A short and efficient route to enantiopure 3,5-diarylpyrrolizidines

Full text of DOI:10.1021/jo981946i

J . Org. Chem. 1999, 64, 1727-1732
1727
A Sh or t a n d Efficien t Rou te to
En a n tiop u r e 3,5-Dia r ylp yr r olizid in es
Dina Scarpi, Ernesto G. Occhiato, and Antonio Guarna*
Dipartimento di Chimica Organica “U. Schiff” and Centro
di Studio sulla Chimica e la Struttura dei Composti
Eterociclici e loro Applicazioni, C.N.R., Universita` di
Firenze, Via G. Capponi 9, I-50121 Firenze, Italy
F igu r e 1.
the cyclization reaction (Scheme 2) a pyrrolidine inter-
mediate is formed as a 1:1 mixture of diastereoisomers.
However, taking into account the relative configuration
of the two aryl groups in final compounds 6 or 7, only
one diastereoisomer should be obtained with the second
cyclization step, provided the pyrrolizidines have only the
expected cis-fused stereochemistry at the ring junction.6
To our knowledge, only one other synthesis of pyrroliz-
idines that started from nitrocompounds has been
reported,2b,c but in that case aliphatic 4-nitro-1,7-dike-
tones were used for the double cyclization step, under
catalytic hydrogenation or different reduction conditions,
thus leading to racemic mixtures of 3,5-dialkylpyrroliz-
idines.
Starting from enantiopure (1R,7R)-1,7-diaryl-4-nitro-
heptane-1,7-diols 3a ,b,5a the reduction of the nitro group
was carried out by hydrogenation over Raney Nickel in
MeOH at atmospheric pressure, providing aminodiols
4a ,b in 80-82% yield. Disappointingly, attempts at
converting directly 4 to the corresponding pyrrolizidines
by treatment with MsCl were quite ineffective, since only
very small amounts (20-23%) of 7a ,b (see below for the
structural and stereochemical assignments) were isolated
after chromatography of complex crude mixtures contain-
ing N-mesyl pyrrolidines and N-mesyl aminodiols as the
major products.7
Since the low yields in pyrrolizidines 7a ,b were due to
the mesylation of the nitrogen atom in the aminodiols,
we decided to convert 4a ,b into the corresponding N-
benzyl derivatives 5a ,b (Scheme 1). These compounds
appeared the best candidates to achieve the double
cyclization: with a benzyl group on the N atom the
increase of sterical hindrance could be sufficient to make
the N-mesylation slower than the O-mesylation, and at
the same time, the amino group should retain its nu-
cleophilic character for displacing the O-mesylates soon
after their formation. The cyclization should thus furnish
quaternary ammonium salts to be eventually trans-
formed into compounds 7a ,b by removal of the protecting
N-benzyl group.
Received September 25, 1998
Since the isolation of xenovenine (Figure 1) from the
venom of the cryptic thief ant Solenopsis xenovenenum,1
several strategies for the preparation of 3,5-disubstituted
pyrrolizidines, in racemic1,2 or enantiopure form,3 have
been devised. Because of the important biological proper-
ties displayed by these compounds and, in general, by
pyrrolizidine alkaloids,4 the development of new efficient
and concise routes to attain their preparation could be
of great interest. For this reason, in continuation of our
studies on the application of chiral nitrodiols to the
synthesis of heterocyclic compounds,5a,b we decided to
investigate if they were also amenable to conversion to
enantiopure 3,5-disubstituted pyrrolizidines, in particu-
lar focusing our attention on the preparation of 3,5-
diarylpyrrolizidines (Figure 1), a class of compounds that
have never been described before.
The synthesis of nitrodiketones 2 from γ-nitroketones
1, and the reduction to enantiopure nitrodiols 3 by using
(+)- or (-)-diisopinocampheylchloroborane (DIP-Cl), as
reported in Scheme 1, have been already described by
us.5a Thus, with nitrodiols 3 in hand, we envisaged a
synthetic strategy for the preparation of enantiopure 3,5-
diarylpyrrolizidines based on the initial reduction of 3
to the corresponding amino derivatives 4 or 5, then
followed by the double intramolecular nucleophilic dis-
placement of the two hydroxy groups by the amino
functionality, which should take place as soon as the two
OH are converted into leaving groups, for instance,
mesylates. This process should lead to compounds 7 or
their quaternary salts 6 with the stereocenters configu-
rationally inverted with respect to their precursors 3. In
* To whom correspondence should be addressed. Tel: 0039-055-
2757611. Fax: 0039-055-2476964. E-mail: guarna@chimorg.unifi.it.
(1) J ones, T. H.; Blum, M. S.; Fales, H. M.; Thompson, C. R. J . Org.
Chem. 1980, 45, 4778-4780.
