Nitrogen Assistance in Intramolecular Nickel-Promoted Tandem Cyclization-Quenching Processes

Article abstract of DOI:10.1021/jo960677y

A diastereoselective and mild cyclization-quenching process based on the treatment of nitrogen-tethered halodienes with stoichiometric Ni(COD)2 is described. The success of this methodology relies on the presence of a distal amino group capable of coordin

Full text of DOI:10.1021/jo960677y

J . Org. Chem. 1996, 61, 5895-5904
5895
Nitr ogen Assista n ce in In tr a m olecu la r Nick el-P r om oted Ta n d em
Cycliza tion -Qu en ch in g P r ocesses
Daniel Sole´,† Yolanda Cancho,† Amadeu Llebaria,† J osep M. Moreto´,† and Antonio Delgado*,‡
Departament de Quı´mica Orga`nica Biolo`gica, C.I.D. (C.S.I.C.), J ordi Girona 18-26, 08034 Barcelona,
Spain, and Universitat de Barcelona, Facultat de Farma`cia, Laboratori de Qu´ımica Farmace`utica,
Avgda. J oan XXIII, s/ n, 08028 Barcelona, Spain
Received April 12, 1996X
A diastereoselective and mild cyclization-quenching process based on the treatment of nitrogen-
tethered halodienes with stoichiometric Ni(COD)2 is described. The success of this methodology
relies on the presence of a distal amino group capable of coordinating with the metal in the transient
vinyl or alkylnickel species, thus controlling the diastereoselectivity of the cyclization step and
preventing Ni-H â-elimination prior to the quenching. In general, better results are obtained in
cyclizations taking place via a 5-exo-trig process, and a diversity of mono- and bicyclic nitrogenated
systems are afforded in high yields by the proper choice of starting halodienes and quenching
reagents. The presence of 2,2′-bipyridine as a ligand results in an acceleration of the process, and
in some cases, higher diastereoselectivities and/or supression of the Ni-H â-elimination are
observed.
Sch em e 1
In tr od u ction
The development of synthetic methodologies combining
the simultaneous formation of several bonds in a single
synthetic sequence (tandem process) represents an at-
tractive and very active field of research.1,2 During recent
years there has been a growing interest in the application
of transition metal-promoted processes toward this end
and, in particular, to the synthesis of heterocyclic sys-
tems.3,4
As part of our ongoing research focused on the develop-
ment of new methodologies leading to functionalized
nitrogen heterocycles as precursors of natural products
and biologically active agents, we recently reported on a
nickel-promoted intramolecular tandem cyclization-
capture of amino-tethered vinyl bromides and alkenes,5
as indicated in Scheme 1.
Treatment of the starting vinyl bromides A with a
stoichiometric amount of Ni(COD)2 in CH3CN at room
temperature affords a presumed σ-alkylnickel intermedi-
ate C after oxidative addition and insertion steps. Di-
astereoselective trapping of C with different quencher
reagents prior to Ni-H â-elimination can be effectively
performed, provided that coordination of the metal with
a suitably placed distal nitrogen atom in C takes place.
This behavior makes this methodology singular and
synthetically more efficient than some other related
intramolecular cyclization processes, such as the Heck
reaction,6 since examples of capture of a transient σ-alkyl-
palladium in species where hydride â-elimination is
possible are scarce.7-11
In this paper, we present a full account of our results
concerning the application of our methodology to the
selective synthesis of several functionalized nitrogen-
containing mono- and bicyclic systems.
Resu lts a n d Discu ssion
Na tu r e of th e Su bstr a te. Two types of starting
aminodienes have been employed in this study (Figures
1 and 2).
Type I compounds (1-6) are potential precursors of
pyrrolidine derivatives through a 5-exo-trig cyclization
mode; by tethering any of the allylic branches of 1a into
a cyclic system (2-6), formation of a diversity of bicyclic
[n + 5] cycloadducts can be envisaged.
On the other side, type II compounds (7-12) are
potential precursors of piperidine derivatives via a 6-exo-
trig cyclization mode and of [n + 6]bicyclic systems by
analogy to the above series.
* To whom correspondence should be addressed. Tel.: 34-3-4006108.
FAX: 34-3-2045904. E-mail: adcqob@cid.csic.es.
† C.I.D. (C.S.I.C.).
‡ Universitat de Barcelona.
X Abstract published in Advance ACS Abstracts, August 1, 1996.
(1) Ho, T.-L. Tandem Organic Reactions; Wiley Interscience: New
York, 1992.
(2) Bunce, R. A. Tetrahedron 1995, 51, 13103 and references therein.
(3) Grigg, R. J . Heterocycl. Chem. 1994, 31, 631.
(4) Vanderbaan, J . L.; Vanderheide, T. A. J .; Vanderlouw, J .;
Klumpp, G. W. Synlett 1995, 1.
(5) Sole, D.; Cancho, Y.; Llebaria, A.; Moreto, J . M.; Delgado, A. J .
Am. Chem. Soc. 1994, 116, 12133.
(6) Heck, R. F. Organic Reactions; J ohn Wiley & Sons: New York,
1982; Vol. 27, p 345.
(8) Oppolzer, W.; Ruiz Montes, J . Helv. Chim. Acta 1993, 76, 1266.
(9) Balme, G.; Bouyssi, D. Tetrahedron 1994, 50, 403.
(10) Stadtmuller, H.; Tucker, C. E.; Vaupel, A.; Knochel, P. Tetra-
hedron Lett. 1993, 34, 7911.
(7) Trost, B. M. Acc. Chem. Res. 1990, 23, 34.
(11) Oppolzer, W.; Schroder, F. Tetrahedron Lett. 1994, 35, 7939.
S0022-3263(96)00677-9 CCC: $12.00 © 1996 American Chemical Society

5896 J . Org. Chem., Vol. 61, No. 17, 1996
Sole´ et al.
According to our hypothesis, substrates 1-5 repre-
sented the better scenario for the present methodology,
since they might afford cycloadducts arising from a 5-exo
cyclization mode, and the corresponding alkylnickel
intermediates C would be stabilized through a five-
membered Ni-N coordination, as depicted in Figure 3.13
As expected, good to excellent yields of the corresponding
cycloadducts were obtained from substrates 1-5, as
indicated in Table 1. Moreover, in the case of 2a -4, the
diastereoselectivity was complete and single cycloadducts
were obtained in each case. On the other hand, the
unavailability of the nitrogen lone pair for coordination
as a result of its incorporation into an amide function
(1d and 2d , Scheme 2) or delocalization across an
aromatic ring (6, Table 1, entries 24 and 25) dramatically
alters the reaction course affording in all cases the
corresponding â-elimination cycloadducts 16,14 23,15 21,16
and 22.17 (see Scheme 2 and Figure 4).
Starting from vinyl bromide 5, an analogue of 2 with
a larger ring as substituent, lower diastereoselectivity
was observed under our standard cyclization-quenching
conditions, and mixtures of cis and trans cycloadducts
were obtained. Additionally, trapping of the correspond-
ing alkylnickel intermediate C arising from 5 with
TMSCN afforded mixtures of quenched and â-elimination
cycloadducts (Table 1, entry 22). These results can be
interpreted on conformational grounds. Thus, the more
flexible cyclooctene moiety present in 5 makes the
insertion of the vinylnickel intermediate B-5 with the
distal olefin compatible with a final cis or trans ring
fusion. Moreover, the higher conformational freedom of
the alkylnickel intermediate C-5-cis or C-5-trans might
disturb coordination of the metal with the distal nitrogen
atom and promote the â-elimination pathway. These
problems could be efficiently solved by the use of a
nitrogen bidentate ligand such as 2,2′-bipyridine (bpy).
Thus, the use of 1:1 Ni(COD)2/bpy complex, followed by
quenching with TMSCN, afforded a single cis-fused [8 +
5] cycloadduct in 83% yield (Table 1, entry 23). Although
the exact role played by bpy in our reaction system is
F igu r e 1.
(13) Coordination in C-6 is not operating as it is discussed later.
For related Ni-heteroatom coordination, see: (a) Ni-N, Tamao, K.;
Kobayashi, K.; Ito, Y. Synlett 1992, 539. (b) Ni-P, Didiuk, M. T.;
Morken, J . P.; Hoveyda, A. H. J . Am. Chem. Soc. 1995, 117, 7273. (c)
Ni-S, Wong, K. T.; Yuan, T. M.; Wang, M. C.; Tung, H. H.; Luh, T. Y.
J . Am. Chem. Soc. 1994, 116, 8920.
(14) Interestingly, in this case the diastereoselectivity was reversed,
since a trans-fused cycloadduct 16 was obtained (determined by 1H-
NMR from the N-ethyl derivative arising from LiAlH4 reduction of 16,
see Experimental Section). This change in trend might represent an
indirect evidence of the role played by intramolecular Ni-N coordina-
tion in a diastereocontrolled insertion in the putative intermediate
vinylnickel B-2a . For a related example of insertion directed by Ni-N
intramolecular coordination, see ref 13a.
F igu r e 2.
Concerning the halide, vinyl bromides were generally
used in this study as starting materials, although vinyl
chlorides behaved similarly (see 1c and 4).12
Among the several structural factors involved in the
final outcome of the process, both the operating cycliza-
tion mode (5-exo vs 6-exo) of vinylnickel intermediate B
(see Scheme 1) and the ability of alkylnickel intermediate
C to develop a stabilizing Ni-N interaction by coordina-
tion to the metal by the distal nitrogen atom seem crucial.
Thus, Ni-H â-elimination can be hampered by geo-
metrical constraints, and trapping of the intermediate
C with an appropriate quencher reagent becomes the
preferred terminating step. In this context, substrate 1b
was tested as a challenging model. Thus, the corre-
sponding intermediate C, arising from 1b after oxidative
addition-insertion, could be effectively trapped, despite
having seven hydrogen atoms available for â-elimination
(Table 1, entries 7 and 8).
(15) Formation of 23 can be explained by a 5-exo cyclization followed
by a cyclopropyl carbinyl rearrangement, Ni-H â-elimination-read-
dition, and quenching. For related examples, see: Owczarczyk, Z.;
Lamaty, F.; Vawter, E. J .; Negishi, E. J . Am. Chem. Soc. 1992, 114,
10091. Trost, B. M.; Dumas, J . Tetrahedron Lett. 1993, 34, 19.
(16) Arising from double dond isomerization of the initially formed
Heck-type cycloadduct (N-benzyl-3-methyleneindoline).
