Enantiocontrolled synthesis of 3-pyrrolines from α-amino allenes

Article abstract of DOI:10.1002/ejoc.200400211

Cyclization of α-amino allenes in the presence of N-bromosuccinimide afforded pyrrolines in good yields. The products were obtained with high enantiomeric excesses when optically active allenes were used as substrates. The synthesis of a 2,5-dehydroprolinol derivative is also presented. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejoc.200400211

FULL PAPER
Enantiocontrolled Synthesis of 3-Pyrrolines from α-Amino Allenes
[a]
[a]
[a]
´
Attila Horvath, Jessica Benner, and Jan-E. Bäckvall*
Keywords: Allenes / Cyclization / Nitrogen heterocycles
Cyclization of α-amino allenes in the presence of N-bromo- ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
succinimide afforded pyrrolines in good yields. The products
were obtained with high enantiomeric excesses when optic-
ally active allenes were used as substrates. The synthesis of
a 2,5-dehydroprolinol derivative is also presented.
Germany, 2004)
Introduction
Electrophile-induced cyclization of allenes bearing a nu-
cleophile in the α-position is a useful route for making par-
tially oxidized five-membered heterocycles [Equation (1)].
(1)
α-Allenyl alcohols,[1,2] acids,[3Ϫ5] and one amide[6] have
been shown to cyclize to dihydrofurans, butenolides, and
pyrrolin-2-one, respectively. A wide variety of electrophiles
have been used to initiate the reactions including
PhSeCl,[2,7] halogens[4,8] and other halonium ion sources,
such as N-bromosuccinimide[2] and CuCl2 or CuBr2.[5,6] In
some cases the axial chirality of the allene was successfully
transferred to central chirality in the product.[2,5] 3-Pyrrol-
ines are important compounds due to their biological
activity,[9] and are also useful intermediates in the synthesis
of amino acid analogues and antibiotics.
Scheme 1. Synthesis of protected α-amino allenes; reagents: (a)
MsCl, Et3N; (b) CuCH2NϭPh2; (c) (COOH)2; (d) NaOH
All of the propargylic alcohols used are commercially
available, with the exceptions of alcohol (R)-1d, which was
prepared by enzymatic kinetic resolution of the racemic
mixture, and alcohol (R)-1f. The latter compound was syn-
thesized from diethyl -tartrate as depicted in Scheme 2.
Results and Discussion
α-Allenylamines 2aϪf were prepared from the corre-
sponding protected propargylic alcohols through copper()-
mediated SN2Ј reactions,[10] as shown in Scheme 1. Protec-
tion of the primary amine by standard methods afforded
allenes 3aϪf.
[a]
Department of Organic Chemistry, Arrhenius Laboratory,
Stockholm University,
106 91, Stockholm, Sweden
Fax: (internat.) ϩ46-9647-7178
E-mail: jeb@organ.su.se
Scheme 2. Reagents: (a) 2,2-dimethoxypropane, pTSA, 97%; (b)
LiAlH4, 62%; (c) BnCl, NaH; (d) CCl4, Ph3P; (e) LDA, 59% overall
for c, d, e
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
3240
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200400211
Eur. J. Org. Chem. 2004, 3240Ϫ3243

Enantiocontrolled Synthesis of 3-Pyrrolines from α-Amino Allenes
FULL PAPER
After protection of the vicinal diol moiety,[11] hydride re-
To test the efficiency of chirality transfer, pyrroline (R)-
duction[12] afforded the dihydroxy-1,3-dioxolane, which was 4cЈ was prepared from the optically active allene (R)-3cЈ.
monobenzylated.[13] Substitution of the remaining unpro- Analysis of the product showed that the selectivity of the
tected hydroxy group,[14] followed by base-induced elimin- overall chirality transfer is 98% [(S)-1c of 98% ee gave (R)-
ation,[15] afforded the desired propargylic alcohol (R)-1f.
4cЈ of 96% ee]. The reaction of the tosyl-protected analogue
Treatment of allenyl amide 3a with 4.5 equiv. of CuBr2 in 3c gave the corresponding heterocycle 4c in better yield
acetonitrile at Ϫ30 °C afforded a mixture of the desired (82%) and with only a slightly lower selectivity of chirality
pyrroline 4a and the dibrominated by-product 5 in a 62:38 transfer (95% chirality transfer; 3c of 98% ee gave 4c of
ratio [Equation (2)]. A better result was obtained with 93% ee).
