Mechanism and the origins of stereospecificity in copper-catalyzed ring expansion of vinyl oxiranes: A traceless dual transition-metal-mediated process

Article abstract of DOI:10.1021/ja310065z

Density functional theory computations of the Cu-catalyzed ring expansion of vinyloxiranes is mediated by a traceless dual Cu(I)-catalyst mechanism. Overall, the reaction involves a monomeric Cu(I)-catalyst, but a single key step, the Cu migration, requires two Cu(I)-catalysts for the transformation. This dual-Cu step is found to be a true double Cu(I) transition state rather than a single Cu(I) transition state in the presence of an adventitious, spectator Cu(I). Both Cu(I) catalysts are involved in the bond forming and breaking process. The single Cu(I) transition state is not a stationary point on the potential energy surface. Interestingly, the reductive elimination is rate-determining for the major diastereomeric product, while the Cu(I) migration step is rate-determining for the minor. Thus, while the reaction requires dual Cu(I) activation to proceed, kinetically, the presence of the dual-Cu(I) step is untraceable. The diastereospecificity of this reaction is controlled by the Cu migration step. Suprafacial migration is favored over antarafacial migration due to the distorted Cu π-allyl in the latter.

Full text of DOI:10.1021/ja310065z

Article
pubs.acs.org/JACS
Mechanism and the Origins of Stereospecificity in Copper-Catalyzed
Ring Expansion of Vinyl Oxiranes: A Traceless Dual Transition-Metal-
Mediated Process
†
‡
,§
,†
Thomas J. L. Mustard, Daniel J. Mack, Jon T. Njardarson,* and Paul Ha-Yeon Cheong*
†
Department of Chemistry, Oregon State University, 153 Gilbert Hall, Corvallis, Oregon 97331-4003, United States
‡
Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, New York 14850, United States
Department of Chemistry and Biochemistry, University of Arizona, 1306 East University Boulevard, Tucson, Arizona 85721, United
§
States
*
S Supporting Information
ABSTRACT: Density functional theory computations of the
Cu-catalyzed ring expansion of vinyloxiranes is mediated by a
traceless dual Cu(I)-catalyst mechanism. Overall, the reaction
involves a monomeric Cu(I)-catalyst, but a single key step, the
Cu migration, requires two Cu(I)-catalysts for the trans-
formation. This dual-Cu step is found to be a true double
Cu(I) transition state rather than a single Cu(I) transition state
in the presence of an adventitious, spectator Cu(I). Both Cu(I)
catalysts are involved in the bond forming and breaking
process. The single Cu(I) transition state is not a stationary
point on the potential energy surface. Interestingly, the reductive elimination is rate-determining for the major diastereomeric
product, while the Cu(I) migration step is rate-determining for the minor. Thus, while the reaction requires dual Cu(I) activation
to proceed, kinetically, the presence of the dual-Cu(I) step is untraceable. The diastereospecificity of this reaction is controlled by
the Cu migration step. Suprafacial migration is favored over antarafacial migration due to the distorted Cu π-allyl in the latter.
1
. INTRODUCTION
Table 1. Copper-Catalyzed Rearrangement of Vinyloxirane
1
a
Cooperative or dual catalysis has become popular in recent
literature; dual organocatalyzed, organo- and transition-metal-
catalyzed, homobimetallic transition-metal-catalyzed, and
even heterobimetallic-catalyzed processes are known. We
have previously reported a simple and scalable Cu(II)-catalyzed
synthetic method for the preparation of dihydrofurans (DHFs)
1
2
3
4
5
entry conditions temp (°C) time (h) conv. (%) DHF:H-shift
6
a,b
7
from vinyloxiranes (VOs)
(Table 1), key structural
1
2
3
4
5
6
7
8
9
A
B
C
A
B
C
A
B
C
150
150
150
100
100
100
80
0.25
0.25
0.25
4
100
100
100
no rxn
84
13:1
components found in natural products, bulk commodity
chemicals, and pharmaceuticals. Herein, we report the complete
mechanism and the origins of diastereospecificity for this
transformation. Specifically, we propose an unusual, traceless
dual catalysis motif. A key step in this reaction requires two
Cu(I)-catalysts, but the rate-determining step only requires a
single catalyst. Ultimately, this renders the dual catalysis motif
kinetically undetectable but crucial for the chemistry.
17:1
15:1
N/A
4
>20: 1
>20: 1
N/A
4
65
10
10
10
no rxn
89
80
>20: 1
>20: 1
80
70
a
Conditions: (A) 5 mol % Cu(hfacac) ; (B) 5 mol % Cu(hfacac) + 5
2
2
2. EXPERIMENTAL SECTION
mol % Sn(2-ethylhexanoate) ; (C) 5 mol % Cu(hfacac)(COD).
