Domino metathesis of 2-azanorbornenones: A new strategy for the enatioselective synthesis of 1-azabicyclic compounds

Article abstract of DOI:10.1021/jo016000e

Domino metathesis of N-alkylated derivatives of (1S)-2-azanorborn-5-en-3-one allowed for the enantioselective synthesis of pyrrolizidine, quinolizidine, pyrrolidinoazepine, and pyrrolidinoazocine derivatives in a straight-forward process.

Full text of DOI:10.1021/jo016000e

1380
J . Org. Chem. 2002, 67, 1380-1383
Dom in o Meta th esis of
2-Aza n or bor n en on es: A New Str a tegy for
th e En a tioselective Syn th esis of
1-Aza bicyclic Com p ou n d s†
F igu r e 1.
Odo´n Arjona,* Aurelio G. Csa´ky¨, Roc´ıo Medel, and
J oaqu´ın Plumet*
Sch em e 1
Sch em e 2
Departamento de Quı´mica Orga´nica, Facultad de Quı´mica,
Universidad Complutense, 28040 Madrid, Spain
plumety@eucmax.sim.ucm.es
Received August 3, 2001
Abstr a ct: Domino metathesis of N-alkylated derivatives of
(1S)-2-azanorborn-5-en-3-one allowed for the enantioselec-
tive synthesis of pyrrolizidine, quinolizidine, pyrrolidi-
noazepine, and pyrrolidinoazocine derivatives in a straight-
forward process.
rolidines from simple starting materials in stepwise
procedures (Scheme 1).
We report herein (Scheme 2) a new method for the
enantioselective synthesis of the azabicyclic γ-lactams 8
starting from (1S)-2-azanorborn-5-en-3-one6 5 as a com-
mon precursor in a two-step procedure: (i) N-alkylation
of 5, (ii) domino metathesis7 (combination of ring opening
(ROM), ring closing (RCM), and cross metatheses (CM)).
(1S)-2-Azanorborn-5-en-3-one 5 was akylated at the
nitrogen atom with the corresponding alkyl halides 6
under solid-liquid PTC conditions to give compounds 7
(Scheme 2),8 which were treated with Grubbs’ ruthenium
catalyst ([Ru]) in the presence of ethylene or allyl acetate
(Scheme 3). The results are given in Table 1.
In the presence of [Ru] (5% mol), the reaction of
compounds 7b,c with ethylene afforded the expected
domino metathesis bicyclic γ-lactones 8b,c. On the other
hand, compounds 7a and 7d did not cyclize under the
aforementioned conditions, and the products of ring-
opening-cross metathesis (ROM-CM)9 9a ,d were in-
stead isolated as the only products (Table 1, entries 1
and 9). No significant improvements were noticed upon
increasing [Ru] catalyst loading to 10% mol or when
[Imes-Ru] was used as catalyst instead of [Ru] (Table 1,
entries 2, 3; 5, 6; 9, 10). In a similar fashion, compound
7b reacted with allyl acetate in the presence of [Ru] to
afford compounds 8b and 8e (Table 1, entries 11 and 12).
The best yield in 8e was obtained with [Imes-Ru] (Table
1, entry 13). It is worth mentioning that no ROM-CM
products were observed in these cases.7
Alkaloids with pyrrolizidine 1, quinolizidine 2, pyrrol-
idinoazepine 3, and pyrrolidinoazocine 4 ring sistems
have a wide and varied distribution in nature. These
compounds display a broad range of interesting biological
activities, and many of them serve as intermediates in
the synthesis of more elaborated compounds. Accordingly,
new strategies for the enantioselective synthesis of these
azabicyclic skeletons continue to receive considerable
attention.1,2 In recent times, olefin metathesis has emerged
as a powerful tool in organic synthesis.3 In particular,
ring-closing metathesis (RCM) has been extensively used
for the preparation of cyclic compounds from acyclic
precursors. However, the application of this procedure
to the synthesis of azabicyclic compounds4,5 usually
requires the elaboration of suitably functionalized pyr-
† Dedicated to Prof. Marcial Moreno on occasion of his 60th birthday.
(1) For general references on the synthesis of alkaloids, see: (a)
Alkaloids, Vol. 55: Chemistry and Biology, Cordell, G. A., Ed.;
Academic Press: San Diego, 2001. (b) Enders, D.; Thiebes, C. Pure
Appl. Chem. 2001, 73, 573. See also: (c) Liddell, J . R. Nat. Prod. Rep.
