Thermal Cyclodimerization of Aliphatic Secondary C,N-Dilithioallylamine Derivatives

Article abstract of DOI:10.1021/jo960048o

β-Nitrogen-functionalized vinylic organolithium compounds derived from secondary aliphatic allylamines have been found to undergo upon heating (reflux of THF) either a dimerization or a regio- and stereoselective cyclodimerization reaction affording diamino 1,4-dienes or cis-2,3-disubstituted 4-methylenepyrrolidines, respectively, according to reaction time.In contrast, the corresponding dianions derived from aromatic allylamines underwent protonation by the solvent under analogous thermal treatment.A mechanism accounting for all these results has been proposed, which involves a spontaneous β-elimination of lithium hydride and an intramolecular nucleophilic cyclization by addition of a lithium amide to an alkene group as critical steps.In addition, experimental evidence is provided about the formation of 3-lithio-1-aza 1,3-dienes as intermediates in these unusual thermal transformations.

Full text of DOI:10.1021/jo960048o

J . Org. Chem. 1996, 61, 3753-3757
3753
Th er m a l Cyclod im er iza tion of Alip h a tic Secon d a r y
C,N-Dilith ioa llyla m in e Der iva tives
J ose´ Barluenga,* Rosa-Mar´ıa Canteli, and J osefa Flo´rez
Instituto Universitario de Quı´mica Organometa´lica “Enrique Moles”, Unidad Asociada al CSIC,
Universidad de Oviedo, J ulia´n Claverı´a 8, 33071 Oviedo, Spain
Received J anuary 4, 1996X
â-Nitrogen-functionalized vinylic organolithium compounds derived from secondary aliphatic
allylamines have been found to undergo upon heating (reflux of THF) either a dimerization or a
regio- and stereoselective cyclodimerization reaction affording diamino 1,4-dienes or cis-2,3-
disubstituted 4-methylenepyrrolidines, respectively, according to reaction time. In contrast, the
corresponding dianions derived from aromatic allylamines underwent protonation by the solvent
under analogous thermal treatment. A mechanism accounting for all these results has been
proposed, which involves a spontaneous â-elimination of lithium hydride and an intramolecular
nucleophilic cyclization by addition of a lithium amide to an alkene group as critical steps. In
addition, experimental evidence is provided about the formation of 3-lithio-1-aza 1,3-dienes as
intermediates in these unusual thermal transformations.
Sch em e 1
Recently, we described the preparation and reactivity
of â-nitrogen-functionalized vinylic organolithium com-
pounds derived from aliphatic secondary allylamines1 and
allylamine itself.2 In the course of this study, we
observed that some of these dilithio derivatives under-
went a cyclodimerization reaction on heating at reflux
of tetrahydrofuran. The results of this unexpected
behavior are reported in the present paper.
Sch em e 2
It is known that the stability of functionalized organo-
lithium compounds is highly dependent on the nature of
the functional group and the hybridization of the carbon
atom attached to the metal and very sensitive to the
relative position of both functionalities.3 In the case of
â-nitrogen-functionalized organolithium compounds, the
sp3 dianionic derivatives 14 (Scheme 1) are very unstable
species which have to be kept at low temperatures (-78
°C) owing to their tendency to undergo at higher tem-
peratures either a â-elimination of ArNLi2 or proton
abstraction from the solvent. On the other hand, the sp2
dianionic compounds 25 and 31 are generally stable at
room temperature, although they show different reactiv-
ity when they are heated at reflux of THF. As we
describe herein, the aromatic derivatives 2 decompose by
abstraction of a proton from the solvent whereas the
aliphatic intermediates 3 undergo a â-elimination of
lithium hydride which represents a very unusual process
in the chemistry of organolithium compounds containing
â-hydrogens.6
Resu lts a n d Discu ssion
In order to examine the thermal stability of organo-
lithium compounds 3, which were prepared from the
appropriate 2-(tributylstannyl)allylamine 4 as previously
described,1 a THF solution of the corresponding dianionic
derivative 3 was heated at reflux for 2-4 h and then
successively treated with D2O and H2O. After workup,
we unexpectedly noted the formation either of the dimer-
ization products 7 or the cyclodimerization compounds 9
in addition to different amounts of the initially expected
protonation derivatives 5 (Scheme 2). The ratio of these
compounds depends on the nature of the dianion 3 (R
group) and on the reflux time. Under these conditions
(THF, 65 °C), incorporation of deuterium was not ob-
served in any reaction product, indicating that organo-
lithium intermediates are not stable at 65 °C and react
with the ethereal solvent via proton abstraction. The
detailed results from this investigation are provided in
Table 1.
