Stereoselective synthesis of 2-methylenepyrrolizidines by tandem cyclization of N-propargylaminyl radicals

Article abstract of DOI:10.1016/S0040-4020(02)01613-7

Tandem cyclization of N-propargylaminyl radicals, generated by N-chlorination of (E)-alk-4-enylamines 2a-d and 2f followed by treatment with tributyltin radical, afforded 2-methylenepyrrolizidines 3a-d and 3f in a highly stereoselective manner. A similar

Full text of DOI:10.1016/S0040-4020(02)01613-7

Tetrahedron 59 (2003) 827–832
Stereoselective synthesis of 2-methylenepyrrolizidines by tandem
cyclization of N-propargylaminyl radicals
*
Hikaru Hasegawa, Hisanori Senboku, Yoshinori Kajizuka, Kazuhiko Orito and Masao Tokuda
Laboratory of Organic Synthesis, Division of Molecular Chemistry, Graduate School of Engineering, Hokkaido University,
Sapporo 060-8628, Japan
Received 12 November 2002; accepted 5 December 2002
Abstract—Tandem cyclization of N-propargylaminyl radicals, generated by N-chlorination of (E)-alk-4-enylamines 2a–d and 2f followed
by treatment with tributyltin radical, afforded 2-methylenepyrrolizidines 3a–d and 3f in a highly stereoselective manner. A similar radical
cyclization of (Z)-N-propargyl-1-methyl-5-phenylpent-4-enylamine (2e) gave pyrrolizidine 3b having the same stereochemistry as that
obtained from the E isomer 2b. q 2003 Elsevier Science Ltd. All rights reserved.
1. Introduction
zation were prepared according to our previously reported
method.12 Thus, reductive aminations of ketones 1a,b and
1d–f with propargylamine in the presence of NaBH(OAc)3
in CH2Cl213 gave the corresponding amines 2a,b and 2d–f
in 78–89% yields (Schemes 1 and 2). On the other hand,
amine 2c was prepared by the reaction of ketone 1c with
propargylamine in benzene in the presence of TiCl4
followed by reduction of the resulting imine with NaBH4 in
MeOH (Scheme 1).
Tandem radical cyclization has been widely investigated as
a readily amenable method for the synthesis of polycarbo-
cyclic as well as polyheterocyclic natural products.1,2
Although various types of methods have been developed
for synthesis of pyrrolizidine,3 indolizidine4 and quino-
lizidine alkaloids,4 there are a few reports on the one-step
synthesis of these bicyclic compounds using tandem radical
cyclization.5 On that account, nitrogen radical cyclization
seems to be very useful for the synthesis of nitrogen
heterocycles.6 Especially, aminyl radical cyclizations are
more feasible because of their high stereoselectivity,7
although cyclization of other nitrogen radicals such as
aminium8 and amidyl radicals9 and that of carbon radicals10
usually gave a mixture of several stereoisomers. Furthermore,
in aminyl radical cyclizations, there are several advantages
such as an easy preparation of starting amines and a simple
procedure without the use of syringe pump technique.11 We
havealreadyreportedanefficientandstereoselectivesynthesis
of 1,2,5-trisubstituted pyrrolizidines by tandem cyclization of
N-allylaminyl radicals.12 In this paper, we report a stereo-
selective synthesis of 2-methylenepyrrolizidines by 5-exo,
5-exo tandem cyclization of aminyl radicals derived from
N-propargylalk-4-enylamines.
14
In the tandem cyclization of N-propargylaminyl radicals,
Scheme 1.
2. Results and discussion
Starting N-propargylamines 2a–f for aminyl radical cycli-
Keywords: tandem radical cyclization; aminyl radical; pyrrolizidine;
N-chloroamine.
*
Corresponding author. Tel.: þ81-11-706-6599; fax: þ81-11-706-6598;
e-mail: tokuda@org-mc.eng.hokudai.ac.jp
Scheme 2.
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)01613-7

828
H. Hasegawa et al. / Tetrahedron 59 (2003) 827–832
Scheme 3.
amine 2 was firstly treated with NCS (1.0 equiv.) in toluene
to give the corresponding N-chloroamine, the precursor of
aminyl radical, quantitatively. To this solution were added
1.0 equiv. of Bu3SnH and catalytic amount of AIBN in one
portion, and the solution was heated under reflux for 7 h.
