Rapid injection NMR in mechanistic organocopper chemistry. Preparation of the elusive copper(III) intermediate

Article abstract of DOI:10.1021/ja067533d

A copper(III) intermediate has been proposed to be crucially involved in many reactions of organocopper reagents, for example, with ∞-enones, alkyl halides, and allylic carboxylates. By using rapid injection NMR (RI-NMR), we have been able to prepare the first example of this elusive species under conditions where it is stable for extended periods of time. Extensive NMR investigations establish its structure and include two-bond ¹³C-¹³C coupling constants ²J across copper, measured on ¹³C-labeled material. Especially noteworthy is the extremely deshielded nature of the methyl C atoms attached to Cu, as indicated by the downfield ¹³C NMR shifts of 12.43 and 25.31 ppm. Large trans couplings, ²J = 38.1 Hz (upfield methyl-ring methine) and ²J = 35.4 Hz (downfield methyl-cyano), are consistent with a square planar complex. Copyright

Full text of DOI:10.1021/ja067533d

Published on Web 05/17/2007
Rapid Injection NMR in Mechanistic Organocopper Chemistry. Preparation of
the Elusive Copper(III) Intermediate1
Steven H. Bertz,*,† Stephen Cope, Michael Murphy,* Craig A. Ogle,* and Brad J. Taylor
Department of Chemistry, UniVersity of North CarolinasCharlotte, Charlotte, North Carolina 28223
Received October 20, 2006; E-mail: sbertz@complexitystudycenter.org; cogle@uncc.edu
Following the pioneering work of Gilman,2 House,3-5 White-
sides,4,5 Corey,6,7 Posner,6,8 and a phalanx of other researchers,9-11
organocopper reagents are now a vital part of many of the
synthetic methods that organic chemists depend upon to selectively
form carbon-carbon bonds. Paradigmatic examples include con-
jugate addition to R-enones,3,4 SN2-like reactions of organic
halides,5,6 and SN2′ reactions of allylic carboxylates.12 The seminal
step that forges the carbon-carbon link in these and related
organocopper reactions has long been posited to be reductive
Figure 1. Representations of copper(III) intermediate 1 in the form of its
contact ion pair. For the solvent-separated ion pair, see ref 22.
elimination from a putative copper(III) intermediate,3,5,8,12-18 where
the prospective partners have been brought together in a cis
relationship. Both square planar15-18 and T-shaped19 complexes have
been proposed.
Scheme 1. Two Routes to Copper(III) Intermediate 1
We have previously reported that rapid injection NMR
(RI-NMR) is an excellent way to access highly reactive and
thermally unstable species.20 By using RI-NMR in conjunction with
a typical substrate, 2-cyclohexenone 2, and common Gilman
reagents, Me2CuLi‚LiI 3a or Me2CuLi‚LiCN 3b, we have now
been able to prepare the first example of this crucial intermediate,
lithium cyanobis(methyl)(3-trimethylsiloxycyclohex-2-en-1-yl)cu-
prate(III) 1 (Figure 1). Moreover, we have found conditions
under which it is stable indefinitely and can therefore be studied
in great detail. In 1995, Snyder unequivocally predicted that it
should be possible to prepare and characterize such a species,21
and the latest calculations from his group underpin our conclu-
sions.22
Before our introduction of RI-NMR into organocopper chemistry,
procedure of Corey and Boaz,7 who treated iodo-Gilman reagents
with TMSCl before adding R-enones, our experiment gave a
serendipitously different result: the TMSCl reacted rapidly with
the LiCN present in 3b25 and quantitatively generated chloro-Gilman
reagent Me2CuLi‚LiCl and TMSCN in situ. Then, a second injection
introduced a THF-d8 solution of 2, which underwent essentially
complete conversion to 1.
A number of formally Cu(III) compounds are known,26 but
only a few of them involve Cu-C bonds. Examples include
difluoromethyl27 and trifluoromethyl derivatives,28 diazamacrocy-
clic29 and triazamacrocyclic complexes,30 and a bis(dicarbollide)
sandwich.31 Most of the characterized Cu(III) complexes are square
planar, and theoretical calculations indicate this geometry for our
case as well.22
relatively stable π-complexes had been prepared from cinnamate
esters23 and 10-methyl-∆1,9-2-octalone.24 However, conventional
techniques were not sufficient to prepare “clean” solutions of
π-complexes from substrate 2. By using rapid injection, a solution
of 2 was introduced directly into the NMR tube containing 3a or
3b, spinning in the spectrometer probe under nitrogen at -100 °C,
where we were able to prepare highly reactive π-complexes 4 and
4‚LiX (X ) I, CN) and study them spectroscopically.20 Now, we
have investigated the chemical reactivity of these π-complexes by
making a second rapid injection, and this has led us to the efficient
preparation of 1.
Two routes can be used to prepare 1 (Scheme 1), both of which
are made possible by the double application of the rapid injection
technique. In route A, a solution of iodo-Gilman reagent 3a in THF-
d8 in an NMR tube at -100 °C was injected with a THF-d8 solution
of 2 in order to obtain the usual mixture of π-complexes 4 and
4‚LiI.21 Then, a second injection introduced a THF-d8 solution of
trimethylsilyl cyanide (TMSCN), which induced an essentially
quantitative conversion of the π-complexes to 1.
Table 1 summarizes the NMR chemical shift data for 1-4. The
