Copper(I)-mediated oxidative cross-coupling between functionalized alkynyl lithium and aryl magnesium reagents

Article abstract of DOI:10.1002/anie.200703097

(Chemical Equation Presented) All crossed: The reaction of unsaturated copper reagents with various alkynyl lithium compounds provides mixed lithium cuprates, which in the presence of chloranil undergo an oxidative coupling, thus leading to polyfunctional

Full text of DOI:10.1002/anie.200703097

Angewandte
Chemie
DOI: 10.1002/anie.200703097
Oxidative Coupling
Copper(I)-Mediated Oxidative Cross-Coupling between
Functionalized Alkynyl Lithium and Aryl Magnesium Reagents**
Srinivas Reddy Dubbaka, Marcel Kienle, Herbert Mayr, and Paul Knochel*
Dedicated to Professor Dieter Seebach on the occasion of his 70th birthday
Polyfunctional alkynes are important intermediates for the
preparation of natural products, pharmaceuticals, and organic
materials[1] such as molecular wires.[2] The Sonogashira
reaction[3] and the Negishi cross-coupling[4] are very powerful
methods for preparing polyfunctional alkynes through the
2
ꢀ
formation of a C(sp ) C(sp) bond. However, the Sonogashira
coupling fails for the selective monocoupling of dihaloarenes
and dihaloalkenes as well as for the coupling of sterically
shielded haloarenes.[3k]
Recently, we reported an oxidative homocoupling of
unsaturated magnesium or zinc reagents using a diphenoqui-
none or chloranil (5) as oxidation agents.[5] Soon after, we
described a related oxidative amination procedure providing
Scheme 1. Proposed mechanism for the oxidative cross-coupling of
a general synthesis of polyfunctional amines.[6] Herein, we
arylcopper reagents 2 with alkynyl lithium compounds 3 using chloranil
(5).
report a new type of oxidative coupling[7] for the preparation
of polyfunctional alkynes. Aryl or heteroaryl magnesium
halides (ArMgX, 1) are transmetalated to the corresponding
copper reagents (ArCu, 2) using the THF-soluble salt
CuCl·2 LiCl.[8] Subsequent reaction with an alkynyl lithium
compound of type 3 results in the formation of a mixed
lithium aryl(alkynyl) cuprate 4.[9] Its treatment with chloranil
(5) provides polyfunctional alkynes of type 6 by an oxidative
cross-coupling reaction (Scheme 1).
providing the alkynylated pyridine derivative 6a in 83% yield
(Scheme 2). Various alkynyl lithium compounds[11] bearing
aliphatic substituents (entries 1 and 2, Table 1), an alkenyl
The scope and the functional-group compatibility of this
reaction proved to be broad. We first examined the coupling
using a range of alkynyl lithium compounds with a typical
heteroaryl magnesium compound. Thus, 3,5-dibromopyridine
(7) was converted to 5-bromo-3-pyridylmagnesium chloride
by a Br–Mg exchange using iPrMgCl·LiCl[10] (1.1 equiv, 08C,
0.5 h; then 258C, 0.5 h) and subsequent transmetalation to the
corresponding organocopper species 2a (CuCl·2LiCl[8]
(1.1 equiv), ꢀ508C, 25 min). After the addition of 3a
(2.0 equiv, ꢀ508C, 1 h), the resulting mixed cuprate 4a was
treated with chloranil (1.3 equiv, ꢀ788C!ꢀ508C, 3 h), thus
[*] Dr. S. R. Dubbaka, Dipl.-Chem. M. Kienle, Prof. Dr. H. Mayr,
Prof. Dr. P. Knochel
Ludwig-Maximilians-Universität München
Department Chemie und Biochemie
Butenandtstrasse 5–13, Haus F, 81377 München (Germany)
Fax: (+49)89-2180-77680
E-mail: paul.knochel@cup.uni-muenchen.de
[**] We thank the Fonds der Chemischen Industrie and the SFB 749 for
financial support. S.R.D. thanks the Alexander von Humboldt
Foundation for a fellowship. We also thank Chemetall GmbH
(Frankfurt), Wacker Chemie AG (Munich), and BASF AG (Ludwig-
shafen) for generous gifts of chemicals.
Scheme 2. Oxidative cross-coupling of polyfunctional copper reagents.
Reaction conditions: a) iPrMgCl·LiCl (1.1 equiv, 08C, 0.5 h; then 258C,
0.5 h); b) CuCl·2 LiCl (1.1 equiv, ꢀ508C, 25 min); c) 3a (2.0 equiv,
ꢀ508C, 1 h); d) 5, 1.3 equiv, ꢀ788C!ꢀ508C, 3 h); e) TMPMgCl·LiCl
(1.1 equiv, 08C, 1 h); f) 3h (2.0 equiv, ꢀ788C, 1 h). TMP=2,2,6,6-
tetramethylpiperidyl, Boc=tert-butoxycarbonyl.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
Angew. Chem. Int. Ed. 2007, 46, 9093 –9096
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
9093
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
&
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
Take advantage of blue reference links
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&

Communications
Table 1: Oxidative coupling of organocopper reagent 2a with various
alkynyl lithium compounds (3b–3g) using chloranil as oxidant.
afford the corresponding 2-alkynylpyridine and 3-alkynyl-
benzofuran derivatives 6x and 6y in 62–66% yield
(entries 16–17, Table 2).
Entry Alkynyl lithium
compound
Alkyne
Yield
[%][a]
This oxidative coupling has been extended to a stereose-
lective preparation of enynes.[4] Thus, (E)-octenyl iodide (9,
E/Z > 99:1)[15] was converted into the corresponding alkenyl
magnesium reagent by treatment with iPrMgCl·LiCl[15]
(ꢀ408C, 7 h). Addition of CuCl·2 LiCl provides the copper
reagent 10, which after the addition of first an alkynyl lithium
compound (3b or 3c) and then chloranil (5, 1.3 equiv, ꢀ788C,
2 h) furnishes the E-enynes (E/Z > 99:1) 11a (R = C6H13,
62%) and 11b (R = (CH2)4Cl, 60%). Similarly, the reaction
of 1,2-dibromocyclopentene (12) with iPrMgCl·LiCl
(1.1 equiv, 258C, 48 h) provides 2-bromocyclopentenylmag-
nesium bromide, which was subsequently transmetalated to
the corresponding copper reagent 13. Addition of first an
alkynyl lithium compound (3a or 3b, 2 equiv, ꢀ508C, 1 h) and
then chloranil (5, 1.3 equiv, ꢀ788C, 2 h) affords the bromo-
enynes 14a (R = Si(iPr)3) and 14b (R = C6H13) in 62% yield
(Scheme 3).
1
2
75[b]
70[b]
3
4
5
6
70[b]
72[b]
68[b]
65[b]
The unsaturated bromine-substituted alkynes 14b, 6u,
and 6y (Scheme 4) are well-suited for the preparation of new
annulated pyridines.[16] The reaction of unsaturated and
saturated bromides 14b and 6u with tBuLi (2 equiv, ꢀ788C,
1 h) provides the corresponding lithium intermediates 15 and
16, which readily react with p-tolylnitrile[17] (p-TolCN,
1.3 equiv, ꢀ788C, 1 h).
In the case of 15, the resulting lithium intermediate
undergoes a remarkable 6-endo-dig ring closure[18] leading to
the 4-lithiated pyridine derivative 17. After iodolysis or
protonation, the polyfunctional annulated pyridines 19a and
19b are obtained in 64 and 60% yield, respectively
(Scheme 4). In the case of the aryl lithium compound 16,
the resulting lithiated imine undergoes a ring closure only
[a] Yield of isolated, analytically pure product. [b] The aryl magnesium
reagent was prepared by a bromine–magnesium exchange reaction with
iPrMgCl·LiCl.
group (entry 3, Table 1), or various aryl or heteroaryl
substituents (entries 4–6, Table 1) provide the desired poly-
functional alkynes 6b–6g in 68–75% yields. In general, an
excess of alkynyl lithium compound (3, 1.5–2.0 equiv) is
necessary to avoid homocoupling reactions.
This cross-coupling is compatible with various aryl and
heteroaryl magnesium reagents. Thus, the direct magnesiation
of the diester 8 with TMPMgCl·LiCl[12] (1.1 equiv, 08C, 1 h)
provides the aryl magnesium chloride 1b, which after trans-
metalation with CuCl·2LiCl[8] (1.1 equiv, ꢀ508C, 25 min)
furnishes the copper species 2b. Its reaction with ethyllithium
propiolate 3h[13] affords the mixed copper organometallic
compound 4b, which by treatment with chloranil (1.3 equiv,
ꢀ788C, 1 h, ꢀ788C!ꢀ508C, 3 h) leads to the unsaturated
triester 6h in 73% yield (Scheme 2). A range of sterically
hindered aryl magnesium reagents[12b] (1b–e) were found to
undergo oxidative couplings with alkynyl lithium compounds
(3a–c, e), thus leading to the polyfunctional alkynes 6i–p in
65–74% yield (entries 1–8, Table 2). Typical substituted aryl
magnesium reagents bearing various substituents (entries 9–
13, Table 2) react under our conditions with alkynyl lithium
compounds (3a,b) to provide the expected alkynes 6q–6u in
68–77% yield. Reaction of 1-naphthylmagnesium bromide
with the alkynyl lithium compounds 3e and 3a furnishes the
1-alkynyl naphthalene derivatives 6v and 6w in 70% yield
(entries 14–15, Table 2).[14] The heterocyclic copper deriva-
tives prepared from 1k[12a] and 1l also react with 3a and 3b to
Scheme 3. Oxidative cross-coupling of acylic and cyclic alkenylcopper
compounds 10, 13 with alkynyl lithium compounds 3 using chloranil
(5).
9094 www.angewandte.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2007, 46, 9093 –9096
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
&
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
Take advantage of blue reference links
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&

Angewandte
Chemie
Table 2: Synthesis of polyfunctional disubstituted alkynes by the oxida-
tive coupling of polyfunctional aryl and heteroaryl mixed cuprates using
chloranil.
Entry Grignard reagent
3
Alkyne
Yield
[%][a]
1
2
3
1b: R=CO2Et
1c: R=H
1d: R=OBoc
3e 6i: R=CO2Et
3e 6j: R=H
3e 6k: R=OBoc
65[b]
70[b]
63[b]
4
1b
3a 6l
74[b]
5
6
7
1c: R=H
1c: R=H
1b: R=CO2Et
3b 6m: R=H, X=C2H5
3c 6n: R=H, X=Cl70
3c 6o: R=CO2Et, X=Cl68
69[b]
[b]
[b]
8
1e
3a 6p
73[c]
9
10
11
1 f: R=OMe
1g: R=I
1h: R=CN
3a 6q: R=OMe
3a 6r: R=I
3a 6s: R=CN
68[c]
77[d]
72[d]
12
13
1i
1i
3a 6t: R=Si(iPr)3
3b 6u: R=C6H13
70[d]
68[d]
14
15
1j
1j
3e 6v: R=Ph
3a 6w: R=Si(iPr)3
70[c]
70[c]
Scheme 4. Reaction of 1-lithio-1,3-enynes with nitriles to give pyridine
derivatives 19a,b, 20a,b, and 23a,b.
after addition of iodine (ꢀ708C!258C, 6 h; Scheme 4). This
method can be extended to other heterocyclic systems. Thus,
the lithiation of the 3-alkynylbenzofuran 6y in the 2-position
(nBuLi (1.1 equiv), ꢀ558C, 4 h) and subsequent addition of
p-TolCN (1.3 equiv, ꢀ408C, 2 h) furnishes the lithiated imine
22, which after the addition of iodine provides the iodoiso-
quinoline 23a in 62% yield (Scheme 4). To test the reversi-
bility of this cyclization, we treated iodoisoquinoline 20a with
nBuLi (ꢀ788C, 1 h), and after protonation we observed no
ring-opening products but only the isoquinoline 20b. Sim-
ilarly, the reaction of 23a with nBuLi (ꢀ788C, 1 h) provided
only the isoquinoline 23b after protonation, thus showing that
the ring closure of 18 and 22 is not reversible.
16
1k
3a 6x
66[b]
17
1l
3b 6y
62[d]
[a] Yield of isolated, analytically pure product. [b] The aryl magnesium
reagent was prepared through deprotonation using TMPMgCl·LiCl
(1.1 equiv). [c] The arylmagnesium reagent was prepared by magnesium
insertion into the bromoarene. [d] The arylmagnesium reagent was
prepared by a bromine–magnesium exchange reaction with iPrMgCl·
LiCl.
Angew. Chem. Int. Ed. 2007, 46, 9093 –9096
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 9095
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
&
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
Take advantage of blue reference links
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&

Communications
Fu, Org. Lett. 2000, 2, 1729; o) A. Köllhofer, T. Pullmann, H.
Plenio, Angew. Chem. 2003, 115, 1086; Angew. Chem. Int. Ed.
2003, 42, 1056; p) V. P. W. Böhm, W. A. Herrmann, Eur. J. Org.
Chem. 2000, 3679; q) S. R. Dubbaka, P. Vogel, Adv. Synth. Catal.
2004, 346, 1793; r) C. Nµjera, J. Gil-Moltó, S. Karlström, L. R.
Falvello, Org. Lett. 2003, 5, 1451; s) M. Ansorge, T. J. J. Müller, J.
Organomet. Chem. 1999, 585, 174; t) S. Thorand, N. Krause, J.
Org. Chem. 1998, 63, 8551.
In summary, we have reported a new oxidative coupling of
lithium aryl(alkynyl) cuprates, which provides polyfunctional
alkynes or enynes in good yields. Several new bromoalkynes
prepared by this method are currently being used for the
preparation of valuable annulated pyridines and isoquino-
lines. Further applications of this reaction are currently
underway.
[4] a) E.-I. Negishi, Acc. Chem. Res. 1982, 15, 340; b) E.-I. Negishi,
J. Organomet. Chem. 2002, 653, 34; c) E.-I. Negishi, L. Anas-
tasia, Chem. Rev. 2003, 103, 1979; d) E.-I. Negishi, M. Qian, F.
Zeng, L. Anastasia, D. Babinski, Org. Lett. 2003, 5, 1597; e) L.
Anastasia, E.-I. Negishi, Org. Lett. 2001, 3, 3111; f) B. Wang, M.
Bonin, L. Micouin, Org. Lett. 2004, 6, 3481.
[5] A. Krasovskiy, A. Tishkov, V. del Amo, H. Mayr, P. Knochel,
Angew. Chem. 2006, 118, 5132; Angew. Chem. Int. Ed. 2006, 45,
5010.
[6] a) V. del Amo, S. R. Dubbaka, A. Krasovskiy, P. Knochel,
Angew. Chem. 2006, 118, 8002; Angew. Chem. Int. Ed. 2006,
45, 7838; b) M. Kienle, S. R. Dubbaka, V. del Amo, P. Knochel,
Synthesis 2007, 1272; for a review, see: c) M. Kienle, S. R.
Dubbaka, K. Brade, P. Knochel, Eur. J. Org. Chem. 2007, 4166.
[7] a) B. H. Lipshutz, K. Siegmann, E. Garcia, J. Am. Chem. Soc.
1991, 113, 8161; b) B. H. Lipshutz, K. Siegmann, E. Garcia,
Tetrahedron 1992, 48, 2579; c) B. H. Lipshutz, K. Siegmann, E.
Garcia, F. Kayser, J. Am. Chem. Soc. 1993, 115, 9276; d) T. D.
Quach, R. A. Batey, Org. Lett. 2003, 5, 4397; see also: e) P. S.
Baran, M. P. DeMartino, Angew. Chem. 2006, 118, 7241; Angew.
Chem. Int. Ed. 2006, 45, 7083, and references therein.
[8] P. Knochel, M. C. P. Yeh, S. C. Berk, J. Talbert, J. Org. Chem.
1988, 53, 2390.
[9] B. H. Lipshutz, S. Sengupta, Org. React. 1992, 41, 135.
[10] a) A. Krasovskiy, P. Knochel, Angew. Chem. 2004, 116, 3396;
Angew. Chem. Int. Ed. 2004, 43, 3333; b) A. Krasovskiy, B. F.
Straub, P. Knochel, Angew. Chem. 2006, 118, 165; Angew. Chem.
Int. Ed. 2006, 45, 159.
[11] The alkynyl lithium compounds were prepared by the reaction of
the corresponding alkyne with nBuLi (1.0 equiv, 08C, 0.5 h); see
also full details in the Supporting Information.
[12] a) A. Krasovskiy, V. Krasovskaya, P. Knochel, Angew. Chem.
2006, 118, 3024; Angew. Chem. Int. Ed. 2006, 45, 2958; b) W. Lin,
O. Baron, P. Knochel, Org. Lett. 2006, 8, 5673.
[13] M. T. Crimmins, D. K. Jung, J. L. Gray, J. Am. Chem. Soc. 1993,
115, 3146.
Experimental Section
Typical procedure: Synthesis of 6a (Scheme 2): A dry, argon-flushed
Schlenk flask equipped with a magnetic stirring bar and a septum was
charged with 7 (237 mg, 1.0 mmol). After cooling to 08C, iPrMgCl·
LiCl (0.92 mL, 1.20m in THF, 1.1 mmol) was added dropwise. The
mixture was stirred for 0.5 h and then for further 0.5 h at 258C to
afford the Grignard reagent 1a. CuCl·2LiCl (1.2 mL, 1.0m in THF,
1.2 mmol) was added dropwise to 1a at ꢀ508C, and the mixture was
stirred for 25 min. Compound 3a (2.0 mmol; prepared by adding
nBuLi (2 mmol) to a 0.5m solution of triisopropylsilylacetylene in
THF (365 mg, 2 mmol) at 08C and stirring for 30 min) was added
dropwise to the resulting cuprate 2a, and the mixture was stirred for
1 h at ꢀ508C. The reaction mixture was cooled to ꢀ788C, and a
solution of 5 (320 mg, 1.3 mmol) in anhydrous THF (7 mL) was added
slowly over a period of 45 min. The reaction mixture was then
warmed to ꢀ508C and stirred for 3 h. Et2O (10 mL) was poured into
the crude reaction mixture, and the reaction mixture was then filtered
through celite and the residue washed with Et2O (ca. 100 mL). The
organic phase was washed with 2 ” 10 mL NH4OH(aq) (2.0m) and
extracted with Et2O. The combined organic layers were dried
(MgSO4), filtered, and concentrated under reduced pressure. Purifi-
cation by flash chromatography (pentane/Et2O 20:1) yielded the
alkyne 6a (281 mg, 83%) as a pale yellow viscous oil.
Received: July 11, 2007
Published online: October 17, 2007
Keywords: alkynes · cross-coupling · cuprates ·
.
nitrogen heterocycles
[1] Modern Acetylene Chemistry (Eds.: P. J. Stang, F. Diederich),
Wiley-VCH, Weinheim, 1995.
[14] These naphthyl derivatives have been used for the preparation
of drugs, pesticides, dyes, polymers, and other goods, see:
a) Kirk-Othmer Concise Encyclopedia of Chemical Technology,
Wiley-VCH, New York, 1985; b) D. M. Bowles, J. E. Anthony,
Org. Lett. 2000, 2, 85.
[2] a) C. S. Hartley, E. L. Elliott, J. S. Moore, J. Am. Chem. Soc.
2007, 129, 4512; for excellent reviews, see: b) W. Zhang, J. S.
Moore, Angew. Chem. 2006, 118, 4524; Angew. Chem. Int. Ed.
2006, 45, 4416; c) J. Wu, W. Pisula, K. Müllen, Chem. Rev. 2007,
107, 718.
[15] H. Ren, A. Krasovskiy, P. Knochel, Org. Lett. 2004, 6, 4215.
[16] For related syntheses of pyridine derivatives, see: a) Q. Huang,
J. A. Hunter, R. C. Larock, Org. Lett. 2001, 3, 2973; b) K. R.
Roesch, R. C. Larock, J. Org. Chem. 2002, 67, 86; c) M. Ohtaka,
H. Nakamura, Y. Yamamoto, Tetrahedron Lett. 2004, 45, 7339;
d) N. Asao, S. Yudha S. , T. Nogami, Y. Yamamoto, Angew.
Chem. 2005, 117, 5662; Angew. Chem. Int. Ed. 2005, 44, 5526;
e) D. Fischer, H. Tomeba, N. K. Pahadi, N. T. Patil, Y. Yama-
moto, Angew. Chem. 2007, 119, 4848; Angew. Chem. Int. Ed.
2007, 46, 4764; f) S. Obika, H. Kono, Y. Yasui, R. Yanada, Y.
Takemoto, J. Org. Chem. 2007, 72, 4462; g) R. Yanada, S. Obika,
H. Kono, Y. Takemoto, Angew. Chem. 2006, 118, 3906; Angew.
Chem. Int. Ed. 2006, 45, 3822; h) M. Nakamura, L. Ilies, S.
Otsubo, E. Nakamura, Org. Lett. 2006, 8, 2803.
[3] a) K. Sonogashira, Y. Tohda, N. Hagihara, Tetrahedron Lett.
1975, 16, 4467; b) K. Takahashi, Y. Kuroyama, K. Sonogashira,
N. Hagihara, Synthesis 1980, 627; c) K. Sonogashira, J. Organo-
met. Chem. 2002, 653, 46; d) L. A. Agrofoglio, I. Gillaizeau, Y.
Saito, Chem. Rev. 2003, 103, 1875; e) Metal-Catalyzed Cross-
Coupling Reactions (Eds.: F. Diederich, P. J. Stang), Wiley-VCH,
Weinheim, 1998; f) J. Hassan, M. SØvignon, C. Gozzi, E. Schulz,
M. Lemaire, Chem. Rev. 2002, 102, 1359; g) S. Kotha, K. Lahiri,
D. Kashinath, Tetrahedron 2002, 58, 9633; h) A. F. Littke, G. C.
Fu, Angew. Chem. 2002, 114, 4350; Angew. Chem. Int. Ed. 2002,
41, 4176; i) S. P. Stanforth, Tetrahedron 1998, 54, 263; j) R. R.
Tykwinski, Angew. Chem. 2003, 115, 1604; Angew. Chem. Int.
Ed. 2003, 42, 1566; k) for a review, see: H. Doucet, J.-C. Hierso,
Angew. Chem. 2007, 119, 850; Angew. Chem. Int. Ed. 2007, 46,
834; for related papers, see: l) D. Gelman, S. L. Buchwald,
Angew. Chem. 2003, 115, 6175; Angew. Chem. Int. Ed. 2003, 42,
5993; m) M. Eckhardt, G. C. Fu, J. Am. Chem. Soc. 2003, 125,
13642; n) T. Hundertmark, A. F. Littke, S. L. Buchwald, G. C.
[17] For cycloaddition of nitriles with mono-and dilithiumbutadiene,
see: J. Chen, Q. Song, C. Wang, Z. Xi, J. Am. Chem. Soc. 2002,
124, 6238.
[18] J. E. Baldwin, J. Chem. Soc. Chem. Commun. 1976, 734.
9096 www.angewandte.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2007, 46, 9093 –9096
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&
&&&&
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
&
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&
Take advantage of blue reference links
&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&