich aryl
iodides proved viable substrates under the ARC/CCR
protocol. Vinyl bromide could also be employed as the
cross-coupling partner to provide diene 16e. In addition to n-
BuLi, methyl, phenyl, 2-methyl vinyl, 2-furanyl, and 2-methyl-
1,3-dithianyl lithiums were examined as the initiating
nucleophile for the ARC process; all worked, leading to
the desired three-component adducts 16f−16j.
a
Conditions 1: (a) 2.0 equiv of nucleophile, Et2O, −78 °C; (b) 2.0
equiv of CuBr·DMS, HMPA/THF (1:1), rt; then (c) and (d).
b
Conditions 2: (a) 1.1 equiv of nucleophile, THF, −78 °C; (b) 2.0
equiv of CuBr·DMS, 1.0 equiv of t-BuOK, HMPA, rt; then (c) and
(d). For conditions 2, step b, 60 °C. for conditions 2, step a, rt.
c
d
Encouraged by the viability of the ARC alkylation and
cross coupling protocols exploiting a [1,5]-Brook rearrange-
B
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ment with phenyl linchpin 14, we turned to evaluate
cyclohexyl-based linchpins, constructed via conjugate addi-
tion18,19 of the vinyl-cuprate derived from 1720 to aldehyde
18 (Scheme 3); a 1:1 mixture of cis- and trans-linchpins (19
Table 4. Three-Component Coupling of Linchpin 19 via
ARC/Alkylation
Scheme 3. Preparation of Cyclohexyl Incorporated
Linchpins 19 and 20
and 20), separable via flash chromatography with the
stereochemistry assigned by NMR, and subsequent chemical
conversion (vide infra) resulted in a combined yield of 63%.
Importantly, cis-linchpin 19 could be readily converted to the
trans-congener (20) by treatment with DBU in MeOH.
With both cyclohexyl-linchpins (19 and 20) in hand, we
first conducted an optimization study with cis-cyclohexyl
linchpin 19 exploiting the conditions outlined in Table 3.
a
Conditions 1: (a) 2.0 equiv of n-BuLi, THF, −78 °C; (b) 2.0 equiv of
b
CuBr·DMS, HMPA/THF (1:1), 60 °C; then (c) and (d). Conditions
2: (a) 1.1 equiv of n-BuLi, THF, −78 °C; (b) 2.0 equiv of CuBr·DMS,
1.0 equiv of t-BuOK, HMPA, 60 °C; then (c) and (d).
Table 5. Three-Component Coupling of Linchpin 19 via
ARC/CCR
Table 3. Optimization of [1,5]-Brook Rearrangement with
cis Linchpin 19
a
n-BuLi
entry (equiv)
Cu(I)
(equiv)
additive
(equiv)
HMPA/
THF
ratio (21/
22/23)
T (h)
b
1
2
3
4
5
6
7
1.1
1.1
1.1
1.5
2.0
1.1
1.1
1:1
1:1
1:1
1:1
1:1
1:1
1:0
0.5
6
1:0: 0
1:0: 0
1.2
2.0
2.0
2.0
2.0
2.0
6
1:0.2:0.1
0.1:1: 0.7
0:1: 0
3
0.75
1.5
0.75
c
1.0
0.1:1: 0.7
0:1: 0
d
c
1.0
a
Ratio of major products (21/22/23) by NMR analysis of the reaction
b
mixture: values are reported as 0 if less than 0.05. Isolated yield for
product 21: 86%. t-BuOK. Isolated yield for product 22: 73%.
c
d
Compared to the phenyl linchpin (14), an increase in
reaction temperature was required to effectively trigger the
[1,5]-Brook rearrangement. Again, t-BuOK could be
employed to promote Brook rearrangement, thus saving 1
equiv of the nucleophile, although a longer reaction time was
required to complete the Brook process. In the case of the
TMS linchpin, the longer reaction time unfortunately resulted
in several side reactions (i.e., loss of TMS group and/or
decomposition of the vinyl-cuprate). To shorten the required
reaction time and thus side product formation, we increased
the solvent polarity to further promote the Brook rearrange-
ment efficiency (entry 7).