Purification of the crude product by preparative TLC
(Al2O3) gave pyrrolizidines 3a–d in 43–63% yields, and
neither monocyclic pyrrolidine nor the starting amine 2 was
obtained (Scheme 3). Atom transferred products 4a and 4b
were also obtained in low yields in the case of 2a and 2b.
Alkyl- and silyl-substituted C–C double bonds such as 2a
and 2d were found to work effectively as an acceptor in the
tandem cyclization of aminyl radicals, although phenyl-
substituted double bond such as 2b and 2c is usually used as
an acceptor of aminyl radicals.5a,b
regulated transition states. In addition, it should be noted
that only one stereoisomer was formed in the tandem radical
cyclization of N-propargylamines 2a–d, showing that these
two consecutive cyclizations of aminyl radicals take place
in completely stereoselective manner.
A tricyclic heterocycle was also obtained in one step by the
tandem cyclization of N-propargylaminyl radical. cis-N-
Propargyl-2-(3-phenyl-2-propenyl)cyclohexylamine (2f)
was subjected to aminyl radical cyclization in a similar
manner as those of 2a–d to give perhydropyrrolo[1,2-
a]indole 3f, as a single diastereomer, in 40% yield together
with the recovered starting amine 2f (20%) (Scheme 5).
We next investigated an effect of the geometry of C–C
double bond in the starting amine on the tandem radical
cyclization. Aminyl radical cyclization of (Z)-alk-4-enyl-
amine 2e was carried out under the same conditions as those
of 2b. As a result, the radical reaction of 2e gave the product
3b, which was completely identical with the product
obtained by the radical reaction of 2b having E geometry
(Scheme 6).15
The stereochemistry of the products 3 was determined by
NOE or NOESY spectra. These spectral data show that all
cyclization products 3a–d have the same stereochemistries
and that all of C1- and C5-substituent, and C7a–H in 3 are
in syn relationships. Furthermore, the stereochemistry of the
products was also confirmed by hydrogenation of the
product 3. Hydrogenation of 3b over 10% Pd/C in methanol
gave a mixture of two stereoisomeric pyrrolidines 5 and 6,
which were completely identical with known compounds
that were previously provided by tandem radical cyclization
of N-allylamine 7 in our group (Scheme 4).12 These results
show that both tandem radical cyclizations of N-propargyl-
amine 3b and N-allylamine 7 proceed via similar well-
These results show that the present tandem cyclization of
N-propargylaminyl radicals proceeds in highly stereo-
selective manner on each step. Proposed reaction pathways
are shown in Scheme 7. Transition state A for aminyl radical
cyclization would be a chair-like form, in which R1
possesses a pseudo-equatorial position,16 and the first ring
Scheme 5.
Scheme 4.
Scheme 6.

H. Hasegawa et al. / Tetrahedron 59 (2003) 827–832
829
Scheme 7.
closure would give trans-2,5-disubstituted pyrrolidine
intermediate B. Spontaneous cyclization of B would give
the intermediate C, which abstracts a hydrogen atom from
tributyltin hydride to give the product 3. On the other hand,
in the case of 2e, the first cyclization of aminyl radical D
would give the intermediate E. In the radical intermediate E,
a rotation around the C–C single bond would occur to give a
more sterically stable intermediate B probably due to a
pseudo-axial substituent of R2. 5-exo Cyclization would,
then, occur onto the C–C triple bond efficiently to give
pyrrolizidine intermediate C as a single diastereomer.
