Rhodium-catalyzed activation of C(sp3)-X (X = Cl, Br) bond: An intermolecular halogen exchange case

Article abstract of DOI:10.1021/ol101995v

A RhCl(PPh₃)₃-catalyzed halogen-exchange reaction between allyl and alkyl halides with β-H atoms was observed. The possible mechanism of the reaction involves oxidative addition and reductive elimination of the C(sp³)-X bonds, which is not common in organometallic chemistry.

Full text of DOI:10.1021/ol101995v

ORGANIC
LETTERS
2010
Vol. 12, No. 23
5370-5373
Rhodium-Catalyzed Activation of
C(sp3)-X (X ) Cl, Br) Bond: An
Intermolecular Halogen Exchange Case
Jianping Wang, Xiaofeng Tong, Xiaomin Xie, and Zhaoguo Zhang*
School of Chemistry and Chemical Engineering, Shanghai Jiao Tong UniVersity, 800
Dongchuan Road, Shanghai 200240, China, and Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 345 Fenglin Road, Shanghai 200032, China
zhaoguo@sjtu.edu.cn
Received August 23, 2010
ABSTRACT
A RhCl(PPh3)3-catalyzed halogen-exchange reaction between allyl and alkyl halides with ꢀ-H atoms was observed. The possible mechanism
of the reaction involves oxidative addition and reductive elimination of the C(sp3)-X bonds, which is not common in organometallic chemistry.
Oxidative addition and reductive elimination are fundamental
organometallic reaction steps in a catalytic process.1 Most
transition-metal-catalyzed cross-coupling reactions involve oxi-
dative addition of aryl or vinyl halides. However, oxidative
addition of alkyl halides is challenging in coupling reactions
due to the relatively low activity of alkyl halides and the facile
ꢀ-hydride elimination of metal-alkyl intermediates.2 Recently,
Fu et al. have achieved a C(sp3)-C(sp3) coupling reaction by
applying the sterically hindered and electron-rich trialkylphos-
phanes as ligands to inhibit the ꢀ-hydrogen elimination of
metal-alkyl intermediates, and impressive results have been
achieved.3 Besides that, only a few examples of some specific
reductive eliminations which were considered unfavorable in
organometallic chemistry have been reported. For instance,
reductive elimination of the alkyl-metal-alkyl bond from the
high-valent transition metal complexes [Pt(PEt3)2(Ph)2I2]4 and
[Rh(CO)(PPh3)3MeCl2]5 was observed. A direct iodomethane
reductive elimination from a Rh(III) species was reported.6
Hartwig and Vigalok reported the observation of reductive
elimination of the aryl-metal-halide bond to form aryl halide
compounds from an arylpalladium halide complex7 and an
arylplatinum halide complex,8 respectively.
In this paper, we report several foundational processes in
the transition-metal-catalyzed reaction: (1) oxidative addition
of alkyl halides occurs through a possible radical chain
(3) For the use of phosphanes as ligands, see: (a) Netherton, M. R.;
Dai, C.; Neuschu¨tz, K.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 10099–
10100. (b) Kirchhoff, J. H.; Dai, C.; Fu, G. C. Angew. Chem., Int. Ed.
2002, 41, 1945–1947. (c) Netherton, M. R.; Fu, G. C. Angew. Chem., Int.
Ed. 2002, 41, 3910–3912. (d) Kirchhoff, J. H.; Netherton, M. R.; Hills,
I. D.; Fu, G. C. J. Am. Chem. Soc. 2002, 124, 13662–13663. (e) Menzel,
K.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 3718–3719. (f) Tang, H.;
Menzel, K.; Fu, G. C. Angew. Chem., Int. Ed. 2003, 42, 5079–5082. (g)
Hills, I. D.; Netherton, M. R.; Fu, G. C. Angew. Chem., Int. Ed. 2003, 42,
5749–5752. For the use of other ligands, see: (h) Smith, S. W.; Fu, G. C.
Angew. Chem., Int. Ed. 2008, 47, 9334–9336. (i) Saito, B.; Fu, G. C. J. Am.
Chem. Soc. 2008, 130, 6694–6695. (j) Son, S.; Fu, G. C. J. Am. Chem.
Soc. 2008, 130, 2756–2757. (k) Saito, B.; Fu, G. C. J. Am. Chem. Soc.
2007, 129, 9602–9603. (l) Arp, F. O.; Fu, G. C. J. Am. Chem. Soc. 2005,
127, 10482–10483. (m) Fischer, C.; Fu, G. C. J. Am. Chem. Soc. 2005,
127, 4594–4595. (n) Netherton, M. R.; Fu, G. C. AdV. Synth. Catal. 2004,
346, 1525–1532.
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12435.
10.1021/ol101995v  2010 American Chemical Society
Published on Web 11/03/2010