X Abstract published in Advance ACS Abstracts, May 1, 1996.
(1) Barluenga, J .; Canteli, R. M.; Flo´rez, J . J . Org. Chem. 1994, 59,
602.
(2) Barluenga, J .; Canteli, R. M.; Flo´rez, J . J . Org. Chem. 1994, 59,
1586.
(3) (a) Barluenga, J . Pure Appl. Chem. 1990, 62, 595. (b) Na´jera,
C.; Yus, M. Trends Org. Chem. 1991, 2, 155.
(4) (a) Barluenga, J .; Fan˜ana´s, F. J .; Yus, M. J . Org. Chem. 1979,
44, 4798. (b) Barluenga, J .; Fan˜ana´s, F. J .; Villaman˜a, J .; Yus, M. J .
Org. Chem. 1982, 47, 1560. (c) Barluenga, J .; Foubelo, F.; Fan˜ana´s, F.
J .; Yus, M. Tetrahedron 1989, 45, 2183. (d) Almena, J .; Foubelo, F.;
Yus, M. J . Org. Chem. 1994, 59, 3210.
(5) Barluenga, J .; Foubelo, F.; Fan˜ana´s, F. J .; Yus, M. J . Chem. Soc.,
Perkin Trans. 1 1989, 553.
(6) Wardell, J . L. Preparation and Use in Organic Synthesis of
Organolithium and Group IA Organometallics. In The Chemistry of
the Metal-Carbon Bond; Patai, S., Hartley, F. R., Eds.; Wiley: New
York, 1987; Vol. 4, p 1.
S0022-3263(96)00048-5 CCC: $12.00 © 1996 American Chemical Society

3754 J . Org. Chem., Vol. 61, No. 11, 1996
Barluenga et al.
Ta ble 1. Th er m a l Sta bility of Or ga n olith iu m s 3. Resu lts
fr om th e Hea tin g of 3 a t Reflu x of THF
T
ta
(°C) (h) products
yieldb
(%)
entry dianion
R
1
2
3
4
5
3a
3a
3a
3b
3c
Bu
Bu
Bu
CH3(CH2)5
(CH2)5CH
65
65
65
65
20
2
3
4
7a
7a
9a
9b
6ce
8ce
9c
5c
9d
5d
5e
7f
18
30c
15
17
37
37
15
12
20
15
73
50
38
10
16
14
3
F igu r e 1. Observed NOEs for pyrrolidine 9a measured at
300.13 MHz in CDCl3.
2d
6
7
3c
3d
(CH2)5CH
65
3
2
Sch em e 3
(EtO)2CH(CH2)3 65
8
9
3e
3f
PhCH2
PhCH2CH2
65
65
2
2
5f
9f
7f
5f
10
3f
PhCH2CH2
65
4
a
b
Reaction time at reflux. Isolated yields based on the corre-
sponding 2-(tributylstannyl)allylamine 4. c A mixture of ether:
d
THF 1.5:1 was used as solvent. Reaction time; the organolithium
3c was kept at room temperature before adding D2O. e Degree of
deuteration was 97% for 6c and 95% for 8c.
In the case of organolithium 3a , the 1,4-diene 7a was
isolated as the only reaction product after 2 h at reflux
of THF or 3 h at reflux of a 1.5:1 mixture of Et2O:THF
(Table 1, entries 1 and 2, respectively). In contrast, after
4 h at reflux pyrrolidine 9a was obtained as a single
diastereoisomer (Table 1, entry 3). This same result was
observed with dianions 3b and 3c which led to the
corresponding 3-methylenepyrrolidines 9b and 9c after
heating for 3 h (Table 1, entries 4 and 6, respectively),
although in the last case allylamine 5c was also isolated.
An analogous behavior was observed with intermediate
3d which afforded a mixture of 9d and 5d (Table 1, entry
7). However, thermal treatment of organolithium 3e
derived from N-benzylallylamine gave rise exclusively to
the corresponding allylamine 5e (Table 1, entry 8).
