Synthesis of allenes by palladium-catalyzed SN2′ reaction of indium organometallics with propargylic esters

Article abstract of DOI:10.1055/s-2007-983849

Allenes have been efficiently prepared by the reaction of propargylic esters (benzoates, acetates, carbonates) with triorganoindium compounds (R ₃In) under palladium catalysis, via an S_N2′ rearrangement. The reaction proceeds smoothl

Full text of DOI:10.1055/s-2007-983849

PRACTICAL SYNTHETIC PROCEDURES
3595
Synthesis of Allenes by Palladium-Catalyzed SN2¢ Reaction of Indium
Organometallics with Propargylic Esters
Synthesis of
A
lle
i
nes via
c
Indium Or
a
r
Departamento de Química Fundamental, Universidade da Coruña, 15071 A Coruña, Spain
Fax +34(981)167065; E-mail: qfsarand@udc.es; E-mail: sestelo@udc.es
PSP
Received 4 April 2007
No102
Abstract: Allenes have been efficiently prepared by the reaction of propargylic esters (benzoates, acetates, carbonates) with triorganoindi-
um compounds (R3In) under palladium catalysis, via an SN2¢ rearrangement. The reaction proceeds smoothly at room temperature with a
variety of aryl-, alkenyl-, and alkynylindium reagents. The yields obtained are high and the regioselectivity is complete both in the case of
terminal and nonterminal propargylic esters.
Key words: allenes, indium organometallics, palladium catalysis, propargylic esters, regioselective reactions
Pd(DPEphos)Cl2
R2
X
R
R2
R3
(2 mol%)
R3
R1
•
R3In
+
THF, r.t.
8–10 h
R1
60–96%
R = aryl, vinyl, alkynyl
X = OBz, OAc, OCO2Me
Scheme 1
lyzed conjugate addition reaction,6 and the palladium-
catalyzed cross-coupling reactions.7 More recently, we
Introduction
Allenes are attractive building blocks in modern organic found that R3In can be regioselectively coupled with allyl
chemistry due to their extensive reactivity and axial halides and esters under palladium catalysis affording the
chirality.1 They can participate as nucleophiles or electro- SN2 product, or, under copper catalysis, affording the SN2¢
philes in different organic transformations and in cycload- product.8 The procedure summarized in Scheme 1 encom-
ditions or metathesis reactions. Additionally, the axial passes a new set of reactions in which the reaction of R3In
chirality has made possible their use in asymmetric syn- with propargylic esters, under palladium catalysis, affords
thesis. The allene functionality is also present in a variety allenes in good yields via SN2¢ displacement.9
of natural products and pharmacologically active com-
pounds.2 Therefore, the development of versatile synthet-
ic methods of allenes has gained considerable interest in Scope and Limitations
recent years.
We explored the reactivity of triorganoindium reagents
Allenes can be generally prepared from propargyl alcohol
towards propargylic substrates under metal catalysis. Un-
der palladium catalysis, we found that the reaction of the
derivatives by SN2¢ displacement with organocopper spe-
cies.3 Additionally, Grignard4 and organozinc reagents5
propargyl benzoate 1 with triphenylindium (120 mol%)
can be also used in SN2¢ propargylic substitution reactions
and Pd(DPEphos)Cl210 (2 mol%) as catalyst, afforded the
under transition metal catalysis. Herein, we report the ef-
allene 5 in 79% yield after eight hours at room tempera-
ficient synthesis of allenes by palladium-catalyzed SN2¢
ture in THF (Table 1, entry 1). During our studies we re-
reaction of indium organometallics with propargylic es-
alized that, despite the ability of R3In in cross-coupling
ters (Scheme 1).
reactions to transfer the three groups attached to indium,
Few years ago, we initiated a research program devoted to
stoichiometric amounts of Ph3In are necessary to totally
the study and application of indium organometallics in
consume the propargylic ester. When lower amounts of
fundamental organic reactions. As a result, we discovered
Ph3In were used, the reaction was not complete due to the
that triorganoindium reagents (R3In) can be used in funda-
formation of biphenyl, a product generated as a conse-
mental organic transformations such as the nickel-cata-
quence of a reductive homodimerization of the nucleo-
phile.