(17) For a related example of formation of indolines in a Ni-promoted
oxidative addition-insertion process, see: Rodriguez, J . G.; Canoira,
L. J . Heterocycl. Chem. 1985, 22, 883.
(12) Aryl chlorides did not react under standard conditions.

Ni-Promoted Cyclization-Capture in N-Tethered Halodienes
Ta ble 1
J . Org. Chem., Vol. 61, No. 17, 1996 5897
entry
substrate
quencher
TMSCN
productsa
R
yield, %
1
2
3
4
5
6
Br
a , CN
99
70
45
47
53c
30
R
CO/MeOH
b, COOCH3
c, H
d , CH2CHdCH2
e, CH2CHdCHCH3
f, COCH3
NaBH4/MeOH
allyl bromideb
crotyl bromideb
CH3COCl
N
N
Ph
Ph
1a
13a-f
7
8
CO/MeOH
TMSCN
g, COOCH3
h , CN
61
50
Br
N
R
N
Ph
Ph
13g,h
1b
9
10
11
12
13
14
Br
N
TMSCN
TMSCNd
CO/MeOH
NaBH4/MeOH
Et3SiH
a , CN
a , CN
b, COOCH3
c, H
c, H
d , OH
99
57
95
70
77
48e
R
H
N
H
Ph
2a
Ph
N2O
14a-e
15
16
17
O2
d , OH
e, CHdCH2
b, COOCH3
45f
40g
85
Bu3SnCHdCH2
CO/MeOHh
18
19
20
TMSCN
CO/MeOH
NaBH4/MeOH
a , CN
b, COOCH3
c, H
80
57
75
Br
N
H
R
N
H
Ph
Ph
3
17a-c
21
TMSCN
CN
84
Ph
Ph
N
R
Cl
N
4
18
22
23
TMSCN
R
H
CN
CN
44i,j
83k
Br
N
TMSCNd
N
Ph
H
5
Ph
19
24
25
Br
N
TMSCN
CH3
48l,m
40
TMSCNd
N
Ph
Ph
6
21
a
b
c
d
Unambigous assignment carried out by NMR techniques. Method C, see Experimental Section. E-isomer. Ni(COD)2/bpy (1:1);
e
f
g
Method B, see Experimental Section. 15 (32%) was also obtained (see Figure 4). 15 (45%) was also obtained. 15 (28%) and 25 (10%)
were also obtained (see Figure 4). DMF as a solvent. Cis/trans 9:1. 20 (44%, cis/trans 9:1) was also obtained (see Figure 4). Cis
isomer only. 6% recovered starting material.
h
i
j
k
l
m
22 (13%) was also isolated (see Figure 4 and ref 17).
not completely understood, the ability of ligands to
modulate the reactivity of organometallic complexes by
altering their steric and/or electronic properties is well
documented.18 In the case of 5, the effect of bpy was
beneficial both to induce a total diastereoselectivity
during the insertion step and to prevent Ni-H â-elimina-
tion. Unfortunately, â-elimination could not be avoided
in the case of 6 (entry 25), which seems to indicate that
the presence of a coordinating nitrogen lone pair is still
required, even when bpy is used as a ligand. Acetamides
1d and 2d also failed to give the corresponding cycliza-
tion-quenching cycloadducts (Scheme 2). Thus, 1d
afforded a complex mixture from which only the self-
coupling adduct 24 could be detected whereas no cyanide
incorporation was observed from acetamide 2d .
Type II substrates were designed as models to test the
efficiency of a 6-exo cyclization mode leading to single or
fused piperidine derivatives. Unfortunately, treatment
of vinyl bromides 7, 8, 11, and 12 under our standard
cyclization-quenching conditions was unsuccessful in
terms of formation of cycloadducts since only uncyclized
vinyl cyanides and coupling adducts could be isolated in
low to moderate yields (Table 2, entries 1, 3, 11, and 13).
Nevertheless, 6-exo mode cyclization-quenching from
10 was successful, since the corresponding cycloadducts
were isolated in acceptable yields as mixtures of 1,2,5,6-
tetrahydropyridines 32 and 3-methylenepiperidines 33,
whose formation can be explained through a common
intermediate, C-10 (Scheme 3). Whereas quenching of
C-10 with the terminating agents leads to the corre-
sponding 3-methylenepiperidines 33a ,b, an alternative
termination process triggered by the relatively high
(18) Togni, A.; Venanzi, L. M. Angew. Chem., Int. Ed. Engl. 1994,
33, 497.

5898 J . Org. Chem., Vol. 61, No. 17, 1996
Sole´ et al.
Moreover, cyclization-quenching with TMSCN from
aryl bromide 9 proved efficient although sluggish, since
tetrahydroisoquinoline 30 was obtained in 47% yield,
together with uncyclized aryl cyanide 31 (25%) and 22%
of starting material by quenching after prolonged reac-
tion times (20 min). These results are indicative of a slow
oxidative addition-insertion process from 9, in addition
to the formation of a highly stabilized alkylnickel inter-
mediate such as C-9, in which coordination of the metal
with the distal nitrogen lone pair via a five-membered
cyclic system could prevent Ni-H â-elimination (Figure
5).
The fact that no cycloadducts were ever isolated from
8, 11, and 12 is in agreement with failure of a 6-exo
insertion of a vinylnickel intermediate onto a cyclohexene
moiety. Steric requirements seem to become very im-
portant in this cyclization mode. Finally, the difference
in behavior of vinyl bromide 7 in comparison to that of
10 would plausibly arise from the difference in stability
and reactivity of both putative alkylnickel intermediates
C-7 and C-10. Thus, oxidative addition of 7 was ex-
tremely fast, and only untractable mixtures were ob-
tained under standard conditions. However, initial
formation of cycloadducts via a 6-exo mode cyclization
could not be ruled out, since trace amounts of the desired
piperidine 26, together with the open-chain nitrile 27,
could be detected at short reaction times (see Table 2,
entry 1). Taking into account that stabilization of
intermediate C-7 by coordination with the distal nitrogen
lone pair would be possible only through a high-energy
conformation in which the nickelalkyl moiety should be
axial (see Figure 5), Ni-H â-elimination to a very
reactive aminodiene can be envisaged as the alternative
preferred process.20
F igu r e 3.
The use of bpy as a ligand in these series was
somewhat puzzling. Thus, no improvement was observed
from substrates that failed to cyclize under standard
conditions (8, 11, and 12). Surprisingly, in the case of
9, the presence of bpy was again favorable, presumably
by promoting oxidative addition and further insertion of
the vinylnickel intermediate, since isoquinoline 30 was
now the only isolated compound in 68% yield under
otherwise similar reaction conditions. Once again, the
effect of bpy showed striking differences between 7 and
10. Thus, whereas in the case of 10, complex mixtures
were obtained and no cyclization products were detected
(entry 10), vinyl bromide 7 afforded the corresponding
cycloadduct 26 as the only isolable product, although in
modest yield (Table 2, entry 2). This partial success could
well be due to a slower Ni-H â-elimination process in
this case in comparison with the results obtained in the
absence of bpy.
F igu r e 4.
Sch em e 2
Effect of th e Solven t. Preliminary experiments
carried out in a low-coordinating solvent such as THF
afforded only starting material, together with deposition
of metallic Ni(0). This relatively high tendency of Ni-
(COD)2 to decompose in the reaction mixture was not
observed when a stronger coordinating solvent, such as
CH3CN or DMF, was used. In general, CH3CN proved
superior to DMF for this process. Typically, oxidative
energy of the boatlike conformation required for intramo-
lecular Ni-N stabilization in C-10 can be considered.
Thus, Ni-H â-elimination and readdition on the 4-me-
thylene double bond to give a π-allylnickel intermediate
D-10, followed by reaction with the terminating agent
to afford cycloadducts 32a -c, can now become a competi-
tive process.19
(19) This process is well precedented in Heck reactions upon vinyl
halides. See, for example: Harris, G. D., J r.; Herr, R. J .; Weinreb, S.
M. J . Org. Chem. 1992, 57, 2528. In our previous communication (see
ref 5), compounds 32 were uncorrectly assigned.
(20) Unlike the results observed from 10, it seems that, in this case,
NiH readdition upon the 3-methylene double bond to generate a
π-allylnickel intermediate is slower than competitive collateral reac-
tions leading to decomposition products.

Ni-Promoted Cyclization-Capture in N-Tethered Halodienes
Ta ble 2
J . Org. Chem., Vol. 61, No. 17, 1996 5899
entry
substrate
complex
quencher
TMSCN
producta
yield, %
producta
yield, %
3b
1
2
Ni(COD)2
Ni(COD)2/bpy TMSCN
2b
30
Ph
N
Ph
N
CN
N
Br
CN
Ph
7
27
26
3
4
Ni(COD)2
Ni(COD)2/bpy TMSCN
TMSCN
8
15
60
Ph
N
Ph
N
N
Ph
Br
CN
2
29
8
28
5
6
Ni(COD)2
Ni(COD)2/bpy TMSCN
TMSCN
47
68
25c
N
Ph
Ph
N
Ph
N
CN
Br
CN
30
9
31
7
8
9
Ni(COD)2
Ni(COD)2
Ni(COD)2
TMSCN
NaBH4/MeOH
CO/MeOH
a , R ) CN, 60d
b, R ) COOCH3, 40
c, R ) H, 41e
f
a , R ) CNd
Ph
Ph
Ph
CH3
N
R
N
N
N
R
c, R ) He
f
Br
10
Ni(COD)2/bpy TMSCN
N
Ph
32a-c
10
Ph
33a,b
11
12
Ni(COD)2
Ni(COD)2/bpy TMSCN
TMSCN
35
Ph
5g
N
Br
CN
N
Ph
N
11
34
2
35
13
14
Ni(COD)2
Ni(COD)2/bpy TMSCN
TMSCN
48
56
24
Ph
Ph
N
Br
CN
2
37
12
36
a
b
c
Unambigous assignment carried out by NMR techniques. After quenching at short reaction times. 22% of recovered starting
d
e
f
g
material. 32a /33a 85:15 unseparable mixture. 32c/33c 75:25 unseparable mixture. Complex mixture. N-(2-Cyclohexenylmethyl-
)benzylamine (43%) was also isolated.
Sch em e 3
F igu r e 5.