2000, 17, 455. (d) Michael, J . P. Nat. Prod. Rep. 1999, 16, 675. (e) Le
Cont, D. J . In Progress in Heterocyclic Chemistry; Gribble, G. W.,
Gilchrist, T. L., Eds.; Pergamon: Oxford, 1999; Vol. 11, Chapter 7.
(2) For azabicycloalkanes as reverse-turn inducer dipeptide mimics,
see: (a) Hanessian, S.; McNaughton-Smith, G.; Lombart, H.-G.; Lubell,
W. D. Tetrahedron 1997, 53, 12789. (b) Cativiela, C.; D´ıaz de Villegas,
M. D. Tetrahedron: Asymmetry 2000, 11, 645. (c) Angiolini, M.; Araneo,
S.; Belvisi, L.; Cesarotti, E.; Checchia, A.; Crippa, L.; Manzoni, L.
Scolastico, C. Eur. J . Org. Chem. 2000, 2571 and cited references
therein.
(3) (a) Schuster, M.; Blechert, S. Angew. Chem., Int. Ed. Engl. 1997,
36, 2036. (b) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413. (c)
Fu¨rstner, A. Angew. Chem., Int. Ed. 2000, 39, 3012. (d) Maier, M. E.
Angew. Chem., Int. Ed. 2000, 39, 2073. (e) Undheim, K.; Efskind, J .
Tetrahedron 2000, 56, 48. (f) Trnka, T. M.; Grubbs, R. H. Acc. Chem.
Res. 2000, 34, 18 and references cited therein.
(4) For reviews, see: (a) Phillips, A. J .; Abell, A. D. Aldrichim. Acta
1999, 32, 75. (b) Schuster, M.; Stragies, R.; Blechert, S. In Targets in
Heterocyclic Systems. Chemistry and Properties; Attanasi, O. A.,
Spinelli, D., Eds.; Italian Society of Chemistry: Rome, 1998; and
references cited therein.
However, the isolated ROM-CM products 9a ,d did
cyclize under ring-closing metathesis (RCM) conditions
with [Ru] or [Mo], giving rise to the expected domino
metathesis products 8a and 8d . The results are gathered
in Table 2.
The outcome of these reactions may be understood on
the basis of the operation of two alternative equilibrating
reaction pathways (Scheme 4).
(6) For the chemistry of substituted 2-azanorbornenes (2-azabicyclo-
[2.2.1]hept-5-enes), see: Brandt, P.; Andersson, P. G. Synthesis 2000,
1092.
(7) Stragies, R.; Blechert, S. Synlett 1998, 169.
(8) Compound 5 is commercially available in both optically pure
forms.
(5) See, for example: (a) Lennartz, M.; Steckhan, E. Synlett 2000,
319. (b) Pandit, U. K.; Overkleeft, H. S.; Borer, B. C.; Biera¨ugel, H.
Eur. J . Org. Chem. 1999, 959. (b) Arisawa, M.; Takezawa, E.; Nishida,
A.; Mori, M.; Nakagawa, M. Synlett 1997, 1179. (c) Huwe, C. M.;
Velder, J .; Blechert, S. Angew. Chem., Int. Ed. Engl. 1996, 35, 2376.
(d) Martin, S. F.; Chen, H.-J .; Courtney, A. K.; Liao, Y. Tetrahedron
1996, 52, 7251.
(9) Schneider, M.; Lucas, N.; Velder, J .; Blechert, S. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 257.
10.1021/jo016000e CCC: $22.00 © 2002 American Chemical Society
Published on Web 01/30/2002

Notes
J . Org. Chem., Vol. 67, No. 4, 2002 1381
Sch em e 3
Sch em e 4
Ta ble 1. RCM a n d Dom in o Meta th esis of 7 w ith
Eth ylen e
no.
7
[Ru] (mol %)
8b (%)
9b (%)
7c (%)
1
2
3
4
5
6
8
9
10
11
12
13
7a
7a
7a
7b
7b
7b
7c
7d
7d
7b
7b
7b
[Ru] (5)a
9a (10)
9a (25)
9a (5)
9b (7)
9b (5)
9b (35)
9c (10)
9d (30)
9d (60)
80
50
80
30
30
20
20
20
20
[Ru] (10)a
[Imes-Ru] (5)a
[Ru] (5)a
8b (60)
[Ru] (10)a
[Imes-Ru] (5)a
[Ru] (10)a
[Ru] (5)a
8b (65)
8b (55)
8c (60)
whereas intermolecular CM with an external alkene
would give rise to the ROM-CM products 9. The latter
may be interconverted to 8 by RCM. Also, intermediate
IV-B could afford the ROM-CM products 9 by CM with
an external alkene.
