Zirconium-mediated intramolecular coupling reactions of unsaturated anilines. Diastereoselective synthesis of azetidines

Article abstract of DOI:10.1021/jo9705780

Imine complexes of zirconocene, generated by a β-hydrogen abstraction process, which possess a carbon-carbon multiple bond, undergo inter- or intramolecular carbometalation to afford 1,4-cyclohexanediamine or cycloalkylaniline derivatives depending on the relative position of the unsaturated moiety with respect to the imine complex. A new diastereoselective synthesis of azetidines has been developed by treatment of azazirconacyclopentanes with iodine.

Full text of DOI:10.1021/jo9705780

J . Org. Chem. 1997, 62, 5953-5958
5953
Zir con iu m -Med ia ted In tr a m olecu la r Cou p lin g Rea ction s of
Un sa tu r a ted An ilin es. Dia ster eoselective Syn th esis of Azetid in es
J ose´ Barluenga,* Roberto Sanz, and Francisco J . Fan˜ana´s
Instituto Universitario de Quı´mica Organometa´lica “Enrique Moles”-Unidad Asociada al CSIC,
J ulia´n Claver´ıa, 8, Universidad de Oviedo, 33071 Oviedo, Spain
Received March 31, 1997X
Imine complexes of zirconocene, generated by a â-hydrogen abstraction process, which possess a
carbon-carbon multiple bond, undergo inter- or intramolecular carbometalation to afford 1,4-
cyclohexanediamine or cycloalkylaniline derivatives depending on the relative position of the
unsaturated moiety with respect to the imine complex. A new diastereoselective synthesis of
azetidines has been developed by treatment of azazirconacyclopentanes with iodine.
In tr od u ction
proton source,11 and further productive elaborations of
the resulting azazirconacyclopentanoids have not yet
been developed. Otherwise, when the C-H activation
route was applied to allylic amines, 1-azadiene complexes
of zirconocene12 were obtained by rearrangement of the
initially formed η2-imine complexes. In this context, we
have recently reported13 the synthesis of 4-substituted
1-aza-1,3-dienes from simple allylic amines by oxidation
of the azazirconacyclopentene intermediates. However,
η2-imine complexes, generated by C-H abstraction of
unsaturated amines other than allyl amines, have not
been described, and only two examples of bicyclization
of unsaturated imines promoted by zirconocene5 or di-
isopropoxy(η2-propene)titanium have been reported.14
On the other hand, although azetidines are an impor-
tant class of four-membered heterocyclic compounds, no
natural products or industrial processes provide a source
of them as starting materials for synthesis.15 The most
important method of azetidine synthesis is cyclization of
open-chain compounds by formation of the C-N bond.16
A few azetidines have been obtained by cycloaddition
methods17 and occasionally by rearrangement of larger
rings.18
Zirconocene η2-imine complexes (zirconaziridines) are
useful carbometalating reagents for unactivated alkenes
and alkynes.1 The formation of these complexes has been
achieved by different routes. The C-H activation from
methylzirconocene amides1,2 is the most used method,
and this reaction is thought to proceed by a concerted
cyclometalation via a four-membered transition state.3
The second way to obtain azazirconacyclopropanes is the
treatment of imines,4 or their derivatives,5 with 1 equiv
of zirconocene in a ligand-exchange reaction. A more
special method is the rearrangement of cyclic (iminoacyl)-
zirconocene complexes generated by the insertion of
phenyl isocyanide into bicyclic zirconabicyclopentanes6
or zirconabicyclopentenes.7 In addition, treatment of a
η2-iminosilaacyl complex with LiEt3BH gives silyl-
substituted azazirconacyclopropanes.8 These imine com-
plexes have been trapped with alkenes, alkynes, allenes,
and carbonyl compounds and recently with isocyanates9
to give azazirconacycles, which afford elaborated amine
derivatives upon protic workup. Remarkably, the forma-
tion of allylic amines was rendered asymmetric by
replacement of zirconocene dichloride by a chiral equiva-
lent and further insertion of alkynes in the imine
complexes.10 As far as we know, in all the examples
reported in the literature, organic products were obtained
free from the metal by treatment of the complex with a
In the present paper, we report the inter- or intramo-
lecular coupling reactions of η2-imine zirconocene com-
plexes bearing a carbon-carbon triple or double bond to
afford 1,4-cyclohexanediamine or cycloalkylaniline de-
rivatives depending on the relative position of the
unsaturated moiety with respect to the imine complex.
X Abstract published in Advance ACS Abstracts, J uly 15, 1997.
(1) (a) Buchwald, S. L.; Watson, B. T.; Wannamaker, M. W.; Dewan,
J . C. J . Am. Chem. Soc. 1989, 111, 4486. (b) Coles, N.; Whitby, R. J .;
Blagg, J . Synlett 1990, 271. (c) Coles, N.; Whitby, R. J .; Blagg, J .
Synlett 1992, 143.
(2) (a) Reaction of Cp2ZrCl2 with t-BuLi affords, after rearrange-
ment, Cp2Zr(i-Bu)Cl, which may be used in situ as a Cp2Zr(Me)Cl
equivalent: Buchwald, S. L.; Watson, B. T.; Barr, K. J . Tetrahedron
Lett. 1991, 32, 5465. (b) Harris, M. C. J .; Whitby, R. J .; Blagg, J .
Tetrahedron Lett. 1994, 35, 2431.
(3) Structure-reactivity correlations for the formation of zircona-
ziridines have been reported: Coles, N.; Harris, M. C. J .; Whitby, R.
J .; Blagg, J . Organometallics 1994, 13, 190.
(4) Ito, H.; Taguchi, T.; Hanzawa, Y. Tetrahedron Lett. 1992, 33,
4469.
(11) A synthesis of pyrroles by treatment of N-silylazazirconacyclo-
pentenes with carbon monoxide has been reported: Buchwald, S. L.;
Wannamaker, M. W.; Watson, B. T. J . Am. Chem. Soc. 1989, 111, 776.
(12) Davis, J . M.; Whitby, R. J .; J axa-Chamiec, A. J . Chem. Soc.,
Chem. Commun. 1991, 1743. (b) Sholz, J .; Nolte, M.; Kru¨ger, C. Chem.
Ber. 1993, 126, 803.
(13) Barluenga, J .; Sanz, R.; Gonza´lez, R.; Fan˜ana´s, F. J . J . Chem.
Soc., Chem. Commun. 1994, 989.
(14) Gao, Y.; Harada, K.; Sato, F. Chem. Commun. 1996, 533.
(15) Moore, J . A.; Seelig Ayers, R. In The Chemistry of Heterocyclic
Compounds. Small Ring Heterocycles; Hassner, A., Ed.; J ohn Wiley
and Sons: New York, 1982; Vol. 42, Part 2.