Ter m in a tin g Agen ts. Incorporation of functional
groups in a stereoselective way by trapping of the
alkylnickel intermediates C prior to â-elimination ex-
pands the versatility of this process from a synthetic
standpoint. Among the different terminating reagents
additions of starting halides by Ni(COD)2 in CH3CN took
a few minutes and provided homogeneous reaction mix-
tures. On the contrary, the oxidative addition in DMF
was slower, and, although cyclization-quenching cy-
cloadducts could be obtained, yields were generally lower
than in CH3CN due to extensive coupling processes.21
Similar results were obtained in noncoordinating apolar
solvents such as benzene and toluene.
used in the present work, those leading to C-C, C-H,
(21) Cyclization-quenching of 2a represents an exception to this
trend (see Table 1, entry 17).

5900 J . Org. Chem., Vol. 61, No. 17, 1996
Sole´ et al.
and C-O bond formation have proved successful.22
Concerning C-C bond formation, CO/MeOH and TMSCN
afforded the corresponding methoxycarbonyl and cyano
derivatives, respectively, in good to excellent yields.
Concerning the cyano group,23 it is worth noting that
quenching with neat TMSCN was superior to KCN/18-
crown-6 as described by Grigg24 for a related Pd-catalyzed
intramolecular cyclization-quenching process.25 Al-
though these results can be explained by the higher
solubility of TMSCN relative to the potassium salt in our
reaction system, the operation of a trialkylsilyl cyanide-
trialkylsilyl isocyanide tautomeric equilibrium to facili-
tate the halide-cyanide exchange in the coordination
sphere of the metal should not be ruled out.26,27
of O2 or N2O32 afforded only 1:1 mixtures of the expected
amino alcohol 14d and the â-elimination cycloadduct 15.
Further attempts to improve this ratio by using white
light irradiation or other oxidizing quenchers, such as
H2O2 or t-BuOOH, as well as H2O or 50% aqueous NaOH
as protic quenchers, were unsuccessful, since â-elimina-
tion was still the predominant process. Finally, in all
the cases studied in this work, the process showed
complete diastereoselectivity, since the functional group
arising from the terminating reagent maintains the
stereochemistry predicted for the alkylnickel intermedi-
ates C after a syn-olefin insertion.33
Con clu sion s
Acetyl and vinyl groups can also be introduced, al-
though in modest yields, by quenching with CH3COCl
and Bu3SnCHdCH2, respectively (Table 1, entries 6 and
16). Finally, irradiation with white light is required for
the introduction of allyl and crotyl groups (Table 1,
entries 4 and 5), an indication that radical intermediates
would operate in this coupling process.28-30 Concerning
C-H bond formation, it was achieved in satisfactory
yields with excess NaBH4 in MeOH (Table 1, entries 3,
12, and 20) or, alternatively, with neat Et3SiH (entry 13).
The efficiency of a terminating reagent seems to
depend on its rate of coupling with the alkylnickel
intermediate C. Despite internal stabilization with the
distal nitrogen atom, alkylnickel species have a relatively
short lifetime, and, if the termination process is slow,
â-elimination cycloadducts are isolated. In addition,
taking 2a as a model substrate, we observed that,
together with the â-elimination cycloadduct 15, a small
amount of amino alcohol 14d was also obtained in cases
where the terminating agent under examination failed
to give any coupling product.22 Formation of 14d can be
explained by oxidation of the intermediate alkylnickel
C-2a by adventitious oxygen during the reaction or, more
probably, by hydrolysis during the workup process.31 In
an attempt to exploit this observation, we assumed that,
by using an oxidant as a terminating reagent, alcohol 14d
could be obtained as a major product. However, the use
A diastereoselective and mild cyclization-capture pro-
cess based on the treatment of nitrogen-tethered halo-
dienes with stoichiometric Ni(COD)2 is described. By
choice of a proper terminating reagent, a variety of
functional groups can be introduced in the last step of
the process. The success of this methodology relies on
the presence of a distal amino group able to stabilize, by
coordination, a transient alkylnickel intermediate, thus
preventing Ni-H â-elimination. In all the substrates
examined in this work, cyclization via a 5-exo mode has
been shown to be more favorable than that by a 6-exo
one. Finally, the results obtained in the presence of bpy
as a ligand seem to indicate in some cases a favorable
effect on the diastereoselectivity of the process, as in 5;
the supression of the Ni-H â-elimination step, as in 5
and, presumably, also in 7; and an acceleration of the
oxidative addition-insertion step, as in 9.
Exp er im en ta l Section
For general experimental procedures, see ref 34. All reac-
tions were conducted under argon atmosphere with rigorous
exclusion of oxygen using standard Schlenk techniques. Ni-
(COD)2 was prepared according to a previously described
procedure.35
Syn th esis of Cycloa d d u cts. Meth od A. To a solution
of Ni(COD)2 (1.5 mmol) in dry CH3CN (5 mL), at room
temperature under argon, was added a solution of the vinyl
bromide (1 mmol) and Et3N (3 mmol) in dry acetonitrile. The
reaction mixture, which turned from yellow to red, was stirred
at room temperature. When all the starting material was
consumed (2.5-30 min, checked by TLC), the quencher (1.5-
3.0 mmol) was added via syringe, and the mixture was stirred
at room temperature for additional time (0.5-3 h). After
filtration through Celite and careful washings with CH2Cl2,
the mixture was partitioned between CH2Cl2 and saturated
Na2CO3. Drying of the organic phases, followed by filtration
and evaporation, afforded the desired cycloadduct.
Meth od B. This method was the same as method A, except
that the starting vinyl halide was added to a previously formed
complex of Ni(COD)2 (1.5 mmol) and 2,2′-bipyridine (bpy, 1.8
mmol) in dry CH3CN (5 mL).
Meth od C. This method was the same as method A, except
that, simultaneously with the addition of the quencher, the
reaction mixture was irradiated with a 500 W sunlight lamp
(22) The following quenchers were tried with no success using 2a
as a model substrate under cyclization conditions A (see Experimental
Section): CO/BuNH2, TMSN3, I2, TMSI, methyl acrylate, Ph4BNa,
KOAc, TMSCHdCH2/Bu4NF, DMSO, Ni2O3, and benzoyl peroxide.
Almost invariably, mixtures of the â-elimination cycloadduct 15 and
alcohol 14d were obtained.
(23) For related methods concerning C-CN formation by means of
organometallic reagents, see: Torii, S.; Okumoto, H.; Ozaki, H.;
Nakayashu, S.; Tadokoro, T.; Kotani, T. Tetrahedron Lett. 1992, 33,
3499. Oppolzer, W.; Schroder, F. Tetrahedron Lett. 1994, 35, 7939.
Sakakibara, Y.; Enami, H.; Ogawa, H.; Fujimoto, S.; Kato, H.;
Kunitake, K.; Sasaki, K.; Sakai, M. Bull. Chem. Soc. J pn. 1995, 68,
3137. Sakakibara, Y.; Ido, Y.; Sasaki, K.; Sakai, M.; Uchino, N. Bull.
Chem. Soc. J pn. 1993, 66, 2776. Piers, E.; Fleming, F. F. Can. J . Chem.
1993, 71, 1867. Ellis, G. P.; Romney-Alexander, T. M. Chem. Rev. 1987,
87, 779. See also ref 24.
(24) Grigg, R.; Santhakumar, V.; Sridharan, V. Tetrahedron Lett.
1993, 34, 3163.
(25) Treatment of 2a with KCN/18-crown-6 in the presence of Pd-
(OAc)2 under Grigg conditions (ref 24) led to recovery of the starting
material.
(26) Seckar, J . A.; Thayer, J . S. Inorg. Chem. 1976, 15, 501.
(27) (a) Berk, S. C.; Grossman, R. B.; Buchwald, S. L. J . Am. Chem.
Soc. 1993, 115, 4912. (b) Berk, S. C.; Grossman, R. B.; Buchwald, S.
L. J . Am. Chem. Soc. 1994, 116, 8593.
(28) Hegedus, L. S.; Thompson, D. H. P. J . Am. Chem. Soc. 1985,
107, 5663.
(32) Matsunaga, P. T.; Hillhouse, G. L. J . Am. Chem. Soc. 1993,
115, 2075.
(33) In some experiments using Bu3SnCHdCH2 (Table 1, entry 18),
KCN, or KOAc as quencher, a small percentage of amino alcohol 25,
epimeric on the hydroxyl group, was isolated (see Figure 4). This
finding would be consistent with an alternative mechanism, probably
through the intermediacy of radical species.
(29) Castan˜o, A. M.; Echavarren, A. M. Organometallics 1994, 13,
2262.
(30) J ohnson, J . R.; Tully, P. S.; Mackenzie, P. B.; Sabat, M. J . Am.
Chem. Soc. 1991, 113, 6172.
(31) Horino, H.; Arai, M.; Inoue, N. Bull. Chem. Soc. J pn. 1974, 47,
1683.
(34) Llebaria, A.; Delgado, A.; Camps, F.; Moreto´, J . M. Organome-
tallics 1993, 12, 2825.
(35) Colquhoun, H. M.; Holton, J .; Thompson, D. J .; Twigg, M. V.
New Pathways for Organic Synthesis; Plenum: New York, 1984; p 389.

Ni-Promoted Cyclization-Capture in N-Tethered Halodienes
J . Org. Chem., Vol. 61, No. 17, 1996 5901
while the reaction temperature was kept below 25 °C by means
of a circulating cool bath.
1664, 882. Anal. Calcd for C15H19NO: C, 78.56; H, 8.35; N,
6.11. Found: C, 78.72; H, 8.16; N, 5.91.
N -Be n zyl-3-(cya n om e t h yl)-4-m e t h yle n e p yr r olid in e
(13a ). Following method A, starting from 220 mg (0.83 mmol)
of 1a , 460 mg (1.66 mmol) of Ni(COD)2, 0.35 mL (2.48 mmol)
of Et3N in 10 mL of acetonitrile, and 0.25 mL (2 mmol) of
TMSCN, 175 mg (99%) of 13a was obtained after flash
chromatography on hexanes/EtOAc 70:30.
N-Ben zyl-3-[1-(m eth oxycar bon yl)-1-m eth yleth yl]-4-m e-
th ylen ep yr r olid in e (13g). Following method A, starting
from 294 mg (1.0 mmol) of 1b, and quenching with CO/MeOH,
13g was obtained in 61% yield after flash chromatography on
hexanes/EtOAc 90:10.
1H-NMR (300 MHz): δ 1.17 (3H, s), 1.20 (3H, s), 2.41 (1H,
dd, J ) 9.3, 7.0 Hz), 2.86-2.96 (1H, m), 3.02 (1H, dm), 3.10-
3.24 (2H, m), 3.58 (2H, s), 3.66 (3H, s), 4.71-4.74 (1H, m),
4.94-4.96 (1H, m), 7.2-7.4 (5 H, m). 13C-NMR (75.4 MHz):
δ 21.5, 23.8, 44.8, 49.0, 51.7, 56.7, 60.5, 60.7, 107.1, 126.9,
128.2, 128.6, 138.8, 148.7, 177.9. IR: ν 1731, 1454. Anal.