1.5 equiv. of Br2 in the presence of 1.5 equiv. of K2CO3 (4a/
To investigate the scope and limitation of the reaction
5, 91:9) or with 1.1 equiv. of NBS (4a/5, 98:2). Performing further, several other racemic and optically active allenes
the latter reaction at 0 °C did not result in any loss of selec- were cyclized to pyrrolines with the use of NBS as the oxi-
tivity, and so these reaction conditions (1.1 equiv. of NBS dant (Table 2). In most cases cyclization proceeded
in a 0.1  solution of acetonitrile at 0 °C) were chosen to smoothly to afford the pyrrolines in good yields and with-
perform the transformations.
out loss of the chiral information. Unfortunately, the reac-
tion of allene 3f was less efficient, the dehydro-prolinol
derivative (R)-4f being isolated in a moderate yield (51%).
Table 2. Cyclization of tosylamino allenes
(2)
Entry[a] Substrate
Product Yield[b] (ee)
1
2
3
4
rac-3a R ϭ n-C5H11, RЈ ϭ H 4a
85%
81%
82% (93%)
44% (72%)[c]
89%
rac-3b R ϭ iPr, RЈ ϭ H
(R)-3c R ϭ Me, RЈ ϭ H
(S)-3d R ϭ H, RЈ ϭ Bn
rac-3e R ϭ Me, RЈ ϭ Et
4b
(R)-4c
(S)-4d
4e
After the optimal reaction conditions had been estab-
lished, several common protecting groups were tested. The
p-toluenesulfonyl (Ts) derivative 3b turned out to be the
preferred substrate (Table 1, Entry 1), while the benzyloxy-
carbonyl-protected (Cbz) amine gave the pyrroline in lower
yield (Entry 2). N-(Allenyl)trifluoroacetamide 3bЈЈ did not
react under the reaction conditions, while the unprotected
primary amine 2b gave the product only in very low yield
(Entries 3 and 4).
5
6[d]
(R)-3f R ϭ CH2OBn, RЈ ϭ H (R)-4f
51% (Ͼ 99%)
[a] Unless otherwise noted, reactions were carried out in acetonitrile
[b]
(0.1 ) at 0 °C with 1.1 equiv. of NBS. Isolated yields after col-
umn chromatography. [c] The optical purity of the precursor alcohol
[d]
1d was 72% ee. 2 equiv. of NBS were used at 20 °C.
The reaction most probably proceeds through a cyclic
bromonium ion formed as Brϩ approaches the double bond
closer to the R group from the direction trans to the amino-
methyl substituent (from above in Scheme 3). It is the rigid-
ity of this intermediate that is responsible for the enantiose-
lectivity and efficiency of the reaction. Coordination of Brϩ
cis to the aminomethyl group (from below in Scheme 3) is
not only sterically disfavored but would place the nitrogen
too far from the electrophilic carbon atoms. Coordination
of Brϩ to the other double bond could produce an aziridine,
but its formation was not observed under the mild reac-
tion conditions.
Table 1. Substrate optimization
Entry[a]
Substrate
Product
Yield[b] (ee)
1
2
3
4
5
6
rac-3b R ϭ iPr, X ϭ Ts
rac-3bЈ R ϭ iPr, X ϭ Cbz
rac-3bЈЈ R ϭ iPr, X ϭ Tfa
rac-2b R ϭ iPr, X ϭ H
4b
4bЈ
Ϫ
Ϫ
(R)-4cЈ
(R)-4c
81%
66%
Ϫ
traces
49% (96%)
82% (93%)
Conclusion
(R)-3cЈ R ϭ Me, X ϭ Boc[c]
(R)-3c R ϭ Me, X ϭ Ts[c]
A mild and enantio-controlled bromocyclization reaction
of α-amino allenes has been developed. This novel trans-
formation affords 3-bromo-pyrrolines in good yields and
with excellent optical purity when optically active allenes
[a]
Reactions were carried out in acetonitrile (0.1 ) at 0 °C with
[b]
1.1 equiv. of NBS. Isolated yields after column chromatography.
[c]
Enantiopurity of the precursor alcohol 1c was 98%.
