Palladium(II)-catalyzed intramolecular 1,2-oxidation of allenes involving nitrogen nucleophiles

Article abstract of DOI:10.1016/S0040-4039(99)02343-6

A series of allenic tosylamides have been prepared and shown to undergo palladium(II)-catalyzed cyclization in the presence of lithium bromide and a copper(II) salt to give pyrrolidines. Palladium-catalyzed 1,2-oxidation of allenic lactams in the presence

Full text of DOI:10.1016/S0040-4039(99)02343-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 1619–1622
Palladium(II)-catalyzed intramolecular 1,2-oxidation of allenes
involving nitrogen nucleophiles
Catrin Jonasson,a Willem F. J. Karstens,b Henk Hiemstra b and Jan-E. Bäckvall a,∗
aDepartment of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden
bLaboratory of Organic Chemistry, Institute of Molecular Chemistry, University of Amsterdam, Nieuwe Achtergracht 129,
1018 WS Amsterdam, The Netherlands
Received 12 November 1999; accepted 16 December 1999
Abstract
A series of allenic tosylamides have been prepared and shown to undergo palladium(II)-catalyzed cyclization
in the presence of lithium bromide and a copper(II) salt to give pyrrolidines. Palladium-catalyzed 1,2-oxidation of
allenic lactams in the presence of LiBr and p-benzoquinone was also studied. © 2000 Elsevier Science Ltd. All
rights reserved.
Keywords: allenes; cyclization; nitrogen heterocycles; palladium catalysis.
Palladium–catalyzed reactions of unsaturated hydrocarbons have been extensively studied and a large
number of selective organic transformations have been reported.1 In addition to dienes, acetylenes and
olefins, allenes have in particular attracted considerable interest in recent years.2–7 We have recently
developed mild procedures for palladium-catalyzed 1,2-oxidation of allenes.7 These reactions are carried
out in acetic acid with palladium acetate as the catalyst and p-benzoquinone as the oxidant in the presence
of two nucleophiles, which are added across the double bond. Nucleophiles that have been used so far
include halides,7a carboxylates,7b and alcohols.7c It would be of great synthetic interest to extend these
1,2-oxidations to other nucleophiles such as carbon and nitrogen nucleophiles. In this communication we
report on the use of nitrogen nucleophiles in the palladium-catalyzed 1,2-oxidation of allenes.
Palladium-catalyzed oxidation of allenic tosylamide 18 in acetic acid employing p-benzoquinone as the
oxidant and LiBr as the external nucleophile afforded only recovered starting material and no pyrrolidine
2 could be detected (Eq. (1)). Apparently, the amide nitrogen cannot act as a nucleophile under the
slightly acidic conditions employed here.
(1)
Since p-benzoquinone requires acidic reaction conditions to work as an oxidant, alternative oxidants
were examined. Thus, allenic tosylamide 1 was reacted with LiBr and Pd(OAc)2 in THF using CuCl2
∗
Corresponding author. Tel: +46 8 6747178; fax: +46 8 154908; e-mail: jeb@organ.su.se (J.-E. Bäckvall)
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02343-6
tetl 16271

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as the reoxidant, which afforded the corresponding pyrrolidine 2 in 30% yield. In order to optimize
the reaction conditions other solvents (CH2Cl2, CH3CN, acetone, ethanol, DMF) were tried, of which
acetonitrile gave the best results. The yield was further improved by using one equivalent of base.
However, the use of CuCl2 as an oxidant gave rise to ca. 4% of a side product, resulting from attack
of a chloride on the middle allene carbon instead of a bromide. To eliminate this side product, other
oxidants (CuBr2, Cu(OTf)2, Cu(OAc)2) were screened. The use of Cu(OAc)2 gave the best result. Thus,
reaction of allenic tosylamide 1 with LiBr, K2CO3 and Cu(OAc)2 in the presence of a catalytic amount
of Pd(OAc)2 in acetonitrile under an O2 atmosphere afforded the desired pyrrolidine 2 in 72% yield, with
mainly Z stereochemistry (Z:E=93:7). The stereochemical assignment was made by NOE measurements.
A few other N-tosylamides 3, 5, 7, 9 and 118 were also shown to cyclize under the palladium-catalyzed
conditions (Table 1) affording the corresponding pyrrolidines 4, 6, 8, 10 and 12, respectively, in good
isolated yields.11 The non-substituted allenic amide 11 did, however, work better with Cu(OTf)2 as
an oxidant and the disubstituted allenic amides 7 and 9 worked best in the presence of CuCl2. The
disubstituted allenes did not show the side product resulting from chloride attack.
Table 1
Palladium-catalyzed 1,2-oxidation of substituted allenic tosylamidesa
A likely mechanism for the palladium-catalyzed intramolecular oxidation is given in Eq. (2). Coordi-
nation of the allene 1 to palladium and subsequent bromide attack at the central allenic carbon produces
a π-allyl palladium intermediate 13, which undergoes an intramolecular nucleophilic attack to give the
pyrrolidine product 2 and Pd(0). The copper(II) salt reoxidizes the Pd(0) back to Pd(II).