Calcd for C17H23NO2: C, 73.48; H, 8.34; N, 5.04. Found: C,
73.82; H, 8.46; N, 5.02.
1H-NMR (200 MHz): δ 2.54 (2H, d, J ) 6.6 Hz), 2.48-2.62
(1H, m), 2.85-3.05 (2H, m), 3.23 (2H, br s), 3.64 (2H, s), 4.98-
5.08 (2H, m), 7.20-7.40 (5H, m). 13C-NMR: δ 21.6, 39.1, 58.7,
58.9, 59.8, 107.1, 118.6, 127.0, 128.2, 128.5, 138.3, 148.9. IR:
ν 1662, 2246. Anal. Calcd for C14H16N2: C, 79.21; H, 7.60; N,
13.20. Found: C, 79.21; H, 7.62; N, 13.27.
N -Be n zyl-3-[(m e t h oxyc a r b on yl)m e t h yl]-4-m e t h yl-
en ep yr r olid in e (13b). Following method A, starting from
261 mg (1.0 mmol) of 1a , and quenching with CO/MeOH, 13b
was obtained in 70% yield after flash chromatography on
hexanes /EtOAc 90:10.
N-Ben zyl-3-(1-cya n o-1-m et h ylet h yl)-4-m et h ylen ep yr -
r olid in e (13h ). Following method A, starting from 294 mg
(1.0 mmol) of 1b, 13h was obtained in 50% yield after flash
chromatography on hexanes/EtOAc 80:20.
1H-NMR (200 MHz): δ 2.35 (1H, dd, J ) 8.8, 6.2 Hz), 2.50
1H-NMR (200 MHz): δ 1.36 (3H, s), 1.42 (3H, s), 2.59 (1H,
dd, J ) 9.4, 5.9 Hz), 2.72-2.86 (1H, m), 2.98 (1H, dd, J ) 9.2,
7.4 Hz), 3.20 (2H, sa), 3.62 (2H, sa), 5.12-5.18 (1H, m), 5.19-
5.24 (1H, m), 7.2-7.4 (5H, m). 13C-NMR (50 MHz): δ 24.1,
25.3, 49.5, 56.9, 60.2, 60.3, 109.7, 124.9, 127.1, 128.3, 128.5,
138.5, 146.7. IR: ν 2236, 1660. Anal. Calcd for C16H20N2:
C, 78.48; H, 8.23; N, 11.44. Found: C, 78.66; H, 8.35; N, 11.41.
(3a RS,4SR,7a RS)-N-Ben zyl-3-m et h ylen ep er h yd r oin -
d ole-4-ca r bon itr ile (14a ). Following method A, starting
from 245 mg (0.8 mmol) of vinyl bromide 2a , 400 mg (1.45
mmol) of Ni(COD)2, 0.33 mL (2.4 mmol) of Et3N, in 10 mL of
acetonitrile, and 0.5 mL (4 mmol) of TMSCN, 200 mg (99%) of
14a was obtained after flash chromatography on hexanes/
EtOAc 75:25.
and 2.59 (2H, AB sys, dd, J AB ) 15.7 Hz, J AX ) 9 Hz J BX
)
,
5.0 Hz), 2.92-3.19 (3H, m), 3.26 (1H, dm, J ) 14.0 Hz), 3.61
(2H, s), 3.67 (3H, s), 4.82-4.88 (1H, m), 4.90-4.95 (1H, m),
7.20-7.40 (5H, m). 13C-NMR (50.3 MHz): δ 38.8, 39.5, 51.9,
59.5, 60.5, 60.6, 105.6, 127.3, 128.6, 129.0, 139.0, 151.5, 173.3.
IR: ν 3026, 2786, 1735, 881. Anal. Calcd for C15H19NO2: C,
73.44; H, 7.81; N, 5.71. Found: C, 73.45; H, 7.85; N, 5.71.
N-Ben zyl-4-m eth yl-3-m eth ylen ep yr r olid in e (13c). Fol-
lowing method A, starting from 250 mg (0.94 mmol) of 1a ,
quenching with NaBH4/MeOH afforded 13c in 45% yield after
flash chromatography on hexanes/t-BuOMe 90:10.
1H-NMR (200 MHz): δ 1.10 (3H, d, J ) 6.6 Hz), 2.06 (1H,
dd, J ) 8.4, 8.5 Hz), 2.56-2.82 (1H, m), 2.92-3.08 (2H, m),
3.43 (1H, br d, J ) 13.6 Hz), 3.55 and 3.64 (2H, AB sys, J )
12.8 Hz), 4.78-4.84 (1H, m), 4.84-4.90 (1H, m), 7.20-7.40 (m,
5 H). 13C-NMR (50.3 MHz): δ 18.1, 38.0, 59.9, 61.1, 62.7,
104.2, 127.3, 128.6, 129.2, 139.3, 154.4. IR: ν 2960, 2783,
1662, 1452, 877. Anal. Calcd for C13H17N: C, 83.37; H, 9.15;
N, 7.48. Found: C, 83.11; H, 9.22; N, 7.20.
N-Ben zyl-4-(3-bu ten yl)-3-m eth ylen ep yr r olid in e (13d ).
Following method C, starting from 288 mg (1.1 mmol) of 1a ,
pyrrolidine 13d (47%) was obtained after flash chromatogra-
phy on hexanes/EtOAc 80:20.
1H-NMR (200 MHz): δ 1.15-2.05 (6H, m), 2.54-2.70 (2H,
m), 2.74 (1H, dt, J ) 14.6, 2.6 Hz), 2.82-2.94 (1H, m), 3.08
and 4.02 (2H, AB sys, J ) 13.6 Hz), 3.68 (1H, d, J ) 14.6 Hz),
4.89 (1H, dd, J ) 3.6, 1.9 Hz), 4.96 (1H, dd, J ) 3.6, 2.5 Hz),
7.10-7.40 (5H, m). 13C-NMR (50.3 MHz): δ 16.8, 24.3, 27.7,
31.2, 45.1, 56.9, 58.2, 61.2, 106.7, 122.0, 126.6, 128.0, 128.2,
139.2, 148.2. IR: ν 2235. Anal. Calcd for C17H20N2: C, 80.91;
H, 7.99; N, 11.10. Found: C, 80.80; H, 7.98; N, 10.94.
Meth yl (3a RS,4SR,7a RS)-N-Ben zyl-3-m eth ylen ep er h y-
d r oin d ole-4-ca r boxyla te (14b). Following method A, start-
ing from 738 mg (2.41 mmol) of vinyl bromide 2a , 1.25 g (4.55
mmol) of Ni(COD)2, 1 mL (7.23 mmol) of Et3N in 10 mL of
acetonitrile, 0.3 mL (7.19 mmol) of MeOH, and excess CO, 660
mg (95%) of 14b was obtained after flash chromatography on
hexanes/EtOAc 80:20.
1H-NMR (300 MHz ): δ 1.30-1.45 (1H, m), 1.58-1.75 (1H,
m), 1.9-2.1 (1H, m), 2.07 (1H, t, J ) 8.4 Hz), 2.55-2.65 (1H,
m), 2.96-3.08 (2H, m), 3.37 (1H, dm, J ) 13.2 Hz), 3.47 and
3.55 (2H, AB sys, J ) 12.8 Hz), 4.83 (1H, q, J ) 2.0 Hz), 4.90
(1H, q, J ) 2.0 Hz), 4.82-4.88 (2H, m), 5.62-5.80 (1H, m),
7.2-7.4 (5 H, m). 13C-NMR (50.3 MHz): δ 31.9, 32.9, 42.2,
59.6, 60.3, 60.6, 104.3, 114.6, 126.9, 128,2, 128.7, 138.5, 138.8,
152.6. IR: ν 3077, 3027, 2925, 1662, 1638, 1451, 908, 879.
Anal. Calcd for C16H21N: C, 84.53; H, 9.31; N, 6.16. Found:
C, 84.32; H, 9.33; N, 6.35.
1H-NMR (300 MHz): δ 1.02-1.95 (6H, m), 2.63 (1H, dt, J
) 12.6, 3.7 Hz), 3.09 (1H, dt, J ) 10.4, 5.4 Hz), 3.24 (1H, ddd,
J ) 14.4, 4.6, 2.2 Hz), 3.44 (1H, br s), 3.52 (1H, ddd, J ) 14.4,
4.0, 2.4 Hz), 3.70 (3H, s), 3.66 and 3.78 (2H, AB sys, J ) 13.4
Hz), 4.61 (1H, dd, J ) 5.2, 2.6 Hz) 4.89 (1H, dd, J ) 4.6, 2.2
Hz), 7.09-7.41 (5H, m). 13C-NMR (75.4 MHz): δ 21.7, 22.0,
23.0, 42.2, 44.0, 51.5, 55.8, 56.5, 62.1, 105.3, 126.8, 128.2, 128.4,
139.4, 146.8, 175.0. IR: ν 1731. Anal. Calcd for C18H23NO2:
C, 75.76; H, 8.12; N, 4.91. Found: C, 75.68; H, 8.10; N, 4.84.
(3a RS,7a RS)-N-Ben zyl-3-m et h ylen ep er h yd r oin d ole
(14c). Following method A, starting from 310 mg (1.01 mmol)
of vinyl bromide 2a , 340 mg (1.24 mmol) of Ni(COD)2, 0.42
mL (3 mmol) of Et3N in 10 mL of acetonitrile, and 151 mg (4
mmol) of NaBH4 in 3 mL (7.19 mmol) of MeOH, 156 mg (70%)
of 14c was obtained after flash chromatography on hexanes/
EtOAc 95:5. Alternatively, using neat Et3SiH as a quencher
(0.4 mL, 2.5 mmol), 14c was obtained in 77% yield.
(E)-N-Ben zyl-4-(3-p en t en yl)-3-m et h ylen ep yr r olid in e
(13e). Following method C, starting from 269 mg (1.0 mmol)
of 1a , 13e (53%) was obtained after flash chromatography on
hexanes/EtOAc 90:10.