(2) (a) Ciganek, E. J . Org. Chem. 1995, 60, 5803-5807. (b) Vavrecka,
M.; J anowitz, A.; Hesse, M. Tetrahedron Lett. 1991, 32, 5543-5546.
(c) J anowitz, A.; Vavrecka, M.; Hesse, M. Helv. Chim. Acta 1991, 74,
1352-1361. (d) Gallagher, T.; Lathbury, D. J . Chem. Soc., Chem.
Commun. 1986, 1017-1018.
(3) (a) Oppolzer, W.; Bochet, C. G.; Merifield, E. Tetrahedron Lett.
1994, 35, 7015-7018. (b) Grandjean, C.; Rosset, S.; Ce´le´rier, J . P.;
Lhommet, G. Tetrahedron Lett. 1993, 34, 4517-4518. (c) Takahata,
H.; Bandoh, H.; Momose, T. J . Org. Chem. 1992, 57, 4401-4404. (d)
Arseniyadis, S.; Huang, P. Q.; Husson, H.-P. Tetrahedron Lett. 1988,
29, 1391-1394. (e) Takano, S.; Otaki, S.; Ogasawara, K. J . Chem. Soc.,
Chem. Commun. 1983, 1172-1174.
(4) Hartmann, T.; Witte, L. In Alkaloids: Chemical and Biological
Perspective; Pelletier, S. W., Ed.; Pergamon: Oxford, 1995; Vol. 9,
Chapter 4.
N-Benzyl aminodiols 5a ,b were prepared in good yields
(84-86%) by reaction of 4a ,b with benzaldehyde and
(6) Cis-fused pyrrolizidines are normally more stable than the
corresponding trans-fused compounds (see ref 13a). 3,5-Dimethylpyr-
rolizidines having the cis relative configuration for the two methyl
groups are instead reported to have a trans-fused stereochemistry for
the ring junction. Antipova, I. V.; Negrebetskii, V. V.; Skvortsov, I. M.
Khim. Geterotsikl. Soed. 1982, 39-46.
(5) (a) Occhiato, E. G.; Scarpi, D.; Menchi, G.; Guarna, A. Tetrahe-
dron: Asymmetry 1996, 7, 1929-1942. (b) Occhiato, E. G.; Guarna,
A.; De Sarlo F.; Scarpi, D. Tetrahedron: Asymmetry 1995, 6, 2971-
2976. (c) Guarna, A.; Occhiato, E. G.; Spinetti, L. M.; Vallecchi, M. E.;
Scarpi, D. Tetrahedron 1995, 51, 1775-1788. (d) Molinari, F.; Occhiato,
E. G.; Aragozzini, F.; Guarna, A. Tetrahedron: Asymmetry 1998, 9,
1389-1394.
(7) We also tried to generate the 4-amino group by hydrogenation
(over Raney Nickel in MeOH) of the 4-nitro-1,7-dimesylate derivatives
obtained by reaction of 3a ,b with MsCl in dichloromethane (route not
shown in Scheme 1). However, this procedure was ineffective in
yielding cyclization products, since solvolysis of the O-mesyl groups
(to give mixtures of 1,7-dimethoxy-substituted products) was much
faster than the reduction of the nitro to amino group.
10.1021/jo981946i CCC: $18.00 © 1999 American Chemical Society
Published on Web 02/17/1999

1728 J . Org. Chem., Vol. 64, No. 5, 1999
Notes
Sch em e 1a
a
Key: (a) H2, Raney-Ni, MeOH, 24 h, 25 °C; (b) MsCl, Et3N, 4 Å molecular sieves, CH2Cl2, 0 f 25 °C, 2 h; (c) ArCHO, NaBH3CN,
MeOH, CH3COOH up to pH 6, 0 f 25 °C, 24 h; (d) K2CO3, MeOH-H2O, 25 °C, 2 h.
Sch em e 2
Sch em e 3
NaBH3CN in MeOH at pH 6. The next step was per-
formed by adding 2 equiv of MsCl to solutions of 5a ,b
and Et3N in anhydrous CH2Cl2 at 0 °C and then leaving
the mixture under stirring for 2 h at room temperature.
Since 5a ,b are very hygroscopic compounds and rapidly
absorb water from the atmosphere, the dichloromethane
solutions of these aminodiols were dried for 30 min with
4 Å molecular sieves prior to the addition of MsCl. With
this expedient procedure the reactions were successful,
and optically active salts 6a ([R]25D -101.3, c 0.82, CHCl3)
N-benzyl pyrrolidine derived from nucleophilic attack of
PhS- to the position 3 (or 5) of the pyrrolizidine ring.
Since quaternary salts 6a ,b were unsuitable to attain
deprotection, we prepared pyrrolizidinium salts 6c and
6d (Scheme 1) bearing differently substituted N-benzyl
groups in order to explore other deprotection methods.