[Ru] (10)a
[Ru] (5)d
8b (20), 8e (20)
8b (30), 8e (40)
8b (30), 8e (65)
[Ru] (10)e
[Imes-Ru] (5)d
The operation of patway A is put forward by the results
obtained in the reactions of compound 7a (n ) 1). In this
case, the intermediate carbene III may be stabilized by
coordination of the metal with the carbonyl group.10 This
extra-stabilization effect would account for the displace-
ment of the equilibria toward III. The low conversion
observed could be explained on the basis of the low
reactivity of the stabilized carbene III due to this
stabilization effect.
a
Reactions carried out in CH2Cl2 (40 mL/mmol) and 1 atm
ethylene. Isolated yield. c Percent recovered. Reactions carried
out in CH2Cl2 (40 mL/mmol) and 1 equiv of allyl acetate. e Reac-
tions carried out in CH2Cl2 (40 mL/mmol) and 10 equiv of allyl
acetate.
b
d
Ta ble 2. Rin g-Closin g Meta th esis of 9a ,d a
no.
9
[Ru] (mol %)
8b (%)
9c (%)
On the other hand, the operation of pathway B is put
forward by the exclusive obtention of the ROM-CM
products 9a ,d in the reactions of compounds 7a ,d .
Intermediacy of species IV-B would render the direct
domino metathesis a more difficult process, as the
formation of 8 would require the CM of 9 in a second
reaction step.
Also, the operation of pathway B is noted in the
reactions of compound 7b with allyl acetate. In this case,
compound 8e, which could stem from intermediate V, is
obtained together with compound 8b, which is the
product or RCM of IV-A. However, as previously stated,
compound 8e could also be formed by CM of 8b with allyl
acetate.
1
2
3
4
5
6
9a
9a
9a
9d
9d
9d
[Ru] (5)
[Ru] (10)
[Mo] (5)
[Ru] (5)
[Ru] (10)
[Mo] (5)
8a (22)
8a (60)
8a (50)
8d (30)
8d (50)
8d (45)
9a (60)
9a (30)
9a (20)
9d (50)
9d (40)
9d (30)
a
b
Reactions carried out in CH2Cl2 (100 mL/mmol). Isolated
yield. c Percent recovered.
Initial cyclobutanametalation of the terminal alkene
moiety of 7 may lead to intermediate I (path A). Intramo-
lecular ROM-CM of I would lead to carbenes III and V,
which would render the domino metathesis products 8
upon reaction with an external alkene by CM.
On the other hand, initial cyclobutanametalation of the
endocyclic CdC bond of 7 may lead to the regioisomeric
intermediates II-A or II-B, which lead, respectively, to
carbenes IV-A and IV-B (path B). Intramolecular RCM
of IV-A would afford the domino metathesis products 8,
The results described herein put forward the operation
of different equilibrating reaction pathways, which ac-
(10) Choi, T.-L.; Chatterjee, A. K.; Grubbs, R. H. Angew. Chem., Int.
Ed. 2001, 40, 1277.

1382 J . Org. Chem., Vol. 67, No. 4, 2002
Notes
Hz), 5.74 (ddt, 1 H, J ) 6.8, 10.3, 17.1 Hz), 6.61 (ddd, 1 H, J )
1.2, 3.2, 4.9 Hz), 6.80 (dd, 1 H, J ) 2.0, 5.0 Hz). 13C NMR (CDCl3,
50 MHz): δ 25.9, 27.1, 33.2, 43.4, 53.8, 58.9, 63.0, 114.6, 138.0,
138.3, 139.5, 180.3. Anal. Calcd for C12H17NO: C, 75.39; H, 8.90.
Found: C, 75.51; H, 9.02.
Met a t h esis of Com p ou n d s 7 w it h E t h ylen e. Gen er a l
P r oced u r e. A solution of 7 (0.31 mmol) in CH2Cl2 (12 mL) was
saturated with ethylene and left under ethylene atmosphere (1
atm). [Ru] (0.015 or 0.031 mmol, see Table 1) dissolved in CH2-
Cl2 (4L or 9 mL ,respectively) was added, and the mixture was
stirred for 24 h. The solvent was removed under reduced
pressure, and the residue was purified by chromatography
(pentane/Et2O ) 1:1).
count for the obtention of the ROM-CM or domino
metathesis products in the reaction of 5 with [Ru] or [Mo]
metathesis catalyst in the presence of an external alkene.