1H-NMR (200 MHz): δ 1.3-1.5 (1H, m), 1.6-1.8 (1H, m),
1.65 (3H, br s), 1.9-2.1 (1H, m), 2.15 (1H, dd, J ) 8.4, 8.6
Hz), 2.55-2.75 (1H, m), 2.96-3.08 (2H, m), 3.37 (1H, dm, J )
13.6 Hz), 3.57 and 3.68 (2H, AB sys, J ) 12.8 Hz), 4.83 (1H, q,
J ) 2.2 Hz), 4.90 (1H, q, J ) 2.0 Hz), 5.4-5.5 (2H, m), 7.2-
7.4 (5H, m). 13C-NMR (50.3 MHz): δ 17.9, 30.8, 33.6, 42.3,
59.6, 60.4, 60.7, 104.1, 125.1, 126.9, 128,2, 128.7, 138.9, 152.8.
IR: ν 3025, 2929, 1682, 1662, 1451. Anal. Calcd for
C17H23N: C, 84.59; H, 9.60; N, 5.80. Found: C, 84.62; H, 9.71;
N, 5.75.
1H-NMR (200 MHz): δ 1.10-1.80 (8H, m), 2.47 (1H, bb),
2.65 (1H, dd, J ) 9.2, 4.8 Hz), 2.88 (1H, dt, J ) 14.4, 2.2 Hz),
3.16 and 3.88 (2H, AB sys, J ) 13.4 Hz), 3.40 (1H, dd, J )
14.4, 1.7 Hz), 4.62-4.72 (2H, m), 7.10-7.40 (5H, m). 13C-NMR
(50.3 MHz): δ 21.4, 24.2, 24.6, 28.6, 44.1, 57.0, 57.8, 62.4,
102.9, 126.7, 128.2, 128.5, 140.0, 152.2. IR: ν 1452, 1664.
Anal. Calcd for C16H21N: C, 84.53; H, 9.31; N, 6.16. Found:
C, 84.51; H, 9.31; N, 5.87.
N-Ben zyl-4-(2-oxopr opyl)-3-m eth ylen epyr r olidin e (13f).
Following method A, starting from 305 mg (1.1 mmol) of 1a ,
ketone 13f was obtained in 30% yield after flash chromatog-
raphy on hexanes /EtOAc 70:30 to 20:80.
1H-NMR (200 MHz): δ 2.13 (3H, s), 2.23 (1H, m), 2.57 (1H,
dd, J ) 17.4, 8.6 Hz), 2.72 (1H, dd, J ) 17.4, 4.6 Hz), 3.07
(4H, m), 3.59 (2H, s), 4,79 (1H, m), 4.89 (1H, m), 7.2-7.4 (5H,
m). 13C-NMR (50.3 MHz): δ 30.1, 37.9, 48.2, 59.1, 60.2, 60.3,
104.9, 127.1, 128.3, 128.8, 138.7, 151.8, 207.9. IR: ν 1714,
(3a RS,4SR,7a RS)-N-Ben zyl-4-h yd r oxy-3-m eth ylen ep e-
r h yd r oin d ole (14d ) a n d (3a RS,7a RS)-N-Ben zyl-3-m eth -
ylen e-2,3,3a ,6,7,7a -h exa h yd r o-1H-in d ole (15). Following

5902 J . Org. Chem., Vol. 61, No. 17, 1996
Sole´ et al.
method A, starting from 290 mg (0.95 mmol) of vinyl bromide
2a , 430 mg (1.56 mmol) of Ni(COD)2, 0.40 mL (2.84 mmol) of
Et3N in 10 mL of acetonitrile, and excess O2, 104 mg (45%) of
14d and 96 mg (45%) of 15 were obtained after flash chroma-
tography on hexanes/EtOAc 75:25 to 80:20. Alternatively,
using excess N2O as a quencher, a mixture of 15 (32%) and
14d (48%) was obtained.
1H-NMR (500 MHz): δ 1.08-1.32 (1H, m), 1.38-1.52 (1H,
m), 1.76-1.84 (1H, m),1.84 (1H, t, J ) 9.2 Hz), 2.00-2.22 (3H,
m), 2.33 (2H, d, J ) 6.4 Hz), 2.68 (1H, br m), 2.80 (1H, m),
3.21 (1H, dd, J ) 9.2, 7.8 Hz), 3.23 and 4.08 (2H, AB sys, J )
12.6 Hz), 5.67 (1H, br s), 7.20-7.40 (5H, m). 13C-NMR (50.3
MHz): δ 19.9, 21.9, 24.9, 27.6, 36.1, 58.0, 58.3, 63.8, 118.5,
121.3, 127.0, 128.1, 128.9, 138.2, 141.3. IR: ν 2246. Anal.
Calcd for C17H20N2: C, 80.91; H, 7.99; N, 11.10. Found: C,
80.70; H, 7.94; N, 10.89.
Meth yl (3RS,7a RS)-(N-ben zyl-2,3,5,6,7,7a -h exa h yd r o-
1H-in d ol-3-yl)a ceta te (17b). Following method A, starting
from 275 mg (0.9 mmol) of vinyl bromide 3, 300 mg (4.55 mmol)
of Ni(COD)2, 0.38 mL (2.7 mmol) of Et3N in 10 mL of
acetonitrile, 0.1 mL (2.7 mmol) of MeOH, and excess CO, 146
mg (57%) of 28 was obtained after flash chromatography on
hexanes/EtOAc 80:20.
14d . 1H-NMR (200 MHz): δ 1.20-2.10 (7H, m), 2.26 (1H,
dd, J ) 9.0, 4.8 Hz), 2.75-2.87 (2H, m), 3.02 and 4.05 (2H,
AB sys, J ) 13.2 Hz), 3.61 (1H, d, J ) 14.4 Hz), 3.68 (1H, ddd,
J ) 11.1, 9, 4 Hz), 4.82 (1H, br s), 4.97 (1H, br s), 7.20-7.40
(5H, m). 13C-NMR (50.3 MHz): δ 19.6, 25.2, 32.9, 53.8, 57.4,
58.3, 64.0, 70.0, 105.0, 126.8, 128.2, 128.4, 139.6, 149.7. IR:
ν 3400, 2931, 1662. Anal. Calcd for C16H21NO: C, 78.97; H,
8.70; N, 5.76. Found: C, 78.80; H, 8.67; N, 5.63.
15. 1H-NMR (200 MHz): δ 1.55-2.45 (4H, m), 2.80-3.02
(2H, m), 3.20 (1H, br s), 3.27 and 4.10 (2H, AB sys, J )13.1
Hz), 3.54 (1H, dd, J )13.8, 1.6 Hz), 4.86-4.98 (2H, m), 5.60
(1H, d, J ) 10.2 Hz), 5.70-5.84 (1H, m), 7.20-7.45 (5H, m).
13C-NMR (50.3 MHz): δ 20.2, 22.2, 43.5, 57.4, 58.3, 61.6, 105.2,
126.0, 126.7, 128.3, 128.3, 128.7, 139.3, 150.9. IR: ν 1662,
1726. Anal. Calcd for C16H19N: C, 85.29; H, 8.99; N, 6.22.
Found: C, 85.16; H, 8.99; N, 6.11.
(3a RS,4RS,7a RS)-N-Ben zyl-3-m eth ylen e-4-vin ylp er h y-
d r oin d ole (14e). Following method A, starting from 320 mg
(1.05 mmol) of vinyl bromide 2a , 380 mg (1.38 mmol) of Ni-
(COD)2, 0.44 mL (3.15 mmol) of Et3N in 10 mL of acetonitrile
and 0.34 mL (1.16 mmol) of Bu3SnCHdCH2 as a quencher, 96
mg (40%) of 14e, 75 mg (28%) of 15, and 24 mg (10%) of alcohol
25 were obtained after flash chromatography with hexanes/
EtOAc 95:5 to 80:20.
1H-NMR (300 MHz): δ 1.05-1.30 (1H, m), 1.31-1.60 (1H,
m), 1.80 (1H, t, J ) 9.0 Hz), 1.76-1.94 (1H, m), 1.96-2.18 (3H,
m), 2.32 and 2.49 (2H, AB sys, dd, J AB ) 15.6, J AX ) 8.8 Hz,
J BX ) 6 Hz), 2.60-2.76 (1H, m), 2.90-3.10 (1H, m), 3.20 and
4.05 (2H, AB sys, J ) 12.8 Hz), 3.23 (1H, t, J ) 9.4 Hz), 3.64
(3H, s), 5.47 (1H, br s), 7.20-7.40 (5H, m). 13C-NMR (75.4
MHz): δ 20.2, 25.0, 27.8, 36.4, 39.4, 51.4, 58.6, 59.1, 63.9,
119.4, 126.9, 128.1,129.0,138.7, 143.2, 172.8. IR: ν 1739.
Anal. Calcd for C18H23NO2: C, 75.76; H, 8.12; N, 4.91.
Found: C, 75.78; H, 8.17; N, 4.98.
(3RS,7a RS)-N-Ben zyl-3-m eth yl-2,3,5,6,7,7a -h exa h yd r o-
1H-in d ole (17c). Following method A, starting from 314 mg
(1.03 mmol) of vinyl bromide 3, 450 mg (1.6 mmol) of Ni(COD)2,
0.43 mL (3.2 mmol) of Et3N in 10 mL of acetonitrile, and 156
mg (4.12 mmol) of NaBH4 in 4 mL of MeOH, 175 mg (75%) of
17c was obtained after flash chromatography with hexanes/
EtOAc 90:10.
1H-NMR (200 MHz): δ 1.10-1.90 (6H, m), 2.47 (1H, br s),
2.86-3.02 (2H, m), 3.16 and 3.40 (2H, AB sys, J ) 15.6 Hz),
3.50 and 3.85 (2H, AB sys, J ) 13.3 Hz), 4.80-5.10 (4H, m),
6.24 (1H, m), 7.10-7.45 (5H, m).13C-NMR (50.3 MHz): δ 20.7,
23.2, 26.8, 41.8, 47.1, 56.7, 58.0, 62.6, 105.5, 113.0, 126.6, 128.1,
128.4, 139.8, 142.4, 149.0. IR: ν 1637, 1662, 1695. Anal. Calcd
for C18H23N: C, 85.32; H, 9.15; N, 5.53. Found: C, 85.27; H,
9.20; N, 5.52.
(3a RS,4RS,7a RS)-N-Ben zyl-4-h yd r oxy-3-m eth ylen ep e-
r h yd r oin d ole (25). 1H-NMR (200 MHz): δ 1.30-2.10 (6H,
m), 2.52 (1H, t, J ) 4.4 Hz), 2.68-2.80 (2H, m), 2.98 and 4.12
(2H, AB sys, J ) 12.8 Hz), 3.56 (1H, d, J ) 14.2 Hz), 3.85 (1H,
br s), 4.91 (1H, s), 4.97 (1H, s), 7.20-7.40 (5H, m). 13C-NMR
(50.3 MHz): δ 21.4, 24.4, 32.4, 48.9, 57.5, 59.3, 63.5, 70.2,
105.3, 127.2, 128.5, 128.6, 138.3, 148.1. IR: ν 1664, 3355.
