Copper-mediated cross-coupling of organostannanes with organic iodides at or below room temperature

Full text of DOI:10.1021/ja9541239

2748
J. Am. Chem. Soc. 1996, 118, 2748-2749
Scheme 1
Copper-Mediated Cross-Coupling of
Organostannanes with Organic Iodides at or below
Room Temperature
Gary D. Allred and Lanny S. Liebeskind*
Sanford S. Atwood Chemistry Center, Emory UniVersity
1515 Pierce DriVe, Atlanta, Georgia 30322
ReceiVed December 7, 1995
Nickel- and palladium-mediated cross-coupling reactions have
revolutionized the practice of organic synthesis in academic and
industrial laboratories over the past few decades. Kumada’s1
use of phosphine ligands to discipline the reactivity of orga-
nonickel intermediates allowed synthetically useful nickel-
catalyzed couplings between Grignard reagents and vinyl/aryl/
heteroaryl halides, thereby significantly extending earlier studies
with simple transition metal salts by Kharash and Fields.2
Negishi expanded the cross-coupling concept to include alu-
minum, zirconium, and zinc reagents using both nickel- and
palladium-based catalysts.3 But it was the discovery of pal-
ladium-catalyzed cross-couplings of organic derivatives of tin
(Stille,4,5 Beletskaya6 ), boron (Suzuki-Miyaura7 ), and silicon
(Hiyama8 ) that meant carbon-carbon bonds could be formed
under neutral reaction conditions between highly-functionalized
substrates, a virtue that has led to the widespread acceptance
of these powerful processes by the synthetic organic community.
In 1990, the beneficial influence of cocatalytic Cu(I) on
nonproductive or sluggish Stille cross-coupling reactions cata-
lyzed by palladium was first pointed out.9 The practical utility
of the “copper effect” was immediately recognized, and it was
quickly extended to numerous other palladium-catalyzed carbon-
carbon bond forming reactions (a few selected examples are
documented in the bibliography).10-17 In the original disclosure
of the copper effect9 it was suggested that transmetalation of
the R group from RSnBu3 to CuI could be responsible for the
catalysis, a process portending a synthetically useful cross-
coupling protocol mediated by simple copper salts alone.18,19
This suggestion has borne fruit. Recent studies support the tin
to copper transmetalation,20 and specific reaction subsets of
organostannane cross-coupling reactions mediated by CuX salts
have been documented by Piers21 and Falck.22
by catalytic quantities of various Cu(I)X salts; for example, 5%
Cu(MeCN)4BF4 in N-methylpyrrolidone (NMP) gave 3-(4-
chlorophenyl)-2-methyl-1-propene in 77% yield after 16 h at
80 °C. Monitoring of this reaction by GLC showed a rapid
initial rate followed by a considerable rate retardation as the
reaction approached 50% completion. Significantly, the addition
of 1 equiV of n-Bu3SnCl at the start of the reaction produced
only a trace of product under identical conditions.
These observations are consistent with a reVersible trans-
metalation from tin to copper that is retarded by the formation
of increasing concentrations of n-Bu3SnX (X ) halogen) as the
cross-coupling reaction proceeds. Since mechanistic studies
support the oxidative addition of certain organic halides to Cu-
(I) salts,23,24 the transmetalation from RSnBu3 could occur either
to a RCuX2 intermediate or to the CuX reagent, as depicted in
the top and bottom cycles of Scheme 1, respectively. Regardless
of the exact timing of the transmetalation step, recognition of
its reversible nature suggests that the copper-mediated cross-
coupling of organostannanes and organic halides should proceed
most rapidly and efficiently either (1) by using an excess of
CuX to drive an unfavorable transmetalation, a tactic explaining
the requirement of greater than 2 equiV of CuCl in Piers’s
account of the intramolecular coupling of vinyl iodides with
alkenyl trimethylstannanes;21 or (2) by the design of reaction
parameters to produce an organostannane byproduct, n-Bu3SnX,
that does not participate in a back reaction with RCu or R′CuX2.
As a first-stage solution to this problem,25 a variety of Cu(I)
carboxylates (CuOCOR: R ) Me, Ph, (E)-CHdCHPh, 2-py-
ridyl, 2-furyl, 2-thienyl) were prepared and surveyed as sto-
ichiometric mediators of the cross-coupling of (E)-â-(tri-n-
butylstannyl)styrene with (E)-â-iodostyrene in NMP. Of these,
copper(I) thiophene-2-carboxylate (CuTC)26 possessed the best
spectrum of properties (inexpensive, easy large-scale synthesis,
air-stable, rapid reactions). Most significantly, and in contrast
to CuCl, CuBr, CuI, and CuCN,27 1.5 equiV of CuTC mediated
the rapid and Very efficient intermolecular cross-coupling of
aryl, heteroaryl, and Vinylstannanes with Vinyl iodides and
certain aryl iodides within minutes in NMP at or below room
temperature!