In any case, the ROM-CM products could be converted
to the final azabicyclic γ-lactams 8 by independent RCM.
This procedure allows for the enantioselective synthesis
of 1-azabicyclic compounds of different ring sizes from a
single starting material, although the low yields obtained
for the pirrolidizidine skeleton makes it of scarce pre-
parative use in this case.
(2S,8a S)-2-Vin yl-1,5,6,8a -tetr a h yd r oin d olizin -3-on e, 8b.
Pale yellow oil. [R]25D ) -17.8 (c 0.8, CHCl3). IR (CHCl3): ν 2928,
2852, 1678. 1H NMR (CDCl3, 300 MHz): δ 1.52 (c, 1 H, J ) 11.8
Hz), 2.12-2.05 (m, 1 H), 2.32-2.18 (m, 1 H), 2.46 (ddd, 1 H,
J ) 6.7, 7.3, 12.1 Hz), 2.87 (td, 1 H, J ) 4.5, 12.4 Hz), 3.21 (dt,
1 H, J ) 7.3, 11.1 Hz), 4.11-4.06 (m, 1 H), 4.21 (dd, 1 H, J )
6.7, 13.2 Hz), 5.18 (dd, 1 H, J ) 0.1, 17.1 Hz), 5.22 (dd, 1 H,
J ) 0.7, 10.4 Hz), 5.72-5.68 (m, 1 H), 5.83-5.78 (m, 1 H), 5.96
(ddd, 1 H, J ) 6.7, 10.4, 17.1 Hz); 13C NMR (CDCl3, 75 MHz):
δ 24.5, 33.3, 36.3, 46.9, 52.8, 117.4, 125.0, 127.7, 135.3, 172.4.
Anal. Calcd for C10H13NO: C, 73.62; H, 7.97. Found: C, 73.51;
H, 8.10.
Exp er im en ta l P a r t
All starting materials were commercially available research-
grade chemicals and used without further purification. CH2Cl2
was distilled after refluxing over CaCl2 under Ar. Silica gel 60
F254 was used for TLC, and the spots were detected with UV or
vainillin solution. Flash column chromatography was carried out
on silica gel 60. IR spectra have been recorded as CHCl3
solutions. 1H and 13C NMR spectra were recorded at 200 and
50.5 MHz, respectively, in CDCl3 solution with TMS as internal
reference.
Syn th esis of th e N-Alk yl-2-a za n or bor n -5-en on es 7. Gen -
er a l P r oced u r e. To a solution of (1S)-(-)-2-azabicyclo[2.2.1.]-
hept-5-en-3-one 5 (109 mg, 1 mmol) in CH3CN (6 mL) were
succesively added K2CO3 (166 mg, 1.2 mmol), triturated KOH
(168 mg, 3 mmol), and TEBA (30 mg, 0.013 mmol). After the
mixture was stirred for 5 min at rt, the corresponding alkyl
halide 6 (1.2 mmol) was added, and the resulting mixture was
heated at reflux temperature for 3 h. After the mixture was
cooled to room temperature, the solid was removed by filtration
and washed with diethyl ether (3 × 10 mL) and the filtrate
concentrated under reduced pressure. The residue was purified
by chromatography (pentane/Et2O ) 1:1).
(2S,9aS)-2-Vin yl-1,2,5,6,7,9a-h exah ydr opyr r olo[1,2-a ]aze-
p in -3-on e, 8c. Pale yellow oil. [R]25 ) +37.1 (c 0.07, CHCl3).