Additionally, dianion 3f afforded amino diene 7f after
heating for 2 h and a mixture of this diene 7f and cis-
2,3-disubstituted pyrrolidine 9f when the reaction mix-
ture was heated for 4 h. In both experiments different
amounts of allylamine 5f were present (Table 1, entries
9 and 10). In general, short reaction times seem to favor
the formation of dimeric compounds 7, while longer times
led to cyclodimeric products 9 (Table 1, entries 1 and 9
vs 3 and 10, respectively), which appears to mean that
dienic derivatives are intermediates in the transforma-
tion of dianions 3 to pyrrolidines 9. As indicated above,
in the reactions with organolithiums 3a and 3b the
corresponding allylamines 5a and 5b have not been
isolated, which could be a consequence of the volatility
and high polarity of these compounds; indeed, these
allylamines were detected in the 13C NMR spectra of the
crude products. It is worthy of note that organolithium
3c derived from N-cyclohexylallylamine is even partially
unstable at room temperature. Thus, treatment of 3c
with D2O at rt provided deuterated allylamine 6c ac-
companied by an equimolecular amount of the monodeu-
terated dimeric compound 8c (Table 1, entry 5), which
means that at rt the organolithium intermediates do not
undergo proton abstraction from the medium. Despite
the fact that no other products were detected in the initial
product mixtures, the isolated yields of the dimeric
compounds 7 and 9 are low to modest. These poor
recoveries could be in part originated by the polar nature
of these products or by the formation of polymeric
materials, given that a large amount of mass is lost
during the silica gel flash column chromatography pu-
rification. The structure and stereochemistry of pyr-
rolidines 9 were established for compound 9a on the basis
of 1H and 13C NMR spectra, including 2D 1H to 13C
1
correlation through J CH and NOE difference experiments
(Figure 1). The enhancements observed between the
methine ring protons indicate a cis orientation between
both atoms. In all other products this stereochemistry
has been assumed by analogy.
A mechanism which is consistent with the results
presented here is proposed in Scheme 3. In light of the
connectivity of dienes 7 and 8, it would appear that on
warming organolithium compounds 3 undergo an initial
â-elimination of LiH,7 affording 3-lithio-1-aza dienes 10
which subsequently are trapped by another molecule of
(7) For LiH eliminations in lithium amides see: (a) Wittig, G.;
Schmidt, H.-J .; Renner, H. Chem. Ber. 1962, 95, 2377. (b) Kowalski,
C.; Creary, X.; Rollin, A. J .; Burke, M. C. J . Org. Chem. 1978, 43, 2601.
(c) Melamed, U.; Feit, B.-A. J . Chem. Soc., Perkin Trans. 1 1980, 1267.
(d) Richey, H. G., J r.; Erickson, W. F. J . Org. Chem. 1983, 48, 4349.
(e) Newcomb, M.; Burchill, M. T. J . Am. Chem. Soc. 1984, 106, 8276.
(f) Majewski, M. Tetrahedron Lett. 1988, 29, 4057 and references
therein.

Cyclodimerization of C,N-Dilithioallylamine Derivatives
J . Org. Chem., Vol. 61, No. 11, 1996 3755
dianion 3 to give intermediate 11.8,9 At reflux of THF
these trianions 11 are unstable and suffer protonation
by the solvent to give bis(lithium amides) 12, which after
hydrolysis yield amino dienes 7. But, at rt trianions 11
are stable which explains the isolation of deuterated
diene 8c in the case of organolithium 3c. On longer
reaction times unsaturated lithium amides 12 undergo,
most likely through conformation 13, a regio- and dia-
stereoselective cyclization affording primary organo-
lithiums 14, which analogously decompose by proton
abstraction from the solvent and upon hydrolysis lead
to cis-2,3-disubstituted 4-methylenepyrrolidines 9.10 The
selective formation of the cis diastereoisomer in the
present intramolecular anionic addition of N-Li bond to
an alkene group11 can be explained in terms of a cyclic
four-center transition state 16 similar to the one reported
by Bailey et al. for the intramolecular addition of a C-Li
bond to an unactivated alkene that resembles a chair
cyclohexane in which substituents preferentially occupy
pseudoequatorial positions.12 In our case the lithium
(bonded to the other amide group present in the struc-
ture)-alkene π-stabilizing interaction presumably serves
to establish the pseudoaxial orientation of the lithium
amide substituent which leads to the cis isomer; further-
more, this orientation enhances the stability of 14 by
intramolecular heteroatom coordination.