Eur. J. Org. Chem. 2004, 3240Ϫ3243
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3241

´
A. Horvath, J. Benner, J.-E. Bäckvall
FULL PAPER
overall yield. The characterization of the title compound has been
published before.[15]
General Procedure for the Preparation of α-Allenyl Amines 2a؊f. 5-
Methylhexa-2,3-dienylamine (2b): A mixture of 4-methyl-1-pentyn-
3-ol (7.73 g, 78.8 mmol) and triethylamine (10.1 mL, 78.8 mmol) in
dichloromethane (79 mL, 1.0 ) was stirred at Ϫ20 °C, and mesyl
chloride (6.10 mL, 78.8 mmol) was added slowly. After 1 h the reac-
tion mixture was quenched with water, the organic layer was sepa-
rated, washed twice with water, and dried with Na2SO4, and the
solvent was evaporated to afford the mesylated propargylic alcohol
in 99% crude yield (13.8 g). This was used without further purifi-
cation.
A solution of benzhydrylidene(methyl)amine (2.44 g,
12.5 mmol) in THF (12.5 mL, 1.0 ) was added over 10 min at Ϫ60
°C under argon to a solution of tBuLi (9.0 mL, 1.7  in pentane,
15.3 mmol) in THF (75 mL, 0.2 ). After the mixture had been
stirred for 5 min, a solution of CuCN (1.34 g, 15.0 mmol) and LiCl
(1.27 g, 30.0 mmol) in THF was added over 2 min, and the mixture
was stirred for another 5 min. The mesylated propargylic alcohol
(2.2 g, 12.5 mmol) in THF (5 mL) was then added to the mixture
over 5 min. The reaction mixture was stirred for 45 min at Ϫ50 °C
and was then allowed to warm up to room temperature. It was
quenched with water, the THF was evaporated, and the residue
was extracted with diethyl ether. The combined organic layers were
washed with a mixture of NaOH (2 ) and satd. NH4Cl solution
(1:3), and the solvent was evaporated. A solution of oxalic acid
(0.99 g, 11.0 mmol) in a 1:6 mixture of 95% ethanol and diethyl
ether (31.4 mL, 0.35 ) was added to the crude product, and the
mixture was stirred for 30 minutes. After the hydrolysis of the imine
and the crystallization of the oxalate salt were complete, the solid
was filtered and washed with diethyl ether. NaOH solution
(2 ) was added to the white powder, and the primary amine was
extracted with dichloromethane. The organic layer was dried with
Na2SO4, and the solvent was evaporated to afford the title com-
pound in 42% yield (0.50 g) as a light yellow liquid: 1H NMR
(CDCl3, 400 MHz): δ ϭ 5.3 (m, 2 H), 3.25 (dd, 2 H), 2.35 (m, 1
H), 2.08 (br. s, 2 H), 1.03 (d, J ϭ 6.9 Hz, 6 H) ppm. 13C NMR
(CDCl3, 100 MHz): δ ϭ 201.4, 101.4, 95.1, 41.1, 28.1, 22.79,
22.77 ppm.
Scheme 3
are used. The products, being vinyl bromides, should be
viable coupling partners in various palladium-catalyzed
coupling reactions.
Experimental Section
General Methods: Acetonitrile was distilled from CaH2, diethyl
ether and THF were distilled from sodium benzophenone ketyl,
diethyl -tartrate was vacuum-distilled, and pyridine was distilled
from LiAlH4 and kept over KOH pellets. All other reagents and
1
solvents were used without further purification. H NMR (400 or
300 MHz) and 13C NMR (100 or 75 MHz) spectra were recorded
with a Varian Mercury spectrometer with use of the residual peaks
of [D]chloroform (δ ϭ 7.26 ppm for 1H and 77 ppm for 13C) or
[D6]DMSO (δ ϭ 2.50 ppm for 1H and 39.51 ppm for 13C) as in-
ternal standards. For the determination of optical purity we used
a Varian 3800 analytical GC fitted with a CP-Chirasil-Dex CB col-
umn for compound 1d and 4cЈ and a Waters 2690 analytical HPLC
with OD-H column for compounds 4c, 4d and 4f. Matrex silica 60-
˚
A (35Ϫ70 mm) was used for column chromatography, and analyti-
cal TLC was performed on Merck precoated silica 60-F254 plates.
Melting points are uncorrected.