reaction; (2) reductive elimination of an alkyl-Rh-halide
and an allylic-Rh-halide bond.
occurred between allyl bromide and the solvent DCE prior to
the cyclization. Further investigation showed that these types
of halogen exchange between allyl and alkyl halides are quite
common in the presence of Wilkinson’s catalyst (Table 1).
Under these catalytic conditions, an allyl ester functional
group could be tolerated (Table 1, entries 1 and 3). Halogen
exchange of a cis-allylic halide occurred with partial isomer-
ization to form trans-allylic product; however, no secondary
halide was detected (Scheme 2).
Recently, we reported the cycloisomerization of 1,6-enynes
catalyzed by Wilkinson’s catalyst, in which an intramelocular
halogen shift was observed.9 During the course of further
investigation of this reaction, we found that when we conducted
the reaction with brominated 1,6-enyne substrate 1a and
RhCl(PPh3)310 in 1,2-dichloroethane, only a trace of desired
product 2a was isolated; instead, an intermolecular halogen
exchange compound 2b was isolated in reasonable yield
(Scheme 1). Apparently, the chloro atom on 2b comes from
Scheme 2. Halogen Exchange of cis-Allylic Halide
Scheme 1. Cyclization of Brominated 1,6-Enyne Substrate
the solvent DCE. To explore whether the halogen exchange
occurred prior to or after the cyclization reaction, we monitored
the reaction with gas chromatography. The GC results showed
that the substrate 1a has been transformed to (Z)/(E)-1b before
the cyclization step.11 This implied that halogen exchange
As far as Wilkinson’s catalyst is concerned, the reaction
can be rationalized by the mechanism illustrated in Scheme
3. First, oxidative addition of an alkyl bromide (the solvent)
Scheme 3. Possible Mechanism
Table 1. Halogen Exchange between Allyl and Alkyl Halidesa
to RhCl(PPh3)n (n ) 2 or 3) generates the intermediate a.
Reductive elimination of a produces the key catalytic species
RhBr(PPh3)n and the compound RCl. Oxidative addition of
an allylic chloride to RhBr(PPh3)n affords intermediate b.
Finally, reductive elimination of intermediate b results in
an allylic bromide.
(7) (a) Roy, A. H.; Hartwig, J. F. J. Am. Chem. Soc. 2001, 123, 1232–
1233. (b) Roy, A. H.; Hartwig, J. F. J. Am. Chem. Soc. 2003, 125, 13944–
13945. (c) Roy, A. H.; Hartwig, J. F. Organometallics 2004, 23, 1533–
1541.
(8) (a) Yahav-Levi, A.; Goldberg, I.; Vigalok, A. J. Am. Chem. Soc.
2006, 128, 8710–8711. (b) Yahav-Levi, A.; Goldberg, I.; Vigalok, A.;
Vedernikov, A. N. J. Am. Chem. Soc. 2008, 130, 724–731.
(9) (a) Tong, X.; Zhang, Z.; Zhang, X. J. Am. Chem. Soc. 2003, 125,
6370–6371. (b) Tong, X.; Li, D.; Zhang, Z.; Zhang, X. J. Am. Chem. Soc.
2004, 126, 7601–7607.
a All of the reactions were carried out with substrate (0.2 mmol) and
RhCl(PPh3)3 (18.5 mg, 0.02 mmol) in 3 mL of a specified solvent within
6 h. b DBE: BrCH2CH2Br. DCE: ClCH2CH2Cl. c Isolated yield. d Conversion
determined by GC-MS.
(10) The Wilkinson’s catalyst was freshly prepared by the standard
procedure; see the Supporting Information.
(11) For details, see the Supporting Information.
Org. Lett., Vol. 12, No. 23, 2010
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Although the activity of oxidative addition of a transition
metal toward alkyl halides is usually lower than that toward
allyl halides, the much larger concentration of alkyl halide
makes the oxidative addition of alkyl halides favorable. In
this proposed mechanism, reductive elimination of interme-
diate a is an irreversible process because of the much lower
concentration of RCl compared to that of the solvent RBr.
Therefore, the chloro atom was accumulated in the form of
RCl. To confirm this hypothesis, we designed the following
control experiments (Scheme 4). The reaction was carried
Scheme 5. Proposed Mechanism of Radical-Chain Reaction
can facilitate an electron transfer to an alkyl halide to form
a radical pair ([Rh]IIClBr + R•). This pair can be collapsed
to the oxidative adduct R[Rh]IIIClBr. Based on this
proposed mechanism involving a radical-chain reaction,
we envision that the cyclopropane of substrate 3 would
progress C-C cleavage through radical cleavage induced
by RhBr(PPh3)3 (Scheme 6). It is obvious that the radical
Scheme 4.
Control Experimenta
Scheme 6. Proposed Radical-Chain Reaction
cleavage preferably forms the intermediate 5b. Then, the
oxidative adduct intermediate 6b undergoes ꢀ-hydride
elimination to give the diene product 7b. The trivalent
Rh complex RhHBr2Ln eliminates HBr to regenerate the
catalyst RhBrLn (n ) 2 or 3).13 If oxidative addition does
not involve radical chain reaction, oxidative addition of
substrate 3 to RhBr(PPh3)n and then ꢀ-carbon elimination
would generate the intermediates 6a and 6b (Scheme 7).14
a The reaction was carried out with 1b (0.2 mmol), 1c (0.2 mmol), and
RhCl(PPh3)3 (0.02 mmol) in toluene (3 mL).
Scheme 7
.
Proposed Mechanism Involving Direct Oxidative
Addition
out in toluene with 1b and 1c in the presence of Wilkinson’s
catalyst. When the molar ratio of 1b and 1c was 1:1, 2a and
2b were isolated in comparable yields with 2c as the
coproduct and partial unreacted 1c (the GC result is shown
in Scheme 4). Meanwhile, we have not detected 2d in the
reaction, which indicated that ꢀ-hydride elimination was
suppressed with the catalyst system. Moreover, when the
ratio of 1b and 1c was increased to 1:20, 2a was the only
product, and no 2b was detected by GC.
In regard to the process of oxidative addition of alkyl
halide in this mechanism, we proposed the mechanism of a
radical chain reaction (Scheme 5).12 The complex [Rh]ICl
The cleavage of bond b in 8 is more unfavorable because
of the steric repulsion between the phenyl on the cyclo-
(12) (a) Ishiyama, T.; Miyaura, N.; Suzuki, A. Tetrahedron Lett. 1991,
32, 6923–6926. (b) Lappert, M. F.; Lednor, P. W. J. Chem. Soc., Chem.
Commun. 1973, 948–949. (c) Ishiyama, T.; Murata, M.; Suzuki, A.; Miyaura,
N. J. Chem. Soc., Chem. Commun. 1995, 295–296. (d) Kramer, A. V.;
Osborn, J. A. J. Am. Chem. Soc. 1974, 96, 7832–7833. (e) Kramer, A. V.;
Bradley, J. S.; Osborn, J. A. J. Am. Chem. Soc. 1974, 96, 7145–7147.
(13) (a) Yasukawa, T.; Satoh, T.; Miura, M.; Nomura, M. J. Am. Chem.
Soc. 2002, 124, 12680–12681. (b) Sugihara, T.; Satoh, T.; Miura, M.;
Nomura, M. Angew. Chem., Int. Ed. 2003, 42, 4672–4674.
5372
Org. Lett., Vol. 12, No. 23, 2010