Sch em e 4
hydride elimination, we attempted to trap the lithiated
azadiene 10 with an external nucleophile which would
be added to the reaction mixture after the generation of
organolithium compound 3. Accordingly, a THF solution
of dianion 3a at rt was treated with an excess (10 equiv)
of an Et2O solution of phenyllithium before the reaction
mixture was warmed to reflux temperature (Scheme 4).
In this reaction, the expected phenyl-substituted allyl-
amine 17 was obtained as the major product accompanied
by the formation of dienes 7a and 18. The isolation of
17, which surprisingly incorporates a deuterium atom
(97%) in its structure, proves the formation of 3-lithio-
1-aza dienes 10 as intermediates in these thermal
dimerization reactions. The unexpected stability of or-
ganolithium 19 under these reaction conditions (reflux
of a mixture THF:Et2O 1.5:1 as solvent; see on a
comparative basis Table 1, entry 2) can be apparently
due to an stabilizing agostic interaction between the
vinylic lithium atom and the ortho hydrogen-carbon
bond of the adequately positioned phenyl group.14 The
dianion 19 was even able to react with aza diene
intermediate 10a (R ) Bu) to give 18. An analogous
Li-H agostic interaction between the nitrogen-bound
lithium and the aromatic ortho hydrogen atoms, as
depicted in Scheme 4 for 3e, could account for the above-
mentioned lack of LiH elimination observed with this
dianion.
The unusual thermal â-elimination of LiH observed in
1,3-dilithio derivatives 3 could be favored by the 1,3
relationship of both lithium atoms which simultaneously
stabilize the transition state of this reaction by σ-π
conjugation as concluded in previous studies.13 In an
effort to provide additional evidence for this lithium
(8) An alternative path for the â-elimination of LiH, which can not
be ruled out, would involve the vinylic lithium atom and lead to an
allenic intermediate which subsequently would undergo isomerization
to 10:
(9) For related thermal eliminations of LiH in alkyllithium com-
pounds see: (a) Bryce-Smith, D. J . Chem. Soc. 1955, 1712. (b) Weiner,
M.; Vogel, G.; West, R. Inorg. Chem. 1962, 1, 654. (c) Finnegan, R. A.;
Kutta, H. W. J . Org. Chem. 1965, 30, 4138. (d) Glaze, W. H.; Lin, J .;
Felton, E. G. J . Org. Chem. 1965, 30, 1258. (e) Melamed, U.; Feit, B.-
A. J . Chem. Soc., Perkin Trans. 1 1978, 1228. (f) Reetz, M. T.; Schinzer,
D. Angew. Chem., Int. Ed. Engl. 1977, 16, 44. This process is facilitated
through â-hydrogen activation by the two carbon-metal bonds in 1,3-
dilithiopropane derivatives: (g) Seetz, J . W. F. L.; Schat, G.; Akkerman,
O. S.; Bickelhaupt, F. J . Am. Chem. Soc. 1982, 104, 6848. (h) Maercker,
A.; Klein, K.-D. Angew. Chem., Int. Ed. Engl. 1989, 28, 83.
(10) For other synthesis of 3-methylenepyrrolidines see: (a) Padwa,
A.; Nimmesgern, H.; Wong, G. S. K. Tetrahedron Lett. 1985, 26, 957.
(b) Hatakeyama, S.; Sugawara, K.; Takano, S. J . Chem. Soc., Chem.
Commun. 1993, 125. (c) Trost, B. M.; Marrs, C. M. J . Am. Chem. Soc.
1993, 115, 6636. (d) van der Heide, T. A. J .; van der Baan, J . L.; de
Kimpe, V.; Bickelhaupt, F.; Klumpp, G. W. Tetrahedron Lett. 1993,
34, 3309. (e) Sole´, D.; Cancho, Y.; Llebar´ıa, A.; Moreto´, J . M.; Delgado,
A. J . Am. Chem. Soc. 1994, 116, 12133.
(11) For intramolecular additions of NLi to olefins see: (a) Evans,
B. E.; Anderson, P. S.; Christy, M. E.; Colton, C. D.; Remy, D. C.; Rittle,
K. E.; Engelhardt, E. L. J . Org. Chem 1979, 44, 3127. (b) Tokuda, M.;
Yamada, Y.; Takagi, T.; Suginome, H. Tetrahedron 1987, 43, 281. (c)
Tokuda, M.; Miyamoto, T.; Fujita, H.; Suginome, H. Tetrahedron 1991,
47, 747. (d) Fujita, H.; Tokuda, M.; Nitta, M.; Suginome, H. Tetrahe-
dron Lett. 1992, 33, 6359. (e) Luo, F.-T.; Wang, R.-T. Tetrahedron Lett.