General Procedure for the Preparation of p-Toluenesulfonamides
3a؊f. N-(5-Methylhexa-2,3-dienyl)-p-toluenesulfonamide (3b): p-
Toluenesulfonyl chloride (0.94 g, 5.0 mmol) was added at Ϫ20 °C
to a solution of amine 2b (0.5 g, 4.5 mmol) in pyridine (4.5 mL,
1.0 ), and the mixture was stirred overnight. After quenching with
water and extraction with diethyl ether the combined organic layers
were washed with NH4Cl (satd.) and brine and dried with Na2SO4.
Column chromatography (pentane/diethyl ether, 1:1) afforded the
(R)-1-Phenylbut-3-yn-2-ol [(R)-1d]: Ethynylmagnesium bromide
(340 mL, 0.5  in THF, 0.17 mol) was stirred at room temperature,
and phenylacetaldehyde (20 mL, 0.17 mol) was added slowly. After
the addition, the mixture was quenched with satd. NH4Cl solution,
the organic layer was separated and dried with Na2SO4, and the
solvent was evaporated. Vacuum distillation gave the racemic 1d
(13.7 g, 55%) as a colorless oil. Vinyl acetate (12.1 mL, 131 mmol)
and immobilized Pseudomonas Species-C lipase (Amano II,
223 mg, 6 mg/mmol) were added to 1d (12.8 g, 87.5 mmol) in tolu-
ene (373 mL, 0.31 ), and the mixture was shaken. After 3 days
and 43% conversion, the solvent and the excess vinyl acetate were
evaporated, and the products were separated by column chroma-
tography (pentane/ethyl acetate, 5:1) to afford the title compound
with 72% ee and (S)-1d acetate with 95% ee. The characterization
of the title compound has been published before.[16]
1
title compound as a yellow liquid in 68% yield (0.82 g): H NMR
(CDCl3, 300 MHz): δ ϭ 7.75 (d, J ϭ 8.2 Hz, 2 H), 7.31 (d, J ϭ
8.2 Hz, 2 H), 5.24 (m, 1 H), 5.10 (m, 1 H), 4.36 (br. m, 1 H), 3.56
(ddd, J ϭ 8.8, 6.1, 3.1 Hz, 2 H), 2.43 (s, 3 H), 2.26 (m, 1 H), 0.97
(dd, J ϭ 7.0, 1.4 Hz, 6 H) ppm. 13C NMR (CDCl3, 100 MHz): δ ϭ
201.9, 143.4, 137.0, 129.6 (2 C), 127.1 (2 C), 101.9, 88.8, 42.0, 27.7,
22.3, 22.2, 21.5 ppm.
General Procedure for the Preparation of 3-Bromo-2,5-dihydropyr-
roles 4aϪ4f. 3-Bromo-2-isopropyl-1-(p-tolylsulfonyl)-2,5-dihydropyr-
role (4b): A solution of NBS (86.2 mg, 0.48 mmol) in acetonitrile
(R)-4-Benzyloxy-3-hydroxybut-1-yne [(R)-1f]: This compound was
prepared over five steps by literature procedures (Scheme 2).
Freshly distilled diethyl -tartrate (42.67 g, 0.207 mol) was first pro- (4.4 mL) was added at 0 °C to allene 3b (115.7 mg, 0.44 mmol).
tected by use of 2,2-dimethoxypropane (2 equiv.).[11] Distillation
The reaction was monitored by TLC [samples quenched with satd.
