Ligand exchange in mixed organocuprate(I) π-complexes

Article abstract of DOI:10.1021/om3006646

π-Complexes of mixed organocuprate(I) reagents with α,β- unsaturated carbonyl compounds can undergo ligand exchange to give the corresponding homocuprate-olefin π-complexes. The mechanism of this metathesis, which has profound implications for synthetic applications, involves a second-order reaction of the mixed cuprate with the mixed cuprate-olefin π-complex.

Full text of DOI:10.1021/om3006646

Communication
pubs.acs.org/Organometallics
Ligand Exchange in Mixed Organocuprate(I) π‑Complexes
Steven H. Bertz,* Kelsey L. Browder, Richard A. Hardin, Michael D. Murphy, Craig A. Ogle,*
and Andy A. Thomas†
Department of Chemistry, University of North CarolinaCharlotte, Charlotte, North Carolina 28223, United States
S
* Supporting Information
ABSTRACT: π-Complexes of mixed organocuprate(I) re-
agents with α,β-unsaturated carbonyl compounds can undergo
ligand exchange to give the corresponding homocuprate−olefin
π-complexes. The mechanism of this metathesis, which has
profound implications for synthetic applications, involves a
second-order reaction of the mixed cuprate with the mixed
cuprate−olefin π-complex.
Scheme 1. Formation and Metathesis of the Me(PhS)CuLi−
Chalcone Complex 2a
he current renaissance in organocopper chemistry is being
led by mixed cuprates R(R′)CuLi and the related
T
organocopper(I) compounds R(L)Cu, where R′ is an anionic
“dummy” ligand (alkynyl, phenylthio, thienyl, etc.) and L is a
neutral ligand (phosphine, thioether, pyridine, etc.).1,2 Anionic
or neutral, the auxiliary ligands R′ and L promote solubility and
thus reactivitywith the prerequisite that they are not
transferred to the substrate under ordinary conditions. These
special organocopper reagents are critically important when the
R group is valuable, since homocuprates R2CuLi only transfer
one of the R groups in most applications.
We have recently shown that several popular mixed cuprates
exhibit a powerful orientation effect in π-complexes, where the
auxiliary ligand R′ is oriented toward the carbonyl or other
activating group.3 This orientation places the transferred group
R in close proximity to the usual site of addition. During the
course of these studies, we noted that some of the mixed
cuprate π-complexes tended to metathesize to the correspond-
ing homocuprate complexes. Considering the importance of
mixed cuprates in the burgeoning field of asymmetric
induction,1,2 we decided to investigate the ligand exchange
phenomenon in more detail.
For kinetic studies we chose Posner’s Me(PhS)CuLi,4 since
the precursor, PhSCu, is commercially available and the cuprate
is free of LiI, which is present when mixed cuprates are
prepared from CuI (vide infra). Organocuprates and their
complexes are known to form aggregates with lithium halides,5
which is a potential complicating factor for the kinetics.
Chalcone (1a), diethyl fumarate (1b; DEF), and methyl vinyl
ketone (1c; MVK) were chosen as substrates, since they are
structurally diverse and give stable π-complexes with a range of
mixed cuprates,3 as well as the homocuprate, Me2CuLi.6,7
For the kinetics measurements, the substrate (20−40 μmol)
was dissolved in THF-d8 and injected into a solution of the
cuprate in THF-d8/benzene-d6 (7:1, 420 μL, 30 μmol) at −100
°C, using our usual rapid injection methodology (30−60 μL
injection).3,6,7 When equilibrium had been established, the
temperature was increased rapidly to −80 °C, and after 2 min
to allow for thermal equilibration and magnetic field shimming,
□
Figure 1. Conversion of Me(PhS)CuLi−chalcone complex 2a ( ) to
○
△
Me2CuLi−chalcone complex 3a ( ). Substrate ( ) and mixed
cuprate ( ) data are also plotted. The continuous curves are
◇
calculated by a least-squares method (see text).
1
single-pulse H NMR spectra were collected. The reaction of
1a with Me(PhS)CuLi is shown in Scheme 1, and the resulting
concentration versus time curves are plotted in Figure 1.
Special Issue: Copper Organometallic Chemistry
Received: July 15, 2012
Published: October 29, 2012
© 2012 American Chemical Society
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Organometallics
Communication
Chart 1 contains the basic kinetic scheme used to fit the data
from all runs. For the reaction in Scheme 1, MC =