Continuing with the envisioned vinyl-cuprate intermediate
derived via the [1,5]-Brook rearrangement, we introduced an
electrophile to complete the tricomponent ARC tactic. As
with phenyl linchpin 14, the vinyl-cuprate was evaluated for
both alkylation (Table 4) and cross coupling (Table 5); both
reactions proceeded, leading to the three-component adducts
in modest to good yield.
a
Conditions 1: (a) 2.0 equiv of nucleophile, THF, −78 °C; (b) 2.0
equiv of CuBr·DMS, HMPA/THF (1:1), 60 °C; then (c) and (d).
b
Conditions 2: (a) 1.1 equiv of nucleophile, THF, −78 °C; (b) 2.0
equiv of CuBr·DMS, 1.0 equiv of t-BuOK, HMPA, 60 °C; then (c) and
(d).
Notably, nucleophilic additions to cis-linchpin 19 proved
highly diastereoselective (>20:1), yielding the Felkin−Anh
product,21 which was confirmed in the case of three-
component adduct 25h by X-ray analysis of the derived 4-
nitrobenzoic ester (26) (Figure 2).
We next extended the [1,5] ARC tactic to trans-linchpin
20. High Felkin−Anh selectivity upon addition of the
nucleophile to the aldehyde was achieved. The stereo-
chemistry of the isolated product was again confirmed by
C
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are summarized in Scheme 5, with the key structures
illustrated in Figure 3.
Scheme 5. Comparisons of [1,4]-Vinyl Brook
Rearrangements Involving Different Substrates and Copper
Reagents
Figure 2. Elucidation of relative configuration via X-ray analysis.
X-ray analysis of the p-nitrobenzoic ester derivative 27
(Figure 2).
The [1,5]-Brook rearrangement of trans-linchpin 20
however proved more challenging than the cis-linchpin. In
particular, difficulties were encountered in retaining the TMS
silyl group during the [1,5]-Brook protocol. As a result,
multiple alkylation byproducts were observed due to
competing O-alkylation when an electrophile was introduced.
To resolve this issue, we turned to the more robust TBS
counterpart 31, which was prepared in similar fashion as the
TMS linchpin (Scheme 4). As expected, loss of the silyl
Scheme 4. Synthesis and Evaluation of trans Linchpin 31
For the [1,4]-Brook rearrangement of substrate A having
an internal CC double bond (Scheme 5a), coordination of
the CuI to both the CC bond and oxygen atom of A
generates an intermediate Ac; this step is exergonic by 28.5
kcal/mol in THF. Subsequently, the oxygen atom attacks the
trimethylsilyl group via transition state TSA (Figure 3), in
which the forming O−Si bond distance is 1.85 Å and the
breaking C−Si bond is 2.37 Å, while the C−Cu distance is
decreased to 1.96 Å. The free energy barrier for this process
is 16.0 kcal/mol (from Ac to TSA). Importantly, the
resultant [1,4]-Brook rearrangement product Ap is more
stable than Ac by 6.3 kcal/mol.
As reported above, our experimental results demonstrate
that the [1,4]-Brook rearrangement is sensitive to the
position of CC double bond (Scheme 2). The computed
reaction pathway of the [1,4]-Brook rearrangement of B
having a terminal CC double bond with 1 equiv of CuI is
illustrated in Scheme 5b. In this case, the formation of
intermediate Bc via coordination of CuI to both the CC
bond and the oxygen atom of B is exergonic by 35.5 kcal/
mol, which is 7 kcal/mol more favorable than that of Ac
(−35.5 versus −28.5 kcal/mol). Subsequent [1,4]-Brook
group was no longer observed, but a higher reaction
temperature was required to trigger Brook rearrangement,
presumably due to the increased steric hindrance of the TBS
group. As mentioned earlier during the optimization of cis-
linchpin, longer reaction times resulted in multiple side
reactions. In this case, decomposition of a significant amount
of the vinyl-cuprate occurred. To decrease the reaction time,
we employed a 5 min pulse of microwave irradiation
(Biotage: high setting) at 100 °C. The derived vinyl-cuprate
was then employed for three-component unions, as
demonstrated by alkylation with benzyl bromide and CCR
with 4-iodobenzonitrile (Scheme 4).