1992, 33, 6835.
(12) (a) Bailey, W. F.; Khanolkar, A. D.; Gavaskar, K.; Ovaska, T.
V.; Rossi, K.; Thiel, Y.; Wiberg, K. B. J . Am. Chem. Soc. 1991, 113,
5720. See also: (b) Chamberlin, A. R.; Bloom, S. H.; Cervini, L. A.;
Fotsch, C. H. J . Am. Chem. Soc. 1988, 110, 4788. (c) Bailey, W. F.;
Khanolkar, A. D.; Gavaskar, K. V. J . Am. Chem. Soc. 1992, 114, 8053.
(d) Bailey, W. F.; J iang, X.-L. J . Org. Chem. 1994, 59, 6528.
(13) Traylor, T. G.; Koermer, G. S. J . Org. Chem. 1981, 46, 3651.
The nature of the R group has great influence on the
thermal behavior of vinylic â-nitrogen-functionalized
organolithium compounds 3. Thus, dianion 2a , which
was directly prepared from the corresponding aromatic
2-bromoallylamine 20 by successive treatment with BuLi
and t-BuLi, was also unstable at 65 °C, but it decomposed
by abstraction of a proton from the solvent to afford 21
without undergoing LiH elimination, probably due to the
enhanced stability of the aromatic lithium amide (Scheme
5).
In conclusion, we have observed that when vinylic
organolithium compounds derived from secondary ali-
phatic allylamines are heated at reflux of THF, they
(14) (a) Brookhart, M.; Green, M. L. H. J . Organomet. Chem. 1983,
250, 395. (b) Bauer, W.; Mu¨ller, G.; Pi, R.; Schleyer, P. v. R. Angew.
Chem., Int. Ed. Engl. 1986, 25, 1103. (c) Bauer, W.; Feigel, M.; Mu¨ller,
G.; Schleyer, P. v. R. J . Am. Chem. Soc. 1988, 110, 6033. (d) Sun˜er, G.
A.; Deya´, P. M.; Saa´, J . M. J . Am. Chem. Soc. 1990, 112, 1467. (e)
Bauer, W.; O'Doherty, G. A .; Schleyer, P. v. R.; Paquette, L. A. J . Am.
Chem. Soc. 1991, 113, 7093. (f) Novoa, J . J .; Whangbo, M.-H.; Stucky,
G. D. J . Org. Chem. 1991, 56, 3181.

3756 J . Org. Chem., Vol. 61, No. 11, 1996
Barluenga et al.
114.6, 139.8 (t, J ) 23.5 Hz), 148.8; MS m/ z 277 (M+, <1),
135 (76), 96 (85), 95 (67).
Sch em e 5
(2R*,3R*)-1-Bu t yl-3-(b u t yla m in o)-2-m et h yl-4-m et h yl-
1
en ep yr r olid in e (9a ): yellow oil; Rf 0.11 (AcOEt); H NMR δ
0.82, 0.83 (2t, J ) 7 Hz, 6H), 0.86 (d, J ) 6.4 Hz, 3H), 1.25-
1.50 (m, 9H), 2.15 (m, 1H), 2.45 (m, 1H), 2.60 (m, 2H), 2.84
(m, 1H), 3.08 (d, J ) 14 Hz, 1H), 3.36 (d, J ) 14 Hz, 1H), 3.40
(d, J ) 5.6 Hz, 1H), 4.92 (m, 2H); 13C NMR δ 9.5, 13.9, 20.4,
20.6, 30.2, 32.3, 47.0, 52.5, 55.8, 60.8, 63.8, 105.8, 149.1; MS
m/ z 224 (M+, 3), 125 (85), 100 (100), 82 (77).