Unfortunately, the synthesis of p-methoxybenzyl deriva-
tive 6c, obtained in 68% yield from aminodiol 5c, was
unproductive, since after treatment of this salt with
cerium ammoniun nitrate (CAN)9 or CF3COOH10 the
starting material was recovered unreacted.
Finally, we found that p-acetyloxybenzyl derivative 6d ,
prepared in 78% yield from aminodiol 5d , was the right
precursor to give 7a . In fact, when the acetyl group in
6d was subjected to hydrolysis with K2CO3 in MeOH/
H2O at 25 °C, a complete debenzylation occurred, provid-
ing pyrrolizidine 7a in 72% yield. This reaction should
take place through the formation of a phenolate inter-
mediate (Scheme 3) that immediately “eliminates” ter-
tiary amine 7a to form unsaturated ketone 8 (not
isolated). This, in turn, undergoes nucleophilic attack by
and 6b ([R]25 -62.2, c 0.24, CHCl3) were obtained in 72
D
and 70% yield, respectively, after chromatographic pu-
rification. With the procedure employed for their isolation
in the course of the workup (see the Experimental
Section), these salts were obtained exclusively as chlo-
rides soluble in water and organic solvents such as
methanol and chloroform.
With compounds 6a ,b in hand, we tried to obtain the
corresponding pyrrolizidines by debenzylation of the N
atom. Unfortunately, deprotection to give 7a ,b proved
very difficult with these simple N-benzyl derivatives. For
example, catalytic hydrogenations over Pd(OH)2 or Pd/C
resulted in the cleavage of the internal benzylic bonds,
providing mixtures of R-branched N-benzyl pyrrolidines
and N-benzyl amines. Similarly, treatment with sodium
thiophenate8 in refluxing CH3CN afforded the R-branched
(9) J ohansson, R.; Samuelsson, B. J . Chem. Soc., Perkin Trans. 1
1984, 2371-2374.
(10) Buckle, D. R.; Rockell, J . M. J . Chem. Soc., Perkin Trans. 1
1982, 627-630.
(8) Shamma, M.; Deno, N. C.; Remar, J . F. Tetrahedron Lett. 1966,
1375-1379.

Notes
J . Org. Chem., Vol. 64, No. 5, 1999 1729
MeOH to give phenol derivative 9, easily identified by
1
the singlets at 4.34 (CH2) and 3.33 ppm (MeO) in the H
NMR spectrum. According to these results, the p-acetyl-
oxybenzyl group could find application as a protecting
group of tertiary amines, as an alternative to the methyl
group in the formation of quaternary ammonium salts.11
The first in fact would require milder conditions to be
removed, since alkaline hydrolysis at room temperature
is sufficient for the deprotection reaction.
With the same protocol pyrrolizidine 7b was prepared
in 78% yield starting from aminodiol 5e. In this particu-
lar case, the quaternary salt 6e was not isolated from
the crude reaction mixture, which was directly used in
the following hydrolytic process.
F igu r e 2. NOE correlations in 6a (left) and MM2* global
minimum conformer of 6a (right).
The reactions leading to 6a -e were highly diastereo-
1
selective, since a careful H and 13C NMR inspection of
the crude mixtures containing 6a -e and all the fractions
collected during the chromatographic purification of these
salts excluded the presence of meso forms of 6 (which
derive from an ionic mechanism competing with that
reported in Scheme 2). Homo- and hetereonuclear cor-
relation NMR experiments allowed the unambiguous
assignment of the 1H and 13C NMR signals of compounds
6a -e and, accordingly, the relative stereochemistry of
the three substituents on the pyrrolizidine ring.
3
13.1 and 5.1 Hz (5-H). Since the J couplings for the two
protons are practically identical, it is possible that these
quaternary salts adopt in solution a predominant con-
formation in which the two phenyl groups are equatori-
ally oriented. Only in this case, in fact, the protons on
C-3 and C-5 would be both axially oriented (Figure 2),
thus accounting for the large (∼13 Hz) and the small (∼5
Hz) couplings with the vicinal axial and equatorial
protons, respectively. A complete conformational analy-
sis12 performed on 6a confirmed that in the global
minimum conformer (Figure 2) the two phenyl groups,
which lie on parallel planes, are both in the equatorial
position. Moreover, only one preferred position for the
N-benzyl group was found, in accordance with the
NOESY data reported above.