To understand the mechanism and reactivity trends of the
[1,4]- and [1,5]-vinyl Brook rearrangements, we conducted
computational studies using DFT (M06 with solvation)
calculations,22,23 in which MeLi was used as a computational
model for the experimentally employed n-BuLi. First, three
[1,4]-vinyl Brook rearrangements were compared to reveal
the effect on the energetics of the position of the CC
double bond and the copper reagent employed. The results
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Figure 3. DFT-optimized structures of intermediates and transition states for [1,4]-vinyl Brook rearrangements; carbon gray, hydrogen white,
oxygen red, silicone yellow, lithium blue, copper green, and iodine purple.
rearrangement via transition state TSB requires an activation
free energy of 29.8 kcal/mol. This barrier is 13.8 kcal/mol
higher than that for Ac with an internal CC double bond
(29.8 versus 16.0 kcal/mol). As shown in Figure 3, the
coordination of the internal CC double bond forms a
strained C−Cu−O−C four membered ring in Ac, with C−
Cu and O−Cu distances of 2.10 and 2.22 Å. However, in the
Brook rearrangement transition state TSA, the corresponding
distances are significantly increased to 2.75 and 2.70 Å,
respectively. This indicates that there is remarkable strain-
release in transition state TSA, leading to a low barrier.24
However, when the position of the CC double bond is
changed from internal to terminal, the strained C−Cu−O−C
four membered ring in Ac evolves to an unstrained C−Cu−
O−C−C−C six membered ring in Bc. As a result, there is
no strain-release in transition state TSB, making the barrier
much higher, and in the product (Bp), which is even 0.2
kcal/mol less stable than Bc (−35.3 versus −35.5 kcal/mol).
This result explains why the [1,4]-Brook rearrangement of B
having a terminal CC double bond does not occur using 1
equiv of CuI.
is involved. Our calculations reveal that the most favorable
reaction between 1 equiv of MeLi with 2 equiv of CuX (X =
I or Br) is to form MeCu (eq 1),
MeLi + 2CuX → MeCu + Li+ + CuX−2
X = I
X = Br
ΔG = − 54.6 kcal/mol
ΔG = − 58.0 kcal/mol
(1)
which is exergonic by more than 50 kcal/mol in THF. This
suggests that under these reaction conditions, MeCu instead
of CuX will trigger Brook rearrangement.
In Scheme 5c, we outline the computed reaction pathway
of [1,4]-Brook rearrangement of B with 1 equiv of MeCu.
Here the MeCu is also coordinated by both the CC bond
and the oxygen atom of B to form intermediate Cc.
However, this process is much less exergonic than that using
CuI (−20.4 versus −35.5 kcal/mol). The subsequent [1,4]-
Brook rearrangement via transition state TSC thus requires
an activation free energy of 25.8 kcal/mol. This barrier is 4
kcal/mol lower than that using CuI (25.8 versus 29.8 kcal/
mol). According to the frontier molecular orbital (FMO)
analysis, the LUMO energies of CuI and MeCu are −15.3
and 1.3 kcal/mol, respectively. This indicates that CuI is a
much better electron acceptor than MeCu, leading to a much
stronger coordination or bonding interaction. As shown in
To achieve efficiency with the [1,4]-Brook rearrangement
of B, experiments demonstrate that 2 equiv of a Cu(I) salt
and a second equivalent of lithium reagent are required
(Scheme 2). However, it was not clear what copper reagent
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Figure 3, the geometries of intermediates Bc and Cc, and
transition states TSB and TSC are very similar. In the Brook
rearrangement transition state TSB or TSC, one C−Cu bond
(TSB, 1.96 Å; TSC, 1.97 Å) is forming, and one O···Cu and
the other C···Cu coordinations (shown as green lines in the
right structures of Figure 3) disappear. When MeCu is
employed instead of CuI, two weaker O···Cu and C···Cu
interactions are needed to be overcome in the transition
state, although one weaker C−Cu bond is forming. Overall,
this decreases the barrier for the Brook rearrangement.
Therefore, the alkyl cuprate is more active than the Cu(I)
salt to trigger Brook rearrangement, in agreement with the
experimental results.
Scheme 6. Comparisons of [1,5]-Vinyl Brook
Rearrangements Involving Different Substrates
Four [1,5]-vinyl Brook rearrangements were next com-
pared to reveal the role of the conformational constraints of
substrates. The results are summarized in Scheme 6, with the
key structures illustrated in Figure 4.