D
1
IR (CHCl3): ν 2937, 1711, 1674. H NMR (CDCl3, 300 MHz): δ
1.73-1.62 (m, 1 H), 1.80-1.74 (m, 1 H), 1.92-1.82 (m, 1 H),
2.24-2.15 (m, 2 H), 2.47 (ddd, 1 H, J ) 7.8, 8.8, 12.7 Hz), 3.10-
2.96 (m, 2 H), 4.02 (ddd, 1 H, J ) 4.9, 7.8, 13.2 Hz), 4.28-4.22
(m, 1 H), 5.14 (dd, 1 H, J ) 1.5, 8.8 Hz), 5.17 (dd, 1 H, J ) 1.5,
17.6 Hz), 5.46 (dd, 1 H, J ) 1.9, 11.7 Hz), 5.72-5.64 (m, 1 H),
5.89 (ddd, 1 H, J ) 6.8, 10.3, 17.1 Hz). 13C NMR (CDCl3, 50
MHz): δ 26.2, 27.9, 33.1, 43.0, 46.0, 57.0, 116.9, 129.9, 131.3,
135.8, 174.2. Anal. Calcd for C11H15NO: C, 74.58; H, 8.47.
Found: C, 74.70; H, 8.35.
(1S)-2-(Allyl)-2-a za bicyclo[2.2.1.]h ep t-5-en -3-on e, 7a . Pale
yellow oil, 90%. [R]25 ) +189.1 (c 0.11, CHCl3). IR (CHCl3): ν
(3S,5S)-1-Allyl-3,5-d ivin ylp yr r olid in -2-on e, 9a . Pale yel-
low oil. [R]25D ) +64.4 (c 0.27, CHCl3). IR (CHCl3): ν 2928, 1678,
1643. 1H NMR (CDCl3, 300 MHz): δ 1.69 (ddd, 1 H, J ) 7.8,
9.3, 12.7 Hz), 2.46 (ddd, 1 H, J ) 7.3, 8.8, 13.2 Hz), 3.13 (c, 1 H,
J ) 8.3 Hz), 3.49 (dd, 1 H, J ) 7.3, 15.1 Hz), 4.01 (c, 1 H, J )
7.8 Hz), 4.28 (dd, 1 H, J ) 4.9, 15.1 Hz), 5.11 (dd, 1 H, J ) 1.0,
17.1 Hz), 5.16 (d, 1 H, J ) 10.3 Hz), 5.31-5.18 (m, 4 H), 5.60
(ddd, 1 H, J ) 1.5, 8.8, 17.1 Hz), 5.76-5.64 (m, 1 H), 5.96 (ddd,
1 H, J ) 6.8, 9.8, 17.1 Hz). 13C NMR (CDCl3, 50 MHz): δ 32.2,
43.3, 45.6, 59.5, 117.1, 117.8, 119.0, 132.2, 135.6, 138.1, 174.3.
Anal. Calcd for C11H15NO: C, 74.58; H, 8.47. Found: C, 74.43;
H, 8.60.
D
2953, 1697, 1645. 1H NMR (CDCl3, 300 MHz): δ 2.09 (d, 1 H,
J ) 7.5 Hz), 2.27 (dd, 1 H, J ) 1.6, 7.5 Hz), 3.33-3.32 (m, 1 H),
3.37 (ddd, 1 H, J ) 1.4, 6.3, 15.5 Hz), 3.84 (dd, 1 H, J ) 5.8,
15.4 Hz), 4.13 (dd, 1 H, J ) 1.6, 3.6 Hz), 5.13 (dt, 1 H, J ) 1.5,
10.0 Hz), 5.16 (dddd, 1 H, J ) 0.8, 1.5, 3.0, 18.0 Hz), 5.72-5.58
(m, 1 H), 5.58 (ddd, 1 H, J ) 1.4, 3.4, 4.9 Hz), 6.79 (dd, 1 H, J )
2.1, 5.2 Hz). 13C NMR (CDCl3, 50 MHz): δ 46.6, 53.8, 58.2, 62.5,
117.7, 133.1, 137.7, 139.5, 180.2. Anal. Calcd for C9H11NO: C,
72.48; H, 7.38. Found: C, 72.61; H, 7.30.
(1S)-2-(Bu t-3-en yl)-2-azabicyclo[2.2.1.]h ept-5-en -3-on e, 7b.
Pale yellow oil, 85%. [R]25 ) +294.8 (c 0.31, CHCl3). IR
D
(CHCl3): ν 2851, 1691, 1641. 1H NMR (CDCl3, 300 MHz): δ
2.21-2.09 (m, 3 H), 2.27 (dt, 1 H, J ) 1.5, 7.3 Hz), 2.93 (q, 1 H,
J ) 6.8 Hz), 3.25 (t, 1 H, J ) 7.3 Hz), 3.32-3.30 (m, 1 H), 4.18
(td, 1 H, J ) 2.0, 3.4 Hz), 5.01 (ddd, 1 H, J ) 1.5, 2.9, 8.8 Hz),
5.05 (ddd, 1 H, J ) 1.5, 3.4, 17.6 Hz), 5.79-5.65 (m, 1 H), 6.62
(ddd, 1 H, J ) 1.5, 3.4, 5.4 Hz), 6.81 (dd, 1 H, J ) 1.5, 5.4 Hz);
13C NMR (CDCl3, 50 MHz): δ 32.3, 43.0, 53.8, 58.9, 63.2, 116.6,
135.1, 138.1, 139.5, 180.3. Anal. Calcd for C10H13NO: C, 73.62;
H, 7.97. Found: C, 73.75; H, 8.09.