(2R*,3R*)-1-Hexyl-3-(h exyla m in o)-2-m eth yl-4-m eth yl-
en ep yr r olid in e (9b): yellow oil; Rf 0.5 (hexane:AcOEt, 1:1);
1H NMR δ 0.88 (m, 6H), 0.93 (d, J ) 6.4 Hz, 3H), 1.20-1.55
(m, 17H), 2.23 (m, 1H), 2.48-2.72 (m, 3H), 2.91 (m, 1H), 3.13
(dt, J ) 14.2, 2.1 Hz, 1H), 3.40 (d, J ) 14 Hz, 1H), 3.47 (d, J
) 5.2 Hz, 1H), 4.98 (m, 2H); 13C NMR δ 9.4, 13.9, 22.5, 26.9,
27.2, 28.0, 30.1, 31.7, 47.4, 52.8, 55.8, 60.8, 63.8, 105.7, 149.1;
MS m/ z 280 (M+, 3), 128 (100), 82 (78), 43 (60).
(2R*,3R*)-1-Cycloh exyl-3-(cycloh exyla m in o)-2-m eth yl-
4-m eth ylen ep yr r olid in e (9c): yellow oil; Rf 0.2 (AcOEt); 1H
NMR δ 0.68 (d, 3H), 1.00-2.00 (m, 20H), 2.20-2.70 (broad
signal with 2m at 2.30 and 2.43, 3H), 3.02 (m, 1H), 3.45 (m,
1H), 3.64 (m, 1H), 3.80 (m, 1H), 4.88, 4.95 (2m, 2H); 13C NMR
δ 6.3, 24.7, 24.9, 25.9, 26.0, 30.0, 31.3, 33.0, 34.3, 51.6, 54.5,
55.3, 57.8, 60.5, 104.6, 149.7; MS m/ z 276 (M+, <1), 126 (35),
55 (81), 41 (100).
mainly decomposed by initial LiH elimination which
finally resulted in the formation, although with low
yields, of dimeric or cyclodimeric products depending on
the reaction time. In contrast, the similar 1,3-dilithio
derivatives prepared from aromatic allylamines decom-
posed by proton abstraction from the solvent upon
warming to 65 °C.
Exp er im en ta l Section
Gen er a l P r oced u r es. General experimental techniques
and analytical measurements were applied as previously
described.1 2-(Tributylstannyl)allylamines 4 were synthesized
as previously reported.1 N-(2-Bromoallyl)aniline 2015 and
PhLi16 were prepared according to literature procedures. The
level of purity of compounds is indicated by the inclusion of
copies of NMR spectra presented in the supporting informa-
tion.
(2R*,3R*)-1-(4,4-Dieth oxybu tyl)-3-[(4,4-d ieth oxybu tyl)-
a m in o]-2-m eth yl-4-m eth ylen ep yr r olid in e (9d ): yellow oil;
1
Rf 0.31 (AcOEt:THF, 10:1); H NMR δ 0.89 (d, 3H), 1.13 (t, J
) 7 Hz, 12H), 1.45-1.65 (m, 9H), 2.21 (m, 1H), 2.49 (m, 1H),
2.63 (m, 2H), 2.84 (m, 1H), 3.05 (d, J ) 14.5 Hz, 1H), 3.42,
3.57 (2m, 10H), 4.43 (t, J ) 5.1 Hz, 2H), 4.90 (m, 2H); 13C NMR
δ 9.7, 15.2, 23.2, 25.3, 31.3, 31.4, 46.8, 52.4, 55.7, 60.9, 61.0,
63.7, 102.6, 102.7, 106.0, 148.6; MS m/ z 400 (M+, 1), 98 (64),
71 (62), 47 (76).
Gen er a l P r oced u r e for th e Th er m a l Tr ea tm en t of
Or ga n olith iu m s 3. To a solution of the corresponding
2-(tributylstannyl)allylamine 4 (5 mmol) in THF (30 mL)
cooled at -60 °C was added BuLi (2.5 M in hexane, 10 mmol)
dropwise. The resulting solution was stirred for 2 h at -60
°C and 2 h at rt and then was refluxed for 2-4 h (the reaction
time for each case is indicated in Table 1). The reaction
mixture was quenched with D2O (3 mL) and, after being stirred
for 10-15 min, was treated with 2 N H2SO4 and extracted with
ether to remove Bu4Sn. The aqueous layer was neutralized
with 2 N NaOH and extracted with ether. The organic phase
was dried and concentrated in vacuo, and the resulting crude
material was purified either by flash column chromatography
on silica gel (in this case, Rf is reported with the eluent solvent
used in the column in each case) or by distillation (in this case,
bp is given at the corresponding pressure). Yields are listed
in Table 1. Compounds 5e and 6c have been previously
described.1 Compounds 5c,d ,f are known as their 2-deuterio-
allyl derivatives and were compared with those samples.1,17
The analytical data of products 7-9 are as follows.