(85Ϫ94 °C, 0.20 mbar) afforded the 1,3-dioxolane in 97% yield Na2S2O3(aq)]. After the reaction was complete, silica was added to
[12]
(49.47 g, 0.201 mol). Reduction with LiAlH4
and subsequent
the reaction mixture at 0 °C. The solvent was evaporated, and col-
umn chromatography (pentane/diethyl ether, 2:1) gave the title
compound in 81% isolated yield (121 mg) as a yellow liquid: 1H
mono-benzylation,[13] followed by substitution of the remaining un-
protected alcohol[14] and elimination,[15] afforded (R)-1f in 36%
3242
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 3240Ϫ3243

Enantiocontrolled Synthesis of 3-Pyrrolines from α-Amino Allenes
FULL PAPER
NMR (CDCl3, 400 MHz): δ ϭ 7.68 (m, 2 H), 7.30 (d, J ϭ 8.0 Hz, 3-Bromo-2-ethyl-2-methyl-1-(p-tolylsulfonyl)-2,5-dihydropyrrole
2 H), 5.73 (m,1 H), 4.39 (m, 1 H), 4.05 (ddd, J ϭ 15.9, 2.7, 1.1 Hz, (4e): This compound was prepared from allene 3e by the general
1 H), 3.91 (ddd, J ϭ 15.9, 4.8, 1.7 Hz, 1 H), 2.42 (s, 3 H), 2.24 (d
sept, J ϭ 2.4, 7.1 Hz, 1 H), 1.12 (d, J ϭ 7.1 Hz, 3 H), 0.94 (d, J ϭ
procedure in 89% yield (74.8 mg); light yellow liquid. 1H NMR
(CDCl3, 400 MHz): δ ϭ 7.75 (d, J ϭ 7.8 Hz, 2 H), 7.28 (d, J ϭ
7.1 Hz, 3 H) ppm. 13C NMR (CDCl3, 100 MHz): δ ϭ 143.8, 134.3, 7.8 Hz, 2 H), 5.88 (t, J ϭ 2.3 Hz, 1 H), 4.05 (dd, J ϭ 13.4, 2.2 Hz,
129.8 (2 C), 127.5 (2 C), 126.4, 118.4, 74.6, 56.1, 31.9, 21.5, 18.7,
16.5 ppm.
1 H), 4.00 (dd, J ϭ 13.4, 2.2 Hz, 1 H), 2.41 (s, 3 H), 2.24 (app.
sext, J ϭ 7.5 Hz, 1 H), 1.66 (app. sext, J ϭ 7.1 Hz, 1 H), 1.51 (s, 3
H), 0.73 (t, J ϭ 7.8 Hz, 3 H) ppm. 13C NMR (CDCl3, 100 MHz):
δ ϭ 143.4, 137.9, 129.7 (2 C), 127.4 (2 C), 124.5, 123.7, 76.8, 54.9,
31.0, 25.5, 21.7, 8.3 ppm.
N-Benzyloxycarbonyl-3-bromo-2-isopropyl-2,5-dihydropyrrole (4bЈ):
This compound was prepared from allene 3bЈ by the general pro-
cedure in 66% yield (86.8 mg); light yellow liquid. 1H NMR
([D6]DMSO, 100 °C, 400 MHz): δ ϭ 7.35 (m, 5 H), 6.19 (m, 1 H),
5.11 (s, 2 H), 4.49 (m, 1 H), 4.23 (ddd, J ϭ 15.7, 2.7, 1.8 Hz, 1 H),
3.92 (ddd, J ϭ 15.7, 5.1, 1.8 Hz, 1 H), 2.24 (d sept, J ϭ 2.4, 7.0 Hz,
1 H), 0.92 (dd, J ϭ 7.0, 3.5 Hz, 6 H) ppm. 13C NMR ([D6]DMSO,
100 °C, 100 MHz): δ ϭ 154.9, 137.5, 129.0, 128.6, 128.5, 128.2,
117.2, 71.9, 67.1, 55.0, 31.7, 18.7, 17.7 ppm.
(R)-2-[(Benzyloxy)methyl]-3-bromo-1-(p-tolylsulfonyl)-2,5-dihydro-
pyrrole [(R)-4f]: This compound was prepared from allene 3f
(100.6 mg, 0.2929 mmol) by the general procedure but with the use
of 2 equiv. NBS at 20 °C in 51% yield (63.6 mg, 0.1506 mmol);
colorless oil. 1H NMR (CDCl3, 400 MHz): δ ϭ 7.70 (m, 2 H),
7.36Ϫ7.25 (m, 7 H), 5.87 (dd, J ϭ 4.0, 2.1 Hz, 1 H), 4.62 (d, J ϭ
12.4 Hz, 1 H), 4.53 (d, J ϭ 12.4 Hz, 1 H), 4.45 (m, 1 H), 4.10 (dd,
J ϭ 4.0, 2.1 Hz, 2 H), 3.86 (dd, 10.7, 2.2 Hz, 1 H), 3.83 (dd, J ϭ
10.7, 2.7 Hz, 1 H), 2.42 (s, 3 H) ppm. 13C NMR (CDCl3,
100 MHz): δ143.8, 138.2, 134.6, 129.8 (2 C), 128.2 (2 C), 127.5,
127.4 (2 C), 127.3 (2 C), 126.6, 116.6, 73.5, 69.6, 69.5, 55.3, 21.5
ppm.