The deprotection step carried out by alkaline hydrolysis
of the acetyloxy group on 6d and 6e did not affect the
relative trans stereochemistry in final pyrrolizidine 7a ,b,
since protons 3-H and 5-H have different chemical shifts
and resonate at 3.67 and 4.32 ppm in 7a and at 4.14 and
4.44 ppm in 7b. Furthermore, pyrrolizidines 7 retained
the cis fusion of the ring junction. This assignment rests
on the analysis of the chemical shifts of 7a-H, which
resonates at 4.02 ppm in 7a and 3.81 ppm in 7b. In cis-
fused pyrrolizidines, proton 7a-H is on the same side of
the N lone pair and, therefore, should undergo a strong
deshielding effect.13 This is true, for example, for cis-fused
3,5-dialkylpyrrolizidines, in which 7a-H resonates in the
3.59-3.66 ppm range,1,14 while in the corresponding
trans-fused compounds 7a-H is found at 2.53-2.72
ppm.1,2c Moreover, the chemical shift values of C-7a in
the 13C NMR spectrum of 7a (64.5 ppm) and 7b (60.1
ppm) confirm the cis-fused stereochemistry, since they
are consistent with those reported for C-7a in other cis-
fused pyrrolizidines; instead, values of chemical shifts
In all these compounds, protons 3-H and 5-H, as well
as carbon atoms C-3 and C-5, have different chemical
shifts. For example, in 6a , which can be taken as a model
for all the 3,5-diphenyl-substituted pyrrolizidinium salts,
3-H and 5-H resonate at 4.74 and 5.05 ppm, and in 6b
at 4.91 and 5.64 ppm. With the two substituents at
positions 3 and 5 being identical, the different resonances
of 3-H and 5-H can be explained only by assuming that
the two aryl groups have a trans relative configuration.
As a direct consequence, because salts 6 were obtained
as single nonracemic (they all are optically active)
diastereoisomers, the absolute configuration of the ste-
reocenters at C-3 and C-5 in the major enantiomer of
these compounds, to which we refer in the discussion,
must be S, the double nucleophilic displacement depicted
in Scheme 2 occurring with inversion of configuration.
The cis-fused stereochemistry of these salts was de-
termined by a NOESY experiment performed on 6a . In
a cis-fused compound, the bridgehead 7a-H and the
benzylic -CH2- protons are on the same side and
therefore should experience a mutual NOE enhancement.
This actually occurs in compound 6a , but quite to our
surprise, only one of the two benzylic protons, in par-
ticular that resonating at 5.55 ppm (8-Ha, Figure 2),
correlated with 7a-H. The other one, found considerably
shielded up to 3.54 ppm (8-Hb), showed instead a NOESY
cross-peak only with the proton resonating at 5.05 ppm
(5-H). These data suggest that the benzyl group, which
is cis with respect to the proton on C-7a, should have a
preferred spatial orientation accounting for the very
(12) The MacroModel (v4.5) molecular modeling software was used
for molecular mechanics calculations and Monte Carlo conformational
searchs (MM2* force field). Mohamadi, F.; Richards, N. G.; Guida, W.
C.; Liskamp, R.; Lipton, M.; Caufield, C.; Chang, G.; Hendrickson, T.;
Still, W. C. J . Comput. Chem. 1990, 11, 440-467.
(13) In cyclic systems, the protons adjacent to the nitrogen atom
and on the same side of the N lone pair undergo a strong deshielding
effect, whereas the protons on the opposite side are strongly shielded:
(a) Crabb, T. A.; Newton, R. F.; J ackson, D. Chem. Rev. 1971, 71, 109-
126. (b) Wilson S. R.; Sawicki, R. A. J . Org. Chem. 1979, 44, 330-336.
(c) King, F. D. J . Chem. Soc., Perkin Trans. 1 1986, 447-453. (d)
Sonnet, P. E.; Netzel, D. A.; Mendoza, R. J . Heterocyclic Chem. 1979,
16, 1041-1047. (e) Bohlmann, F.; Shumann, D. In The Alkaloids;
Manske, R. H. F., Ed.; Academic Press: New York, 1967; Vol IX,
Chapter 5.
1
different chemical shift of 8-Ha and 8-Hb in the H NMR
spectrum but, most of all, for the NOE enhancements
found in 6a .
The inspection of the coupling constants for protons
3-H and 5-H in 6a -e suggests that these compounds
could be conformationally restricted. The averaged coup-
ling constants of protons 3-H and 5-H with the vicinal
protons on C-2 and C-6 are 12.7 and 5.3 Hz (3-H) and
(11) Greene, T. W.; Wuts, P. G. M. In Protective Groups in Organic
Synthesis; J ohn Wiley & Sons: New York, 1991; Chapter 7, p 364.
(14) Skvortsov, I. M.; Elvidge, J . A. J . Chem. Soc. B 1968, 1589-
1595.