(3S,5S)-2-(Bu t-3-en yl)-3,5-divin ylpyr r olidin -2-on e, 9b. Pale
yellow oil. IR (CHCl3): ν 2928, 1690, 1650. 1H NMR (CDCl3, 300
MHz): δ 1.71-1.63 (m, 1 H), 2.36-2.18 (m, 2 H, Hz), 2.43 (ddd,
1 H, J ) 6.9, 8.8, 13.0 Hz), 3.02 (ddd, 1 H, J ) 5.5, 7.8, 13.3 Hz),
3.10 (c, 1 H, J ) 8.4 Hz), 3.66 (dt, 1 H, J ) 7.8, 13.7 Hz), 4.01
(c, 1 H, J ) 8.1 Hz), 5.03 (dt, 1 H, J ) 1.5, 8.9 Hz), 5.07 (dt, 1 H,
J ) 1.5, 15.6 Hz), 5.18 (dt, 1 H, J ) 1.1, 8.0 Hz), 5.24 (dt, 1 H,
J ) 0.7, 9.5 Hz), 5.26 (dt, 1 H, J ) 0.7, 19.0 Hz), 5.34 (dt, 1 H,
J ) 0.7, 17.1 Hz), 5.70-5.58 (m, 1 H), 5.82-5.71 (m, 1 H), 5.95
(ddd, 1 H, J ) 6.9, 10.7, 17.1 Hz). Anal. Calcd for C12H17NO: C,
75.39; H, 8.90. Found: C, 75.49; H, 9.02.
(1S)-2-(P en t-4-en yl)-2-a za bicyclo[2.2.1.]h ep t-5-en -3-on e,
7c. Pale yellow oil, 80%. [R]25 ) +239.6 (c 0.54, CHCl3). IR
D
(CHCl3): ν 2953, 1689, 1641. 1H NMR (CDCl3, 300 MHz): δ 1.48
(q, 2 H, J ) 7.4 Hz), 1.98 (c, 2 H, J ) 7.9 Hz), 2.09 (dt, 1 H, J )
1.5, 8.1 Hz), 2.25 (dt, 1 H, J ) 1.6, 7.5 Hz), 2.86 (dt, 1 H, J )
7.1, 13.7 Hz), 3.16 (dt, 1 H, J ) 7.4, 13.9 Hz), 3.29-3.28 (m, 1
H), 4.14 (dd, 1 H, J ) 1.9, 3.7 Hz), 4.92 (dt, 1 H, J ) 1.4, 10.3
Hz), 4.97 (ddd, 1 H, J ) 1.6, 3.4, 17.5 Hz), 5.81-5.68 (m, 1 H),
6.60 (ddd, 1 H, J ) 1.8, 3.3, 4.9 Hz), 6.79 (dd, 1 H, J ) 1.5, 5.2
Hz). 13C NMR (CDCl3, 50 MHz): δ 27.0, 30.9, 43.1, 53.8, 58.8,
(3S,5S)-1-(P en t -4-en yl)-3,5-d ivin ylp yr r olid in -2-on e, 9c.
Pale yellow oil. IR (CHCl3): ν 2932, 1709, 1676. 1H NMR (CDCl3,
300 MHz): δ 1.70-1.43 (m, 3 H), 2.02 (c, 2 H, J ) 6.8 Hz), 2.48-
2.39 (m, 1 H), 2.97 (ddd, 1 H, J ) 4.9, 8.8, 13.7 Hz), 3.09 (c, 1 H,
J ) 8.3 Hz), 3.55 (ddd, 1 H, J ) 1.9, 6.8, 13.2 Hz), 3.98 (c, 1 H,
J ) 7.8 Hz), 4.96 (d, 1 H, J ) 11.2 Hz), 5.01 (d, 1 H, J ) 19.5
Hz), 5.34-5.14 (m, 4 H), 5.60 (ddd, 1 H, J ) 3.4, 8.8, 17.1 Hz),
5.79 (m, 1 H), 5.95 (m, 1 H). 13C NMR (CDCl3, 50 MHz): δ 26.4,
31.0, 32.3, 40.4, 45.7, 60.0, 114.9, 117.0, 118.8, 135.7, 137.7,
138.4, 174.4. Anal. Calcd for C13H19NO: C, 76.10; H, 9.27.