4.2. Preparation of ketones 1a–f
Ketones 1a–c and 1f were prepared according to our
reported methods.17
4.2.1. (E)-6-Triethylsilylhex-5-en-2-one (1d). Hydro-
silylation of hex-5-yn-2-one18 with triethylsilane provided
ketone 1d. Thus, to a CH2Cl2 solution (1.6 ml, 1.0 M)
ofhex-5-yn-2-one (150 mg, 1.56 mmol) were added triethyl-
silane (0.3 ml, 1.9 mmol) and H2PtCl6·H2O (0.1 mg) as a
catalyst, and the reaction mixture was stirred for 4 h at room
temperature under an argon atmosphere. After evaporation
of the solvent, a crude mixture was separated by preparative
TLC (SiO2, hexaneþAcOEt 10:1) to give ketone 1d
(201 mg, 0.95 mmol, 61%): Rf¼0.44; oil; 1H NMR dH
0.54 (6H, q, J¼7.9 Hz), 0.91 (9H, t, J¼7.9 Hz), 2.15 (3H, s),
2.41 (2H, m), 2.55 (2H, m), 5.58 (1H, dt, J¼1.7, 18.8 Hz),
6.02 (1H, dt, J¼6.0, 18.8 Hz); 13C NMR dC 3.43 [(CH2)£3],
7.35 [(CH3)£3], 29.99 (CH3), 30.87 (CH2), 42.71 (CH2),
126.88 (CH), 146.13 (CH), 208.39 (CvO); IR 1717, 1657,
1239, 1017, 719 cm21; MS (EI) m/z 212 (Mþ, 1.9), 183
[(M2C2H5)þ, 49.8], 103 (100%); HRMS calcd for
C12H24OSi: m/z 212.1596. Found: m/z 212.1598.
3. Conclusion
In conclusion, a tandem cyclization of N-propargylalk-4-
enylaminyl radicals readily took place stereoselectively to
give 2-methylenepyrrolizidines in moderate to good yields.
These tandem cyclizations of N-propargylaminyl radicals
gave only one stereoisomer. A similar reaction of aminyl
radical having Z geometry in alk-4-enyl moieties afforded
the same product as that obtained from (E)-alk-4-enyl-
aminyl radicals. These results indicate that the present
5-exo, 5-exo tandem cyclization of aminyl radicals proceeds
in highly stereoselective manner on each step.
4.2.2. (Z)-6-Phenylhex-5-en-2-one (1e).19 Ketone 1e was
prepared from hex-5-yn-2-one by the Sonogashira reaction
and hydrogenation. Thus, to triethylamine solution (104 ml,
0.3 M) of hex-5-yn-2-one were added iodobenzene (3.5 ml,
31.2 mmol),
dichlorobis(triphenylphosphine)palladium
4. Experimental
4.1. General
(365 mg, 0.52 mmol) and CuI (49 mg, 0.26 mmol), and
the reaction mixture was stirred for 12 h at 458C under
nitrogen atmosphere. The mixture was diluted with Et2O
(100 ml) and then washed successively with water and 2N
HCl. After concentration of the ethereal solution, the crude
product was distilled in vacuo to give 6-phenylhex-5-yn-2-
one (3.7 g, 21.8 mmol, 70%). This ketone (300 mg,
1.74 mmol) was hydrogenated in MeOH (20 ml) with
Lindlar catalyst (5 mg), quinoline (0.1 ml) and H2 (1
atom). After filtration and concentration of the solution,
the crude product was purified by column chromatography
(SiO2, hexaneþAcOEt 10:1, Rf¼0.33) to give ketone 1e
IR spectra were determined in a neat form with a JASCO
1
IR-810 infrared spectrophotometer. The H and 13C NMR
spectra were determined in CDCl3 (SiMe4 as an internal
reference) with a JEOL JNM EX-270 high-resolution
spectrometer. Mass spectra were recorded using a JOEL
JMS-FABmate or JMS-700TZ spectrometer (70 eV).
Measurement of mass spectra was performed by the staff
of Center for Instrumental Analysis, Hokkaido University.
Preparative TLC was carried out with Merck Silica gel 60
PF254 or Merck Aluminum oxide 60 PF254 or 60 PF254þ366
(Type E).