1730 J . Org. Chem., Vol. 64, No. 5, 1999
Notes
isomers, and in the 13C NMR spectrum of the mixture,
two doublets attributable to C-7a are found at 70.0 and
72.6 ppm. These values, as mentioned in discussing the
stereochemistry of pyrrolizidines 7, could be accounted
for by assuming a trans-fused stereochemistry for the
ring junction in 13.1,2c,15 This would be also consistent
with the observation that 3,5-dimethylpyrrolizidines with
cis relative stereochemistry of the substituents are more
stable in the trans-fused form.6
Sch em e 4a
In conclusion, we have presented a short and efficient
route for the preparation of enantiomerically pure 3,5-
diarylpyrrolizidines 7, obtained in 41-56% overall yield
after four steps. The methodology was based on a double
nucleophilic displacement occurring in chiral 1,7-diaryl-
4-[(N-benzyl)amino]heptane-1,7-diols as soon as the two
hydroxy groups were converted into mesylates. The
cyclization reactions were diastereo- and enantioselective,
affording configurationally inverted, cis-fused 3,5-disub-
stituted pyrrolizidinium salts 6. The presence of a p-
acetyloxy substituent on the N-benzyl group in these salts
was a prime requirement to permit the removal of the
N-protection by alkaline hydrolysis, thus providing target
tertiary amines 7. Cis-3,5-diaryl-substituted pyrroliz-
idines such as 13 can be also prepared by using the same
methodology. The synthesis of pyrrolizidines 7 and 13
was accomplished starting from chiral nitro alcohols or
nitrodiols, which in turn can be prepared by enantiose-
lective reduction of nitroketones or nitrodiketones using
either yeasts or chemical reducing reagents depending
on the type of substrate. This should allow for the
preparation of a wide range of chiral precursors that can
be easily converted into the corresponding 3,5-disubsti-
tuted pyrrolizidines by the methodology described in this
paper.
a
Key: (a) (+)-DIP-Cl, CH2Cl2, -25 °C, 5 h; (b) H2, Raney-Ni,
MeOH, 24 h, 25 °C; (c) p-AcOC6H4CHO, NaBH3CN, MeOH,
CH3COOH up to pH 6, 0 f 25 °C, 24 h; (d) MsCl, Et3N, 4 Å
molecular sieves, CH2Cl2, 0 f 25 °C, 2 h; (e) K2CO3, MeOH-H2O,
25 °C, 2 h.
greater than 70 ppm for this carbon atom are typical of
trans-fused compounds.1,15
The complete enantioselectivity of the process leading
to pyrrolizidines 7 was ascertained by determining the
enantiomeric excess in the case of pyrrolizidine (3S,5S)-
7a . This was accomplished by the analysis of the 1H NMR
spectrum of the pyrrolizidinium salt obtained by treat-
ment of 7a with 1 equiv of (+)-MPTA (Mosher’s acid)16
in CDCl3. The ee was calculated by measuring the areas
of the signals of the MeO group, splitted at 3.59 and 3.52
ppm in the diastereomeric salts, and corresponded, as
expected, to the enantiomeric purity of the starting nitro
alcohol 3a (96%).
Since most of the biologically active pyrrolizidine
alkaloids have a cis relative configuration at C-3 and C-5,
we considered it useful to ascertain if the strategy
described above could be applied to the synthesis of cis-
3,5-diarylpyrrolizidines, choosing compound 13 as the
simplest target (Scheme 4), i.e., the diaryl analogue of
7a with the 3,5-cis relative configuration as in xenovenine
(Figure 1). However, the direct reduction of nitrodiketone
2a by (+)- or (-)-DIP-Cl is in this case unsuitable for
the preparation of meso-nitrodiol 12, which instead could
be obtained as depicted in Scheme 4. Addition of (S)-nitro
alcohol 10,5d in the presence of Amberlyst A21, to phenyl
vinyl ketone gave nitro compound 11 as a 1:1 diastere-
omeric mixture.5a The stereoselective reduction of the
carbonyl group in 11 was then performed by using (+)-
DIP-Cl, affording the expected meso-diols 12 with
1S,4R,7R and 1S,4S,7R configuration in 1:1 ratio and
68% yield. (In the 13C NMR spectrum of the mixture only
the signals at 88.9 and 87.8 ppm attributable to the C-4
atom of the two meso-nitrodiols are present).5a The
mixture of diols 12 was then converted by the usual
methodology into pyrrolizidine 13, obtained in 18%
overall yield as a 1:1 mixture of meso isomers having a
3,5-cis relative configuration. Although separation of the
two isomers was not carried out, this stereochemical
assignment is immediate from the analysis of the 1H
NMR spectrum of the mixture: protons 3-H and 5-H,
which are enantiotopic in compounds such as 13, have
in fact the same chemical shift and resonate at 3.91 ppm
in one isomer and at 3.20 ppm in the other one. Proton
7a-H resonates below 3 ppm (2.81 and 2.49 ppm) in both
Exp er im en ta l Section
Melting points are uncorrected. Chromatographic separations
were performed under pressure on silica gel using flash-column
techniques; Rf values refer to TLC carried out on 25-mm silica
gel plates (Merck F254), with the same eluant indicated for the
column chromatography. 1H and 13C NMR spectra were recorded
at 200 and 50.33 MHz, respectively. NOESY spectra were
recorded at 500 MHz. Mass spectra were carried out in EI at 70
eV ionizing voltage. CH2Cl2 was distilled from CaH2. All reac-
tions requiring anhydrous conditions were performed in flame-
dried glassware. Compounds 1-3, 10, and 11 were prepared as
reported.5a,d
(1R,7R)-(+)-1,7-Dip h en yl-4-a m in oh ep ta n e-1,7-d iol (4a ).