For the MeCu mediated [1,5]-Brook rearrangement of
substrate D having a terminal CC double bond (Scheme
6a), the reaction free energy for the coordination step is
−20.1 kcal/mol, which is very close to that of [1,4]-Brook
rearrangement substrate C (−20.4 kcal/mol, Scheme 5c).
However, the barrier for the [1,5]-Brook rearrangement is 3.7
kcal/mol higher than that for the [1,4] reaction (29.5 versus
25.8 kcal/mol). As shown in Figures 3 and 4, the forming
and breaking bond distances in transition states TSC and
TSD are almost identical; the main difference is the
conformational change of the tether. In intermediate Dc,
the dihedral angle along the (CH2)2 tether is −73.2°, but this
angle becomes −57.9° in transition state TSD. This means a
15.3° conformational change, requiring additional energy as
compared to [1,4]-Brook rearrangement from Cc to TSC, in
which the tether is CH2 without the dihedral angle change.
This explains why efficient [1,5]-Brook rearrangements are
more challenging.
In Scheme 6b−d, we illustrate the computed reaction
pathways of the three experimentally studied [1,5]-vinyl
Brook rearrangements involving phenyl, cis-cyclohexyl, and
trans-cyclohexyl linchpins. The activation free energies for
these rearrangements are 23.3 (from Ec to TSE), 25.6 (from
Fc to TSF), and 29.7 (from Gc to TSG) kcal/mol,
respectively. This reactivity trend is in accordance with the
increase in reaction temperature for Brook rearrangement
observed experimentally. More importantly, the calculations
demonstrate that there is a good correlation between the
conformational change of the tether and the barrier for the
[1,5]-Brook rearrangement. As illustrated in Figure 4, when
the tether is switched from phenyl, to cis-cyclohexyl, and to
trans-cyclohexyl, the corresponding conformational change is
increased from 4.8° (from −1.4° to −6.2°), to 6.1° (from
−41.4° to −47.5°), and to 13.5° (from 39.8° to 53.3°).
Consequently, the barrier is increased from 23.3 to 25.6 and
29.7 kcal/mol (Scheme 6b−d). These results indicate that
using the tether with conformational constraints can
efficiently lower the [1,5]-Brook rearrangement barrier.
that introduction of an additional amount of organolithium
or t-BuOK as additive lowers the energy barrier to facilitate
the requisite Brook rearrangement. As such, this ARC
protocol now holds considerable synthetic promise for the
rapid elaboration of advanced intermediates for complex
molecule synthesis.
CONCLUSIONS
■
In summary, we have achieved extension of the ARC tactic
exploiting more challenging [1,5]-Brook rearrangements with
a series of conformationally anchored bifunctional vinyl
linchpins. Phenyl, cis-cyclohexyl, and trans-cyclohexyl linch-
pins were systematically evaluated via both experimental and
computational approaches. Of importance, we demonstrated
F
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Figure 4. DFT-optimized structures of intermediates and transition states for [1,5]-vinyl Brook rearrangements; carbon gray, hydrogen white,
oxygen red, silicone yellow, lithium blue, and copper green.
ORCID
ASSOCIATED CONTENT
■
K. N. Houk: 0000-0002-8387-5261
Yong Liang: 0000-0001-5026-6710
Amos B. Smith III: 0000-0002-1712-8567
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/jacs.7b04149.
Notes
Experimental procedures and computational details
(PDF)
The authors declare no competing financial interest.
NMR spectra for obtained compounds (PDF)
X-ray data for compound 26 (CIF)
X-ray data for compound 27 (CIF)
ACKNOWLEDGMENTS
■
Financial support was provided by the National Institutes of
Health (National Cancer Institute) through Grant No. CA-
19033 and the National Science Foundation (CHE-1361104).
Y.L. thanks the National Thousand Young Talents Program
and Jiangsu Specially-Appointed Professor Plan in China for
financial support. We also thank China Scholarship Council
for a scholarship for Q.L. We thank Drs. George Furst and
Jun Gu and Dr. Rakesh Kohli at the University of
AUTHOR INFORMATION
■
Corresponding Authors
*yongliang@nju.edu.cn
*smithab@sas.upenn.edu
G
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Eschenmoser, A.; Newhouse, T. R.; Baran, P. S.; Houk, K. N. J. Org.
Chem. 2013, 78, 4037.
Pennsylvania for help in obtaining the NMR and high-
resolution mass spectral data, respectively, and Dr. Patrick J.