3-Bromo-2-pentyl-1-(p-tolylsulfonyl)-2,5-dihydropyrrole (4a): This
compound was prepared from allene 3a (106.1 mg, 0.3616 mmol)
by the general procedure in 85% yield (114.5 mg, 0.3075 mmol);
colorless oil. 1H NMR (CDCl3, 400 MHz): δ ϭ 7.75 (dm, J ϭ
8.4 Hz, 2 H), 7.31 (m, 2 H), 5.76 (app q, J ϭ 2.0 Hz, 1 H), 4.46
(m, 1 H), 4.08 (app dt, J ϭ 14.7, 2.6 Hz, 1 H), 4.02 (ddd, J ϭ 14.7,
5.2, 2.0 Hz, 1 H), 2.43 (s, 3 H), 1.94 (m, 1 H), 1.76 (m, 1 H),
1.40Ϫ1.13 (m, 6 H), 0.88 (t, J ϭ 6.9 Hz, 3 H) ppm. 13C NMR
(CDCl3, 100 MHz): δ ϭ 143.7, 134.4, 129.8 (2 C), 127.4 (2 C),
125.2, 118.9, 69.2, 55.4, 32.3, 31.6, 22.6, 22.0, 21.5, 14.0 ppm.
N-(3,4-Dibromooct-2-enyl)-p-toluenesulfonamide (5): This com-
pound was isolated as a by-product from the treatment of allene
1
3a with CuBr2. H NMR (CDCl3, 300 MHz): δ ϭ 7.75 (m, 2 H),
7.33 (m, 2 H), 6.07 (t, J ϭ 6.2 Hz, 1 H), 4.65 (br. t, J ϭ 6.1 Hz, 1
H), 4.48 (t, J ϭ 7.3 Hz, 1 H), 3.73 (t, J ϭ 6.2 Hz, 2 H), 2.44 (s, 3
H), 1.93 (m, 2 H), 1.28 (m, 6 H), 0.88 (m, 3 H) ppm. 13C NMR
(CDCl3, 75 MHz): δ ϭ 143.8, 136.6, 131.6, 129.9 (2 C), 127.6, 127.2
(2 C), 57.0, 43.8, 37.9, 30.9, 27.0, 22.3, 21.6, 13.9 ppm.
(R)-3-Bromo-2-methyl-1-(p-tolylsulfonyl)-2,5-dihydropyrrole [(R)-
4c]: This compound was prepared from allene (R)-3c (93.9 mg,
0.3957 mmol) by the general procedure in 82% yield (102.6 mg,
0.3244 mmol); colorless oil, crystallizable from pentane/ether, 95:5.
Recrystallization from hexane gave enantiomerically pure white
needles; m.p. 51Ϫ57 °C. 1H NMR (CDCl3, 300 MHz): δ ϭ 7.70
(dm, J ϭ 8.3 Hz, 2 H), 7.32 (m, 2 H), 5.73 (app q, J ϭ 2.0 Hz, 1
H), 4.36 (m, 1 H), 4.10 (ddd, J ϭ 14.5, 5.5, 2.0 Hz, 1 H), 4.01 (app
dt, J ϭ 14.5, 2.5 Hz, 1 H), 2.43 (s, 3 H), 1.51 (d, J ϭ 6.4 Hz, 3 H)
ppm. 13C NMR (CDCl3, 100 MHz): δ ϭ 143.8, 134.2, 129.9 (2 C),
127.4 (2 C), 124.3, 120.5, 65.4, 54.6, 21.5, 21.2 ppm.
Acknowledgments
Financial support from the Swedish Research Council is grate-
fully acknowledged.
[1] [1a]
[1b]
L.-I. Olsson, A. Claesson, Synthesis 1979, 743.
P. L .
Beaulieu, V. M. Morisset, D. G. Garratt, Tetrahedron Lett.
1980, 21, 129.