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(2)
In most palladium-catalyzed reactions with allenes, nucleophiles (such as nitrogen and oxygen nucleo-
philes) attack one of the terminal sp2–carbon atoms.9 However, some unexpected regioselectivity was
recently observed in an intramolecular palladium(0)-catalyzed reaction. Thus, a lactam nitrogen atom,
with a two-carbon tether between the allene and the nitrogen atom, reacted at the middle sp-carbon of the
allene to form five-membered ring enamides.10 It was, therefore, of interest to study these compounds in
the present palladium(II)-catalyzed 1,2-oxidations. The allenic lactams were prepared using a copper(I)-
mediated displacement of propargylic tosylates with the zinc reagent of the corresponding lactam to
afford different substituted allenes in moderate yields.10b
Allenic lactam 14 was subjected to the previously developed cyclization conditions with p-
benzoquinone as the reoxidant,7 which gave the 1,2-dibromo product 16 as an 8:1 mixture of double
bond isomers (Scheme 1). No cyclic enamide product could be detected. To find out if there was any
steric influence on the outcome of the reaction, the allenic lactam was substituted with a t-butyl group
(15). This did not give rise to nitrogen atom attack at the middle sp-carbon but instead the two products
17 and 1812 were isolated. Here, a nitrogen attack had occurred at the terminal sp2-carbon, probably via
an intramolecular attack on the intermediate (π-allyl)palladium complex. Interestingly, subjecting the
TBDMS (t-butyldimethylsilyl) substituted allene 19 to the same reaction conditions led to product 20 in
which the nitrogen had indeed attacked the central sp-carbon (Scheme 1). The TBDMS group increases
the electrophilicity of the sp-carbon making it easier for the nitrogen atom to attack.
Scheme 1.
The difference between 14 and 15 in the palladium-catalyzed oxidation can be explained from the
equilibrium between the (π-allyl)palladium complexes A and B (Scheme 2). A large substituent in the
C-3 position of the allene is expected to shift the equilibrium towards π-allyl complex B, whereas with a
small substituent (R=H), A should predominate. Thus, after the first bromide attack at C-2, 14 would give
mainly π-allyl complex A, whereas 15 would give π-allyl complex B. The latter complex is required for
intramolecular attack by nitrogen at C-1.
Scheme 2.

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Acknowledgements
Financial support from the Swedish Natural Science Research Council, the Swedish Foundation for
Strategic Research, and the Council for Chemical Sciences of the Netherlands Organization for Scientific
Research (CW-NWO) is gratefully acknowledged.
References
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8. (a) The mono- and non-substituted allenic tosylamides were prepared from a copper(I)-mediated reaction of 2-
cyanoethylzinc iodide and the corresponding propargylic tosylate. 2-Cyanoethylzinc iodide could be generated from 3-
iodopropionitrile and activated zinc. The organozinc iodides were then transmetallated into copper compounds of the type
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alcohol8d to give the corresponding allenic nitriles. The disubstituted allenic nitriles were prepared according to literature
procedures.8e The resulting allenic nitriles were then reduced with LiAlH4 and tosylated8f to give the N-tosylamides 1, 3,
5, 7, 9 and 11. (b) Yeh, M.-C. P.; Knochel, P. Tetrahedron Lett. 1988, 29, 2395. (c) Yeh, M.-C. P.; Sheu, B.-A.; Fu, H.-W.;
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11. Selected NMR data: 2-(1-Bromo-2-methyl-1-propenyl)-1-(toluene-4-sulfonyl)pyrrolidine (8) 1H NMR (400 MHz; CDCl3)
δ 7.69 (d, J=8.4 Hz, 2H), 7.27 (m, 2H), 4.87 (dd, J=7.9, 6.2 Hz, 1H), 3.64 (m, 1H), 3.39 (ddd, J=10.2, 8.7, 6.0 Hz, 1H), 2.42
(s, 3H), 1.93 (s, 3H), 1.87–2.10 (m, 3H), 1.80 (s, 3H), 1.64 (m, 1H); 13C NMR (100 MHz; CDCl3) δ 142.9, 136.6, 133.4,
129.1, 127.2, 124.3, 60.4, 49.3, 32.4, 25.8, 25.2, 21.6, 21.1.
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