In our laboratory, a cursory survey of the reaction of
(4-chlorophenyl)-tri-n-butylstannane with 2-methyl-3-bromo-1-
propene revealed a slow but efficient cross-coupling mediated
(1) Tamao, K.; Sumitani, K.; Kiso, Y.; Zembayashi, M.; Fujioka, A.;
Kodama, S.-i.; Nakajima, I.; Minato, A.; Kumada, M. Bull. Chem. Soc.
Jpn. 1976, 49, 1958.
(2) Kharasch; Fields J. Am. Chem. Soc. 1941, 63, 2316.
(3) Negishi, E.-i. Acc. Chem. Res. 1982, 15, 340.
(4) Mitchell, T. N. Synthesis 1992, 803.
(5) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508.
(6) Beletskaya, I. P. J. Organomet. Chem. 1983, 250, 551.
(7) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457.
(8) Hatanaka, Y.; Hiyama, T. Syn. Lett. 1991, 845.
(9) Liebeskind, L. S.; Fengl, R. W. J. Org. Chem. 1990, 55, 5359.
(10) Ye, J. H.; Bhatt, R. K.; Falck, J. R. J. Am. Chem. Soc. 1994, 116,
1.
Results of this study are depicted in Table 1. The cross-
coupling possesses useful chemoselectivity; carbonyl groups
(11) Saa, J. M.; Martorell, G. J. Org. Chem. 1993, 58, 1963.
(12) Undheim, K.; Benneche, T. Acta Chem. Scand. 1993, 47, 102.
(13) Liebeskind, L. S.; Riesinger, S. W. J. Org. Chem. 1993, 58, 408.
(14) Hinkle, R. J.; Poulter, G. T.; Stang, P. J. J. Am. Chem. Soc. 1993,
115, 11626.
(21) Piers, E.; Wong, T. J. Org. Chem. 1993, 58, 3609.
(22) Falck, J. R.; Bhatt, R. K.; Ye, J. J. Am. Chem. Soc. 1995, 117,
5973.
(23) Cohen, T.; Cristea, I. J. Org. Chem. 1975, 40, 3649.
(24) Cohen, T.; Cristea, I. J. Am. Chem. Soc. 1976, 98, 748.
(25) As deduced from Scheme 1, production of an impotent form of
n-Bu3SnX requires control over all halide or pseudo-halide species that are
introduced into the reaction; i.e., both the copper(I) salt, CuX, and the
organic halide, R′X, must possess a moiety X that produces the same form
of n-Bu3SnX. Therefore, effective catalysis with substoichiometric copper-
(I) salts should eventually be feasible if a viable reaction partner, R′X, can
be found that both participates in efficient coupling with RSnBu3 and
possesses a group X that leads to an unreactive form of n-Bu3SnX.
(26) See Supporting Information for complete details.
(27) From control experiments, it was determined that a large excess of
CuCl (but not CuBr, CuI, or CuCN) will induce intermolecular cross-
coupling of organostannanes and alkenyl iodides. In contrast to the use of
1.5 equiv of CuTC, more than 5 equiv of CuCl is required to drive the
reaction to completion.
(15) Gronowitz, S.; Bjork, P.; Malm, J.; Hornfeldt, A. B. J. Organomet.
Chem. 1993, 460, 127.
(16) Johnson, C. R.; Adams, J. P.; Braun, M. P.; Senanayake, C. B. W.
Tetrahedron Lett. 1992, 33, 919.
(17) Go´mez-Bengoa, E.; Echavarren, A. M. J. Org. Chem. 1991, 56,
3497.
(18) Wipf, P. Synthesis 1993, 537.
(19) A synthetically powerful process based on transmetalation from
organostannanes to higher order cuprates is well-known: Behling, J.;
Babiak, K.; Ng, J.; Campbell, A.; Moretti, R.; Koerner, M.; Lipshutz, B. J.
Am. Chem. Soc. 1988, 110, 2641. Behling, J.; Ng, J.; Babiak, K.; Campbell,
A.; Elsworth, E.; Lipshutz, B. Tetrahedron Lett. 1989, 30, 27.
(20) Farina, V.; Kapadia, S.; Krishnan, B.; Wang, C.; Liebeskind, L. S.