SYNTHESIS 2007, No. 22, pp 3595–3598
x
x.
x
x
.
2
0
0
7
In the reaction we observed that different leaving groups,
such as the acetate 2 and carbonate 3, also reacted effi-
Advanced online publication: 08.08.2007
DOI: 10.1055/s-2007-983849; Art ID: Z08707SS
© Georg Thieme Verlag Stuttgart · New York

3596
R. Riveiros et al.
PRACTICAL SYNTHETIC PROCEDURES
ciently with Ph3In, affording the allene 5 in similar yields
than using benzoate as leaving group (96% and 90%
yields, respectively, Table 1, entries 2 and 3).
Table 1 Allenes 5–13 Prepared from Terminal Alkynes
Pd(DPEphos)Cl2
R1
X
R
H
R1
R2
(2 mol%)
R2
R3In
+
•
The versatility of this novel reaction was studied using in-
dium reagents furnished with aryl, alkenyl, and alkynyl
groups, and the results are shown in Table 1. The reaction
of substituted arylindium reagents such as tri(2-methoxy-
phenyl)indium with the benzoates 1 and 4 gave aryl al-
lenes 6 and 11 in good yields (Table 1, entries 4 and 9,
respectively). For alkenylindium reagents, the reaction of
trivinylindium with benzoate 1 also afforded the corre-
sponding alkenyl allene 7 in high yield (Table 1, entry 5).
The alkynyl group can also be efficiently transferred from
indium reagents as shown in the reaction of tri(phenyl-
ethynyl)indium or tris[(trimethylsilyl)ethynyl]indium
with benzoates 1 and 4 to give the corresponding al-
lenynes 8, 9, 12 and 13 (Table 1, entries 6, 7, 10 and 11).
The reactions with alkylindium reagents did not afford the
corresponding cross-coupling products in good yields. In
these cases it seems that the b-hydride elimination reac-
tion takes place prior to the formation of the carbon–car-
bon bond by reductive elimination.
THF, r.t.
8–10 h
1: R1 = Ph, R2 = Me, X = OBz
2: R1 = Ph, R2 = Me, X = OAc
3: R1 = Ph, R2 = Me, X = OCO2Me
4: R1 = Me, R2 = H, X = OBz
5–13
Entry R
Propargylic Product
ester
Yield
(%)a
Ph
Me
Ph
•
1
Ph
1
79
H
5
2
3
2
3
5
96
90
5
OMe Me
4
5
6
2-MeOC6H4
CH2=CH
1
1
1
81b
85
•
Ph
H
The reactivity of R3In with nonterminal alkynes was test-
ed using the propargyl benzoate 14 derived from but-3-
yn-2-ol.11 Under the previous conditions reported before,
6
7
Me
•
H
Ph
Table 2 Allenes 15–19 Prepared from Nonterminal Alkynes
Me
Pd(DPEphos)Cl2
Me3Si
H
R
H
(2 mol%)
•
Ph
Me3SiC≡C
83
Ph
R3In
n-Bu
•
+
THF, r.t.
8–10 h
OBz
n-Bu
Ph
H
•
8
14
15–19
Me
Ph
Entry
1
R
Product
Yield (%)a
7
8
9
PhC≡C
Ph
1
4
4
85c
80
Ph
Ph
H
H
•
Ph
88
9
Ph
n-Bu
Ph
H
15
•
OMe
•
H
H
Me
10
2
3
4
2-MeOC6H4
CH2=CH
70b
75
Ph
OMe
H
n-Bu
2-MeOC6H4
60b
•
Me
16
H
H
•
11
n-Bu
Ph
H
Me3Si
17
•
Me
H
10
11
Me3SiC≡C
PhC≡C
4
4
70
90
Me3Si
H
•
Ph
Me3SiC≡C
84
12
n-Bu
H
Ph
18
H
•
Me
Ph
•
Ph
H
5
PhC≡C
81
13
n-Bu
a Isolated yield.