(5) J ensen, M.; Livinghouse, T. J . Am. Chem. Soc. 1989, 111, 4495.
(6) Davis, J . M.; Whitby, R. J .; J axa-Chamiec, A. Tetrahedron Lett.
1992, 33, 5655.
(7) (a) Davis, J . M.; Whitby, R. J .; J axa-Chamiec, A. Synlett 1994,
110. (b) Davis, J . M.; Whitby, R. J .; J axa-Chamiec, A. Tetrahedron
Lett. 1994, 35, 1445.
(8) (a) Honda, T.; Satoh, S.; Mori, M. Organometallics 1995, 14, 1548.
(b) Honda, T.; Mori, M. J . Org. Chem. 1996, 61, 1196.
(9) Gately, D. A.; Norton, J . R.; Goodson, P. A. J . Am. Chem. Soc.
1995, 117, 986.
(10) Grossman, R. B.; Davis, M. D.; Buchwald, S. L. J . Am. Chem.
Soc. 1991, 113, 2321.
(16) Synthesis of N-arylazetidines: (a) Bird, R.; Knipe, A. C.;
Stirling, C. J . M. J . Chem. Soc., Perkin Trans. 2 1973, 1215. (b) Gogte,
V. N.; Kulkarni, S. B.; Tilak, B. D. Tetrahedron Lett. 1973, 1867. (c)
Tilak, B. D.; Gogte, V. N. Heterocycles 1977, 7, 1339.
(17) (a) Delyagina, N. I.; Dyatkin, B. L.; Knunyants, I. L. Zh. Org.
Khim. 1974, 10, 935. (b) Schaumann, E.; Mrotzek, H. Tetrahedron
1979, 35, 1965.
(18) (a) Chen, T.-Y.; Sanjiki, T.; Kato, H.; Ohta, M. Bull. Chem. Soc.
J pn. 1967, 40, 2398. (b) Banks, R. E.; Haszeldine, R. N.; Matthews,
V. J . Chem. Soc. C 1967, 2263. (c) Banks, R. E.; Haszeldine, R. N.;
Barlow, M. G. J . Chem. Soc. 1965, 6149. (d) Kaminsky, L. S.;
Lamchem, M. J . Chem. Soc. C 1966, 2295.
S0022-3263(97)00578-1 CCC: $14.00 © 1997 American Chemical Society

5954 J . Org. Chem., Vol. 62, No. 17, 1997
Barluenga et al.
Sch em e 1a
F igu r e 1.
moieties in pseudoequatorial position. Likewise, the
formation of diastereoisomers 6 and 7 starting from
homoallylaniline 4a can be explained by assuming the
intermolecular approach of the zirconocene η2-imine
complex 5a according to the two possibilities outlined as
II and III in Figure 1, which furnishes the symmetric
cyclohexanediamine derivative 6, with all the susbstitu-
ents in equatorial position, and 7, having the two amino
groups in equatorial and the two methyl groups in axial
positions. However, the different behavior of 4a and 4b
could be understood if we assume that the dimerization
of η2-imine complexes 5 is very sensitive to steric effects.
When the R-position to the nitrogen is substituted the
intermolecular reaction is not allowed. In this case,
â-hydride transfer to the metal from the unstabilized η2-
imine complex occurs to generate the amidezirconocene
hydride 8. This complex undergoes an intramolecular
hydrozirconation giving rise to 9 (Scheme 1). Whitby et
al. have reported the formation of an (η3-1-azaallyl)zir-
conocene hydride from zirconocene η2-imine complexes
in the absence of a trap.3
Im in e Com p lexes fr om Hexen yl- a n d Hep ten yl-
a m in es. Reaction of a THF solution of N-[6-(trimethyl-
silyl)-5-hexynyl]aniline (11) with butyllithium at -40 °C
followed by treatment with zirconocene methyl chloride
at -78 °C yielded the azazirconacyclopentene 12 upon
warming to room temperature and further refluxing (67
°C) for 3 h. The zirconacycle 12 was characterized by
hydrolysis to the corresponding N-cyclopentylaniline
derivative 13, which was isolated in 79% yield. The same
procedure was then applied to 5-hexenylanilines 14a ,b.
Insertion of the double bonds in the zirconaziridines
readily proceeded to generate the corresponding zircon-
abicycles 15a ,b, which were characterized by deuterioly-
sis or hydrolysis. N-Cyclopentylaniline derivatives 16a
and 16b were isolated in 78 and 83% yield, respectively,
after purification. The formation of six-membered rings
under the same reaction conditions was also possible
starting from N-(1-phenyl-6-heptenyl)aniline (14c). In
this case, N-cyclohexylaniline derivative 16c was ob-
tained in 78% yield. A noteworthy fact is that the
coupling of ketimine complexes from amines 14b ,c
provides a convenient method for the synthesis of cyclo-
alkylamines with stereoselective formation of a new
quaternary center (16b,c). In this context, the treatment
of N-(2-allylbenzyl)aniline (18) under the reaction condi-
tions described above afforded azazirconatricyclopentane
19, which yielded N-indanylaniline derivative 20 in 82%
a
Reagents and conditions: (i) n-BuLi, -40 °C; (ii) Cp2Zr(Me)Cl,
-78 to 67 °C; (iii) H2SO4 (D2SO4), 20 °C; (iv) O2, 20 °C.
We also describe a simple and straightforward synthesis
of azetidines by treatment of azazirconacyclopentanes
with iodine, which could be seen as a formal [2 + 2]
cycloaddition between alkenes and imines.
Resu lts a n d Discu ssion
Im in e Com p lexes fr om Hom oa llyl- a n d Hom op r o-
p a r gyla n ilin es. Successive treatment of N-(3-pentyn-
yl)aniline (1) in THF with 1 equiv of butyllithium at -40
°C and zirconocene methyl chloride at temperatures
ranging between -78 and 20 °C followed by refluxing (67
°C) for 3 h led, after hydrolysis or deuteriolysis and
further purification, to the 1,4-cyclohexanediamine de-
rivatives 3 as a single diastereoisomer in 41% yield
(Scheme 1). When the reaction was carried out with
N-(3-butenyl)aniline (4a ) under the same reaction condi-
tions, the diastereoisomeric 1,4-cyclohexanediamines, 6
and 7, were isolated as a 1:1 mixture in 57% yield after
column chromatography. The structure of both diaste-
reoisomers was determined on the basis of their spec-
troscopic data. Compound 6 has all the substituents in
equatorial position and, although the other isomer could
not be obtained in a pure form, the stereochemistry
shown in Scheme 1 could be assigned to it. However,
starting from N-(1-phenyl-3-butenyl)aniline (4b), no in-
termolecular coupling occurred and the azazirconacyclo-
pentene 9 was detected by NMR. Oxidation of this
intermediate, according to our previously reported meth-
odology,13 afforded the 1-aza-1,3-diene 10 as a mixture
of diastereoisomers (Scheme 1). It is important to note
that these ketimines are not easy to obtain since the
treatment of R,â-unsaturated ketones with primary
amines affords Michael addition products.19
The diastereoselective formation of diamine 3 is inter-
preted by considering the intermolecular approach of two
previously formed zirconocene η2-imine complexes 2
outlined as I in Figure 1, which leads, after hydrolysis,
to the cyclohexane derivative 3 with both phenylamino
(19) Dayagi, S.; Degani, Y. In The Chemistry of the Carbon-Nitrogen
Double Bond; Patai, S., Ed.; J ohn Wiley and Sons: New York, 1970;
Chapter 2.