A solution of 3a (3.31 g, 10.5 mmol) in MeOH (40 mL) was added
under stirring to a prehydrogenated suspension of wet Raney-
Ni (3.99 g, washed three times with 5 mL of MeOH before the
addition of the solution of 3a ) in the same solvent (20 mL). The
mixture was left under a hydrogen atmosphere for 24 h at room
temperature and then filtered twice on a Celite layer and finally
evaporated to give pure 4a (2.59 g, 82%) as a white solid: mp
35-36 °C; [R]25D +43.6 (c 0.78, CHCl3); 1H NMR (CDCl3) δ 7.40-
7.15 (m, 10 H), 4.61 (m, 2 H), 3.03 (m, 1 H), 1.90-1.45 (m, 8 H);
13C NMR (CDCl3) δ 144.6 (s), 144.4 (s), 128.4 (d, 4 C), 127.2 (d,
2 C), 125.8 (d, 4 C), 74.1 (d), 73.4 (d), 51.9 (d), 36.4 (t), 34.8 (t),
32.2 (t), 31.9 (t); MS m/z 299 (M+, 1), 146 (100); IR (CDCl3) 3601,
3550-3150 cm-1. Anal. Calcd for C19H25NO2: C, 76.22; H, 8.42;
N, 4.68. Found: C, 76.01; H, 8.53; N, 4.52.
(1R,7R)-(+)-1,7-Bis(2-m eth oxyp h en yl)-4-a m in oh ep ta n e-
1,7-d iol (4b). According to the procedure reported above,
starting from 3b (1.85 g, 4.75 mmol) aminodiol 4b (1.37 g, 80%)
(15) (a) Skvortsov, I. M.; Antipova, I. V. Zh. Org. Khim. 1979, 15,
868-875. (b) Skvortsov, I. M.; Subbotin, O. A. Zh. Org. Khim. 1977,
13, 466-467.
(16) (a) Dale, J . A.; Dull, D. L.; Mosher, H. S. J . Org. Chem. 1969,
34, 2543-2549. (b) Dale, J . A.; Mosher, H. S. J . Am. Chem. Soc. 1973,
95, 512-519.
was obtained as a white solid: mp 56-57 °C; [R]25 +33.0 (c
D
0.20, CHCl3); 1H NMR (CDCl3) δ 7.35 (m, 2 H), 7.24-7.12 (m, 2
H), 6.91-6.75 (m, 4 H), 4.91 (m, 2 H), 3.73 (s, 6 H), 3.27 (m, 1
H), 3.20-2.40 (m, 4 H), 1.80-1.60 (m, 8 H); 13C NMR (CDCl3) δ
155.8 (s), 155.7 (s), 132.5 (s, 2 C), 127.8 (d, 2 C), 126.5 (d), 126.4

Notes
J . Org. Chem., Vol. 64, No. 5, 1999 1731
(d), 120.6 (d, 2 C), 110.0 (d), 109.9 (d), 69.0 (d), 68.0 (d), 55.0 (q,
2 C), 52.0 (d), 34.2 (t), 32.7 (t), 30.6 (t), 28.3 (t); MS m/z 359
(M+, 5), 83 (100); IR (CDCl3) 3607, 3600-3000 cm-1. Anal. Calcd
for C21H29NO4: C, 70.17; H, 8.13; N, 3.90. Found: C, 70.10; H,
8.43; N, 3.71.
H), 3.78 (s, 3 H), 2.70 (m, 1 H), 2.27 (s, 3 H), 1.90-1.40 (m, 8 H);
13C NMR (CDCl3) δ 169.6 (s), 156.2 (s, 2 C), 151.2 (s), 136.7 (s),
132.9 (s, 2 C), 129.6 (d, 2 C), 128.1 (d), 128.0 (d), 126.7 (d, 2 C),
121.7 (d, 2 C), 120.7 (d, 2 C), 110.3 (d, 2 C), 70.1 (d), 69.6 (d),
56.9 (d), 55.2 (q, 2 C), 50.2 (t), 34.5 (t), 33.3 (t), 30.5 (t), 29.8 (t),
21.1 (q); MS m/z 489 (M+ - 18, 3), 324 (100); IR (CDCl3) 3595,
3050-2850, 1756 cm-1. Anal. Calcd for C30H37NO6: C, 70.98;
H, 7.35; N, 2.76. Found: C, 70.89; H, 7.55; N, 2.55.