Anal. Calcd for C16H21NO: C, 78.97; H, 8.70; N, 5.76.
Found: C, 78.89; H, 8.73; N, 5.78.
1H-NMR (300 MHz): δ 1.03 (3H, d, J ) 6.8 Hz), 1.06-1.28
(1H, m), 1.34-1.58 (1H, m), 1.68 (1H, t, J ) 8.8 Hz), 1.76-
1.94 (1H, m), 1.98-2.16 (3H, m), 2.50-2.74 (2H, m), 3.09 (1H,
dd, J ) 9.0, 7.5 Hz), 3.17 and 4.05 (2H, AB sys, J ) 12.8 Hz),
5.42 (1H, br s), 7.20-7.40 (5H, m). 13C-NMR (75.4 MHz): δ
19.3, 20.4, 25.0, 27.8, 34.8, 58.9, 61.2, 64.2, 117.6, 126.8, 128.0,
129.1, 138.9, 146.3. IR: ν 1452, 1494. Anal. Calcd for
C16H21N: C, 84.53; H, 9.31; N, 6.16. Found: C, 84.47; H, 9.31;
N, 6.19.
(5RS,6RS)-N-Ben zyl-6-cya n o-4-m eth ylen e-2-a za sp ir o-
[4.5]d eca n e (18). Starting from 220 mg (0.80 mmol) of vinyl
chloride 4, 246 mg (0.89 mmol) of Ni(COD)2, and 0.15 mL (1.1
mmol) of TMSCN, following method A, 179 mg (0.67 mmol,
83%) of 18 was obtained.
1H-NMR (300 MHz): δ 1.13-1.29 (1H, m), 1.46 (1H, br d, J
) 12.3 Hz), 1.60-1.77 (4H, m), 1.86 (1H, dd, J ) 13.5, 3.6 Hz),
1.90-1.99 (1H, m), 2.20 and 2.96 (2H, AB sys, d, J AB ) 9.2
Hz), 2.98 (1H, AB sys, dt, J AB ) 13.8 Hz, J t ) 2.3 Hz), 3.11
(1H, br s), 3.55 (1H, AB sys, br d, J AB ) 13.8 Hz), 3.59 and
3.62 (2H, AB sys, J AB ) 13.2 Hz), 5.07 (1H, t, J ) 2.3 Hz),
5.21 (1H, t, J ) 2.3 Hz), 7.24-7.36 (5H, m). 13C-NMR (50.3
MHz): δ 21.5, 22.7, 26.6, 31.8, 35.8, 46.55, 58.79, 59.56, 62.52,
107.6, 121.5, 127.0, 128.3, 138.7, 152.1. IR: ν 2233, 1660.
Anal. Calcd for C18H22N2: C, 81.16; H, 8.32; N, 10.52.
Found: C, 81.11; H, 8.35; N, 10.48.
(3aRS,7aSR)-N-Acetyl-3-m eth ylen e-2,3,3a,6,7,7a-h exah y-
d r o-1H-in d ole (16). Following method A, starting from 333
mg (1.3 mmol) of vinyl bromide 7, 650 mg (2.34 mmol) of Ni-
(COD)2, 0.54 mL (3.9 mmol) of Et3N, and 0.4 mL (3.254 mmol)
of TMSCN, 86 mg (38%) of 16 was obtained after flash
chromatography (EtOAc).
1H-NMR: δ 1.50-1.90 (1H, m), 2.00 (1.5H, s, CH3 rotamer),
2.09 (1.5H, s, CH3 rotamer), 2.10-2.60 (3H, m), 2.70-3.02 (1H,
m), 3.82-4.48 (3H, m), 4.91 (1H, bs), 5.06 (1H, br s), 5.46-
5.72 (2H, m). 13C-NMR (50.3 MHz): δ 21.4 and 22.1, 23.1 and
23.4, 25.7 and 26.7, 38.9 and 40.0, 48.9 and 50.9, 53.1 and 55.3,
105.7 and 105.8, 122.6 and 123.9, 124.5 and 124.8, 145.5 and
146.8, 168.5 and 168.8. IR: ν 1643, 1643.
Reduction of the acetamide group with excess LiAlH4 in dry
Et2O (5 mL) gave quantitatively the N-ethyl derivative.
(3a R S ,7a S R )-N -E t h y l-3,3-m e t h y le n e -2,3,3a ,6,7,7a -
h exa h yd r o-1H-in d ole. 1H-NMR (200 MHz): δ 1.09 (3H, t,
J ) 7.2 Hz), 1.90-2.40 (5H, m), 2.56-2.70 (1H, m), 2.71-2.91
(2H, m), 3.05 and 3.56 (2H, AB sys, J ) 14 Hz), 4.80-4.90
(2H, m), 5.60-5.80 (2H, m). 13C-NMR (50.3 MHz): δ 13.3,
24.3, 26.9, 40.7, 47.3, 56.9, 60.5, 103.5, 125.0, 126.1, 151.8.
(3R S ,7a R S )-N -Be n zyl-3-(cya n om e t h yl)-2,3,5,6,7,7a -
h exa h yd r o-1H-in d ole (17a ). Following method A, starting
from 305 mg (1 mmol) of vinyl bromide 3, 450 mg (1.6 mmol)
of Ni(COD)2, 0.42 mL (3 mmol) of Et3N in 10 mL of acetonitrile,
and 0.31 mL (2.5 mmol) of TMSCN as a quencher, 204 mg
(80%) of 17a was obtained after flash chromatography on CH2-
Cl2/MeOH 99:1.
(1RS,2SR,8RS)-N-Ben zyl-11-m et h ylen e-9-a za b icyclo-
[6.3.0]u n d eca n -2-ca r bon itr ile (19-cis), (1RS,2SR,8SR)-N-
Ben zyl-11-m eth ylen e-9-a za bicyclo[6.3.0]u n d eca n -2-ca r -
bon itr ile (19-tr a n s), a n d N-Ben zyl-11-m eth ylen e-9-a za -
bicyclo[6.3.0]u n d ec-2-en e (20). Following method A, start-
ing from 312 mg (0.93 mmol) of vinyl bromide 5, 350 mg (1.3
mmol) of Ni(COD)2, 0.39 mL (2.79 mmol) of Et3N in 10 mL of
acetonitrile, and 0.3 mL (2.33 mmol) of TMSCN as a quencher,
105 mg (44%) of a 9:1 cis/trans mixture of diastereomers 20,
and 114 mg (44%) of a 9:1 mixture of 19-cis and 19-trans were
obtained after flash chromatography on hexanes/EtOAc 90:
10 to 75:25. Alternatively, following method B, from 351 mg
(1.05 mmol) of 5, 318 mg (1.16 mmol) of Ni(COD)2, 199 mg
(1.27 mmol) of bpy, and 0.40 mL (2.9 mmol) of TMSCN, 19-cis
was obtained as a single cycloadduct in 83% yield after flash
chromatography on hexanes/EtOAc 75:25.
19-cis. 1H-NMR (C6D6, 300 MHz): δ 1.0-1.1 (1H, m), 1.12-
1.42 (7H, m), 1.42-1.58 (1H, m), 1.64-1.76 (1H, m), 2.25-

Ni-Promoted Cyclization-Capture in N-Tethered Halodienes
J . Org. Chem., Vol. 61, No. 17, 1996 5903
2.30 (1H, HC1, m), 2.37-2.46 (1H, HC2, m), 2.72 (1H, HC8, dt,
J ) 4.7, 8.2 Hz), 2.91 (1H, AB sys, J AB ) 12.9 Hz), 3.01 (1H,
AB sys, dq, J AB ) 12.9 Hz, J q ) 2.4 Hz), 3.34 (1H, AB sys, d,
J AB ) 12.9 Hz), 3.87 (1H, AB sys, J AB ) 12.9 Hz), 4.55 (1H,
m), 4.79 (1H, m), 7.0-7.3 (5H, m). 13C-NMR (50.3 MHz): δ
22.9, 23.0, 27.5, 27.7, 33.8, 37.4, 47.8, 58.7, 58.8, 66.2, 106.9,
121.3, 127.0, 128.3, 128.8, 139.1, 149.1. IR: ν 2235, 1666.
Anal. Calcd for C19H24N2: C, 81.38; H, 8.63; N, 9.99. Found:
C, 81.40; H, 8.73; N, 9.94.
mmol) of amine 7, 198 mg (0.72 mmol) of Ni(COD)2, 135 mg
(0.86 mmol) of bpy, and 0.16 mL (1.2 mmol) of TMSCN
afforded 45 mg (0.20 mmol, 30%) of 26 after chromatography
with hexanes/t-BuOMe 4:1. Employing method A, 26 (2%) and
open-chain nitrile 27 (3%) were the only isolated products.
26. 1H NMR (300 MHz): δ 2.1-2.7 (9H, m), 3.43 and 3.46
(2H, AB sys, J AB ) 13.2 Hz), 4.71 (1H, s), 4.77 (1H, s), 7.2-7.4
(5H, m). 13C-NMR (75.4 MHz): δ 19.7, 32.4, 54.5, 58.1, 62.3,
109.7, 118.7, 127.1, 128.2, 128.7, 138.1, 145.3. IR: ν 3027,
2938, 2244, 1650, 1494. Anal. Calcd for C15H18N2: C, 79.61;
H, 8.02; N, 12.38. Found: C, 79.71; H, 8.06; N, 12.25.
27. 1H-NMR (200 MHz): δ 2.34-2.44 (2H, m), 2.63-2.75
(2H, m), 3.11 (2H, br d, J ) 6.6 Hz), 3.60 (2H), 5.11-5.25 (2H,
m), 5.67 (1H, br s), 5.76-6.00 (1H, m), 5.85 (1H, br s), 7.20-
7.40 (5H, m). 13C-NMR (50.3 MHz): δ 32.6, 51.3, 56.8, 58.1,
117.7, 121.6, 127.0, 128.1, 128.8, 131.2, 135.3, 139.0. IR: ν
2223, 1642, 1621. HRMS: m/ z [M+] calcd for C15H18N2
226.1471, obsd 226.1466.