Found: C, 75.98; H, 9.43.
63.0, 114.9, 137.6, 138.0, 139.5, 180.3. Anal. Calcd for C11H15
NO: C, 74.58; H, 8.47. Found: C, 74.67; H, 8.36.
-
(1S)-2-(Hex-5-en yl)-2-a za bicyclo[2.2.1.]h ep t -5-en -3-on e,
7d . Pale yellow oil, 80%. [R]25 ) +229.2 (c 0.67, CHCl3). IR
(3S,5S)-(Hex-5-en yl)-3,5-d ivin ylp yr r olid in -2-on e, 9d . Pale
D
(CHCl3): ν 2935, 1689, 1639. 1H NMR (CDCl3, 200 MHz): δ
1.49-1.22 (m, 4 H), 2.16-1.97 (m, 3 H), 2.26 (dt, 1 H, J ) 1.5,
7.6 Hz), 2.85 (dt, 1 H, J ) 6.8, 13.7 Hz), 3.17 (dt, 1 H, J ) 6.8,
13.7 Hz), 3.25 (d, 1 H, J ) 1.0 Hz), 4.14 (c, 1 H, J ) 1.7 Hz),
4.95-4.89 (dm, 1 H, J ) 10.3 Hz), 5.01-4.92 (dm, 1 H, J ) 17.1
yellow oil. [R]25 ) +18.2 (c 0.22, CHCl3). IR (CHCl3): ν 2932,
D
1
1678, 1641. H NMR (CDCl3, 300 MHz): δ 1.35 (c, 2 H, J ) 7.2
Hz), 1.56-1.40 (m, 2 H), 1.64 (ddd, 1 H, J ) 8.1, 9.6, 13.2 Hz),
2.05 (c, 2 H, J ) 6.9 Hz), 2.42 (ddd, 1 H, J ) 6.9, 9.0, 12.9 Hz),
2.94 (ddd, 1 H, J ) 5.4, 8.4, 13.8 Hz), 3.09 (cd, 1 H, J ) 1.5, 8.4

Notes
J . Org. Chem., Vol. 67, No. 4, 2002 1383
Hz), 3.52 (ddd, 1 H, J ) 6.9, 8.1, 13.8 Hz), 3.97 (c, 1 H, J ) 8.4
Hz), 4.94 (dt, 1 H, J ) 1.5, 10.8 Hz), 4.99 (dt, 1 H, J ) 1.5, 17.1
Hz) 5.33-5.15 (m, 4 H), 5.62 (dt, 1 H, J ) 9.3, 16.5 Hz), 5.77
(ddt, 1 H, J ) 6.6, 10.5, 17.1 Hz), 5.94 (ddd, 1 H, J ) 6.3, 10.8,
17.1 Hz). 13C NMR (CDCl3, 50 MHz): δ 26.0, 26.6, 32.3, 33.3,
40.6, 45.7, 59.9, 114.7, 117.0, 118.7, 135.7, 138.4, 138.4, 174.3.
Anal. Calcd for C14H21NO: C, 76.71; H, 9.59. Found: C, 76.85;
H, 9.48.