(1R,7R)-(+)-1,7-Dip h en yl-4-[(N-b en zyl)a m in o]h ep t a n e-
1,7-d iol (5a ). NaBH3CN (121 mg, 1.93 mmol) and benzaldehyde
(213 µL, 2.11 mmol) were added to a stirred solution of 4a (578
mg, 1.93 mmol) in MeOH (2 mL) cooled at 0 °C. A few drops of
glacial CH3COOH were added up to pH 6, and the solution was
left under stirring at room temperature. After 24 h, the solution
was diluted with water (10 mL), and Na2CO3 (s) was added to
adjust pH 9-10. The resulting mixture was saturated with NaCl
(s), and finally the product was extracted with chloroform (3 ×
15 mL). The organic layer was dried over Na2SO4, filtered, and
evaporated, furnishing crude 5a . This was purified by chroma-
tography (CH2Cl2-MeOH, 20:1, 1% NH4OH in MeOH, Rf 0.18),
obtaining pure 5a (632 mg, 84%) as a low-melting compound:
(3S,4S,5S,7a R)-(-)-3,5-Dip h en yl-4-b en zylp yr r olizid in i-
u m Ch lor id e (6a ). A solution of 5a (453 mg, 1.09 mmol) and
Et3N (765 µL, 5.45 mmol) in anhydrous CH2Cl2 (39 mL) was
stirred for 30 min over activated 4 Å molecular sieves under a
nitrogen atmosphere. After the solution was cooled to 0 °C, MsCl
(186 µL, 2.40 mmol) was added dropwise and the resulting
solution left under stirring at room temperature. After 2 h, the
solution was diluted with water (50 mL), the aqueous layer was
saturated with NaCl (s), and the two phases were separated.
The organic layer was dried over Na2SO4, filtered, and evapo-
rated, affording a crude that was purified by chromatography,
first eluting with CH2Cl2-MeOH, 20:1, and then with MeOH,
obtaining pure 6a (306 mg, 72%) as a white solid: mp 109-110
[R]25 +29.9 (c 0.60, CH3OH); 1H NMR (CDCl3) δ 7.40-7.15 (m,
D
15 H), 4.66 (m, 2 H), 3.77 (AB system, J ) 12.8 Hz, 2 H), 2.69
(m, 1 H), 1.90-1.45 (m, 8 H); 13C NMR (CDCl3) δ 145.1 (s), 145.0
(s), 138.6 (s), 128.4 (d, 4 C), 128.1 (d, 2 C), 127.2 (d, 2 C), 127.0
(d), 126.9 (d, 2 C), 125.7 (d, 4 C), 73.8 (d), 73.7 (d), 56.4 (d), 50.6
(t), 36.1 (t), 35.1 (t), 29.9 (t), 29.2 (t); MS m/z 389 (M+, 20), 91
(100); IR (CDCl3) 3605 cm-1. Anal. Calcd for C26H31NO2: C,
80.17; H, 8.02; N, 3.60. Found: C, 79.85; H, 8.30; N, 3.20.
(1R,7R)-(+)-1,7-Bis(2-m eth oxyp h en yl)-4-[(N-ben zyl)a m i-
n o]h ep ta n e-1,7-d iol (5b). According to the procedure reported
for the preparation and purification of 5a , N-benzyl aminodiol
5b (920 mg) was obtained starting from 4b (856 mg, 2.38 mmol)
°C; [R]25 -101.3 (c 0.82, CHCl3); 1H NMR (CDCl3) δ 8.09 (m, 2
D
H), 7.70-7.35 (m, 8 H), 7.17 (d, J ) 7.3 Hz, 1 H), 7.04 (m, 2 H),
6.54 (d, J ) 7.7 Hz, 2 H), 5.68 (m, 1 H), 5.55 (d, J ) 12.6 Hz, 1
H), 5.05 (dd, J ) 13.5, 5.1 Hz, 1 H), 4.74 (dd, J ) 13.5, 5.1 Hz,
1 H), 3.84 (m, 1 H), 3.54 (d, J ) 12.6 Hz, 1 H), 2.79 (m, 1 H),
2.68 (m, 1 H), 2.20-1.80 (m, 3 H), 1.74 (m, 1 H), 1.14 (m, 1 H);
13C NMR (CDCl3) δ 133.5 (d, 2 C), 131.3 (d, 2 C), 130.9 (d, 2 C),
130.9 (s), 129.9 (s), 129.9 (d, 2 C) 129.7 (d, 2 C), 129.3 (d), 129.0
(d, 2 C), 128.5 (s), 127.8 (d, 2 C), 78.4 (d), 77.6 (d), 72.3 (d), 62.2
(t), 31.0 (t), 30.8 (t), 27.5 (t), 27.1 (t); MS m/z 389 (M+, 3), 91
(100). Anal. Calcd for C26H28NCl: C, 80.08; H, 7.24; N, 3.59.