propane ring and the ligands of the catalyst.15 Therefore,
in this case, 7a would be the main product.16 It is noted
that we only isolated 7b in 22% yield and have not
detected the diene 7a during the course of reaction. The
compound 3 can be recovered without RhBr(PPh3)3 under
reflux in toluene. In addition, we have observed a
substantial decrease of conversion in the transformation
of 9a to 9b when we added the radical scanvenger
4-hydroxy-TEMPO to the reaction system (Scheme 8, eq
catalyst efficiency, we have also performed a control
experiment (Scheme 8, eq 2). The result showed that the
employment of iPrOH as additive could achieve high yield
under the same reaction conditions. On the basis of this
consideration and the experimental results above, we
prefer the proposed mechanism involving a radical chain
reaction.
In conclusion, we have found a RhCl(PPh3)3-catalyzed
halogen-exchange reaction between allyl and alkyl halide
with ꢀ-H atoms. Further studies on the scope and applications
of the reaction are ongoing in our laboratory and will be
reported in due course.
i
Scheme 8
.
Experiments with 4-Hydroxy-TEMPO and PrOH as
Additives
Acknowledgment. We thank the National Natural Science
Foundation of China, the Science and Technology Commis-
sion, and the Education Commission of Shanghai Municipal-
ity for financial support.
Supporting Information Available: Experimental pro-
cedures along with copies of spectra. This material is
available free of charge via the Internet at http://pubs.acs.org.
1).17 To explore whether the coordinating ability of the
hydroxyl group on 4-hydroxy-TEMPO may influence the
OL101995V
(14) (a) Bart, S. C.; Chirik, P. J. J. Am. Chem. Soc. 2003, 125, 886–
887. (b) Wender, P. A.; Hisashi, T.; Bernhard, W. J. Am. Chem. Soc. 1995,
117, 4720–4721.
(16) Since intermediate 6b is more stable because the Rh center is at
the more stabilized benzylic position, we envisioned both 7a and 7b could
be detected in the mechanism without radical chain reaction.
(15) Hayashi, M.; Ohmatsu, T.; Meng, Y.; Saigo, K. Angew. Chem.,
Int. Ed. 1998, 37, 837–839.
(17) We presumed the chloro atom on 9b may come from the catalyst.
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