Me(PhS)CuLi, Sub = 1a, MC−Sub = 2a, and HC−Sub = 3a.
The theoretical curves plotted in Figure 1 were calculated using
Mathcad and a global least-squares program in which the initial
concentrations were set and the values of k1, k−1, and k2 were
varied. Optimal values for the rate constants were k1 = 0.016
min−1 mM−2, k−1 = 3.0 min−1 mM−1 and k2 = 0.0035 min−1
mM−2.
mixed cuprate. The first mixed cuprate reagents were based on
alkynes; however, they were much less reactive than the
corresponding homocuprates, which is why there has been a
great deal of subsequent research to find more reactive mixed
cuprates.2−4 We chose Corey’s second-generation alkynylcup-
rate CH3(R″CC)CuLi (R″ = CH3O(CH3)2C) for further
study.8
The Corey cuprate was prepared from the corresponding
alkynyllithium reagent and MeCu, derived from CuI.8 When 1c
in THF-d8 was injected as usual into a solution of Corey’s
cuprate in THF-d8/benzene-d6 at −100 °C, the product was
complex 2c, which underwent metathesis at this temperature to
give the corresponding homocuprate complex 3c (Scheme 3;
N.B.: it was not necessary to warm the sample to −80 °C in this
case). Figure 3 shows stacked 1H NMR spectra for the reaction
in Scheme 3.
Chart 1. Metathesis Mechanism for Mixed Cuprate
Complexes
Scheme 3. Formation and Metathesis of the Me(R″C
C)CuLi−MVK Complex 2c
When the kinetics experiment was repeated with 1b as the
substrate (Scheme 2), the reaction was significantly slower,
since DEF forms much “tighter” π-complexes than chalcone.6
Complexes 2b and 3b each had major and minor species, which
were integrated together. The data are plotted in Figure 2, and
optimal values for the rate constants are k1 = 0.025 min−1
mM−2, k−1 = 0.0040 min−1 mM−1, and k2 = 0.000 90 min−1
mM−2, calculated using the global least-squares method.
Scheme 2. Formation and Metathesis of the Me(PhS)CuLi−
DEF Complex 2b
Figure 3. Stacked 1H NMR spectra (Me−Cu region, 4 min apart) for
the conversion of 2c (−0.41 ppm) to 3c (major, −0.27, −1.01 ppm;
minor, −0.08, −0.94 ppm). Mixed cuprate appears at −1.06 ppm in
the initial spectrum.
Only one mixed cuprate π-complex, 2c, was observed;
however, the presence of LiI gave rise to major complex 3c and
minor complex 3c·LiI,3,6 which were integrated together. The
global least-squares fit gave k1 = 0.15 min−1 mM−2, k−1 = 0.20
min−1 mM−1, and k2 = 0.030 min−1 mM−2. In this case the data
were not quite as good as the previous two examples, owing to
the usual complications observed with MVK.3 Nevertheless, the
kinetic data are consistent with the mechanism in Chart 1 and
not an alternative mechanism involving two molecules of 2c.
In summary, popular phenylthio and alkynyl mixed cuprates
and typical α,β-unsaturated carbonyl compounds give π-
complexes that undergo a facile ligand exchange reaction to
generate the corresponding homocuprate π-complexes. The
metathesis was more rapid with excess mixed cuprate, and it
was arrested by excess substrate. Conditions that favor fast
reductive elimination may serve to minimize this complication.
In some applications the homocuprate complex may well be the
key intermediate for subsequent product formation.
□
Figure 2. Conversion of Me(PhS)CuLi−DEF complex 2b ( ) to
○
△
Me2CuLi−DEF complex 3b ( ). Substrate ( ) and mixed cuprate
◇
(
) data are also plotted. The continuous curves are calculated by a
least-squares method (see text).
The reaction of Me(PhS)CuLi with 1c was too fast to get
useful kinetic data; therefore, we looked for a less reactive
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Communication
ASSOCIATED CONTENT
* Supporting Information
Figures and a table giving typical spectra, raw data, and sample
calculations. This material is available free of charge via the
Internet at http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
*E-mail: sbertz1@uncc.edu (S.H.B.); cogle@uncc.edu
(C.A.O.).
■
Present Address
†Department of Chemistry, University of Illinois at Urbana−
Champaign, Champaign, IL 61820.
Author Contributions
The manuscript was written through contributions of all
authors. All authors have given approval to the final version of
the manuscript.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank the National Science Foundation for support of this
work via Grant Nos. 0353061 and 0321056.
■
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