1
(285 mg, 1.64 mmol, 94%). Oil; H NMR dH 2.13 (3H, s),
2.5–2.6 (4H, m), 5.62 (1H, m), 6.45 (1H, d, J¼11.5 Hz),
7.2–7.4 (5H, m); 13C NMR dC 22.84 (CH2), 29.90 (CH3),

830
H. Hasegawa et al. / Tetrahedron 59 (2003) 827–832
43.63 (CH2), 126.74 (CH), 128.23 [(CH)£2], 128.71
[(CH)£2], 129.94 (CH), 130.64 (CH), 137.19 (C), 208.12
(CvO); IR 1713, 1160, 769, 700 cm21; MS (EI) m/z 174
(Mþ, 100), 131 (88.9%); HRMS calcd for C12H14O: m/z
174.1045. Found: m/z 174.1045.
[(M2C2H5)þ, 11.7], 82 (100%); HRMS calcd for
C15H28NSi: m/z 250.1991. Found: m/z 250.1991.
4.3.4. (Z)-N-Propargyl-1-methyl-5-phenylpent-4-enyl-
amine (2e). Al2O3-TLC (hexaneþAcOEt (10:1),
1
Rf¼0.54); oil; H NMR dH 1.03 (3H, d, J¼6.3 Hz), 1.4–
4.3. General procedure for the preparation of N-pro-
pargylamines 2a,b and 2d–f
1.7 (3H, m), 2.17 (1H, t, J¼2.3 Hz), 2.3–2.4 (2H, m), 2.90
(1H, sext, J¼6.3 Hz), 3.38 (1H, dd, J¼2.3, 17.2 Hz), 3.45
(1H, dd, J¼2.3, 17.2 Hz), 5.65 (1H, dt, J¼7.3, 11.9 Hz),
6.43 (1H, d, J¼11.9 Hz); 13C NMR dC 19.68 (CH3), 24.94
(CH2), 35.54 (CH2), 36.82 (CH2), 51.03 (CH), 71.09 (C),
82.30 (CH), 126.56 (CH), 128.16 [(CH)£2], 128.71
[(CH)£2], 129.16 (CH), 132.38 (CH), 137.55 (C); IR
3296, 1495, 768, 699 cm21; MS (EI) m/z 212 [(M2H)þ,
10.5], 198 [(M2CH3)þ, 7.4], 82 (100%); HRMS calcd for
C15H18N: m/z 212.1439. Found: m/z 212.1431.
N-Propargylamines 2a,b and 2d–f were prepared by
reductive amination of the corresponding ketones 1a,b
and 1d–f with propargylamine and NaBH(OAc)3. Thus, a
CH2Cl2 solution of ketone (0.3 M) was reacted with
propargylamine (2.0 equiv.), AcOH (0.2 equiv.) and
NaBH(OAc)3 (1.5 equiv.) at room temperature under an
argon atmosphere until the starting ketone had disappeared
(monitored by TLC). The reaction mixture was quenched
with 2N NaOH, and then the mixture was extracted with
Et2O. The combined organic layers were washed with water
and brine, and it was dried over MgSO4. After evaporation
of the solvent, crude product was purified by preparative
TLC (Al2O3) to give N-propargylamine 2a,b and 2d–f in
78–89% yields.
4.3.5. cis-N-Propargyl-2-(3-phenylprop-2-enyl)cyclo-
hexylamine (2f). Al2O3-TLC (hexaneþAcOEt (10:1),
1
Rf¼0.56); oil; H NMR dH 1.3–1.5 (4H, m), 1.5–1.7 (4H,
m), 1.78 (1H, m), 2.16 (1H, m), 2.16 (1H, t, J¼2.3 Hz), 2.32
(1H, m), 2.94 (1H, m), 3.38 (1H, dd, J¼2.3, 17.2 Hz), 3.48
(1H, dd, J¼2.3, 17.2 Hz), 6.20 (1H, ddd, J¼6.6, 7.6,
15.8 Hz), 6.40 (1H, d, J¼15.8 Hz), 7.2–7.4 (5H, m); 13C
NMR dC 22.27 (CH2), 23.47 (CH2), 27.28 (CH2), 28.43
(CH2), 33.03 (CH2), 35.65 (CH2), 39.73 (CH), 55.47 (CH),
70.93 (C), 82.71 (CH), 125.89 [(CH)£2], 126.77 (CH),
128.43 [(CH)£2], 129.83 (CH), 130.87 (CH), 137.83 (C); IR
3302, 1601, 1450, 966, 735 cm21; MS (EI) m/z 253 (Mþ,
8.8), 252 [(M2H)þ, 18.2], 124 (100%); HRMS calcd for
C18H23N: m/z 253.1830. Found: m/z 253.1818.