19
b Reaction performed at reflux.
a Isolated yield.
b Reaction performed at reflux.
c Reaction performed with Pd2dba3/P(2-furyl)3 (1:4, 2 mol%) as cata-
lyst.
Synthesis 2007, No. 22, 3595–3598 © Thieme Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
Synthesis of Allenes via Indium Organometallics
3597
Buta-1,2-dienylbenzene (10)16
the palladium-catalyzed reactions of aryl-, alkenyl- and
alkynylindium reagents with 14 proceeded with complete
SN2¢ regioselectivity (the SN2 product was not detected in
the reaction mixture by NMR spectroscopy). As in the
previous examples, the corresponding allenes 15–19 were
obtained in good yields (60–82%, Table 2).
1H NMR (CDCl3): d = 1.78 (dd, J = 6.9, 3.0 Hz, 3 H), 5.53 (dq,
J = 6.9, 6.6 Hz, 1 H), 6.09 (dq, J = 6.6, 3.0 Hz, 1 H), 7.14–7.32 (m,
5 H).
13C NMR (CDCl3): d = 14.1 (CH3), 89.6 (CH), 93.9 (CH), 126.6
(3 × CH), 128.5 (2 × CH), 135.1 (C), 206.0 (C).
MS (EI): m/z (%) = 130 (M+, 71), 115 [(M+ – CH3), 86], 84 (100).
In summary, triorganoindium reagents react with propar-
gyl esters under palladium catalysis to afford allenes in
good yields and in high regioselectivity. The reaction can
be performed using various propargylic esters and triaryl-,
trialkenyl-, and trialkynylindium reagents. The reaction
proceeds smoothly at room temperature and the scope of
the propargylic substitution is comparable with that of
other organometallics used in this procedure.
HRMS (EI): m/z calcd for C10H10: 130.0783; found: 130.0786.
1-(Buta-1,2-dienyl)-2-methoxybenzene (11)17
1H NMR (CDCl3): d = 1.78 (dd, J = 3.4, 5.9 Hz, 3 H), 3.85 (s, 3 H),
5.51 (m, 1 H), 6.46–6.54 (m, 1 H), 6.84–6.99 (m, 2 H), 7.13–7.40
(m, 2 H).
13C NMR (CDCl3): d = 14.1 (CH3), 55.6 (CH3), 87.8 (CH), 88.8
(CH), 110.9 (CH), 120.7 (CH), 123.5 (C), 127.7 (CH), 127.7 (CH),
156.0 (C), 206.4 (C).
MS (EI): m/z (%) = 160 (M+, 23), 145 [(M+ – CH3), 100].
Procedures
HRMS (EI): m/z calcd for C11H12O: 160.0888; found: 160.0885.
All reactions were conducted in flame-dried glassware under argon.
NMR spectra were performed in a Bruker Avance 300 (300 MHz
for 1H and 75 MHz for 13C) spectrometer in CDCl3 using the resid-
ual solvent signal at d = 7.26 (1H) or d = 77.0 (13C) as internal stan-
dard. DEPT was used to assign carbon types. Low-resolution
electron-impact mass spectra were measured on a Thermo Finnigan
Trace MS spectrometer at 70 eV. Low-resolution FAB and high-
resolution mass spectra were measured on a Thermo Finnigan MAT
95XP spectrometer.12
Hexa-3,4-dien-1-ynyltrimethylsilane (12)16
1H NMR (CDCl3): d = 0.19 (s, 9 H), 1.73 (dd, J = 3.0, 3.9 Hz, 3 H),
5.31–5.44 (m, 2 H).
13C NMR (CDCl3): d = –0.1 (3 × CH3), 13.5 (CH3), 75.2 (CH), 88.1
(CH), 95.0 (C), 98.2 (C), 213.5 (C).
MS (EI): m/z (%) = 150 (M+, 16), 135 [(M+ – CH3), 100].