(2R*,3R*)-1-(2-P h en yleth yl)-3-[(2-p h en yleth yl)a m in o]-
2-m eth yl-4-m eth ylen ep yr r olid in e (9f): yellow oil; Rf 0.33
(hexane:AcOEt, 1:1); 1H NMR δ 0.85 (d, 3H), 1.30-1.70 (broad
signal, 1H), 2.50 (m, 1H), 2.75-2.95 (m, 8H), 3.11 (d, J ) 14.6
Hz, 1H), 3.39 (m, 2H), 4.89 (s, 2H), 7.25 (m, 5H); 13C NMR δ
9.6, 34.7, 36.5, 48.8, 54.7, 55.8, 60.9, 63.8, 106.3, 125.9, 126.0,
128.2, 128.5, 128.6, 140.1, 140.4, 148.6; MS m/ z 320 (M+, <1),
173 (66), 148 (72), 82 (100).
Rea ction of Or ga n olith iu m 3a w ith P h Li. To a solution
of N-butyl-2-(tributylstannyl)allylamine (4a , 2.0 g, 5 mmol) in
THF (30 mL) cooled at -60 °C was added BuLi (2.5 M in
hexane, 4 mL, 10 mmol) dropwise. The resulting solution was
stirred for 2 h at -60 °C and then 2 h at rt. To this was added
phenyllithium (1.25 M in ether, 40 mL, 50 mmol) at rt. The
mixture was heated under reflux for 3 h and then treated with
D2O (3 mL). After being stirred for 10-15 min, the reaction
mixture was treated with 2 N H2SO4 and extracted with ether
to remove Bu4Sn. The aqueous layer was neutralized with 2
N NaOH and extracted with ether. The organic phase was
dried and concentrated in vacuo, and the resulting crude
material was purified by flash column chromatography on
silica gel (Rf is reported with the eluent solvent used in the
column). This reaction yielded 7a , described above, and the
following compounds. Yields are reported in Scheme 4.
N-Bu tyl-2-d eu ter io-1-p h en yla llyla m in e (17): clear oil; Rf
6-Eth en yl-7-m eth ylen e-5,9-d ia za tr id eca n e (7a ): yellow
1
oil; Rf 0.20 (AcOEt:THF, 2:1); H NMR δ 0.90, 0.91 (2t, J )
7.3 Hz, 6H), 1.25-1.50 (m, 10H), 2.55 (m, 4H), 3.22 (AB q, ∆υ
) 17.0, J ) 14.8 Hz, 2H), 3.64 (d, J ) 7.3 Hz, 1H), 5.05-5.20
(m, 4H), 5.75 (m, 1H); 13C NMR δ 13.9, 20.3, 31.8, 32.1, 47.0,
48.9, 51.9, 65.8, 111.9, 115.5, 139.5, 147.4; MS m/ z 223 (M+
- 1, <1), 109 (24), 108 (100), 79 (29), 41 (24).
4 -E t h e n y l -5 -m e t h y l e n e -1 ,9 -d i p h e n y l -3 ,7 -d i a z a -
1
1
0.59 (hexane:THF, 10:1); H NMR δ 0.90 (t, J ) 7.2 Hz, 3H),
n on a n e (7f): yellow oil; Rf 0.43 (AcOEt:THF, 5:1); H NMR
1.30-1.70 (m, 5H), 2.45-2.65 (m, 2H), 4.18 (s, 1H), 5.10-5.20
(2s, 2H), 7.20-7.40 (m, 5H); 13C NMR δ 13.7, 20.2, 32.0, 47.0,
66.0, 114.4, 126.7, 126.9, 128.1, 140.7 (t, J ) 23.5 Hz), 142.8;
MS m/ z 190 (M+, 2), 147 (16), 118 (100), 116 (21).