4.3.1. (E)-N-Propargyl-1-methyloct-4-enylamine (2a).
Al2O3-TLC (hexaneþAcOEt (30:1), Rf¼0.33); oil; 1H
NMR dH 0.88 (3H, t, J¼7.3 Hz), 1.03 (3H, t, J¼6.3 Hz),
1.2–1.6 (5H, m), 1.9–2.1 (4H, m), 2.18 (1H, t, J¼2.3 Hz),
2.86 (1H, sext, J¼6.3 Hz), 3.39 (1H, dd, J¼2.3, 17.2 Hz),
3.47 (1H, dd, J¼2.3, 17.2 Hz), 5.42 (2H, m); 13C NMR dC
13.66 (CH3), 19.71 (CH3), 22.68 (CH2), 28.98 (CH2), 34.68
(CH2), 35.56 (CH2), 36.64 (CH2), 51.00 (CH), 70.96 (CH),
82.48 (C), 129.88 (CH), 130.62 (CH); IR 3306, 1459,
4.3.6. (E)-N-Propargyl-1,5-diphenylpent-4-enylamine
(2c). This amine was prepared by reduction of the
corresponding imine, prepared from (E)-1,5-diphenylpent-
4-en-1-one (1c) according to a literature.12 Thus, to a
benzene (4.2 ml) solution of ketone 1c (200 mg, 0.85 mmol)
and propargylamine (0.58 ml, 8.5 mmol) was slowly added
a benzene (1 ml) solution of TiCl4 (0.06 ml, 0.51 mmol) at
08C and the reaction mixture was stirred at room
temperature for 12 h. After usual work-up, the crude
product was dissolved in EtOH (3 ml) and then treated
with NaBH4 until the starting imine had disappeared
(monitored by TLC). Usual work-up and purification by
preparative TLC (Al2O3) afforded the corresponding
N-propargylamine 2c (193 mg, 0.70 mmol, 82%). Al2O3-
968 cm21
;
MS (EI) m/z 178 [(M2H)þ, 5], 164
[(M2CH3)þ, 27], 137 (60), 82 (100%); HRMS calcd for
C12H20N: m/z 178.1596. Found: m/z 178.1599.
4.3.2. (E)-N-Propargyl-1-methyl-5-phenylpent-4-enyl-
amine (2b). Al2O3-TLC (hexaneþAcOEt (10:1),
1
Rf¼0.43); oil; H NMR dH 1.08 (3H, d, J¼6.3 Hz), 1.49
(1H, m), 1.53 (1H, m), 2.18 (1H, t, J¼2.6 Hz), 2.2–2.3 (2H,
m), 2.93 (1H, m), 3.41 (1H, dd, J¼2.6, 17.2 Hz), 3.48 (1H,
dd, J¼2.6, 17.2 Hz), 6.21 (1H, dd, J¼6.6, 15.8 Hz), 6.41
(1H, d, J¼15.8 Hz), 7.2–7.4 (5H, m); 13C NMR dC 19.75
(CH3), 29.34 (CH2), 35.58 (CH2), 36.24 (CH2), 50.92 (CH),
71.10 (C), 82.39 (CH), 125.93 [(CH)£2], 126.88 (CH),
128.48 [(CH)£2], 130.06 (CH), 130.42 (CH), 137.72 (C); IR
3273, 1462, 699 cm21; MS (EI) m/z 213 (Mþ, 4), 212
[(M2H)þ, 10], 129 (37), 82 (100%); HRMS calcd for
C15H19N: m/z 213.1517. Found: m/z 213.1501.