N -B e n zy l-N -(2-c y c lo h e x e n y l)-3-c y a n o -3-b u t e n y l-
a m in e (28) a n d N,N′-Diben zyl-N,N′-bis(2-cycloh exen yl)-
3,4-dim eth ylen eh exan e-1,6-diam in e (29). Following method
A, starting from 357 mg (1.1 mmol) of vinyl bromide 8, 342
mg (1.35 mmol) of Ni(COD)2, 0.40 mL (3.1 mmol) of Et3N in
18 mL of acetonitrile, and 0.25 mL (1.8 mmol) of TMSCN, 23
mg (0.09 mmol, 8%) of 28 and 29 mg (0.06 mmol, 15%) of 29
were obtained after flash chromatography with hexanes/EtOAc
95:5. Employing method B, diene 29 (60%) was the only
isolated product.
28. 1H-NMR (200 MHz): δ 1.40-1.65 (2H, m), 1.60-1.90
(2H, m), 1.90-2.05 (2H, m); 2.38 (2H, t, J ) 6.3 Hz), 2.6-2.8
(2H, m), 3.34 (1H, br s), 3.57 and 3.76 (2H, AB sys, J AB ) 14.3
Hz), 5.50-5.90 (4H, m), 7.20-7.35 (5H, m). 13C-NMR (75.4
MHz): δ 21.8, 23.8, 25.2, 34.5, 48.8, 54.8, 56.8, 121.7, 126.7,
128.0, 128.1, 128.4, 130.2, 130.4, 131.1, 140.6. IR: ν 2223,
1453.
29. 1H-NMR (300 MHz): δ 1.22-1.55 (4H, m), 1.76-1.90
(4H, m), 1.96 (4H, m), 2.24-2.40 (4H, m), 2.48-2.64 (4H, m),
3.36 (2H, br s), 3.52-3.77 (4H, AB sys, δA ) 3.55, δB ) 3.72,
J AB ) 14.1 Hz), 4.83 (2H, s), 4.96 (2H, s), 5.67 (2H, br d, J )
10.2 Hz), 5.76-5.84 (2H, m), 7.20-7.40 (10H, m). 13C-NMR
(75.4 MHz): δ 21.0, 23.9, 25.3, 34.3, 50.4, 54.7, 56.6, 112.6,
126.5, 128.1, 128.4, 129.7, 130.9, 141.4, 145.6. IR: ν 1593,
1492, 1451. Anal. Calcd for C34H44N2: C, 84.95; H, 9.23; N,
5.83. Found: C, 84.80; H, 9.48; N, 5.73
N-Ben zyl-4-(cya n om eth yl)-1,2,3,4-tetr a h yd r oisoqu in o-
lin e (30) a n d 2-[(N-Allyl-N-ben zyla m in o)m eth yl]ben zon i-
tr ile (31). According to method A, 194 mg (0.61 mmol) of aryl
bromide 9, 186 mg (0.67 mmol) of Ni(COD)2, and 0.25 mL (1.8
mmol) of TMSCN gave 75 mg (0.29 mmol, 47%) of 30, 40 mg
(0.15 mmol, 25%) of 31, and 41 mg (0.13 mmol, 22%) of
recovered starting material 9 after column chromatography
with hexanes/t-BuOMe 6:1. When 9 was subjected to method
B conditions, 30 was the only isolated product in 68% yield.
30. 1H-NMR (300 MHz): δ 2.68 (1H, AB sys, dd, J AB ) 12.0
Hz, J d ) 3.3 Hz), 2.70 (1H, AB sys, dd, J AB ) 16.8 Hz, J d) 6.5
Hz), 2.87 (1H, AB sys, d, J AB ) 16.8 Hz, J d ) 9.0 Hz), 2.99
(1H, AB sys, dm, J AB ) 12.0 Hz), 3.16 (1H, m), 3.55 and 3.85
(2H, AB sys, J AB ) 15.1 Hz), 3.69 and 3.73 (2H, AB sys, J )
13.2 Hz), 7.00-7.03 (1H, m), 7.15-7.40 (8H, m). 13C-NMR
(75.4 MHz): δ 24.2 36.3, 53.9, 56.0, 62.6, 119.1, 126.6, 126.7,
127.0, 127.3, 128.4, 128.4, 128.9, 134.9, 135.0, 137.9. IR: ν
3060, 2921, 2245, 1652, 1494. Anal. Calcd for C18H18N2: C,
82.41; H, 6.91; N, 10.68. Found: C, 82.44; H, 6.87; N, 10.65.
31. 1H-NMR (200 MHz): δ 3.10 (2H, br d, J ) 6.3 Hz), 3.62
(2H, s), 3.80 (2H, s), 5.16-5.28 (2H, m), 5.88-6.02 (1H, m),
7.22-7.42 (6H, m), 7.50-7.72 (3H, m).13C-NMR (75.4 MHz):
δ 55.8, 56.6, 58.0, 112.4, 117.9, 117.9, 127.0, 127.3, 128.2, 128.7,
129.6, 132.6, 132.8, 135.2, 139.0, 144.0. IR: ν 3062, 3028,
2223, 1641, 1598. Anal. Calcd for C18H18N2: C, 82.41; H, 6.91;
N, 10.68. Found: C, 82.38; H, 7.16; N, 10.28.
19-trans. 1H-NMR (200 MHz): δ 1.20-2.20 (10H, m), 2.55
(1H, br s), 2.84-3.08 (2H, m), 2.90 and 3.35 (2H, AB sys, J )
14 Hz, 10-H), 3.28 and 4.53 (2H, AB sys, J ) 12.9 Hz), 4.80
(1H, br s), 4.86 (1H, br s), 7.20-7.40 (5H, m). 13C-NMR (50.3
MHz): δ 24.8, 25.0, 25.2, 26.2, 36.2, 36.7, 46.0, 58.5, 60.0, 71.2,
105.2, 122.6, 127.1, 128.3, 128.8, 138.7, 150.7. Anal. Calcd
for C19H24N2: C, 81.38; H, 8.63; N, 9.99. Found: C, 81.48; H,
8.60; N, 9.87.
20 (major isomer). 13C-NMR (50.3 MHz): δ 23.8, 24.5, 32.1,
34.4, 47.2, 58.5, 59.1, 70.7, 104.2, 126.9, 128.2, 128.9, 129.5,
130.4, 139.2, 152.7.
20 (minor isomer). 13C-NMR (50.3 MHz): δ 24.3, 25.1, 27.4,
28.6, 51.1, 58.2, 59.0, 71.2, 103.0, 126.9, 128.2, 128.9, 129.2,
130.0, 138.8, 150.4.
N-Ben zyl-3-m eth ylin d ole (21) a n d N-Ben zyl-3-m eth yl-
2,3-d ih yd r o-1H-in d ole (22). Starting from 302 mg (1.0
mmol) of bromoaniline 6, 325 mg (1.2 mmol) of Ni(COD)2, and
0.15 mL (1.1 mmol) of TMSCN, following method A, 18 mg
(0.06 mmol, 6%) of starting bromide 6, 106 mg (0.48 mmol,
48%) of 21,36 and 29 mg (0.13 mmol, 13%) of 2236 were
obtained.
21. 1H-NMR (200 MHz): δ 2.35 (3H, s), 5.28 (2H, s), 6.91
(1H, s), 7.08-7.36 (8H, m), 7.6 (1H, d, J ) 6 Hz). 13C-NMR
(50.3 MHz): δ 9.6, 49.8, 109.4, 110.9, 118.8, 119.0, 121.6, 125.8,
126.8, 127.5, 128.7, 128.9, 136.7, 137.9. IR: ν 2917, 1465,
1328.
22. 1H NMR (200 MHz): δ 1.30 (3H, d, J ) 6.8 Hz), 2.84
(1H, t, J ) 8.4 Hz), 3.20-3.40 (1H, m), 3.51 (1H, t, J ) 8.4
Hz), 4.10 and 4.38 (2H, AB sys, J ) 15 Hz), 6.50 (1H, d, J )
6.9 Hz ), 6.70 (1H, t, J ) 7.5 Hz ), 7.02-7.12 (2H, m), 7.22-
7.42 (5H, m). 13C-NMR (50.3 MHz): δ 18.6, 35.2, 53.4, 61.6,
106.9, 117.7, 123.2, 127.1, 127.4, 127.9, 128.9, 135.0, 138.5,
152.1. IR: ν 2958, 1604, 1486, 1251.
N-Acetyl-3-[(m eth oxyca r bon yl)m eth yl]-1,2,5,6-tetr a h y-
d r op yr id in e (23). Following method A, from 290 mg (1.03
mmol) of amide 1d and CO/MeOH as a quencher, 23 (52 mg,
0.18 mmol, 18%) was obtained after flash chromatography on
elution with hexanes/EtOAc 60:40.
1H-NMR (200 MHz): δ 2.08 (3H, s), 2.04-2.26 (2H, m), 2.99
(2H, br s), 3.46 (1H, t, J ) 8.4 Hz), 3.61 (1H, t, J ) 8.4 Hz),
3.65 and 3.67 (3H, s, amide rotamers), 3.92 (1H, br s), 4.01
(1H, br s), 5.6 and 5.8 (1H, br s, amide rotamers). 13C-NMR
(50.3 MHz) (two amide rotamers): δ 21.8 and 22.3, 25.0 and
25.9, 38.1 and 40.4, 40.7 and 43.1, 44.5 and 48.2, 52.0 and 52.3,
123.8 and 126.0, 128.1 and 129.6, 169.5 and 169.7, 171.7 and
171.8. IR: ν 2945, 1650, 1419.
N,N′-Diacetyl-N,N′-diallyl-3,4-dim eth ylen e-1,6-h exan edi-
a m in e (24). Following method B, cyclization and quenching
with TMSCN from 296 mg (1.36 mmol) of 1d afforded 86 mg
(0.31 mmol, 23%) of 24 after flash chromatography on elution
with 50% hexanes/EtOAc.
1H-NMR (300 MHz):37 δ 2.03-2.04 (3H, d), 2.11-2.12 (3H,
d), 3.81-3.83 (2H, m), 3.92-3.97 (2H, m), 4.02-4.05 (2H, m),
4.21-4.23 (2H, m), 4.95-5.01 (2H, m), 5.05-5.24 (4H, m),
5.28-5.32 (2H, m), 5.66-5.84 (2H, m). 13C-NMR (75.4 MHz):
37
21.0, 21.33, 21.39, 47.32, 47.39, 48.20, 48.30, 49.63, 49.64,
111.3, 112.3, 113.4, 114.2, 116.6, 116.8, 117.2, 117.4, 132.2,
132.3, 132.9, 133.0, 139.8, 140.7, 170.7, 171.1. IR: ν 3076,
2978, 1650, 1471, 1434, 1415, 1249. MS: m/ z 276, 233, 134,
122, 94, 70.