2
6
As previously reported, Cu(hfacac) catalyzes the transformation of
2
vinyloxirane 1 to dihydrofuran 2. In these reactions, a significant initial
induction period was observed, suggesting that a more active catalyst
was being formed in situ. We have since discovered that this ring
expansion reaction is significantly accelerated by the use of Cu(I)
catalysts. This was accomplished using reducing agents such as Sn(II)-
observed, and ring expansions could be run at lower temperatures
(
Table 1). All conditions perform similarly at 150 °C (entries 1−3),
but at 100 or 80 °C the Cu(II) conditions (A) fail (entries 4 and 7),
while the new Cu(I) catalyzed conditions successfully ring expand 1 to
8
a
8b
2
-ethylhexanoate and cobaltocene, or alternatively by using
preformed Cu(I) catalysts such as Cu(hfacac)(cod). Employing
9
Received: October 16, 2012
either one of these conditions, significant reaction acceleration was
©
XXXX American Chemical Society
A
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Article
7
Figure 1. Reaction coordinate of Cu(I)-catalyzed ring expansion of cis-2,3-epoxy-trans-4-hexene (cis-2-methyl-trans-3-propenoxirane) (above) and
structures of stationary points along the reaction coordinate for the formation of the major products (below). All structures, energies, and free energy
1
0a−d
corrections computed at the B3LYP/def2-SVP level of theory, as implemented in Turbomole.
Å. Computed structures rendered using Pymol.
Energies displayed in kcal/mol, and distances in
10e
B
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Figure 2. Complete catalytic cycle for the Cu(I)-catalyzed stereospecific rearrangement of vinyloxiranes to dihydrofurans.
selectively form 2 (entries 5−6 and 8−9). Equally important evidence
reported. Stationary points were verified by frequency calculations and
wave function stability tests.
in favor of Cu(I)-catalysis was the absence of the initial induction
6a,7,8a,9
period previously observed in all Cu(hfacac) kinetic traces.
2
Similar Cu(I) supportive insights were also observed for the analogous
vinylaziridine expansion.
4
. RESULTS AND DISCUSSION
9
Initially, the entire reaction coordinate involving a single Cu(I)-
catalyst was computed. The catalytic cycle begins with the
initial exothermic complexation of a free Cu(I) catalyst with a
substrate alkene. Oxidative epoxide ring opening affords the s-
trans-metalaoxetane. Upon isomerization to s-cis-metalaoxetane,
the copper is poised for migration to the distal olefin carbon.
However, computations showed that this key Cu(I)-migration
step to form the metalaoxinane is not a stationary point on the
3
. METHODS
The geometries and thermal corrections for all stationary points along
the reaction coordinate were computed with the B3LYP and the def2-
SVP basis set, as implemented in the Turbomole suite of programs.
Manual, exhaustive conformational searches, including all possible
single or dual Cu ligation isomers, were performed for all species
1
0
C
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potential energy surface with a single Cu(I) catalyst. If the
metalaoxinane could be produced, the system would undergo
reductive elimination to afford the dihydrofuran product.
In the monocopper migration process, the endocyclic
Cu(III) migrates to the distal olefin carbon to form the
metalaoxinane directly. However, shortening the Cu−C bond
along the expected reaction coordinate results in the
reformation of the oxirane ring, reverting back to the starting
VO−Cu complex. In sharp contrast, a dual Cu(I)-catalyzed
migration step to form the metalaoxinane was a true stationary
point along the reaction coordinate. In the dual-copper process,
the exocyclic Cu(I) migrates to the distal olefin carbon forming
the metalaoxinane. These computational evidence collectively
suggest that this dual Cu step is distinctly different from a single
Cu mechanism in the presence of an adventitious, spectator
Cu(I); the second Cu(I) is essential for this transformation.
This reaction involves both single and dual copper
Diastereodifferentiation arises at the copper migration
(Figure 3). The migration of the exocyclic Cu(I) to the olefin
12
intermediates and transition states (Figures 1 and 2). The
reaction coordinate diagram as well as the computed structures
for the formation of the major product is shown in Figure 1.