Acetic Acid 3-[(2S,8a S)-3-Oxo-1,2,3,5,6,8a -h exa h yd r oin -
d olizin -2-yl]a llyl Ester , 8e. To a solution of 7b (0.31 mmol) in
CH2Cl2 (12 mL) was added allyl acetate (0.31 mmol) followed
by a solution of [Imes-Ru] (0.015 mmol) in CH2Cl2 (4 mL). The
mixture was was stirred for 24 h at rt. The solvent was removed
under reduced pressure, and the residue was purified by
chromatography (pentane/Et2O ) 1:1). Pale yellow oil, 65%. IR
(CHCl3): ν 2854, 1734, 1682. 1H NMR (CDCl3, 300 MHz): δ 1.50
(c, 1 H, J ) 11.8 Hz), 2.07 (s, 3 H), 2.13-2.09 (m, 1 H), 2.28-
2.17 (m, 1 H), 2.47 (ddd, 1 H, J ) 6.3, 7.8, 12.1 Hz), 2.87 (tdd, 1
H, J ) 1.2, 5.1, 12.7 Hz), 3.28-3.20 (m, 1 H), 4.11-4.07 (m, 1
H), 4.20 (dd, 1 H, J ) 6.6, 13.0 Hz), 4.54 (d, 1 H, J ) 12.9 Hz),
4.61 (d, 1 H, J ) 12.6 Hz), 5.96-5.75 (m, 4 H). 13C NMR (CDCl3,
75 MHz): δ 24.5, 30.3, 33.5, 36.3, 45.5, 52.8, 64.6, 125.1, 126.7,
127.5, 131.9, 170.7, 176.6. Anal. Calcd for C13H17NO3: C, 66.38;
H, 7.23.Found: C, 66.50; H, 7.37.
(3S,7a S)-2-Vin yl-1,5,6,7a -tetr a h yd r op yr r olizin -3-on e, 8a .
Pale yellow oil. [R]25D ) -8.0 (c 0.15, CHCl3). IR (CHCl3): ν 2930,
1688, 1643. 1H NMR (CDCl3, 300 MHz): δ 1.75 (td, 1 H, J )
9.8, 12.2 Hz), 2.62 (dt, 1 H, J ) 6.7, 11.9 Hz), 3.49 (dt, 1 H, J )
6.9, 12.6 Hz), 3.72 (dd, 1 H, J ) 4.0, 15.5 Hz), 4.42 (dd, 1 H,
J ) 3.9, 15.7 Hz), 4.64-4.56 (m, 1 H), 5.16 (d, 1 H, J ) 17.2
Hz), 5.22 (d, 1 H, J ) 10.4 Hz), 5.91 (s, 2 H), 5.95 (ddd, 1 H,
J ) 6.6, 10.6, 17.1 Hz). 13C NMR (CDCl3, 75 MHz): δ 36.5, 48.6,
50.0, 65.1, 117.4, 128.4, 130.2, 134.8, 177.2. Anal. Calcd for
C9H11NO: C, 72.48; H, 7.38. Found: C, 72.60; H, 7.29.
(2S,10a S)- 2-Vin yl-1,5,6,7,8,10a -h exa h yd r o-2H-p yr r olo-
[1,2-a ]a zocin -3-on e, 8d . Pale yellow oil. [R]25D ) +67.6 (c 0.17,
CHCl3). IR (CHCl3): ν 2928, 1672, 1558. 1H NMR (CDCl3, 300
MHz): δ 1.55-1.47 (m, 2 H), 1.76-1.66 (m, 2 H), 1.99-1.90 (m,
1 H), 2.22-2.11 (m, 1 H), 2.37-2.25 (m, 1 H), 2.52 (ddd, 1 H,
J ) 6.7, 8.5, 15.4 Hz), 3.22-3.10 (m, 2 H), 3.70 (dd, 1 H, J )
9.3, 14.5 Hz), 4.27 (c, 1 H, J ) 7.5 Hz), 5.21 (d, 1 H, J ) 10.0
Hz), 5.21 (d, 1 H, J ) 17.4 Hz), 5.40 (dd, 1 H, J ) 7.0, 10.8 Hz),
6.04-5.88 (m, 2 H). 13C NMR (CDCl3, 75 MHz): δ 26.2, 27.3,
27.3, 33.0, 40.9, 46.7, 54.2, 117.0, 129.5, 134.1, 135.7, 173.8. Anal.
Calcd for C12H17NO: C, 75.39; H, 8.90. Found: C, 75.50; H, 9.02.
Ack n ow led gm en t. Ministerio de Ciencia y Tecno-
log´ıa (Project No. BQU2000-0653) is gratefully thanked
for financial support. One of us (R.M.) thanks the
Ministerio de Educacio´n y Cultura (Spain) for a pre-
doctoral grant.
Rin g-Closin g Meta th esis of 8. Gen er a l P r oced u r e. A
solution of 8 (0.16 mmol) and [Mo] or [Ru] (8 × 10-3 mmol, see
Table 2) in anhydrous, degassed CH2Cl2 (15 mL) was stirred at
room temperature for 12 h. After removal of the solvent under
reduced pressure, the crude reaction product was purified by
chromatography (pentane/Et2O ) 1:1).
J O016000E