δ 1.12-1.61 (broad signal, 2H), 2.71 (m, 8H), 3.09 (AB q, ∆υ
) 13.85, J ) 14.4 Hz, 2H), 3.52 (d, J ) 7.3 Hz, 1H), 4.90-5.10
(m, 4H), 5.61 (m, 1H), 7.00-7.20 (m, 10H); 13C NMR δ 36.2,
48.4, 50.4, 51.6, 65.3, 111.6, 115.6, 125.9, 128.3, 128.6, 139.4,
139.9, 147.5.
1,5-Dicycloh exyl-2-(1-d eu t er ioet h en yl)-3-m et h ylen e-
1,5-d ia za p en ta n e (8c): colorless oil; Rf 0.36 (THF); 1H NMR
δ 1.00-1.90 (m, 22H), 2.35 (m, 2H), 3.18 (AB q, ∆υ ) 20.8, J
) 14.6 Hz, 2H), 3.75 (s, 1H), 5.00 (m, 4H); 13C NMR δ 24.8,
24.9, 26.0, 33.3, 33.4, 33.5, 33.6, 48.9, 53.0, 55.9, 61.6, 111.1,
6-E t h en yl-8-p h en yl-7-m et h ylen e-5,9-d ia za t r id eca n e
1
(18): yellow oil; Rf 0.29 (hexane:THF, 10:1); H NMR δ 0.93
(m, 6H), 1.21-1.52 (m, 8H), 2.21-2.52 (m, 6H), 3.53 (d, J )
7.1 Hz, 1H), 4.30 (s, 1H), 5.05-5.25 (m, 4H), 5.72 (m, 1H),
7.20-7.51 (m, 5H); 13C NMR δ 13.9, 20.3, 20.4, 31.9, 32.2, 46.8,
47.5, 63.6, 65.8, 112.5, 114.8, 126.8, 128.0, 128.2, 140.0, 142.3,
151.8; MS m/ z 300 (M+, <1), 227 (77), 226 (45), 184 (100),
170 (45).
(15) D’Amico, J . J .; Harman, M. W.; Cooper, R. H. J . Am. Chem.
Soc. 1957, 79, 5270.
(16) Nobis, J . F.; Moormeier, L. F. Ind. Eng. Chem. 1954, 46, 539.
(17) For 5d see the supporting information.
Th er m a l Tr ea tm en t of Or ga n olith iu m 2a . To a solution
of N-(2-bromoallyl)aniline (20, 1.06 g, 5 mmol) in ether (25
mL) was added BuLi (2.5 M in hexane, 2 mL, 5 mmol) at -80

Cyclodimerization of C,N-Dilithioallylamine Derivatives
J . Org. Chem., Vol. 61, No. 11, 1996 3757
°C. After being stirred for 20 min at this temperature, the
reaction mixture was treated with t-BuLi (1.7 M in pentane,
5.9 mL, 10 mmol) dropwise. The resulting solution was stirred
for 1.5 h at -80 °C and then 1.5 h at rt. Solvents were
removed under reduced pressure (0.1 mmHg), and the residue
was dissolved in 25 mL of dry THF. This reaction mixture
was refluxed for 2 h and then treated with D2O (3 mL) with
stirring for 10-15 min. The reaction was hydrolyzed with H2O
and extracted with ether. The organic phase was dried and
concentrated in vacuo, and the resulting crude material was
purified by distillation (0.1 mmHg) to give 0.59 g (90%) of
N-allylaniline (21).18
Ack n ow led gm en t. This work was supported by the
Direccio´n General de Investigacio´n Cient´ıfica y Te´cnica
(DGICYT, PB92-1005). R.-M.C. thanks the Ministerio
de Educacio´n y Ciencia for a predoctoral fellowship. Dr.
P. Bernad is acknowledged for expert assistance in mass
spectral analysis.
Su p p or tin g In for m a tion Ava ila ble: Analytical data of
the 2-deuterioallyl derivative of 5d . Copies of 1H and 13C NMR
spectra of 7a ,f, 8c, 9a -d ,f, 17, and 18 (11 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.
(18) Barluenga, J .; Foubelo, F.; Fan˜ana´s, F. J .; Yus, M. J . Chem.
Soc., Perkin Trans. 1 1989, 553.
J O960048O