Diastereoselective Synthesis of Azetidines
J . Org. Chem., Vol. 62, No. 17, 1997 5955
Sch em e 2a
Sch em e 3a
a
Reagents and conditions: (i) n-BuLi, -40 °C; (ii) Cp2Zr(Me)Cl,
-78 to 0 °C; (iii) R2CHdCH2 (R2 ) Et, nBu, (CH2)4I, CH2N(Me)Ph,
CH2TMS), 0-67 °C; (iv) I2, 20 °C; (v) K2CO3, H2O, 60 °C; (vi)
norbornene, 0-67 °C.
Ta ble 1. P r ep a r a tion of Azetid in es 23-25, 27, a n d 28
fr om Zir con iu m -Med ia ted In ter m olecu la r Cou p lin g of
Am in es 21 or 26 a n d Ter m in a l Alk en es
starting
amine
alkene
yielda
(%)
a
Reagents and conditions: (i) n-BuLi, -40 °C; (ii) Cp2Zr(Me)Cl,
R
R1
R2CHdCH2
product
-78 to 67 °C; (iii) H2SO4 (D2SO4), 20 °C; (iv) I2, 20 °C; (v) K2CO3,
H2O, 60 °C.
21a
21a
21a
21b
21b
21c
21c
21c
21d
21e
21a
26
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me Bu
23a
23b
82
Me (CH2)4I
Me CH2N(Me)Ph 23c
73
79
77
76
68
72
62
80
78
Pr
Pr
Ph Et
Bu
23d
23e
23f
23g
23h
23i
23j
CH2TMS
Ph Bu
Ph (CH2)4I
Me Bu
4-MeOC6H4 Me Bu
Ph Me Norbornene
Bu
4-MeC6H4
24 + 25b 55 + 27
27/28
69
a
b
Isolated yield based on the starting amine 21 or 26. Easily
separated by flash column chromatography.
F igu r e 2.
of convenient routes to their synthesis is important. The
regio- and diastereoselective coupling of N-aryl and
N-silylzirconaziridines with terminal alkenes has been
reported.1 This reaction is synthetically equivalent to the
regio- and diastereoselective addition of an R-amino
carbanion to an unactivated terminal olefin. However,
few synthetic applications of this interesting reaction
have been reported.21 The successive treatment of amines
21 with butyllithium at -40 °C and zirconocene methyl
chloride at temperatures ranging between -78 and 0 °C
and further addition of the corresponding terminal alkene
afforded azazirconacyclopentane derivatives 22 upon
warming to room temperature for R1 ) Ph (67 °C for R1
) alkyl). Intermediates 22 were in situ treated first with
iodine to cleave the zirconium-carbon bond and then
with aqueous potassium carbonate, furnishing azetidines
23 in good yield (Scheme 3 and Table 1). The relative
configuration of the substituents in the ring was expected
to be trans on the basis of previously reported carbo-
yield after hydrolysis and silica gel chromatography
(Scheme 2). In contrast with the results reported in the
literature14 for the nondiastereoselective titanium-medi-
ated bicyclization of olefinic imines, we have obtained
only the cis diastereoisomer in all cases, probably because
of the successive formation of the imine complex and the
alkene insertion. This was supported by NOE experi-
ments on 16 and 20. Results on aniline 16a are given
in Figure 2.
In order to extend the synthetic utility of this kind of
azazirconacycles, a solution of 15a was treated with 2
equiv of iodine at room temperature. The basic workup
afforded a mixture of the bicyclic azetidine 17a and the
corresponding iodide precursor. Warming the mixture
in an aqueous solution of K2CO3 for several hours led to
a complete consumption of the open product and allowed
the isolation of 17a in 68% yield (Scheme 2). Again, only
the cis diastereoisomer was obtained as shown by NOE
experiments on 17a (Figure 2).
When the reaction with iodine was applied to 15c, the
corresponding azetidine 17c was detected in the crude
but 1-phenylcyclohexene was isolated after silica gel
chromatography, probably due to a retro [2 + 2] cycload-
dition.
(20) Two different syntheses of diastereo- and enantiomerically pure
azetidines have been recently reported by our group: (a) Barluenga,
J .; Ferna´ndez-Mar´ı, F.; Viado, A.-L.; Aguilar, E.; Olano, B. J . Org.
Chem. 1996, 61, 5659. (b) Barluenga, J .; Baragan˜a, B.; Concello´n, J .
M. J . Org. Chem. 1997, in press.
(21) A convergent synthesis of five- to seven-membered-ring N-
heterocycles has been reported: Harris, M. C. J .; Whitby, R. J .; Blagg,
J . Tetrahedron Lett. 1995, 36, 4287.
Syn th esis of Azetid in es. Since azetidines are het-
erocyclic compounds of great interest,20 the development

5956 J . Org. Chem., Vol. 62, No. 17, 1997
Barluenga et al.
metalation of alkenes by zirconaziridines1 and it was
further supported by NOE experiments. Figure 2 shows
the results for azetidine 23f.
As shown in Scheme 3, several kinds of terminal
olefines could be used. It is interesting to note that when
6-iodo-1-hexene was used, the imine complex selectively
attacked the alkene rather than the alkyl iodide. More-
over, further ring closure of the corresponding diiodide
led chemoselectively to the formation of the four-
membered ring instead of the corresponding azepine
derivative.
However, when norbornene was used as unsaturated
substrate, two diastereoisomeric azetidines 24 and 25 in
a 2:1 ratio were isolated, whose stereochemistry was
assigned on the basis of NOE experiments. In order to
test the scope of this transformation with respect to the
starting amine, we tried the reaction with N-isopropyl-
aniline 26 in the same reaction conditions as described
above. In this case, two regioisomeric azetidines 27 and
28 were isolated as a 1.2:1 mixture. The insertion of the
alkene was not regioselective, probably due to the steric
hindrance of the two methyl groups in the imine complex,
avoiding the R group of the olefin to accommodate, as
well as in the other cases, at the â-position of the
azazirconacycle (Scheme 3).
In conclusion, we have described the inter- or intramo-
lecular insertion reactions of unsaturated aromatic imine
complexes. The outcome of this process depends on the
relative position of the carbon-carbon multiple bond with
respect to the imine complex. Moreover, we have devel-
oped a useful and diastereoselective synthesis of aze-
tidines that expands the synthetic applications of aza-
zirconacycles. This reaction could be seen as a formal
regio- and diastereoselective [2 + 2] cycloaddition be-
tween an imine and an alkene that is usually difficult to
carry out and occurs only in the presence of substituents
that impart a high degree of polarization.
toluene a mixture of benzaldehyde and aniline in presence of
a catalytic amount of p-toluenesulfonic acid in a system
equipped with a Dean-Stark trap; 5-hexynol and 3-pentynol
were tosylated with p-toluenesulfonic chloride and KOH in
Et2O;23 secondary starting amines 1, 4a , 11, 14a , 21, and 26
were prepared by warming 2 equiv of the primary arylamine
with the corresponding bromide, iodide, or tosylate in water;
amines 4b and 14b,c were synthesized by reaction of ben-
zylideneaniline with the corresponding Grignard reagent in
THF. Amine 18 was synthesized by treatment of the dianion
generated from N-benzylaniline with n-BuLi in the presence
of TMEDA24 with 0.5 equiv of CuCN and further addition of
allyl chloride.
P r ep a r a tion of Cycloh exyld ia m in es 3, 6, a n d 7. Gen -
er a l P r oced u r e. A solution of the starting amine 1 or 4a (2
mmol) in 10 mL of THF was treated with n-BuLi (2 mmol) at
-40 °C. The reaction was stirred for 30 min and then was
added to a solution of Cp2Zr(Me)Cl (0.57 g, 2.1 mmol) in 10
mL of THF at -78 °C. The mixture was stirred for 30 min
and then the bath was removed, allowing the reaction to
achieve room temperature for several hours. The resulting
solution was refluxed in THF for 3 h, cooled to 0 °C, and
treated with H2SO4 (2 N) or D2SO4 (2 N). The solvents were
removed at reduced pressure, and the residue was dissolved
in ethyl acetate (3 × 20 mL) and filtered through Celite.
Extraction with ethyl acetate and saturated NaHCO3 aqueous
solution afforded the organic layer, which was dried over
Na2SO4 and filtered. Solvents were removed under reduced
pressure, and the crude residue was chromatographed on silica
gel.
(1R,4S)-2,5-Bis[(E)-1-d eu ter ioeth ylid en e]-N,N′-d ip h en -
yl-1,4-cycloh exa n ed ia m in e (3D): Rf ) 0.26 (Hex:AcOEt, 15:
1
1); H NMR (CDCl3, 300 MHz) δ 7.2-6.6 (m, 10 H), 4.0-3.8
(m, 4 H), 2.6 (dd, J ) 14.3, 2.6 Hz, 2 H), 2.3 (dd, J ) 14.3, 7.0
Hz, 2 H), 1.6 (s, 6 H); 13C NMR (CDCl3, 75 MHz) δ 147.6, 137.5,
129.3, 120.4, 120.1, 119.8, 117.8, 114.2, 53.6, 30.8, 13.1; HRMS
calcd for C22H24D2N2 320.2221, found 320.2212.
(1R,4S)-2,5-Bis[(E)-et h ylid en e]-N,N′-d ip h en yl-1,4-cy-
cloh exa n ed ia m in e (3): Rf ) 0.26 (Hex:AcOEt, 15:1); 1H
NMR (CDCl3, 400 MHz) δ 7.1-6.6 (m, 10 H), 5.5 (q, J ) 6.9
Hz, 2 H), 3.9-3.7 (m, 4 H), 2.6 (dd, J ) 14.4, 2.6 Hz, 2 H), 2.3
(dd, J ) 14.4, 7.4 Hz, 2 H), 1.5 (d, J ) 6.9 Hz, 6 H); 13C NMR
(CDCl3, 50 MHz) δ 147.6, 137.6, 129.3, 120.4, 117.8, 114.2,
53.6, 30.8, 13.2; HRMS calcd for C22H26N2 318.2096, found
318.2084. Anal. Calcd for C22H26N2: C, 82.97; H, 8.23; N, 8.80.
Found: C, 82.74; H, 8.32; N, 8.69.
(1R,2R,4S,5S)-2,5-Dim et h yl-N,N′-d ip h en yl-1,4-cyclo-
h exa n ed ia m in e (6): Rf ) 0.24 (Hex:AcOEt, 10:1); mp 144-
146 °C; 1H NMR (CDCl3, 400 MHz) δ 7.3-6.6 (m, 10 H), 3.5 (s
broad, 2 H), 3.1 (dt, J ) 10.6, 3.7 Hz, 2 H), 2.3 (td, J ) 7.4, 3.6
Hz, 2 H), 1.6-1.5 (m, 2 H), 1.1 (d, J ) 6.6 Hz, 6 H), 1.1-1.0
(m, 2 H); 13C NMR (CDCl3, 50 MHz) δ 147.9, 129.2, 116.7,
112.8, 57.3, 41.3, 38.1, 19.0; IR (neat) 3410, 1600 cm-1; HRMS
calcd for C20H26N2 294.2096, found 294.2098. Anal. Calcd for
C20H26N2: C, 81.59; H, 8.90; N, 9.51. Found: C, 81.32; H, 8.75;
N, 9.21.
(1R,2S,4S,5R)-2,5-Dim et h yl-N,N′-d ip h en yl-1,4-cyclo-
h exa n ed ia m in e (7): Rf ) 0.20 (Hex:AcOEt, 7:1); 1H NMR
(CDCl3, 400 MHz) δ 7.3-6.6 (m, 10 H), 3.5 (s broad, 2 H), 3.1
(dt, J ) 10.6, 3.7 Hz, 2 H), 2.3 (td, J ) 7.4, 3.6 Hz, 2 H), 1.6-
1.5 (m, 2 H), 1.1 (d, J ) 6.6 Hz, 6 H), 1.1-1.0 (m, 2 H); 13C
NMR (CDCl3, 50 MHz) δ 147.5, 129.3, 116.8, 112.7, 52.6, 34.0,
33.2, 18.7; IR (neat) 3410, 1600 cm-1; HRMS calcd for C20H26N2
294.2096, found 294.2104.
1,2-Dip h en yl-1-a za p en ta -1,3-d ien e (10). N-(1-Phenyl-3-
butenyl)aniline (0.45 g, 2 mmol) in THF (10 mL) was cooled
to -40 °C and n-BuLi (2 mmol) added. The solution was
stirred for 30 min, and then it was added to a solution of
Cp2Zr(Me)Cl (0.57 g, 2.1 mmol) in THF (10 mL) at -78 °C.
The mixture was warmed to room temperature, and stirring
was continued for 3 h. Dry oxygen was bubbled through the
solution at 20 °C for 1 h. The solvents were removed at
Exp er im en ta l Section
Gen er a l Meth od s. Solvents were dried according to
established protocols by distillation under nitrogen from an
appropriate drying agent. Thus, THF was distilled from
sodium/benzophenone ketyl. Solvents used in extraction and
purification were distilled prior to use.
Compounds were visualized on analytical thin-layer chro-
matograms (TLC) by UV light (254 nm) or iodine. Silica gel
(230-400 mesh) was used for flash chromatography. NMR
spectra were recorded at 400, 300, and 200 MHz for proton
frequency and 100, 75, and 50 MHz for carbon frequency using
the DEPT pulse sequence. IR spectra were recorded as neat
samples. Elemental analyses were performed by the Micro-
analytical laboratory, Universidad de Oviedo. Mass Spectra
were usually carried out by electron impact at 70 eV. Only
the most significant IR absortions and the molecular ions and/
or base peaks in MS are given. Melting points are uncorrected.
Reactions requiring an inert atmosphere were conducted
under dry nitrogen, and the glassware was oven dried,
evacuated, and purged with nitrogen. Temperatures are
reported as bath temperatures.
Zirconocene dichloride, aniline, benzaldehyde, 4-bromo-1-
butene, allyl bromide, 6-bromo-1-hexene, 5-hexynol, iodine,
ethyl bromide, butyl bromide, isopropyl bromide, norbornene,
1-hexene, 1-butene, and allyltrimethylsilane were purchased
from Aldrich or Acros and were used without further purifica-
tion. n-BuLi was used as a 2.5 M solution in hexane.
Cp2Zr(Me)Cl was prepared according to a published proce-
dure.22 N-Benzylideneaniline was prepared by refluxing in
(23) Brandsma, L. Preparative Acetylenic Chemistry; Elsevier Sci-
ence Publishers B. V.: Amsterdam, 1988.
(24) Ludt, R. E.; Hauser, C. R. J . Org. Chem. 1971, 36, 1607.
(22) Wailes, P. C.; Weigold, H.; Bell, A. P. J . Organomet. Chem.
1971, 33, 181.

Diastereoselective Synthesis of Azetidines
J . Org. Chem., Vol. 62, No. 17, 1997 5957
reduced pressure, and the residue was dissolved in ethyl
acetate and filtered through Celite. After the addition of a
saturated aqueous solution of NaHCO3, the organic product
was extracted with ethyl acetate (3 × 20 mL). The combined
organic layers were dried (Na2SO4) and concentrated in vacuo.
Flash column chromatography over silica gel (15:1, hexane:
ethyl acetate) provided 0.3 g (68% yield) of azadiene 10 as a
mixture of diastereoisomers: Rf ) 0.35 (Hex:AcOEt, 10:1); 1H
NMR (CDCl3, 200 MHz) δ 8.0-6.6 (m, 10 H), 6.4-6.0 (m, 2
H), 2.0, 1.95 and 1.8 (3d, J ) 6.4, 7.0, 4.9 Hz, 3 H); 13C NMR
(CDCl3, 50 MHz) δ 168.7, 166.9, 150.9, 150.5, 144.8, 141.0,
140.4, 139.3, 135.5, 132.4, 129.4, 128.9, 128.6, 128.3, 128.1,
127.9, 127.6, 127.3, 125.5, 123.2, 122.8, 120.8, 120.1, 18.5, 18.4;
IR (neat) 1670, 1645 cm-1; HRMS calcd for C16H15N 221.1204,
found 221.1213. Anal. Calcd for C16H15N: C, 86.84; H, 6.83;
N, 6.33. Found: C, 86.55; H, 6.92; N, 6.05.
P r ep a r a tion of Cycloa lk yla n ilin es 13, 16, a n d 20. To
a stirred solution of the amines 11, 14, or 18 (2 mmol) in THF
(10 mL) was added n-BuLi (2 mmol) at -40 °C. The resulting
mixture was stirred at this temperature for 30 min and then
added to a solution of Cp2Zr(Me)Cl (0.57 g, 2.1 mmol) in THF
(10 mL) at -78 °C. The reaction mixture was stirred for 30
min while the temperature reached room temperature (warmed
to 67 °C for 11 and 14a ), and stirring was continued for 3 h.
After the mixture was quenched with H2O or D2O, the solvents
were removed in vacuo and the residue was dissolved in ethyl
acetate and then filtered through a short pad of Celite. The
filtrate was dried over Na2SO4 and concentrated at reduced
pressure. Purification by flash chromatography on silica gel
afforded the corresponding cycloalkylanilines 13, 16, and 20.
N-{2-[(E)-(Tr im eth ylsilyl)m eth ylen e]cyclop en tyl}a n i-
lin e (13): Rf ) 0.32 (Hex:AcOEt, 20:1); 1H NMR (CDCl3, 300
MHz) δ 7.2-6.6 (m, 5 H), 5.6 (dd, J ) 4.7, 2.15 Hz, 1 H), 4.1
(dd, J ) 7.3, 6.9 Hz, 1 H), 3.4 (s broad, 1 H), 2.5-1.4 (m, 6 H),
0.1 (s, 9 H); 13C NMR (CDCl3, 50 MHz) δ 162.3, 148.0, 129.1,
119.3, 116.8, 112.7, 59.7, 33.1, 30.9, 22.3, -0.5; IR (neat) 3415,
1600 cm-1; HRMS calcd for C15H23NSi: 245.1600, found
245.1596.
secondary amine 14a , 21, or 26 (2 mmol) in THF (10 mL) was
added n-BuLi (2 mmol) at -40 °C. The mixture was stirred
for 30 min at this temperature and then added to a solution
of Cp2Zr(Me)Cl (2.1 mmol) in THF (10 mL) at -78 °C. The
mixture was stirred while the temperature reached 0 °C, and
then the corresponding terminal alkene (2.1 mmol) was added.
The mixture was refluxed (67 °C) for 4 h to give a bright red
solution. After the mixture was cooled to room temperature,
iodine (4 mmol) was added and the red color rapidly dis-
charged. After the mixture was stirred for 1 h at room
temperature, an aqueous solution of K2CO3 was added, and
the reaction mixture was warmed at 60 °C overnight. The
mixture was poured into water (50 mL), and the organic
products were extracted in ethyl acetate (3 × 20 mL). The
combined extracts were washed with aqueous Na2S2O3, and
then with saturated aqueous NaHCO3, dried over Na2SO4, and
filtered. The solvents were removed by rotatory evaporation,
and the products were isolated by flash column chromatogra-
phy. Isolated yields of N-arylazetidines are reported in Table
1.
cis-6-P h en yl-6-a za bicyclo[3.2.0]h ep ta n e (17a ): Rf
)
0.32 (Hex:AcOEt. 15:1); 1H NMR (CDCl3, 200 MHz) δ 7.4-6.5
(m, 5 H), 4.6 (dd, J ) 5.4, 5.1 Hz, 1 H), 4.0 (dd, J ) 7.9, 7.3
Hz, 1 H), 3.6 (dd, J ) 7.3, 3.5 Hz, 1 H), 3.2-3.0 (m, 1 H), 2.2-
1.4 (m, 6 H); 13C NMR (CDCl3, 50 MHz) δ 149.5, 128.8, 115.8,
110.1, 68.9, 55.0, 34.1, 32.0, 30.6, 24.1. Anal. Calcd for
C12H15N: C, 83.19; H, 8.73; N, 8.08. Found: C, 82.88; H, 8.81;
N, 8.05.
tr a n s-3-Bu tyl-2-m eth yl-1-p h en yla zetid in e (23a ): Rf )
0.37 (Hex:AcOEt, 15:1); 1H NMR (CDCl3, 200 MHz) δ 7.3-6.6
(m, 5 H), 4.1 (t, J ) 7.2 Hz, 1 H), 3.7 (quint, J ) 6.2 Hz, 1 H),
3.2 (dd, J ) 7.2, 7.0 Hz, 1 H), 2.5-2.3 (m, 1 H), 1.6-1.3 (m, 6
H), 1.5 (d, J ) 6.2 Hz, 3 H), 1.0-0.9 (m, 3 H); 13C NMR (CDCl3,
50 MHz) δ 152.4, 128.7, 117.3, 111.6, 66.4, 55.8, 39.2, 33.5,
29.1, 22.5, 22.3, 13.9; IR (neat) 1600 cm-1; HRMS calcd for
C14H21N 203.1674, found 203.1662. Anal. Calcd for C14H21N:
C, 82.70; H, 10.41; N, 6.89. Found: C, 82.76; H, 10.32; N, 6.61.
tr a n s-3-(4-Iodobu tyl)-2-m eth yl-1-ph en ylazetidin e (23b):
Rf ) 0.31 (Hex:AcOEt, 15:1); 1H NMR (CDCl3, 200 MHz) δ 7.3-
6.6 (m, 5 H), 4.1 (t, J ) 7.3 Hz, 1 H), 3.8-3.7 (m, 1 H), 3.3-
3.2 (m, 3 H), 2.4-2.3 (m, 1 H), 1.9-1.8 (m, 2 H), 1.6-1.3 (m,
4 H), 1.5 (d, J ) 6.0 Hz, 3 H); 13C NMR (CDCl3, 50 MHz) δ
152.2, 128.7, 117.5, 111.7, 66.4, 55.7, 38.9, 33.0, 32.6, 27.7, 22.3,
6.8; IR (neat) 1600 cm-1. Anal. Calcd for C14H20IN: C, 51.08;
H, 6.12; N, 4.25. Found: C, 50.82; H, 6.21; N, 4.19.
cis-N-(2-Meth ylcyclop en tyl)a n ilin e (16a ): Rf ) 0.33
1
(Hex:AcOEt, 25:1); H NMR (CDCl3, 300 MHz) δ 7.2-6.6 (m,
5 H), 3.8-3.7 (m, 1 H), 3.7 (s broad, 1 H), 2.4-2.3 (m, 1 H),
2.1-1.4 (m, 6 H), 0.9 (d, J ) 7.3 Hz, 3 H); 13C NMR (CDCl3,
75 MHz) δ 148.1, 129.1, 116.5, 112.8, 57.0, 35.6, 31.8, 31.4,
21.1, 14.2; IR (neat) 3410, 1600 cm-1; HRMS calcd for C12H17
175.1361, found 175.1353.
N
(1R*,2S*)-N-[2-(Deu ter iom eth yl)-1-p h en ylcyclopen tyl]-
a n ilin e (16b): Rf ) 0.39 (Hex:AcOEt, 20:1); mp 86-88 °C;
1H NMR (CDCl3, 200 MHz) δ 7.6-6.5 (m, 10 H), 4.1 (s broad,
1 H), 2.7-1.6 (m, 7 H), 1.0 (d, J ) 6.4 Hz, 2 H); 13C NMR
(CDCl3, 50 MHz) δ 145.5, 144.5, 128.5, 128.1, 126.1, 125.9,
116.5, 115.2, 67.5, 49.3, 35.1, 31.8, 21.8, 12.2, 11.9, 11.5; IR
(neat) 3440, 1600 cm-1; HRMS calcd for C18H20DN 252.1737,
found 252.1727. Anal. Calcd for C18H20DN: C, 85.66; H/D,
8.79; N, 5.55. Found: C, 85.28; H/D, 8.56; N, 5.25.
(1R*,2S*)-[2-(Deu ter iom eth yl)-1-ph en ylcycloh exyl]a n i-
lin e (16c): Rf ) 0.42 (Hex:AcOEt, 15:1); mp 57-59 °C; 1H
NMR (CDCl3, 300 MHz) δ 7.6-6.5 (m, 10 H), 4.0 (s broad, 1
H), 2.7 (dd, J ) 13.7, 2.0 Hz, 1 H), 2.1-1.4 (m, 8 H), 0.8-0.7
(m, 2 H); 13C NMR (CDCl3, 50 MHz) δ 145.4, 145.2, 128.4,
127.8, 127.0, 126.0, 116.7, 115.7, 61.0, 43.8, 30.9, 30.7, 26.0,
21.2, 15.7, 15.4, 15.0; IR (neat) 3430, 1600 cm-1; HRMS calcd
for C19H22DN 266.1893, found 266.1895. Anal. Calcd for
C19H22DN: C, 85.66; H/D, 9.08; N, 5.26. Found: C, 85.26; H/D,
8.79; N, 5.13.
tr a n s-2-Meth yl-3-[(N-m eth yl-N-p h en yla m in o)m eth yl]-
1-p h en yla zetid in e (23c): Rf ) 0.40 (Hex:AcOEt, 5:1); 1H
NMR (CDCl3, 300 MHz) δ 7.3-6.6 (m, 10 H), 4.1 (t, J ) 6.9
Hz, 1 H), 3.9-3.8 (m, 1 H), 3.6 (dd, J ) 14.6, 7.0 Hz, 1 H), 3.5
(dd, J ) 14.6, 6.9 Hz, 1 H), 3.4 (t, J ) 7.3 Hz, 1 H), 3.0 (s, 3
H), 2.9-2.7 (m, 1 H), 1.5 (dd, J ) 6.0, 1.3 Hz, 3 H); 13C NMR
(CDCl3, 75 MHz) δ 152.1, 149.1, 129.1, 128.8, 117.8, 116.7,
112.5, 111.8, 64.8, 55.5, 54.2, 38.7, 37.4, 21.9; IR (neat) 1600
cm-1; HRMS calcd for C18H22N2 266.1783, found 266.1783.
tr a n s-3-Bu tyl-1-p h en yl-2-p r op yla zetid in e (23d ): Rf )
0.39 (Hex:AcOEt, 15:1); 1H NMR (CDCl3, 200 MHz) δ 7.3-6.5
(m, 5 H), 4.1 (dd, J ) 7.4, 7.2 Hz, 1 H), 3.7-3.6 (m, 1 H), 3.2
(dd, J ) 7.1, 6.7 Hz, 1 H), 2.5-2.3 (m, 1 H), 2.0-1.2 (m, 10 H),
1.0 and 0.9 (2t, J ) 7.1 Hz, 6 H); 13C NMR (CDCl3, 50 MHz)
δ 152.4, 128.7, 117.1, 111.5, 70.4, 56.1, 38.6, 37.4, 34.4, 29.2,
22.5, 18.2, 14.3, 13.9; IR (neat) 1600 cm-1; HRMS calcd for
C16H25N 231.1987, found 231.1983. Anal. Calcd for C16H25N:
C, 83.06; H, 10.89; N, 6.05. Found: C, 82.79; H, 10.95; N, 6.08.
tr a n s-1-P h en yl-2-p r op yl-3-[(tr im eth ylsilyl)m eth yl]a ze-
1
cis-2-Meth yl-N-p h en yl-1-in d a n a m in e (20): Rf ) 0.30
tid in e (23e): Rf ) 0.42 (Hex:AcOEt, 15:1); H NMR (CDCl3,
1
(Hex:AcOEt, 15:1); H NMR (CDCl3, 300 MHz) δ 7.4-6.7 (m,
200 MHz) δ 7.3-6.5 (m, 5 H), 4.1 (dd, J ) 7.3, 7.0 Hz, 1 H),
3.7-3.6 (m, 1 H), 3.1 (dd, J ) 7.3, 7.0 Hz, 1 H), 2.6-2.4 (m, 1
H), 2.1-1.7 (m, 2 H), 1.6-1.4 (m, 2 H), 1.0 (t, J ) 7.0 Hz, 3
H), 1.0-0.7 (m, 2 H), 0.0 (s, 9 H); 13C NMR (CDCl3, 50 MHz)
δ 152.7, 128.7, 117.3, 111.9, 74.0, 58.2, 38.7, 34.1, 22.9, 18.0,
14.4, -1.3; IR (neat) 1600 cm-1; HRMS calcd for C16H27NSi
261.1913, found 261.1913.
9 H), 5.1 (d, J ) 6.5 Hz, 1 H), 4.0 (s broad, 1 H), 3.15 (dd, J )
15.5, 6.9 Hz, 1 H), 3.1-2.9 (m, 1 H), 2.7 (dd, J ) 15.5, 2.15
Hz, 1 H), 0.9 (d, J ) 7.3 Hz, 3 H); 13C NMR (CDCl3, 50 MHz)
δ 147.8, 143.2, 141.8, 129.2, 127.6, 126.5, 125.0, 124.0, 117.1,
112.8, 60.5, 38.3, 36.9, 14.3; IR (neat) 3405, 1600 cm-1; HRMS
calcd for C16H17N 223.1361, found 223.1359. Anal. Calcd for
C16H17N: C, 86.06; H, 7.67; N, 6.27. Found: C, 86.21; H, 7.52;
N, 6.13.
tr a n s-3-Eth yl-1,2-d ip h en yla zetid in e (23f): Rf ) 0.41
1
(Hex:AcOEt, 15:1); H NMR (CDCl3, 200 MHz) δ 7.6-6.5 (m,
P r ep a r a tion of Azetid in es 17, 23-25, 27, a n d 28.
Gen er a l P r oced u r e. To a solution of the corresponding
10 H), 4.6 (d, J ) 6.7 Hz, 1H), 4.2 (t, J ) 7.2 Hz, 1 H), 3.4 (dd,
J ) 7.2, 7.0 Hz, 1 H), 2.7-2.5 (m, 1 H), 1.9-1.6 (m, 2 H), 0.9

5958 J . Org. Chem., Vol. 62, No. 17, 1997
Barluenga et al.
(t, J ) 7.3 Hz, 3 H); 13C NMR (CDCl3, 50 MHz) δ 152.0, 143.1,
128.7, 128.6, 127.2, 125.9, 117.7, 112.0, 73.6, 55.2, 43.6, 26.8,
11.3; HRMS calcd for C17H19N 237.1520, found 237.1518.
tr a n s-3-Bu tyl-1,2-d ip h en yla zetid in e (23g): Rf ) 0.42
1.3 (m, 6 H), 1.3 (d, J ) 6.1 Hz, 3 H); 13C NMR (CDCl3, 75
MHz) δ 147.2, 129.0, 116.6, 112.4, 60.6, 52.7, 45.0, 38.8, 37.1,
33.8, 29.4, 27.9, 20.2; IR (neat) 1600 cm-1; HRMS calcd for
C
15H19N 213.1518, found 213.1512.
1
(Hex:AcOEt, 15:1); H NMR (CDCl3, 300 MHz) δ 7.6-6.5 (m,
(1R*,2S*,4S*,5S*,6S*)-4-Meth yl-3-p h en yl-3-a za tr icyclo-
10 H), 4.6 (d, J ) 6.5 Hz, 1 H), 4.3 (t, J ) 7.3 Hz, 1 H), 3.5 (dd,
J ) 7.3, 6.9 Hz, 1 H), 2.8-2.6 (m, 1 H), 1.9-1.4 (m, 6 H), 1.0
(t, J ) 6.5 Hz, 3 H); 13C NMR (CDCl3, 50 MHz) δ 152.0, 143.0,
128.7, 128.5, 127.2, 125.9, 117.7, 112.0, 73.8, 55.6, 42.1, 33.5,
[4.2.1.02,5]n on a n e (25): Rf ) 0.27 (Hex:AcOEt, 15:1); mp 80-
1
82 °C; H NMR (CDCl3, 300 MHz) δ 7.3-6.6 (m, 5 H), 4.3 (d,
J ) 7.3 Hz, 1 H), 3.4-3.3 (m, 2 H), 2.85 and 2.35 (2s, 2 H), 2.0
(d, J ) 9.2 Hz, 1 H), 1.6-1.2 (m, 8 H); 13C NMR (CDCl3, 75
MHz) δ 146.5, 128.9, 116.8, 113.5, 55.8, 53.0, 50.0, 40.2, 39.3,
34.9, 31.1, 28.1, 19.5; HRMS calcd for C15H19N 213.1518, found
213.1517. Anal. Calcd for C15H19N: C, 84.46; H, 8.98; N, 6.56.
Found: C, 84.28; H, 8.95; N, 6.46.
29.1, 22.5, 13.9; IR (neat) 1600 cm-1; HRMS calcd for C19H23
N
265.1830, found 265.1819. Anal. Calcd for C19H23N: C, 85.99;
H, 8.73; N, 5.28. Found: C, 85.75; H, 8.59; N, 5.35.
tr a n s-3-(4-Iod obu tyl)-1,2-d ip h en yla zetid in e (23h ): Rf
) 0.34 (Hex:AcOEt, 15:1); 1H NMR (CDCl3, 300 MHz) δ 7.5-
6.4 (m, 10 H), 4.5 (d, J ) 6.4 Hz, 1 H), 4.2 (t, J ) 7.3 Hz, 1 H),
3.4 (dd, J ) 7.3, 6.9 Hz, 1 H), 3.2 (t, J ) 6.9 Hz, 2 H), 2.7-2.6
(m, 1 H), 1.8-1.3 (m, 6 H); 13C NMR (CDCl3, 50 MHz) δ 151.8,
142.7, 128.8, 128.6, 127.4, 125.9, 117.9, 112.1, 73.8, 55.4, 41.8,
33.0, 32.6, 27.8, 6.7; IR (neat) 1600 cm-1; HRMS calcd for
C19H22IN 391.0797, found 391.0815.
tr a n s-3-Bu t yl-2-m et h yl-1-(4-m et h ylp h en yl)a zet id in e
(23i): Rf ) 0.38 (Hex:AcOEt, 15:1); 1H NMR (CDCl3, 200 MHz)
δ 7.05 (d, J ) 8.4 Hz, 2 H), 6.5 (d, J ) 8.4 Hz, 2 H), 4.1 (dd, J
) 7.3, 7.0 Hz, 1 H), 3.7-3.6 (m, 1 H), 3.2 (dd, J ) 7.3, 7.0 Hz,
1 H), 2.4-2.3 (m, 1 H), 2.3 (s, 3 H), 1.6-1.5 (m, 2H), 1.5 (d, J
) 6.1 Hz, 3 H), 1.4-1.2 (m, 4 H), 1.0-0.9 (m, 3 H); 13C NMR
(CDCl3, 50 MHz) δ 150.6, 129.3, 126.6, 111.9, 66.8, 56.3, 39.4,
33.5, 29.2, 22.5, 22.4, 20.3, 13.9; IR (neat) 1620 cm-1; HRMS
calcd for C15H23N 217.1830, found 217.1817. Anal. Calcd for
C15H23N: C, 82.89; H, 10.67; N, 6.44. Found: C, 82.95; H,
10.55; N, 6.35.
t r a n s-3-Bu t yl-1-(4-m e t h oxyp h e n yl)-2-m e t h yla ze t i-
d in e (23j): Rf ) 0.33 (Hex:AcOEt, 10:1); 1H NMR (CDCl3, 200
MHz) δ 6.8 (d, J ) 7.6 Hz, 2 H), 6.5 (d, J ) 7.6 Hz, 2 H), 4.05
(dd, J ) 7.3, 7.0 Hz, 1 H), 3.8 (s, 3 H), 3.65-3.5 (m, 1 H), 3.15
(dd, J ) 7.3, 7.0 Hz, 1 H), 2.4-2.3 (m, 1 H), 1.6-1.4 (m, 2 H),
1.5 (d, J ) 6.1 Hz, 3 H), 1.4-1.2 (m, 4 H), 1.0-0.9 (m, 3 H);
13C NMR (CDCl3, 50 MHz) δ 152.1, 147.2, 114.5, 112.9, 67.0,
56.6, 55.5, 39.4, 33.4, 29.2, 22.5, 22.4, 13.9; HRMS calcd for
C15H23NO 233.1780, found 233.1793.
(1R*,2S*,4R*,5S*,6S*)-4-Meth yl-3-p h en yl-3-a za tr icyclo-
[4.2.1.02,5]n on a n e (24): Rf ) 0.38 (Hex:AcOEt, 15:1); 1H NMR
(CDCl3, 200 MHz) δ 7.3-6.6 (m, 5 H), 4.15-4.1 (m, 1 H), 3.85-
3.75 (m, 1 H), 3.3-3.1 (m, 1 H), 2.45 and 2.1 (2s, 2 H), 1.95-
4-Bu tyl-2,2-d im eth yl-1-p h en yla zetid in e (27) a n d 3-Bu -
tyl-2,2-d im eth yl-1-p h en yla zetid in e (28): Mixture of regio-
1
isomers 1.2:1; Rf ) 0.38 (Hex:AcOEt, 15:1); H NMR (CDCl3,
200 MHz) δ 7.3-6.6 (m, 10 H), 3.95 (dq, J ) 7.7, 3.4 Hz, 1 H),
3.90 (dd, J ) 7.8, 6.7 Hz, 1 H), 3.35 (dd, J ) 7.1, 6.7 Hz, 1 H),
2.45 (m, 1 H), 2.25 (dd, J ) 10.3, 8.3 Hz, 1 H), 2.10 (m, 1 H),
2.0 (dd, J ) 10.3, 7.3 Hz, 1 H), 1.7 (s, 6 H), 1.6 (s, 6 H), 1.8-
1.3 (m, 11 H), 1.1 (m, 6 H); 13C NMR (CDCl3, 50 MHz) δ 148.8,
148.7, 128.6, 117.2, 116.8, 113.4, 112.9, 67.9, 63.0, 56.6, 51.9,
41.5, 38.3, 35.6, 31.5, 29.8, 28.8, 28.7, 26.9, 23.1, 22.7, 19.0,
14.1, 14.0; IR (neat) 1600 cm-1; HRMS calcd for C15H23
217.1831, found 217.1820.
N
Ack n ow led gm en t. Financial support from the Di-
reccio´n General de Investigacio´n Cient´ıfica y Te´cnica
(DGICYT, PB92-1005) is gratefully acknowledged. R.S.
thanks the Ministerio de Educacio´n y Ciencia for a
fellowship.
Su p p or tin g In for m a tion Ava ila ble: 13C-NMR spectra of
3, 6, 7, 10, 13, 16, 17, 20, and 23-28 are given (24 pages).
This material is contained in libraries on microfiche, im-
mediately follows this article in the microfilm version of the
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