HRMS (EI): m/z calcd for C8H11Si (M+ – CH3): 135.0625; found:
Propargyl acetates and benzoates 1, 2, and 4 were prepared from the
corresponding commercial alcohols by treatment with acetyl or
benzoyl chloride in pyridine, in the presence of a catalytic amount
of DMAP.13 Carbonate 3 was prepared by the reaction of the corre-
sponding lithium alkoxide with methyl chloroformate.14 Propargyl
benzoate 14 was prepared from but-3-yn-2-ol by alkylation [n-BuLi
(2 equiv), THF, –78 °C, then n-BuI, HMPA, THF, r.t.] followed by
benzoylation (BzCl, Py, DMAP, CH2Cl2).11
135.0622.
Hexa-3,4-dien-1-ynylbenzene (13)16
1H NMR (CDCl3): d = 1.77 (dd, J = 3.3, 3.8 Hz, 3 H), 5.41–5.59 (m,
2 H), 7.27–7.38 (m, 3 H), 7.41–7.47 (m, 2 H).
13C NMR (CDCl3): d = 13.7 (CH3), 75.3 (CH), 82.7 (C), 88.1 (CH),
89.8 (C), 123.5 (C), 128.0 (CH), 128.2 (2 × CH), 131.4 (2 × CH),
213.1 (C).
MS (EI): m/z (%) = 154 (M+, 14), 139 [(M+ – CH3), 9], 84 (100).
Triorganoindium Reagents
According to previously reported methods,7b triorganoindium com-
pounds were prepared by treatment of the corresponding organo-
lithium or Grignard reagents (3 equiv) with InCl3 (1.1 equiv) in
anhyd THF at –78 °C and warming to r.t. In this procedure triphe-
nyl-, tris[(trimethylsilyl)ethynyl]-, and tri(phenylethynyl)indium
were prepared from the corresponding organolithium reagents, and
trivinylindium and tri(2-methoxyphenyl)indium were prepared
from vinylmagnesium bromide and 2-methoxyphenylmagnesium
bromide, respectively. All organolithium and Grignard solutions
were commercially available and used as received, except (trimeth-
ylsilyl)ethynyl- and (phenylethynyl)lithium which were prepared,
prior to use, by metalation of (trimethylsilyl)acetylene and phenyl-
acetylene, respectively, with n-BuLi in anhyd THF at –78 °C, and
warming to r.t.
HRMS (EI): m/z calcd for C12H10: 154.0777; found: 154.0773.
1,3-Diphenylhepta-1,2-diene (15)18
1H NMR (CDCl3): d = 0.95 (t, J = 7.1 Hz, 3 H), 1.41–1.69 (m, 4 H),
2.51–2.68 (m, 2 H), 6.56 (t, J = 3.0 Hz, 1 H), 7.21–7.64 (m, 10 H).
13C NMR (CDCl3): d = 13.9 (CH3), 22.6 (CH2), 29.9 (CH2), 30.1
(CH2), 97.8 (CH), 110.0 (C), 126.1 (2 × CH), 126.7 (2 × CH), 126.9
(CH), 127.0 (CH), 128.5 (2 × CH), 128.7 (2 × CH), 206.5 (C).
MS (EI): m/z (%) = 248 (M+, 6), 219 [(M+ – C2H5), 6], 206 [(M+ –
C3H6), 100].
HRMS (EI): m/z calcd for C19H20: 248.1560; found: 248.1554.
1-Methoxy-2-(1-phenylhepta-1,2-dien-3-yl)benzene (16)
1H NMR (CDCl3): d = 0.92 (t, J = 7.1 Hz, 3 H), 1.38–1.59 (m, 4 H),
2.53–2.59 (dt, J = 2.8, 7.4 Hz, 2 H), 3.82 (s, 3 H), 6.28 (t, J = 2.8 Hz,
1 H), 6.85–7.02 (m, 3 H), 7.18–7.45 (m, 6 H).
13C NMR (CDCl3): d = 13.9 (CH3), 22.5 (CH2), 30.2 (CH2), 32.5
(CH2), 55.5 (CH3), 94.5 (CH), 107.3 (C), 111.1 (CH), 120.6 (CH),
126.5 (CH), 126.8 (2 × CH), 126.9 (C), 128.3 (CH), 128.5 (2 × CH),
129.4 (CH), 135.5 (C), 156.9 (C), 205.8 (C).