Carroll for X- ray crystallographic data.
REFERENCES
■
(1) Smith, A. B.; Xian, M. J. Am. Chem. Soc. 2006, 128, 66.
(2) Brook, A. G. Acc. Chem. Res. 1974, 7, 77.
(3) Seebach, D.; Corey, E. J. J. Org. Chem. 1975, 40, 231.
(4) Fischer, M. R.; Kirschning, A.; Michel, T.; Schaumann, E.
Angew. Chem., Int. Ed. Engl. 1994, 33, 217.
(5) Tietze, L. F.; Geissler, H.; Gewert, J. A.; Jakobi, U. Synlett
1994, 1994, 511.
(6) For reviews on anion relay chemistry, see: (a) Smith, A. B., III;
Adams, C. M. Acc. Chem. Res. 2004, 37, 365. (b) Smith, A. B., III;
Wuest, W. M. Chem. Commun. 2008, 5883.
(7) Sokolsky, A.; Wang, X.; Smith, A. B. Tetrahedron Lett. 2015,
56, 3160.
(8) Han, H.; Smith, A. B. Org. Lett. 2015, 17, 4232.
(9) Melillo, B.; Chen, M. Z.; Forestieri, R.; Smith, A. B. Org. Lett.
2015, 17, 6242.
(10) Ai, Y.; Kozytska, M. V.; Zou, Y.; Khartulyari, A. S.; Smith, A.
B. J. Am. Chem. Soc. 2015, 137, 15426.
(11) Nguyen, M. H.; Imanishi, M.; Kurogi, T.; Smith, A. B. J. Am.
Chem. Soc. 2016, 138, 3675.
(12) Devarie-Baez, N. O.; Kim, W.-S.; Smith, A. B.; Xian, M. Org.
Lett. 2009, 11, 1861.
(13) Smith, A. B.; Kim, W.-S.; Tong, R. Org. Lett. 2010, 12, 588.
(14) Taguchi, H.; Takami, K.; Tsubouchi, A.; Takeda, T.
Tetrahedron Lett. 2004, 45, 429.
(15) For previous success of a coupling reaction exploiting [1,5]-
Brook rearrangement, see: (a) Smith, A. B.; Xian, M.; Kim, W.-S.;
Kim, D.-S. J. Am. Chem. Soc. 2006, 128, 12368. (b) Gao, L.; Lu, J.;
Song, Z.; Lin, X.; Xu, Y.; Yin, Z. Chem. Commun. 2013, 49, 8961.
(16) Tsubouchi, A.; Itoh, M.; Onishi, K.; Takeda, T. Synthesis
2004, 2004, 1504.
(17) Yan, L.; Sun, X.; Li, H.; Song, Z.; Liu, Z. Org. Lett. 2013, 15,
1104.
(18) Corey, E. J.; Boaz, N. W. Tetrahedron Lett. 1985, 26, 6015.
(19) Zou, Y.; Melvin, J. E.; Gonzales, S. S.; Spafford, M. J.; Smith,
A. B. J. Am. Chem. Soc. 2015, 137, 7095.
(20) Boeckman, R. K. J.; Blum, D. M.; Ganem, B.; Halvey, N. Org.
Synth. 1978, 58, 152.
(21) Anh, N. T.; Eisenstein, O. Tetrahedron Lett. 1976, 17, 155.
(22) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci,
B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian,
H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.;
Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida,
M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.;
Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.;
Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi,
R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.;
Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene,
M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.;
Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi,
R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.;
Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.;
Dapprich, S.; Daniels, A. D.; Farkas, O.; Foresman, J. B.; Ortiz, J.
V.; Cioslowski, J.; Fox, D. J. Gaussian 09, revision D.01; Gaussian,
Inc.: Wallingford, CT, 2009.
(23) Geometry optimizations and frequency calculations were
performed at the M06/6-31G(d)[SDD, for Cu, Br, and I] level.
Single-point energy calculations in THF using the CPCM model
were performed at the M06/6-311+G(d,p)[SDD, for Cu, Br, and I]
level. For details, see the SI.
(24) (a) Hong, X.; Liang, Y.; Griffith, A. K.; Lambert, T. H.;
Houk, K. N. Chem. Sci. 2014, 5, 471. (b) Zou, L.; Paton, R. S.;
H
DOI: 10.1021/jacs.7b04149
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX