Synthesis of polyfunctional allenes by successive copper-mediated substitutions

Article abstract of DOI:10.1002/chem.201003273

Readily available 1,1-dichloro-2-alkynes are versatile starting materials for the synthesis of polyfunctionalized allenes. They can be prepared from commercially available terminal alkynes in a two-step procedure. The Cu-mediated reaction of several 1,1-propargylic derivatives with functionalized alkyl, benzylic, or allylic zinc reagents proceeds exclusively with S _N2′ selectivity and allows a rapid and efficient synthesis of functionalized chloroallenes. These chloroallenes undergo a novel Cu ^I-catalyzed substitution reaction with functionalized arylmagnesium reagents with excellent S_N2 selectivity to give trisubstituted polyfunctionalized allenes. The functional group tolerance is excellent and functionalities, such as cyano, keto, ester, phosphate, trifluoromethyl, and halogens, are well tolerated. Copyright

Full text of DOI:10.1002/chem.201003273

DOI: 10.1002/chem.201003273
Synthesis of Polyfunctional Allenes by Successive Copper-Mediated
Substitutions
Matthias A. Schade, Shigeyuki Yamada, and Paul Knochel*[a]
Abstract: Readily available 1,1-di-
chloro-2-alkynes are versatile starting
materials for the synthesis of polyfunc-
tionalized allenes. They can be pre-
pared from commercially available ter-
minal alkynes in a two-step procedure.
The Cu-mediated reaction of several
1,1-propargylic derivatives with func-
tionalized alkyl, benzylic, or allylic zinc
reagents proceeds exclusively with SN2’
selectivity and allows a rapid and effi-
cient synthesis of functionalized chloro-
tion with functionalized arylmagnesium
reagents with excellent SN2 selectivity
to give trisubstituted polyfunctionalized
allenes. The functional group tolerance
is excellent and functionalities, such as
cyano, keto, ester, phosphate, trifluoro-
methyl, and halogens, are well tolerat-
ed.
AHCTUNGTRENNaGUN llenes. These chloroallenes undergo a
novel CuI-catalyzed substitution reac-
Keywords: alkynes · allenes · cop-
per · nucleophilic substitution · zinc
Introduction
In contrast, the substitution reaction of allenyl bromides
of type 3 usually provides a mixture of alkyne 4 (SN2’ substi-
tution) and allene 5 (SN2 substitution) (Scheme 1b).[6] In all
of these substitution reactions on bromoallenes of type 3,
the copper organometallics were prepared from organomag-
nesium or -lithium reagents.[7]
Since arylmagnesium reagents of type 6 (ArMgX) that
tolerate various functional groups can be readily prepared
and have proven to be versatile organometallic intermedi-
ates for the preparation of various polyfunctional mole-
cules,[8] we have investigated their reactivity with bromo- or
chloroallenes in the presence of copper salts and have found
complete SN2 selectivity providing only allenes. Herein, we
wish to report a new reaction sequence allowing the prepa-
ration of various polyfunctional allenes 5 starting from com-
mercially available terminal alkynes.
Allenes have found increasing synthetic applications over
the years.[1] They are either target molecules or versatile in-
termediates for the preparation of various cyclic or hetero-
cyclic compounds.[2] The preparation of polyfunctionalized
allenes is especially important[3] and there is a need for syn-
thetic methods that allow the buildup of allenes with various
functional groups.[4]
The preparation of allenes from propargylic halides and
sulfonates by substitution reactions with copper organo-
ACHTUNGTRENNUNG
metallics is well known.[5] Generally, an SN2’ substitution is
observed with high regio- and stereoselectivity. Thus, prop-
argylic derivatives of type 1 react with organocopper re-
agents (R3Cu) providing allenes of type 2 (Scheme 1a).
Results and Discussion
In preliminary studies, we examined the copper-catalyzed
substitution of two unfunctionalized allenes[9] 3a (R=Me)
and 3b (R=Et) with 4-carbethoxyphenylmagnesium chlor-
AHCTUNGTREGiNNNU de (6a) using catalytic amounts of various copper salts
(Table 1). In all cases, the reaction produces only the SN2
substitution product.[10]
Scheme 1. Reactivity pattern of organocopper reagents with propargylic
and allenyl halides.
CuCN·2LiCl[11] provides the highest yields and the reac-
tion scope varying the nature of the arylmagnesium reagents
6 was examined (Table 2). Thus, the ester-substituted aro-
matic organomagnesium reagents 6b and 6c (1.0 equiv)
were treated with 1-bromo-3-methylbuta-1,2-diene (3a,
1.2 equiv, 258C, 1 h) and gave the corresponding trisubstitut-
ed allenes 5c and 5d in 76 and 85% yield, respectively
(Table 2, entries 1 and 2). Similarly, the treatment of
[a] M. A. Schade, Dr. S. Yamada, Prof. Dr. P. Knochel
Department Chemie, Ludwig-Maximilians-Universitꢀt Mꢁnchen
Butenandtstrasse 5–13, 81377 Mꢁnchen (Germany)
Fax : (+49)89-21809977680
E-mail: Paul.Knochel@cup.uni-muenchen.de
2-cyano
ACHTUNGTRENNUNG
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201003273.
3,5-bis(trifluoromethyl)phenylmagnesium
4232
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 4232 – 4237

FULL PAPER
Table 1. Influence of the nature of the copper catalyst.
Table 2. CuI-mediated substitution on allenic bromides leading to substi-
tuted allenes.
Organomagnesium Bromoallene
reagent[a]
Product of
type 5
Yield
[%][b]
CuI salt
R
Yield [%][a]
1
2
3
6b
6c
6d
3a
3a
3b
5c
5d
5e
76
85
92
1
2
3
4
5
6
CuBr (10 mol%)
CuCN·2LiCl (10 mol%)
CuBr (10 mol%)
CuCl·2LiCl (10 mol%)
CuI (10 mol%)
CuCN·2LiCl (10 mol%)
Et
Et
Me
Me
Me
Me
85
89
73
79
75
80
[a] Yield of the isolated analytically pure product.
1.0 equiv) with 1-bromo-3-methylpenta-1,2-diene (3b,
1.2 equiv) at 258C provided the allenes 5e and 5 f in 92 and
89% yield, respectively, within 1 h reaction time (Table 2,
entries 3 and 4). Aromatic Grignard reagents with halogen
substituents, such as 6 f–6h react smoothly with the bro-
moallene 3a leading to the polyfunctional allenes 5g–5i
(64–84%, Table 2, entries 5–7).
4
6e
3b
5 f
89
Furthermore, treatment of the electron-rich 4-methoxy-
phenylmagnesium chloride (6i) with the bromoallene 3a af-
forded the desired allene 5j in 69% yield (Table 2, entry 8).
The functionalized 2-chloromethylphenylmagnesium chlor-
5
6
7
6 f
6g
6h
3a
3a
3a
5g
5h
5i
67
64
84
ACHTUNGTRENNUNGide (6j), prepared by I/Mg-exchange from 2-iodobenzyl
chloride (iPrMgCl·LiCl, À208C, 30 min),[12] reacts with the
bromoallene 3a to give the expected allene 5k in 82% yield
(Table 2, entry 9). Finally, the pyridylmagnesium derivative
6k undergoes a copper-catalyzed substitution with 3a to
give the 3-allenylpyridine 5l (87%, Table 2, entry 10).
To expand the reaction scope of our method, we also de-
veloped a general method for the preparation of functional-
ized chloroallenes of type 7 starting from commercially
available alkynes of type 8.
Thus, the alkynes 8b–8e were treated with BuLi
(1.1 equiv, À208C, 30 min) in THF followed by reaction
with DMF (2 equiv, À208C to 258C, 1 h) leading to the ace-
tylenic aldehydes 9b–9e.[13] After work up, the crude unsatu-
rated aldehydes 9 were dissolved in CH2Cl2 and treated with
PCl5 providing the 1,1-dichloro-2-alkynes 10a–10e in 57–
84% yield (Scheme 2a).[14] The 1,1-dichloropropargylic re-
agents of type 10 prove to be versatile starting materials for
the preparation of various polyfunctional allenes. Thus, we
have developed a two-step reaction sequence leading to
functionalized allenes of type 5: 1) a highly regioselective
copper-mediated SN2’ substitution of alkyl and benzylic zinc
reagents[15] with the dichloropropargyl derivatives 10a–10e
leading to the chloroallenes 7a–7m in 41–96% yield
(Scheme 2b) and 2) a highly regioselective copper-catalyzed
SN2 substitution of chloroallenes of type 7 with functional-
ized arylmagnesium reagents 6 providing the polyfunc-
tionalized allenes 5m–5u in 67–86% yield (Scheme 2c).
The preparation of chloroallenes from propargylic alco-
hols using SOCl2 or HCl is well known.[16] Due to the strong-
ly acidic conditions the tolerance towards functional groups
8
9
6i
6j
3a
3a
5j
69
82
5k
10
6k
3a
5l
87
[a] Complexed salts are omitted for the sake of clarity. [b] Yield of the
isolated analytically pure product.
is limited. Starting from 1,1-dichloro-2-alkynes, a copper-cat-
alyzed SN2’ substitution using organozinc reagents of type 11
allows a simple preparation of functionalized 1-chloro-
AHCTUNGTREGaNNNU llenes. Thus, the alkylzinc reagent 11a (1.0 equiv) reacts
with 1,1-dichlorobut-2-yne (10a, 1.1 equiv, À208C, 30 min)
in the presence of CuCN·2LiCl (1 equiv) to give the chloro-
Chem. Eur. J. 2011, 17, 4232 – 4237
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4233

P. Knochel et al.
Table 3. CuI-mediated substitution on geminal progargylic dichlorides of
type 10 leading to substituted chloroallenes.
Organozinc
reagent[a]
Propargylic
dichloride
Product of
type 7
Yield [%][b]
1
2
11a
11a
10a: R=Me
10b:
7a: R=Me
7b:
90
66
R=Cl
G
R=ClACHTGNUETRNNU(G CH2)4
Scheme 2. Reaction sequence allowing the preparation of polyfunc-
tionalized allenes of type 5.
3
11b
10c
7c
91
ACHTUNGTRENNUNGallene 7a in 90% yield (Table 3, entry 1). The reaction of
4
5
11c
11c
10a: R=Me
10d: R=Pent
7d: R=Me
7e: R=Pent
76
96
11a with 1,1,7-trichlorohept-2-yne (10b) affords exclusively
the allene 7b in 66% yield (Table 3, entry 2). Similarly, 4-
chlorobutylzinc chloride (11b) undergoes a smooth substitu-
tion reaction with 1,1-dichloronon-2-yne (10c) to give the
desired chloroallene 7c in 91% yield (Table 3, entry 3). The
ester-substituted alkylzinc reagent 11c reacts with the prop-
argylic dichlorides 10a and 10d to give the corresponding
6
7
11d
11e
10a
10a
7 f
7g
76
79
chloroACHTUNGTRENNUNGallenes 7d and 7e in 76 and 96% yield, respectively
(Table 3, entries 4 and 5). Furthermore, 4-cyanobutylzinc
chloride (11d) affords, after a copper-catalyzed substitution
reaction, the cyanobutyl functionalized chloroACTHNUGRTNEUNGallene 7 f
(76%, Table 3, entry 6). The highly functionalized alkylzinc
reagent 11e containing a diethylphosphate group[17] reacts
with 10a to give the allene 7g in 79% yield (Table 3,
entry 7).
8
9
11 f
11 f
10a: R=Me
10b:
7h: R=Me
7i:
R=ClACHTGNUETRNNU(G CH2)4
76
87
R=Cl
A
Also, benzylic zinc reagents, such as 3-cyanobenzylzinc
chloride (11 f), the keto-substituted benzylic zinc reagent
11g, and 2-chlorobenzylzinc chloride (11h) react under
copper catalysis with 10a, 10b, or 10d to give the benzyl-
substituted chloroallenes 7h–7k in 41–89% yield (Table 3,
entries 8–11). Finally, the ester-substituted allylic zinc re-
agent 11i[18] provided, by a reaction with 10d and 10e, the
highly functionalized chloroallenes 7l and 7m in 70 and
50% yield, respectively (Table 3, entries 12 and 13).
10
11
11g
11h
10a
10d
7j
41
7k
89[c]
Encouraged by the good results found in the copper-cata-
lyzed substitution of bromoallenes, we applied the method
to chloroallenes of type 7. To our delight, this novel substi-
tution reaction occurred with SN2 selectivity leading to
highly functionalized trisubstituted allenes. Hence, the
12
13
11i
11i
10d: R=Pent
10e:
R=CNACTHUNRTGENNUG(CH2)4 R=CNACHTUGNTREN(NUGN CH2)4
7l: R=Pent
7m:
70[d]
50[d]
chloroACHTUNGTRENNUNGallene 7 f (1.2 equiv) that has a remote nitrile func-
[a] Additional salts generated during the organometallic synthesis are
omitted for the sake of clarity. [b] Yield of the isolated analytically pure
product. [c] 30% CuCN·2LiCl was used. [d] The reaction was performed
at À508C.
tional group smoothly reacts with 4-carbethoxyphenylmag-
nesium chloride (6a, 1.0 equiv, À20 to 258C, 1 h) in the pres-
ence of CuCN·2LiCl as the catalyst (10 mol%) to give the
polyfunctionalized allene 5m in 82% yield (Scheme 3).
To show the scope of this novel SN2 substitution with re-
spect to functionalized chloroallenes, we examined the reac-
tion of diverse substituted chloroallenes with various aryl-
magnesium reagents[19] (Table 4). Thus, 2-chloro-5-trifluoro-
methylphenylmagnesium chloride (6l, 1.0 equiv) reacts with
chloroallene 7 f (1.2 equiv) to give the trisubstituted allene
5n in 86% yield (Table 4, entry 1). Organomagnesium re-
agents with electron-withdrawing groups, such as 3-cyano-
phenylmagnesium chloride (6n) react smoothly with the al-
lenyl chloride 7l to afford the functionalized trisubstituted
allene 5o in 67% yield (Table 4, entry 2). Furthermore,
remote halogen substituents are well tolerated and the reac-
tion of the arylmagnesium reagent 6d with the chloroallene
4234
www.chemeurj.org
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 4232 – 4237

Synthesis of Polyfunctional Allenes
FULL PAPER
Table 4. CuI-mediated substitutions on allenyl chlorides leading to poly-
functional allenes of type 5.
Grignard
Chloroallene
Product
of type 5
Yield [%][b]
Reagent[a]
Scheme 3. Preparation of 5m by CuI-mediated coupling of arylmagnesi-
um reagent 6a with chloroallene 7g.
1
6l
7 f
5n
86
7c gives the expected trisubstituted allene 5p in 76% yield
(Table 4, entry 3). The copper-catalyzed reaction of the
Grignard reagent 6d with the 2-chlorobenzyl-substituted
chloroallene 7k provides the highly substituted allene 5q in
71% yield (Table 4, entry 4). 4-Ethoxycarbonylphenylmag-
nesium chloride (6a), prepared from ethyl 4-iodobenzoate
(iPrMgCl·LiCl, À208C, 30 min), reacts smoothly with the
substituted chloroallenes 7e and 7a to the highly functional-
ized allenes 5r and 5s (83 and 67% yield, Table 4, entries 5
and 6).
2
3
6n
6d
7l
5o
5p
67
76
7c
Moreover, functionalized heterocyclic Grignard reagents,
such as the pyridylmagnesium derivatives 6o and 6j, under-
go clean substitution reactions with the chloroallenes 7e and
7h providing the polyfunctionalized trisubstituted allenes 5t
and 5u in 76 and 71% yield (Table 4, entries 7 and 8).
4
5
6
6d
6a
7k
7e
5q
5r
71
83
Conclusion
By using readily available 1,1-dichloro-2-alkynes of type 10
(prepared in two steps from commercially available al-
kynes), we have reported a convenient synthesis of poly-
functional allenes by using two successive copper-catalyzed
substitution reactions. The first substitution of alkyl and
benzylic zinc halides on the 1,1-dichloromethyl alkynes 10
proceeds with complete SN2’ selectivity leading to 1-chloro-
6a
6o
7a
7e
5s
5t
67
76
ACHTUNGTRENNUNGallenes, whereas the second copper-catalyzed substitution on
chloroallenes 7 with aromatic and heteroaromatic Grignard
reagents proceeds with complete SN2 selectivity leading to
polyfunctional trisubstituted allenes of type 5. The function-
al group compatibility is excellent and functionalities such
as ester, cyano, keto, trifluoromethyl, and halogens are read-
ily tolerated. Further extensions of this methodology are un-
derway in our laboratories.
7
8
6j
7h
5u
71
[a] Additional salts generated during the organometallic synthesis are
omitted for the sake of clarity. [b] Yield of the isolated analytically pure
product.
Experimental Section
For experimental procedures, analytical data and NMR spectra, see the
Supporting Information.
and the reaction mixture was stirred at room temperature for 1 h. Then,
the reaction mixture was poured into an ice-cooled saturated aqueous
NH4Cl solution (25 mL). After extraction with Et2O (3ꢃ25 mL), the or-
ganic layers were dried (Na2SO4), filtered, and concentrated in vacuo.
The crude residue obtained was purified by column chromatography
(SiO2, pentane/Et2O=10:1) to give 5b as a colorless oil (410 mg, 89%).
1H NMR (300 MHz, CDCl3): d=7.97 (d, J=8.5 Hz, 2H), 7.32 (d, J=
Preparation of 5b from 3b: A dry, argon-flushed Schlenk flask equipped
with a magnetic stirring bar and a septum was charged with ethyl 4-iodo-
benzoate (552 mg, 2 mmol) in THF (1.0 mL). iPrMgCl·LiCl (2.0 mL,
2.4 mmol, 1.19m in THF) was added at À308C and the mixture was
stirred for 1 h at this temperature. CuCN·2LiCl (0.2 mmol, 0.2 mL, 1.0m
in THF) followed by 1-bromo-3-methyl-1,2-pentadiene (3b, 386 mg,
2.4 mmol) was added to the freshly prepared Grignard reagent at À208C,
Chem. Eur. J. 2011, 17, 4232 – 4237
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4235

P. Knochel et al.
8.5 Hz, 2H), 6.13 (sxt, J=3.0 Hz, 1H), 4.37 (q, J=7.1 Hz, 2H), 2.19–2.05
(m, 2H), 1.84 (d, J=2.7 Hz, 3H), 1.40 (t, J=7.1 Hz, 3H), 1.07 ppm (t,
J=7.5 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=203.7, 166.5, 141.1,
129.8, 128.2, 126.2, 106.0, 94.1, 60.7, 27.1, 18.5, 14.3, 12.2 ppm; HRMS:
m/z: calcd for C15H18O2: 230.1307; found: 230.1303. MS (EI, 70 eV): m/z
(%): 230 (71) [M+], 157 (100), 142 (96), 129 (59), 128 (70); IR n˜ =2968
(w), 1712 (s), 1606 (m), 1366 (w), 1268 (vs), 1172 (m), 1097 (s), 1018 (m),
864 (m), 760 (m), 696 cmÀ1 (m).
demic Press, London, 1983; d) Allenes in Organic Synthesis (Eds.:
H. E. Schuster, G. M. Coppola), Wiley, New York, 1984.
[2] a) A. Hoffmann-Rçder, N. Krause, Angew. Chem. 2004, 116, 1216–
1236; Angew. Chem. Int. Ed. 2004, 43, 1196–1216; b) N. Krause, A.
Hoffmann-Rçder, Tetrahedron 2004, 60, 11671–11694; c) S. Ma,
Acc. Chem. Res. 2003, 36, 701–712; d) S. Ma, Chem. Rev. 2005, 105,
2829–2871; e) S. Ma, E.-i. Negishi, J. Am. Chem. Soc. 1995, 117,
6345–6357; f) A. S. K. Hashmi, Angew. Chem. 2000, 112, 3737–
3740; Angew. Chem. Int. Ed. 2000, 39, 3590–3593.
[3] a) A. Hoffmann-Rçder, N. Krause, Angew. Chem. 2002, 114, 3057–
3059; Angew. Chem. Int. Ed. 2002, 41, 2933–2935; b) R. Zimmer,
C. U. Dinesh, E. Nandanan, F. A. Khan, Chem. Rev. 2000, 100,
3067–3125; c) C. Deutsch, B. H. Lipshutz, N. Krause, Org. Lett.
2009, 11, 5010–5012; d) K. M. Brummond, J. E. DeForest, Synthesis
2007, 795–818; e) A. H. Stoll, S. B. Blakey, J. Am. Chem. Soc. 2010,
132, 2108–2109.
[4] a) K. M. Brummond, D. Chen, M. M. Davis, J. Org. Chem. 2008, 73,
5064–5068; b) J. P. Varghese, P. Knochel, I. Marek, Org. Lett. 2000,
2, 2849–2852; c) M. Ogasawara, H. Ikeda, T. Hayashi, Angew.
Chem. 2000, 112, 1084–1086; Angew. Chem. Int. Ed. 2000, 39, 1042–
1044.
[5] a) P. Rona, P. J. Crabbꢅ, J. Am. Chem. Soc. 1968, 90, 4733–4734;
b) P. Rona, P. J. Crabbꢅ, J. Am. Chem. Soc. 1969, 91, 3289–3292;
c) N. Krause, A. Hoffmann-Rçder in Modern Organocopper
Chemistry (Ed.: N. Krause), Wiley-VCH, Weinheim, 2002, pp. 145–
166.
Preparation of 7c from 10c: A dry, argon-flushed Schlenk flask equipped
with a magnetic stirring bar and a septum was charged with 4-chlorobu-
tylzinc bromide (11b, 21.4 mL, 18.0 mmol, 0.84m in THF) and cooled to
À208C. Then CuCN·2LiCl (18 mL, 18 mmol, 1m in THF) was added, fol-
lowed by 1,1-dichloronon-2-yne (10c, 3.86 g, 20 mmol). After stirring for
30 min at À208C, the reaction was quenched with saturated NH4Cl solu-
tion (30 mL), extracted with Et2O (3ꢃ50 mL), washed with brine (1ꢃ
30 mL) and dried over Na2SO4. The crude residue obtained after evapo-
ration of solvents was purified by column chromatography (SiO2, pen-
tane) to give 7c as a colorless oil (4.09 g, 91%). 1H NMR (300 MHz,
CDCl3): d=6.04 (quin, J=2.2 Hz, 1H), 3.56 (t, J=6.6 Hz, 2H), 2.16–2.00
(m, 4H), 1.92–1.73 (m, 2H), 1.71–1.54 (m, 2H), 1.54–1.17 (m, 8H), 0.98–
0.78 ppm (m, 3H); 13C NMR (100 MHz, CDCl3): d=198.6, 116.7, 89.1,
44.8, 33.1, 32.2, 31.9, 31.6, 28.8, 27.1, 24.4, 22.6, 14.0 ppm; HRMS: m/z:
calcd for C13H22Cl2: 248.1099; found: 248.1077; MS (EI, 70 eV): m/z
(%):248 (>1) [M+], 143 (25), 104 (30), 102 (100), 79 (19), 67 (19), 41
˜
(23). IR n=3056 (vw), 2954 (s), 2928 (vs), 2858 (s), 1958 (w), 1720 (vw),
1456 (w), 1378 (w), 1310 (w), 1206 (w), 722 (m), 652 cmÀ1 (w).
Preparation of 5m from 7 f: A dry, argon-flushed Schlenk flask equipped
with a magnetic stirring bar and a septum was charged with ethyl 4-iodo-
benzoate (552 mg, 2 mmol) in THF (1.0 mL). iPrMgCl·LiCl (1.6 mL,
2.1 mmol, 1.3m in THF) was added at À208C and the mixture was stirred
for 30 min at this temperature. CuCN·2LiCl (0.2 mmol, 0.2 mL, 1.0m in
THF) followed by 7-chloro-5-methylhepta-5,6-dienenitrile (7 f, 373 mg,
2.4 mmol) were added to the freshly prepared Grignard reagent at
À208C and the reaction mixture was stirred at room temperature for 1 h.
Then, the reaction mixture was poured into an ice-cooled saturated aque-
ous NH4Cl solution (25 mL). After extraction with Et2O (3ꢃ25 mL), the
organic layers were dried (Na2SO4), filtered, and concentrated in vacuo.
The crude residue obtained was purified by column chromatography
(SiO2, pentane/Et2O=7:3) to give 5m as a light yellow oil (444 mg,
82%). 1H NMR (300 MHz, CDCl3): d=7.94 (d, J=8.2 Hz, 2H), 7.26 (d,
J=8.4 Hz, 2H), 6.14 (d, J=2.8 Hz, 1H), 4.34 (q, J=7.11 Hz, 2H), 2.41–
2.29 (m, 2H), 2.29–2.16 (m, 2H), 1.89–1.74 (m, 5H), 1.36 ppm (t, J=
7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=203.5, 166.4, 140.1, 129.9,
128.7, 126.3, 119.3, 102.6, 94.8, 60.8, 32.4, 23.2, 18.8, 16.6, 14.3 ppm;
HRMS: m/z: calcd for C17H19NO2: 269.1416, found: 269.1407; MS (EI,
70 eV): m/z (%):269 (15) [M+], 224 (30), 216 (27), 196 (81), 155 (27),
[6] a) E. J. Corey, N. W. Boaz, Tetrahedron Lett. 1984, 25, 3059–3062;
b) A. M. Caporusso, C. Polizzi, L. Lardicci, J. Org. Chem. 1987, 52,
3920–3923; d) C. Polizzi, C. Consoloni, L. Lardicci, A. M. Caporus-
so, J. Organomet. Chem. 1991, 417, 289–304; e) A. M. Caporusso, S.
Filippi, F. Barontini, P. Salvadori, Tetrahedron Lett. 2000, 41, 1227–
1230; f) A. M. Caporusso, C. Polizzi, L. Lardicci, Tetrahedron Lett.
1987, 28, 6073–6076; g) A. M. Caporusso, A. Zampieri, L. A. Aroni-
ca, D. Banti, J. Org. Chem. 2006, 71, 1902–1910.
[7] a) M. Kalli, P. D. Landor, S. R. Landor, J. Chem. Soc. Perkin Trans.
1 1973, 1347–1349; b) R. K. Dieter, N. Chen, V. K. Gore, J. Org.
Chem. 2006, 71, 8755–8760; c) for the use of organozinc reagents,
see: K. Kobayashi, H. Naka, A. E. Wheatley, Y. Kondo, Org. Lett.
2008, 10, 3375–3377; d) for the use of organoindium reagents, see:
R. Riveiros, D. Rodrꢆguez, J. P. Sestelo, L. A. Sarandeses, Org. Lett.
2006, 8, 1403–1406; e) K. Lee, P. H. Lee, Org. Lett. 2008, 10, 2441–
2444; f) for an allene synthesis by sulfoxide–metal exchange, see: T.
Satoh, N. Hanaki, Y. Kuramochi, Y. Inoue, K. Hosoya, K. Sakai, Tet-
rahedron 2002, 58, 2533–2549.
[8] a) P. Knochel, W. Dohle, N. Gommermann, F. F. Kneisel, F. Kopp, T.
Korn, I. Sapountzis, V. A. Vu, Angew. Chem. 2003, 115, 4438–4456;
Angew. Chem. Int. Ed. 2003, 42, 4302–4320; b) F. M. Piller, P. Ap-
pukkuttan, A. Gavryushin, M. Helm, P. Knochel, Angew. Chem.
2008, 120, 6907–6911; Angew. Chem. Int. Ed. 2008, 47, 6802–6806;
c) F. M. Piller, A. Metzger, M. A. Schade, B. A. Haag, A. Gavryush-
in, P. Knochel, Chem. Eur. J. 2009, 15, 7192–7202.
˜
143 (100), 128 (42); IR n=2982 (w), 2940 (w), 2906 (w), 1950 (vw), 1710
(vs), 1606 (m), 1446 (w), 1426 (w), 1392 (w), 1368 (w), 1272 (vs), 1174
(m), 1100 (s), 1018 (m), 868 (w), 762 (w), 698 cmÀ1 (w).
[9] a) S. R. Landor, A. N. Patel, P. F. Whiter, P. M. Greaves, J. Chem.
Soc. C 1966, 1223–1226; b) M. Montury, J. Gorꢅ, Synth. Commun.
1980, 10, 873–879.
[10] We observed the formation of the isomeric alkyne of type 4 only if
stoichiometric amounts of CuBr were used.
Acknowledgements
The research leading to these results has received funding from the Euro-
pean Research Council under the European Communityꢄs Seventh
Framework Programme (FP7/2007–2013) ERC grant agreement no.
227763. Furthermore, we thank the DFG (SFB 749) for a financial sup-
port. We also thank Chemetall GmbH (Frankfurt), Umicore AG (An-
gleur, Belgium), Heraeus Holding GmbH (Hanau), and BASF SE (Lud-
wigshafen) for their generous gift of chemicals.
[11] P. Knochel, M. C. P. Yeh, S. C. Berk, J. Talbert, J. Org. Chem. 1988,
53, 2390–2392.
[12] a) T. Delacroix, L. Bꢅrillon, G. Cahiez, P. Knochel, J. Org. Chem.
2000, 65, 8108–8110; b) A. Krasovskiy, P. Knochel, Angew. Chem.
2004, 116, 3396–3399; Angew. Chem. Int. Ed. 2004, 43, 3333–3336;
c) C. B. Rauhut, C. Cervino, A. Krasovskiy, P. Knochel, Synlett 2009,
67–70.
[13] M. Journet, D. Cai, L. M. DiMichele, R. D. Larsen, Tetrahedron
Lett. 1998, 39, 6427–6428.
[14] K. N. Shavrin, I. V. Krylova, I. B. Shvedova, G. P. Okonnishnikova,
I. E. Dolgy, O. M. Nefedov, J. Chem. Soc. Perkin Trans. 2 1991,
1875–1881.
[1] a) Modern Allene Chemistry (Eds.: N. Krause, A. S. K. Hashmi),
Wiley-VCH, Weinheim, 2005; b) The Chemistry of Ketenes, Allenes,
and Related Compounds (Ed.: S. E. Patai), Wiley, New York, 1980;
c) The Chemistry of the Allenes: Synthesis (Ed.: S. R. Landor), Aca-
4236
www.chemeurj.org
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 4232 – 4237

Synthesis of Polyfunctional Allenes
FULL PAPER
[15] a) A. Krasovskiy, V. Malakhov, A. Gavryushin, P. Knochel, Angew.
Chem. 2006, 118, 6186–6190; Angew. Chem. Int. Ed. 2006, 45, 6040–
6044; b) A. Metzger, M. A. Schade, P. Knochel, Org. Lett. 2008, 10,
1107–1110; c) A. Metzger, C. Argyo, P. Knochel, Synthesis 2010,
882–891.
[16] a) H. Mayr, I. K. Halberstad-Kausch, Chem. Ber. 1982, 115, 3479–
3515; b) T. L. Jacobs, W. L. Petty, E. G. Teach, J. Am. Chem. Soc.
1960, 82, 4094–4097.
[18] N. ElAlami, B. Belaud, J. Villiꢅras, J. Organomet. Chem. 1988, 348,
1.
[19] a) M. Mosrin, M. Petrera, P. Knochel, Synthesis 2008, 3697–3702;
b) L. Melzig, C. B. Rauhut, P. Knochel, Synthesis 2009, 1041–1048;
c) C. Despotopoulou, C. Gignoux, D. McConnell, P. Knochel, Syn-
thesis 2009, 3661–3671; d) A. Metzger, A. Gavryushin, P. Knochel,
Synlett 2009, 1433–1436; e) G. Monzon, P. Knochel, Synlett 2010,
304–308.
[17] C. Retherford, T.-S. Chou, R. M. Schelkun, P. Knochel, Tetrahedron
Lett. 1990, 31, 1833–1836.
Received: November 13, 2010
Published online: March 7, 2011
Chem. Eur. J. 2011, 17, 4232 – 4237
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4237