J. Org. Chem. 1994, 59, 5905.
0002-7863/96/1518-2748$12.00/0 © 1996 American Chemical Society

Communications to the Editor
J. Am. Chem. Soc., Vol. 118, No. 11, 1996 2749
Table 1. Copper(I) 2-Thiophenecarboxylate (CuTC) Mediated Cross-Coupling Reactions
1.5 equiv of (2-thienyl)COOCu
RSnBu3 + R′I NMP, 0 °C to room temperature, minutes8 RR′
(entries 7-11, 16) and most aryl and heteroaryl bromides and
2,2-disubstituted alkenyl iodides reacted well, as did 5,5-
dimethyl-3-iodocyclohexenone, but 1-iodocyclohexene did not.
Alkyl iodides and benzyl bromides were unreactive, while allyl
bromides reacted rapidly, but suffered from competing esteri-
fication by the copper carboxylate.
In conclusion, the simplicity of this CuTC-mediated cross-
coupling protocol, which features a rapid reaction rate at low
temperature, should allow its use in many situations where
thermally sensitive substrates are studied, or where copper-
mediated coupling provides a functional group selectivity not
achievable with palladium. Workup is straightforward. Prod-
ucts generally crystallized upon removal of solvent in vacuo
after the reaction mixture was diluted with ether, filtered, washed
with water, and dried. Though stoichiometric in copper, the
new process is economical in terms of money and time, and it
could prove competitive in many situations with traditional
palladium-catalyzed protocols.
iodides (entries 2-4, 7, 8, 12, 13) remain untouched. Since
the latter react with organostannanes under typical Stille reaction
conditions, this chemoselectivity should allow further function-
alization of the products using various palladium-based proto-
cols. The CuTC cross-coupling occurs with excellent retention
of stereochemistry of both the organostannane and alkenyl iodide
(entries 1, 15 and 12, 13), precluding a radical chain mechanism
and supporting a cross-coupling mechanism composed of trans-
metalation, oxidative addition, and reductive elimination steps.
In some cases, the cross-coupling could also be effected with
catalytic quantities of Cu(I) salts in the presence of stoichio-
metric carboxylate salts or alkali metal fluorides, although, to
date, a general process has not been found. For instance, the
addition of 1.2 equiv of CsF as an in situ tri-n-butylstannane
scavenger to a mixture of 1.0 equiv of (4-chlorophenyl)-
tributyltin, 1.2 equiv of â-iodostyrene, and 20% CuBr in NMP
produced 4-chlorostilbene in 91% yield after 8 h at 60 °C.
Analysis of the reaction of (E)-â-(tri-n-butylstannyl)styrene
with CuTC in NMP in the absence of a reactiVe alkenyl iodide
showed slow (2 h) protodestannylation to styrene with con-
comitant formation of (E,E)-1,4-diphenylbutadiene and the
appearance of a Cu(0) mirror, suggesting at least partial
transmetalation from tin to copper(I). Providing further support
for the direct oxidative addition of certain Cu(I) salts to alkenyl
iodides,24 excess CuTC reacted rapidly with various alkenyl
iodides to produce symmetrical dienes in high yield.28
Acknowledgment. This investigation was supported by Grant No.
CA40157, awarded by the National Cancer Institute, DHHS, and by
partial funding from Bristol-Myers Squibb. We acknowledge the use
of a VG 70-S mass spectrometer purchased through funding from the
National Institutes of Health, S10-RR-02478, and a 300 MHz NMR
and 360 MHz NMR purchased through funding from the National
Science Foundation, NSF CHE-85-16614 and NSF CHE-8206103,
respectively. We gratefully acknowledge many stimulating and insight-
ful conversations with Dr. Vittorio Farina of Boehringer Ingelheim,
Dr. James P. Snyder of the Cherry L. Emerson Center for Scientific
Computation of Emory University, and our co-worker Dr. Jiri Srogl.
Although simple aryl iodides were ineffective coupling
partners, o-iodonitrobenzene (but not p-iodonitrobenzene) re-
acted rapidly and efficiently with (E)-â-(tri-n-butylstannyl)-
styrene (Table 1, entry 14). Steric and electronic factors
imparted by the alkenyl iodide combine to play subtle and
presently undefined roles in determining the success of the cross-
coupling process. For example, E- and Z-monosubstituted and
Supporting Information Available: Complete description of the
synthesis and characterization of all compounds in the paper (14 pages).
This material is contained in many libraries on microfiche, immediately
follows this article in the microfilm version of the journal, can be
ordered from the ACS, and can be downloaded from the Internet; see
any current masthead page for ordering information and Internet access
instructions.
(28) The addition of 2.5 equiv of CuTC to â-iodostyrene in NMP gave
1,4-diphenylbutadiene in 95% yield after only 30 min at room temperature.
A study of this mild Ullman-like coupling of alkenyl iodides is underway
(cf.: Cohen, T.; Cristea, I. J. Am. Chem. Soc. 1976, 98, 748).
JA9541239