[2] [2a]
J. A. Marshall, X. J. Wang, J. Org. Chem. 1991, 56, 4913.
A. Hoffmann-Röder, N. Krause, Org. Lett. 2001, 2537.
[2b]
(R)-tert-Butyl 3-Bromo-2-methyl-2,5-dihydro-1-pyrrolecarboxylate
[(R)-4cЈ]: This compound was prepared from allene (R)-3cЈ
(97.1 mg, 0.5299 mmol) by the general procedure in 49% yield
(55.2 mg, 0.2106 mmol); colorless liquid. 1H NMR ([D6]DMSO,
300 MHz): δ ϭ 6.07 (dd, J ϭ 3.9, 2.1 Hz, 1 H), 4.39 (m, 1 H), 4.08
(app dt, J ϭ 15.3, 2.3 Hz, 1 H), 3.95 (ddd, J ϭ 15.3, 5.4, 2.1 Hz, 1
H),1.45 (s, 9 H), 1.33 (d, J ϭ 6.3 Hz, 3 H) ppm. 13C NMR
([D6]DMSO, 100 MHz): δ ϭ 152.2, 128.8, 127.8 (2 C), 125.2 (2 C),
119.2, 78.6, 61.8, 52.1, 27.6, 18.0 ppm.
[3]
[4]
[5]
[6]
[7]
[8]
G. B. Gill, M. S. H. Idris, Tetrahedron Lett. 1985, 26, 4811.
J. A. Marshall, M. A. Wolf, J. Org. Chem. 1996, 61, 3238.
S. Ma, S. Wu, Chem. Commun. 2001, 441.
S. Ma, H. Xie, Org. Lett. 2000, 2, 3801.
R. W. Friesen, Tetrahedron Lett. 1990, 31, 4249.
S. Ma, Z. Shi, Z. Yu, Tetrahedron 1999, 55, 12137.
[9] [9a]
K. Ishii, H. Ohno, Y. Takemoto, E. Osawa, Y. Yamaoka,
N. Fujii, T. Ibuka, J. Chem. Soc., Perkin Trans. 1 1999, 2155.
[9b] A. B. Mauger, J. Nat. Prod. 1996, 59, 1205. [9c] J. M. Phang,
Current Topics in Cellular Regulation 1985, 25, 91.
A. Claesson, C. Sahlberg, Tetrahedron 1982, 38, 363.
B. A. Murrer, J. M. Brown, P. A. Chaloner, P. N. Nicholson,
D. Parker, Synthesis 1979, 350.
E. V. Dehmlow, C. Sauerbier, Liebigs Ann. Chem. 1989, 181.
S. Clough, M. E. Raggatt, T. J. Simpson, C. L. Willis, A. Whit-
ing, S. K. Wrigley, J. Chem. Soc., Perkin Trans. 1 2000, 2475.
L. Gruber, I. Tömösközi, L. Radics, Synthesis 1975, 708.
T. Kanger, M. Liiv, T. Pehk, M. Lopp, Synthesis 1993, 91.
K. Burgess, L. D. Jennings, J. Am. Chem. Soc. 1991, 113,
6129Ϫ6139.
[10]
[11]
(S)-2-Benzyl-3-bromo-1-(p-tolylsulfonyl)-2,5-dihydropyrrole [(S)-4d]:
This compound was prepared from allene (S)-3d by the general
procedure but with the use of 2 equiv. NBS at 20 °C in 44% yield
(71 mg); white solid. 1H NMR (CDCl3, 400 MHz): δ ϭ 7.71 (d,
J ϭ 9.6 Hz, 2 H), 7.37Ϫ7.19 (m, 7 H), 5.54 (app. br. q, J ϭ 1.9, 1
H), 4.66 (m, 1 H), 3.82 (app. dt, J ϭ 14.6, 2.3 Hz, 1 H), 3.77 (ddd,
14.6, 5.2, 1.9 Hz, 1 H), 3.31 (dd, J ϭ 13.9, 4.8 Hz, 1 H), 3.12 (dd,
J ϭ 13.9, 2.3 Hz, 1 H), 2.43 (s, 3 H) ppm. 13C NMR (CDCl3,
100 MHz): δ ϭ 144.1, 135.6, 134.6, 131.1 (2 C), 130.2 (2 C), 128.1
(2 C), 127.5(2 C), 127.0, 126.9, 117.9, 70.2, 55.5, 38.6, 21.8 ppm.
[12]
[13]
[14]
[15]
[16]
Received March 30, 2004
Eur. J. Org. Chem. 2004, 3240Ϫ3243
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3243