salient feature of the 13C NMR spectrum of 1 is the presence of
Me peaks at 12.43 and 25.31 ppm, which are dramatically downfield
from their positions in 3 or 4. The Me group at 25.31 ppm has
NOESY cross-peaks with the ring (H atoms on C1, C2, C5, and C6)
and with the Me group at 12.43 ppm; the latter has no cross-peaks
with the ring. Hence, the downfield peak is from Mec, cis to the
ring, while the upfield peak is from Met, trans to it.
In route B, a solution of cyano-Gilman reagent 3b in THF-d8 in
an NMR tube at -100 °C was injected with a THF-d8 solution of
trimethylsilyl chloride (TMSCl). While superficially similar to the
The large chemical shift difference between Mec and Met can
be rationalized by observing that they are trans to cyano and
† Complexity Study Center, 88 East Main St., Suite 220, Mendham, NJ 07945.
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10.1021/ja067533d CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
Table 1. 13C NMR (1H NMR) Chemical Shifts for 1-4a
group
2
3a
3b
4
4·LiI
4·LiCN
1
t
CH3 (CH3 )b
-9.12 (-1.40)
-9.12 (-1.40)
-9.04 (-1.35)
-9.04 (-1.35)
158.89
-5.02 (-1.12)
-0.57 (-0.10)
-5.56 (-1.16)
-1.85 (-0.24)
-5.76 (-1.15)
-2.14 (-0.21)
159.20
12.43 (0.05)
25.31 (0.53)
153.78
144.73
116.28 (5.02)
39.68 (2.74)
c
CH3 (CH3 )b
CN
C1 (C3)b
198.65
130.12 (5.90)
151.65 (7.08)
194.75
77.45 (3.77)
61.50 (3.26)
193.34
75.82 (3.68)
61.50 (3.19)
193c
C2-H (C2-H)b
C3-H (C1-H)b
75.27 (3.71)
61.51 (3.17)
a Parts per million from TMS. Values for C atoms attached to Cu are in boldface. b Labeling for 1. Note that C1 of 2 becomes C3 of 1 and C3 of 2 becomes
C1 of 1. c Shift could not be measured accurately, owing to broadening.
injection equipment, JEOL for their technical assistance, and J.P.
Snyder for many helpful discussions.
Supporting Information Available: NMR spectra (1H NMR, 13
C
NMR, HMQC, COSY, and NOESY). This material is available free
of charge via the Internet at http://pubs.acs.org.
References
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A.; Rastogi, A. J. Am. Chem. Soc. 2005, 127, 1372-3.
Figure 2. Selected 13C NMR traces for labeled 1 (+ solvent peaks). The
lower are for RCu(13CH3)213CNLi. The upper is for RCu(CH3)213CNLi. Note
the different scale for the rightmost traces. R is defined in the text.
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Scheme 2. Further Reaction of Copper(III) Intermediate 1
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R ) 3-trimethylsiloxycyclohex-2-en-1-yl ligands, respectively,
which are very different electronically.
The ring methine and cyano carbon resonances are shifted
upfield, the former owing to a change in hybridization (from ∼sp2
to sp3). The latter appears at 153.78 ppm, between the values of
158.89 ppm for 3b (no Cu-CN bond32) and 148.99 ppm for
MeCuCNLi (demonstrable Cu-CN bond33).
The presence of the TMS group was confirmed by a NOE
between the H atoms of the Me groups on Si and the H atoms on
C2 and C4 of the ring.34
(15) Johnson, C. R.; Dutra, G. A. J. Am. Chem. Soc. 1973, 95, 7783-8.
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3, 392-4.
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Applications of Organotransition Metal Chemistry; University Science
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A.; Seagle, P. H. J. Am. Chem. Soc. 2002, 124, 13650-1.
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present as LiCNLi+: (a) Boche, G.; Bosold, F.; Marsch, M.; Harms, K.
Angew. Chem., Int. Ed. 1998, 37, 1684-6. (b) Kronenburg, C. M. P.;
Jastrzebski, J. T. B. H.; Spek, A. L.; van Koten, G. J. Am. Chem. Soc.
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F.; Crump, W. Angew. Chem., Int. Ed. Engl. 1993, 32, 1482-3.
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(34) Me3Si: 1H NMR, 0.16 ppm; 13C NMR, 0.49 ppm; 29Si NMR, 12.68 ppm.
Without the TMS group, a Cu(III) intermediate was not observed.
(35) Carty, A. J.; Jacobson, S. E. J. Chem. Soc., Chem. Commun. 1975, 175-6.
The preparation of 1 was repeated with 13CH3Li and Cu13CN in
order to measure 13C-13C coupling constants 2J across Cu (Figure
2). This method was first used to prove that both CH3 and CN are
attached to the same Cu in CH3CuCNLi.33 The ring methine is
2
coupled to Met with J ) 38.1 Hz, and the cyano is coupled to
2
Mec (trans to it) with J ) 35.4 Hz; the cyano is coupled to Met
2
2
(cis to it) with J ) 5.4 Hz, and Mec is coupled to Met with J )
2.9 Hz. The methine-cyano and methine-Mec couplings are not
resolved under our conditions; they are predicted to be the smallest
of the six possible ones.22 The relative magnitudes of the calculated
2J values agree with experiment: methine-Met > cyano-Mec .
cyano-Met > Mec-Met > methine-cyano ∼ methine-Mec.22 The
pattern, trans . cis, is consistent with a square planar complex.35
Finally, when the spectrometer probe was warmed from -100
to -80 °C, 1 was converted smoothly into MeCuCNLi and 5, the
expected conjugate addition product (Scheme 2).
Acknowledgment. NSF Grants 0353061 and 0321056 (JEOL
ECA 500 NMR spectrometer) supported this work. The authors
thank D. Deadwyler for the fabrication and maintenance of the rapid
JA067533D
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