Palladium-Catalyzed Cross-Coupling Reaction of Propargylic
Esters with Indium(III) Organometallics; General Procedure
To a suspension of Pd(DPEphos)Cl2 (14.3 mg, 0.02 mmol) and the
appropriate propargylic ester 1–4 (1 mmol) in anhyd THF (7 mL)
was added slowly a solution of R3In (1.2 mmol, ca. 0.24 M in anhyd
THF). The resulting solution was stirred at r.t. for 8–10 h and the re-
action quenched by the addition of a few drops of MeOH. The mix-
ture was concentrated and the residue was purified by flash
chromatography (hexanes) affording, after concentration and high-
vacuum drying, the corresponding allenes as colorless to yellowish
oils.15
MS (EI): m/z (%) = 278 (M+, 21), 263 [(M+ – CH3), 35], 84 (100).
HRMS (EI): m/z calcd for C20H22O: 278.1671; found: 278.1665.
Synthesis 2007, No. 22, 3595–3598 © Thieme Stuttgart · New York

3598
R. Riveiros et al.
PRACTICAL SYNTHETIC PROCEDURES
1-(3-Vinylhepta-1,2-dienyl)benzene (17)
Meijere, A.; Diederich, F., Eds.; Wiley-VCH: Weinheim,
2004, 585. (b) Alexakis, A. Pure Appl. Chem. 1992, 64,
387. (c) Hoffmann-Röder, A.; Krause, N. In Modern Allene
Chemistry; Krause, N.; Hashmi, A. S. K., Eds.; Wiley-VCH:
Weinheim, 2004, 51.
1H NMR (CDCl3): d = 0.93 (t, J = 7.4 Hz, 3 H), 1.35–1.59 (m, 4 H),
2.26–2.33 (m, 2 H), 5.11 (d, J = 10.4 Hz, 1 H), 5.29 (d, J = 16.5 Hz,
1 H), 6.35 (m, 2 H), 7.20–7.35 (m, 5 H).
13C NMR (CDCl3): d = 13.9 (CH3), 22.6 (CH2), 27.9 (CH2), 95.8
(CH), 109.3 (C), 113.1 (CH2), 126.8 (2 × CH), 128.6 (2 × CH),
134.4 (CH), 134.8 (C), 108.6 (C).
(4) (a) Pasto, D. J.; Hennion, G. F.; Shults, R. H.; Waterhouse,
A.; Chou, S.-K. J. Org. Chem. 1976, 41, 3496. (b) Jeffery-
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5019.
MS (EI): m/z (%) = 198 (M+, 8), 183 [(M+ – CH3), 6], 141 (100).
(5) Negishi, E.; Liu, F. In Handbook of Organopalladium
Chemistry for Organic Synthesis; Negishi, E., Ed.; Wiley:
New York, 2002, 551.
HRMS (EI): m/z calcd for C15H18: 198.1409; found: 198.1415.
3-[2-(Phenylethenylidene)hept-1-ynyl]trimethylsilane (18)
1H NMR (CDCl3): d = 0.20 (s, 9 H), 0.92 (t, J = 7.4 Hz, 3 H), 1.34–
1.61 (m, 4 H), 2.23–2.29 (m, 2 H), 6.35 (t, J = 3.0 Hz, 1 H), 7.21–
7.36 (m, 5 H).
(6) Pérez, I.; Pérez Sestelo, J.; Maestro, M. A.; Mouriño, A.;
Sarandeses, L. A. J. Org. Chem. 1998, 63, 10074.
(7) (a) Pérez, I.; Pérez Sestelo, J.; Sarandeses, L. A. Org. Lett.
1999, 1, 1267. (b) Pérez, I.; Pérez Sestelo, J.; Sarandeses, L.