1
TLC (hexaneþAcOEt (10:1), Rf¼0.47); oil; H NMR dH
1.8–1.9 (2H, m), 2.1–2.2 (2H, m), 2.18 (1H, t, J¼2.3 Hz),
3.10 (1H, dd, J¼2.3, 17.2 Hz), 3.34 (1H, dd, J¼2.3,
17.2 Hz), 3.88 (1H, m), 6.15 (1H, dt, J¼6.6, 15.8 Hz),
6.33 (1H, d, J¼15.8 Hz), 7.1–7.4 (10H, m); 13C NMR dC
29.67 (CH2), 35.83 (CH2), 37.23 (CH2), 61.01 (CH), 71.28
(C), 82.26 (CH), 125.93 [(CH)£2], 126.90 (CH), 127.38
(CH), 127.62 [(CH)£2], 128.48 [(CH)£4], 130.03 (CH),
130.28 (CH), 137.68 (C), 142.62 (C); IR 3274, 1461, 738,
700 cm21; MS (EI) m/z 274 [(M2H)þ, 13.8], 220 (16.5),
144 (100%); HRMS calcd for C20H20N: m/z 274.1596.
Found: m/z 274.1601.
4.3.3. (E)-N-Propargyl-1-methyl-5-triethylsilylpent-4-
enylamine (2d). Al2O3-TLC (hexaneþAcOEt (10:1),
1
Rf¼0.67); oil; H NMR dH 0.54 (6H, q, J¼7.9 Hz), 0.92
(9H, t, J¼4.0 Hz), 1.04 (3H, t, J¼4.0 Hz), 1.4–1.6 (3H, m),
2.1–2.2 (2H, m), 2.18 (1H, t, J¼2.6 Hz), 2.88 (1H, sext,
J¼6.3 Hz), 3.39 (1H, dd, J¼2.6, 17.2 Hz), 3.47 (1H, dd,
J¼2.6, 17.2 Hz), 5.58 (1H, dt, J¼1.3, 18.8 Hz), 6.04 (1H, dt,
J¼6.3, 18.8 Hz); 13C NMR dC 3.45 [(CH2)£3], 7.39
[(CH3)£3], 19.68 (CH3), 33.35 (CH2), 35.54 (CH2), 35.74
(CH2), 50.91 (CH), 71.01 (C), 82.37 (CH), 126.20 (CH),
147.92 (CH); IR 3386, 1618, 1460, 1237, 1016 cm21; MS
(EI) m/z 250 [(M2H)þ, 3.1], 236 [(M2CH3)þ, 7.6], 222
4.4. General procedure for the tandem cyclization of
aminyl radicals
To a toluene solution of N-propargylamines 2a–f (0.02 M)

H. Hasegawa et al. / Tetrahedron 59 (2003) 827–832
831
was added N-chlorosuccinimide (1.0 equiv.) under nitrogen
atmosphere at room temperature. After stirring for 30 min,
Bu3SnH (1.0 equiv.) and AIBN (0.2 equiv.) were added and
the solution was heated under reflux for 7 h. After
evaporation of toluene, the residue was diluted with 5 ml
of ethyl acetate and stirred vigorously with 10%-KF
aqueous solution for several hours to remove tin by-product.
The precipitate (Bu3SnF) was filtered off, and the aqueous
phase was made basic by 2N NaOH and was extracted
with Et2O. The combined organic layers were washed with
water and brine, and dried over MgSO4. After evaporation
of the solvent, the resultant crude product was purified with
TLC (Al2O3) to give 2-methylenepyrrolizidines 3a–f and
4a,b.
3.36 (1H, d, J¼9.9 Hz), 3.5–3.6 (2H, m), 3.89 (1H, dt,
J¼2.6, 17.2 Hz), 5.47 (1H, dd, J¼2.6, 5.3 Hz), 7.1–7.3 (5H,
m); 13C NMR dC 20.47 (CH3), 27.46 (CH2), 33.69 (CH2),
55.04 (CH2), 56.30 (CH), 60.16 (CH), 75.29 (CH), 111.91
(CH), 126.94 (CH), 128.50 [(CH)£2], 128.73 [(CH)£2],
140.32 (C), 149.76 (C); IR 1650, 1458, 1377, 700 cm21; MS
(EI) m/z 247 (Mþ, 72), 212 [(M2Cl)þ, 51], 129 (100%);
HRMS calcd for C15H18NCl: m/z 247.1128. Found: m/z
247.1164.