N-Ben zyl-4-m eth ylen e-3-(cya n om eth yl)p ip er id in e (26)
a n d N-Allyl-N-ben zyl-3-cya n o-3-bu ten yla m in e (27). Ac-
cording to method B, cyclization-quenching from 182 mg (0.65
N-Ben zyl-3-(cyan om eth yl)-4-m eth yl-1,2,5,6-tetr ah ydr o-
p yr id in e (32a ) a n d N-Ben zyl-4-(cya n om eth yl)-3-m eth yl-
en ep ip er id in e (33a ). Following method A, starting from 395
mg (1.4 mmol) of 10, a mixture of 32a and 33a (85:15 from
1HNMR, 60% combined yield) was obtained after quenching
(36) Kiguchi, T.; Kuninobu, N.; Takahashi, Y.; Yoshida, Y.; Naito,
T.; Ninomiya, I. Synthesis 1989, 778.
(37) Mixture of rotameric species due to the amide groups.

5904 J . Org. Chem., Vol. 61, No. 17, 1996
Sole´ et al.
with TMSCN and flash chromatography on hexanes/EtOAc 70:
30. Repeated attempts to separate these compounds were not
successful.
(1H, s), 7.20-7.50 (5H, m). 13C-NMR (50.3 MHz): δ 21.0, 25.4,
27.2, 33.3, 57.0, 58.2, 59.1, 118.3, 122.1, 127.1, 128.1, 128.3,
128.7, 129.5, 131.7, 138.5. IR: ν 2223.
35. 1H NMR (200 MHz): δ 1.02-2.00 (12H, m), 2.00-2.40
(6H, m), 3.07 and 3.20 (4H, AB sys, J ) 13.7 Hz), 3.30-3.60
(4H, m), 5.19 (2H, s), 5.24 (2H, s), 5.50-5.70 (4H, m), 7.10-
7.45 (10H, m).13C NMR (50.3 MHz): δ 21.0, 25.5, 27.4, 33.1,
58.8, 58.9, 59.5, 115.2, 126.6, 127.3, 127.9, 129.0, 130.4, 139.8,
146.0. IR: ν 1450, 1494. Anal. Calcd for C34H44N2: C, 84.95;
H, 9.23; N, 5.83. Found: C, 84.94; H, 9.33; N, 5.85.
Selected data for 32a (signals taken from the mixture of
32a and 33a ). 1H-NMR (200 MHz): δ 1.61 (3H, s), 2.03 (2H,
sa), 2.46 (2H, t, J ) 5,9 Hz), 2.92 (4H, sa), 3.51 (2H, br s),
7.01-7.4 (5H, m). 13C-NMR (50.3 MHz): δ 18.3, 19.1, 32.0,
49.3, 55.5, 62.3, 117.2, 117.5, 127.0, 128.1, 129.0, 131.1, 138.0.
IR (mixture of 32a and 33b): ν 3020, 2912, 2245 , 1450, 1452.
Selected data for 33a (signals taken from the mixture of
32a and 33a ). 1H NMR (200 MHz): δ 4.83 (s, 1 H, CH2dC),
4.60 (s, 1 H, CH2dC). 13C NMR (50.3 MHz): δ 20.2, 31.4, 37.5,
52.0, 59.7, 109.0, 117.2, 144.1
N-Ben zyl-4-m eth yl-3-[(m eth oxycar bon yl)m eth yl]-1,2,5,6-
tetr a h yd r op yr id in e (32b). Following method A, starting
from 423 mg (1.5 mmol) of 10, using CO/MeOH as a quencher,
32b (40%)was isolated after flash chromatography on hexanes/
EtOAc 75:25.
N-Ben zyl-N-[2-(1-cycloh exen yl)eth yl]-2-cya n o-2-p r op e-
n yla m in e (36) a n d N,N′-d iben zyl-N,N′-bis[2-(1-cycloh ex-
en yl)eth yl]-2,3-d im eth ylen ebu ta n e-1,4-d ia m in e (37). Fol-
lowing method A, starting from 370 mg (1.1 mmol) of vinyl
bromide 12, 331 mg (1.3 mmol) of Ni(COD)2, 0.40 mL (3.1
mmol) of Et3N in 22 mL of acetonitrile, and 0.25 mL (1.8 mmol)
of TMSCN, 125 mg (0.53 mmol, 48%) of 36 and 68 mg (0.14
mmol, 24%) of 37 were obtained after flash chromatography
with hexanes/EtOAc 90:10. Employing method B for the
cyclization, 36 (56%) was isolated.
36. 1H-NMR (300 MHz): δ 1.44-1.65 (4H, m), 1.85 (2H, br
m), 1.96 (2H, br m), 2.13 (2H, br t, J ) 7.2 Hz), 2.57 (2H, dd,
J ) 6.0, 7.8 Hz), 3.20 (2H, s), 3.62 (2H, s), 5.40 (1H, br m),
5.92 (1H, br q, J ) 0.9 Hz), 5.96 (1H, br q, J ) 0.9 Hz), 7.20-
7.40 (5H, m). 13C-NMR (75.4 MHz): δ 22.4, 22.9, 25.2, 29.0,
35.4, 51.8, 56.4, 57.7, 118.4, 122.1, 122.5, 127.1, 128.3, 128.7,
131.6, 135.5, 138.8. IR: ν 2927, 2223, 1623, 1600. Anal.
Calcd for C19H24N2: C, 81.38; H, 8.63; N, 9.99. Found: C,
81.60; H, 8.51; N, 10.15.
37. 1H-NMR (300 MHz): δ 1.44-1.65 (4H, m), 1.80 (2H, br
m), 1.94 (2H, br m), 2.06 (2H, br t, J ) 7.0 Hz), 2.57 (2H, dd,
J ) 5.4, 8.1 Hz), 3.19 (2H, s), 3.48 (2H, s), 5.18 (1H, s), 5.29
(1H, d, J ) 2.1 Hz), 5.33 (1H, br s), 7.20-7.40 (5H, m). 13C-
NMR (75.4 MHz): δ 22.4, 23.0, 25.3, 28.4, 34.9, 52.1, 58.0, 58.3,
114.94, 121.7, 126.6, 128.0, 128.9, 136.3, 140.1, 146.0. IR: ν
2927, 2223, 1664, 1595. Anal. Calcd for C36H48N2: C, 84.99;
H, 9.51; N, 5.50. Found: C, 85.11; H, 9.71; N, 5.71
1H-NMR (200 MHz): δ 1.67 (3 H, s ), 2.10 (2 H, sa), 2.52 (2
H, t, J ) 5.8 Hz), 2.9-3.1 (4 H, m), 3.55 (2 H, s), 3.65 (3H, s),
7.1-7.40 (5 H, m).13C-NMR (50.3 MHz): δ 18.6, 32.1, 36.8,
49.7, 51.7, 56.8, 62.6, 121.5, 127.0, 128.1, 129.2, 129.5, 138.1,
172.0. IR: ν 2948, 2812, 1737, 1434. HRMS: m/ z [M+] calcd
for C18H21NO2 259.1572, obsd 259.1563.
N-Ben zyl-3,4-dim eth yl-1,2,5,6-tetr ah ydr opyr idin e (32c)
a n d N-Ben zyl-4-m eth yl-3-m eth ylen ep ip er id in e (33c). Fol-
lowing method A, starting from 427 mg of 10, a mixture of
32c and 33c (41%) was obtained after quenching with NaBH4
and flash chromatography with hexanes/EtOAc 90:10. Re-
peated attempts to separate these compounds were not suc-
cessful.
Selected data for 32c (signals taken from the mixture of 32c
and 33c). 1H-NMR (200 MHz): δ 1.49 (3H, s, CH3), 1.56 (3H,
s), 1.99 (2H, br s), 2.44 (2H, t, J ) 5.6 Hz), 2.77 (s, 2 H), 3.49
(2 H, s), 7.1-7.4 (5 H, m).13C-NMR (50.3 MHz): δ 16.6, 18.3,
32.1, 50.3, 58.2, 63.0, 124.0, 124.5, 127.0, 128.2, 129.2 , 138.5.
Selected data for 33c (signals taken from the mixture of 32c
and 33c). 1H-NMR (200 MHz): δ 1.02 (3H, d, J ) 6.4 Hz),
4.65 (1H, s), 4.75 (1H, s). 13C-NMR (50.3 MHz): δ 17.7, 34.6,
35.6, 53.4, 60.8, 107.0, 149.0. IR (mixture of 32c and 33c): ν
2910, 2796, 1652, 1454.
Ack n ow led gm en t. Financial support from CICYT
and Comissionat per a Universitats i Recerca, Gener-
alitat de Catalunya (Projects QFN 95-4718, GRQ 93-
8016, and GRQ 94-1035), is gratefully acknowledged.
Y.C. also thanks CIRIT (Generalitat de Catalunya) for
a predoctoral fellowship.
N-Ben zyl-N-[(2-cycloh exen yl)m et h yl]-2-cya n o-2-p r o-
p en yla m in e (34) a n d N,N′-Diben zyl-N,N′-bis[(2-cycloh ex-
en yl)m eth yl]-2,3-dim eth ylen ebu tan e-1,4-diam in e (35). Fol-
lowing method A, starting from 326 mg (1.0 mmol) of vinyl
bromide 11, 423 mg (1.5 mmol) of Ni(COD)2, 0.43 mL (3.2
mmol) of Et3N in 20 mL of acetonitrile, and 0.25 mL (1.8 mmol)
of TMSCN, 91 mg (0.35 mmol, 35%) of 34 was obtained after
flash chromatography with hexanes/EtOAc 90:10. Employing
method B for the cyclization, diene 35 (5%) and N-(2-cyclo-
hexenylmethyl)benzylamine (43%) were the only isolated
products.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures, spectroscopic data for starting compounds 1-12, and
stereochemical assignment for 17c, 18, and 19 (17 pages). This
material is contained in libraries on microfiche, immediately
follows this article in the microfilm version of the journal, and
can be ordered from the ACS; see any current masthead page
for ordering information.
34. 1H NMR (200 MHz): δ 1.20-2.10 (6H, m), 2.36 (3H, br
s), 3.12 and 3.25 (2H, AB sys, J ) 14.5 Hz), 3.55 and 3.70 (2H,
AB sys, J ) 13.8 Hz), 5.52-5.56 (2H, m), 5.89 (1H, s), 5.96
J O960677Y