A. J. Am. Chem. Soc. 2001, 123, 4155. (c) Pena, M. A.;
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Commun. 2002, 2246. (d) Pena, M. A.; Pérez Sestelo, J.;
Sarandeses, L. A. Synthesis 2003, 780. (e) Pena, M. A.;
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(f) Pena, M. A.; Pérez Sestelo, J.; Sarandeses, L. A. J. Org.
Chem. 2007, 72, 1271.
(8) (a) Rodríguez, D.; Pérez Sestelo, J.; Sarandeses, L. A. J.
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Org. Chem. 2004, 69, 3957. (c) Rodríguez, D.; Pérez
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(9) Riveiros, R.; Rodríguez, D.; Pérez Sestelo, J.; Sarandeses, L.
A. Org. Lett. 2006, 8, 1403.
(10) (a) DPEphos = bis[o-(diphenylphosphino)phenyl] ether.
(b) Kranenburg, M.; van der Burgt, Y. E. M.; Kamer, P. C.
J.; van Leeuwen, P. W. N. M.; Goubitz, K.; Fraanje, J.
Organometallics 1995, 14, 3081. (c) Huang, Z.; Qian, M.;
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1984, 49, 3394. (b) Wang, S.; Zhang, L. J. Am. Chem. Soc.
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13C NMR (CDCl3): d = 0.0 (3 × CH3), 13.8 (CH3), 22.1 (CH2), 29.8
(CH2), 33.6 (CH2), 94.4 (C), 96.3 (C), 96.5 (CH), 99.7 (C), 127.27
(2 × CH), 127.32 (CH), 128.7 (2 × CH), 133.6 (C), 211.8 (C).
MS (EI): m/z (%) = 268 (M+, 4), 253 [(M+ – CH3), 27], 211 (100).
HRMS (EI): m/z calcd for C18H24Si: 268.1642; found: 268.1634.
3-Butyl-1,5-diphenylpenta-1,2-dien-4-yne (19)
1H NMR (CDCl3): d = 0.95 (t, J = 7.4 Hz, 3 H), 1.41–1.70 (m, 4 H),
2.33–2.40 (m, 2 H), 6.42 (t, J = 2.7 Hz, 1 H), 7.15–7.40 (m, 10 H).
13C NMR (CDCl3): d = 13.9 (CH3), 22.1 (CH2), 30.1 (CH2), 33.8
(CH2), 84.2 (C), 91.4 (C), 94.5 (C), 96.2 (CH), 123.5 (C), 127.3 (2
× CH), 127.4 (CH), 128.1 (CH), 128.2 (2 × CH), 128.7 (2 × CH),
131.5 (2 × CH), 133.7 (C), 211.5 (C).
MS (EI): m/z (%) = 272 (M+, 11), 257 [(M+ – CH3), 17], 229 (100).
HRMS (EI): m/z calcd for C21H20: 272.1560; found: 272.1553.
Acknowledgment
We are grateful to the Ministerio de Educación y Ciencia (Spain,
BQU2003-00301 and CTQ2006-06166), Xunta de Galicia
(PGIDIT04PXIC10308PN), and FEDER for financial support. R.R.
thanks Xunta de Galicia for an ‘Isidro Parga Pondal’ contract.
(12) For general experimental methods, see ref. 8a.
(13) Höffe, G.; Steglich, W.; Vorbrüggen, H. Angew. Chem., Int.
Ed. Engl. 1978, 17, 569.
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124, 9072.
(15) Spectroscopic and analytical data for allenes 5–9 in Table 1
have been previously reported in ref. 9. Spectroscopic and
analytical data for allenes 10–13 and 15–19 are reported
herein.
(16) Ruitenberg, K.; Kleijn, H.; Elsevier, C. J.; Meijer, J.;
Vermeer, P. Tetrahedron Lett. 1981, 22, 1451.
(17) Caporusso, A. M.; Zampieri, A.; Aronica, L. A.; Banti, D. J.
Org. Chem. 2006, 71, 1902.
References
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(3) For general references, see: (a) Tsuji, J.; Mandai, T. In
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Synthesis 2007, No. 22, 3595–3598 © Thieme Stuttgart · New York