4.4.3. Radical cyclization of 2c; 1,5-diphenyl-2-methyl-
enepyrrolizidine (3c). Al2O3-TLC (hexaneþAcOEt (10:1),
Rf¼0.83); oil; 1H NMR dH 1.8–2.0 (2H, m), 2.16 (1H, m),
2.35 (1H, m), 3.4–3.6 (2H, m), 3.8–3.9 (3H, m), 4.61 (1H,
dd, J¼2.0, 4.3 Hz), 4.97 (1H, dd, J¼2.0, 4.3 Hz), 7.2–7.4
(10H, m); 13C NMR dC 29.15 (CH2), 36.39 (CH2), 57.25
(CH), 57.68 (CH2), 69.70 (CH), 74.12 (CH), 107.04 (CH2),
126.54 (CH), 126.97 (CH), 127.17 [(CH)£2], 128.37
[(CH)£2], 128.53 [(CH)£2], 128.73 [(CH)£2], 141.49 (C),
143.84 (C), 155.70 (C); IR 1458, 1378, 699 cm21; MS (EI)
m/z 275 (Mþ, 100%); HRMS calcd for C20H21N: m/z
275.1674. Found: m/z 275.1672.
4.4.1. Radical cyclization of 2a; 5-methyl-2-methylene-1-
propylpyrrolizidine (3a) and 2-chloromethylene-5-
methyl-1-propylpyrrolizidine (4a). Compound 3a.
Al2O3-TLC (hexaneþAcOEt (10:1), Rf¼0.44); oil; 1H
NMR dH 0.92 (3H, t, J¼6.9 Hz), 1.08 (3H, d, J¼6.3 Hz),
1.3–1.4 (3H, m), 1.5–1.6 (3H, m), 1.97 (1H, m), 2.1–2.2
(2H, m), 2.63 (1H, m), 3.26 (1H, m), 3.29 (1H, dt, J¼1.7,
14.8 Hz), 3.61 (1H, ddd, J¼1.7, 3.6, 14.8 Hz), 4.83 (1H,
ddd, J¼0.7, 2.0, 4.3 Hz), 4.89 (1H, dd, J¼2.0, 3.6 Hz); 13C
NMR dC 14.47 (CH3), 20.59 (CH3), 20.81 (CH2), 31.03
(CH2), 35.04 (CH2), 35.25 (CH2), 49.51 (CH), 57.25 (CH2),
60.66 (CH), 71.61 (CH), 104.24 (CH2), 155.00 (C); IR 1457,
1376 cm21; MS (EI) m/z 179 (Mþ, 44), 164 [(M2CH3)þ,
100], 150 [(M2C2H5)þ, 87], 136 [(M2C3H7)þ, 54%];
HRMS calcd for C12H21N: m/z 179.1674. Found: m/z
179.1681.
4.4.4. Radical cyclization of 2d; 1-triethylsilyl-5-methyl-
2-methylenepyrrolizidine (3d). Al2O3-TLC (hexaneþ
AcOEt (30:1), Rf¼0.44); oil; 1H NMR dH 0.61 (6H, q,
J¼7.6 Hz), 0.97 (9H, t, J¼7.6 Hz), 1.07 (3H, t, J¼5.9 Hz),
1.48 (2H, m), 1.81 (1H, m), 1.97 (1H, m), 2.17 (1H, m), 2.55
(1H, m), 3.31 (1H, d, J¼15.2 Hz), 3.47 (1H, dd, J¼2.3,
15.2 Hz), 3.70 (1H, dt, J¼3.0, 7.6 Hz), 4.74 (1H, s), 4.82
(1H, s); 13C NMR dC 2.32 [(CH2)£3], 7.60 [(CH3)£3],
20.20 (CH3), 31.81 (CH2), 34.09 (CH2), 38.11 (CH), 57.68
(CH), 58.38 (CH2), 67.69 (CH), 102.87 (CH2), 152.94 (C);
IR 1647, 1240, 867 cm21; MS (EI) m/z 251 (Mþ, 33.2), 236
(55.5), 222 (58.3), 136 (100%); HRMS calcd for
C15H29NSi: m/z 251.2069. Found: m/z 251.2061.