The complete detailed catalytic cycle is shown in Figure 2. The
resting state of the catalytic process is the cyclic substrate−
catalyst−product−catalyst complex I. Both Cu(I) catalysts are
found to be square pyramidal, coordinating to the π-systems of
a substrate or product and an oxygen of another substrate or
product. The dissociation of this complex to the monocopper
vinyl oxirane complex is endothermic by 2.3 kcal/mol. In the
oxidative epoxide ring opening TS-II, the Cu(I)-hfacac inserts
into the epoxide C−O bond. The metalaoxetane Cu(III) is also
in a square planar configuration, with the coordinating C, O,
and the hfacac in the plane. Upon complexation of a free Cu(I)
catalyst to the metalaoxetane oxygen, the s-trans/s-cis isomer-
ization of this species affords the dual-copper s-cis-metal-
aoxetane III. In the following copper migration TS-IV, the
exocyclic Cu(I) migrates to the distal olefin carbon, forming the
metalaoxinane, while simultaneously breaking the metalaox-
13
etane C−Cu bond. This metalaoxinane V is in an envelope
conformation with the newly formed metalaoxinane endocyclic
Cu(III) puckered. The dissociation of the exocyclic oxygen
bound Cu(I) leads to the reductive elimination of TS-VI,
closing the ring to produce the DHF product and regenerating
the Cu(I) catalyst.
The title reaction is diastereospecific: E-cis and Z-trans yield
Figure 3. Dual Cu(I) migration transition structures leading to the
major and minor products, computed at the B3LYP/def2-SVP level of
the trans-DHF product, whereas the E-trans and Z-cis yield the
1
0a−d
6a,11
theory, as implemented in Turbomole.
π-allyl atoms are
cis-DHF product (Scheme 1).
The complete reaction
highlighted in green. Energies displayed in kcal/mol, distances in Å,
and dihedrals in degrees. Computed structures rendered using
coordinate of the Cu(I)-catalyzed rearrangement involving all
VOs shown in Scheme 1 were computed and are included in
the Supporting Information. In all cases, computations
reproduce the experimental diastereoselectivities.
10e
Pymol.
can be either suprafacial or antarafacial to the breaking
endocyclic Cu(III)−C bond. The major pathway proceeds
through the energetically preferred suprafacial copper migra-
tion, while the minor pathway proceeds through the disfavored
antarafacial migration. In all cases, suprafacial rearrangements
were energetically more favorable than the antarafacial. In the
case shown in Figure 3, the preference for the suprafacial
migration was 7.7 kcal/mol. This is because (1) the antarafacial
transition structure is destabilized by the loss of conjugation in
the nonplanar π-allyl. This distortion (39° from planarity) is
necessary to realize Cu(I)-catalyst migration to the distal
prochiral face of the π-allyl (Figure 3, highlighted in green).
Analogous distortion from planarity in the parent allyl anion
corresponds to 4.6 kcal/mol of destabilization. (2) The rest of
a
Scheme 1. Diastereospecificity of the Title Reaction
a
E-cis and Z-cis yield the trans-DHP product, whereas the E-trans and
6a,11
Z-trans yield the cis.
D
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the selectivity most likely arises from the strains in the Cu
bonds.
Interestingly, the rate-determining steps are different for the
formation of the major and minor diastereomeric products. The
computed barriers suggest that the dual-Cu(I) migration step is
not rate determining for the formation of the major product
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5. CONCLUSION
In summary, we have used computations and experiments to
elucidate the complete mechanism and origins of the
diastereospecificity of a Cu(I)-catalyzed rearrangement of
vinyloxiranes to dihydrofurans. DFT computations reveal that
an unusual, traceless dual transition-metal-mediated process is
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ASSOCIATED CONTENT
Supporting Information
■
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(7) See Supporting Information.
Cartesian coordinates, energies, and reaction coordinate
diagrams. Detailed explanation of relative energies between
monomeric and dual copper species also included. This
material is available free of charge via the Internet at http://
pubs.acs.org.
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AUTHOR INFORMATION
Corresponding Author
paulc@science.oregonstate.edu; njardars@email.arizona.edu
■
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C.; Yang, W.; Parr, R. G. Phys. Rev. B 1998, 37, 785−789. (c) Schafer,
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11) The Z-cis/trans substrates afford ketones as the major product,
̈
̈
̈
Notes
̈
The authors declare no competing financial interest.
(
as a result of a competing hydride shift mechanism.
(12) Conversion between monomeric and dual copper species is
shown in the Supporting Information.
(13) For the unsubstituted VO the suprafacial Cu migration is
stepwise. Cu attacks the allyl, forming a tricyclic intermediate followed
by Cu-allyl dissociation to form the metalaoxinane intermediate. In
contrast, the antarafacial copper migration is concerted. See
Supporting Information.
ACKNOWLEDGMENTS
We thank the NSF (CHE-0848324 to J.T.N.) and Oregon State
University (P.H.Y.C.) for financial support.
■
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