Compound 4a. Rf¼0.50; oil; 1H NMR dH 0.92 (3H, t,
J¼7.3 Hz), 1.10 (3H, d, J¼6.3 Hz), 1.2–1.4 (3H, m), 1.5–
1.6 (3H, m), 1.98 (1H, m), 2.12 (1H, m), 2.31 (1H, m), 2.61
(1H, m), 3.31 (1H, dt, J¼4.3, 7.6 Hz), 3.52 (1H, dd, J¼2.3,
16.8 Hz), 3.68 (1H, dt, J¼2.3, 16.8 Hz), 5.83 (1H, dd,
J¼2.3, 4.6 Hz); 13C NMR dC 14.38 (CH3), 20.56 (CH3),
20.59 (CH2), 30.17 (CH2), 34.45 (CH2), 35.56 (CH2), 49.38
(CH2), 54.64 (CH), 60.32 (CH), 72.18 (CH), 108.91 (CH),
148.82 (C); IR 1650, 1458, 1377, 734 cm21; MS (EI) m/z
213 (Mþ, 19), 198 [(M2CH3)þ, 32], 184 [(M2C2H5)þ, 36],
178 [(M2Cl)þ, 100%]; HRMS calcd for C12H20N: m/z
178.1596. Found: m/z 178.1612.
4.4.5. Radical cyclization of 2f; perhydro-2-methylene-1-
phenylpyrrolo[1,2-a]indole (3f). Al2O3-TLC (hexaneþ
1
AcOEt (10:1), Rf¼0.50); oil; H NMR dH 1.1–1.9 (10H,
m), 2.16 (1H, m), 2.89 (1H, d, J¼3.6 Hz), 3.34 (1H, d,
J¼9.6 Hz), 3.45 (1H, dd, J¼1.0, 14.8 Hz), 3.73 (1H, m),
3.86 (1H, d, J¼14.8 Hz), 4.50 (1H, d, J¼2.0 Hz), 4.97 (1H,
d, J¼2.0 Hz), 7.2–7.3 (5H, m); 13C NMR dC 20.58 (CH2),
24.69 (CH2), 27.82 (CH2), 28.79 (CH2), 36.89 (CH2), 39.73
(CH), 57.79 (CH), 57.92 (CH2), 64.85 (CH), 71.99 (CH),
106.34 (CH2), 127.39 (CH), 128.43 [(CH)£2], 128.82
[(CH)£2], 140.72 (C), 155.29 (C); IR 1659, 1454, 746,
700 cm21; MS (EI) m/z 253 (Mþ, 100), 210 (51), 129
(40%); HRMS calcd for C18H23N: m/z 253.1830. Found:
m/z 253.1834.
4.4.2. Radical cyclization of 2b; 5-methyl-2-methylene-1-
phenylpyrrolizidine (3b) and 2-chloromethylene-5-
methyl-1-phenylpyrrolizidine (4b). Compound 3b.
Al2O3-TLC (hexaneþAcOEt (4:1), Rf¼0.63); oil; 1H
NMR dH 1.14 (3H, d, J¼6.3 Hz), 1.5–1.7 (2H, m), 2.0–
2.1 (2H, m), 2.80 (1H, m), 3.33 (1H, d, J¼9.2 Hz), 3.54 (1H,
d, J¼15.5 Hz), 3.62 (1H, m), 3.85 (1H, dd, J¼1.7, 15.5 Hz),
4.58 (1H, d, J¼2.0 Hz), 5.00 (1H, d, J¼1.3 Hz), 7.2–7.3
(5H, m); 13C NMR dC 21.08 (CH3), 28.93 (CH2), 34.63
(CH2), 57.27 (CH), 57.77 (CH2), 61.01 (CH), 74.77 (CH),
107.24 (CH2), 126.88 (CH), 128.88 [(CH)£2], 129.13
[(CH)£2], 141.85 (C), 156.17 (C); IR 1661, 1454, 748,
700 cm21; MS (EI) m/z 213 (Mþ, 99.7), 198 [(M2CH3)þ,
100], 136 [(M2C6H5)þ, 11.0%]; HRMS calcd for C15H19N:
m/z 213.1517. Found: m/z 213.1531.
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´ ´ ´ ´
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