Found: C, 79.96; H, 7.37; N, 3.22.
as a low-melting compound in 86% yield: [R]25 +52.2 (c 1.13,
D
CHCl3); 1H NMR (CDCl3) δ 7.39-7.16 (m, 9 H), 6.97-6.82 (m, 4
H), 4.89 (m, 2 H), 3.87-3.67 (m, 8 H), 2.65 (m, 1 H), 2.60-2.50
(br s, 3 H), 1.88-1.78 (m, 8 H); 13C NMR (CDCl3) δ 159.9 (s, 2
C), 139.2 (s), 133.2 (s), 133.1 (s), 128.4 (d, 2 C), 127.7 (d, 2 C),
127.6 (d, 2 C), 127.1 (d), 126.5 (d, 2 C), 120.5 (d, 2 C), 110.1 (d),
110.0 (d), 69.3 (d), 69.0 (d), 56.6 (d), 55.0 (q, 2 C), 50.6 (t), 34.4
(t), 33.3 (t), 30.3 (t), 29.6 (t); MS m/z 449 (M+, 42), 266 (100), 91
(3S,4S,5S,7a R)-(-)-3,5-Bis(2-m et h oxyp h en yl)-4-b en zyl-
p yr r olizid in iu m Ch lor id e (6b). Prepared as reported for 6a .
Starting from 5b (189 mg, 0.42 mmol), pure 6b (132 mg, 70%)
was obtained, after chromatography (CH2Cl2-MeOH, 20:1, Rf
0.19), as a white solid: mp 82-83 °C; [R]25 -62.2 (c 0.24,
D
(100); IR (CDCl3) 3609, 3480-3120 cm-1. Anal. Calcd for C28H35
-
CHCl3); H NMR (CDCl3) δ 7.95 (m, 2 H), 7.60-7.38 (m, 4 H),
1
NO4: C, 74.80; H, 7.85; N, 3.12. Found: C, 74.47; H, 7.64; N,
2.98.
7.30-7.20 (m, 3 H), 7.00-6.63 (m, 4 H), 5.64 (dd, J ) 12.8, 5.8
Hz, 1 H), 5.22 (m, 1 H), 4.98 (d, J ) 12.8 Hz, 1 H), 4.91 (dd, J )
10.6, 6.2 Hz, 1 H), 4.50 (d, J ) 12.8 Hz, 1 H), 3.73 (s, 3 H), 3.70
(m, 1 H), 3.65 (s, 3 H), 2.96 (m, 1 H), 2.75 (m, 1 H), 2.22 (m, 2
H), 2.00-1.70 (m, 2 H), 0.97 (m, 1 H); 13C NMR (CDCl3) δ 158.8
(s), 158.5 (s), 133.2 (d, 2 C), 132.9 (d), 132.5 (d), 131.6 (d), 131.4
(d), 130.1 (d), 129.6 (s), 129.2 (d, 2 C), 121.8 (d), 120.8 (d), 119.3
(s), 118.8 (s), 111.5 (d), 111.4 (d), 77.9 (d), 71.7 (d), 70.2 (d), 62.2
(t), 55.6 (q), 54.9 (q), 31.0 (t), 29.3 (t), 28.0 (t), 27.8 (t); MS m/z
449 (M+, 0.1), 91 (100). Anal. Calcd for C28H32NO2Cl: C, 74.73;
H, 7.17; N, 3.11. Found: C, 74.55; H, 7.21; N, 3.01.
(1R,7R)-(+)-1,7-Dip h en yl-4-[N-((4-m eth oxyp h en yl)m eth -
yl)a m in o]h ep ta n e-1,7-d iol (5c). As reported for 5a , starting
from 4a (332 mg, 1.11 mmol) and p-anisaldehyde (150 µL, 1.24
mmol), pure 5c (396 mg) was obtained as
a low-melting
1
compound in 85% yield: [R]25 +40.0 (c 0.18, CHCl3); H NMR
D
(CDCl3) δ 7.40-7.15 (m, 12 H), 6.84 (m, 2 H), 4.62 (m, 2 H),
3.76 (s, 3 H), 3.72 (AB system, J ) 12.4 Hz, 2 H), 2.66 (m, 1 H),
1.90-1.45 (m, 8 H); 13C NMR (CDCl3) δ 145.1 (s), 145.0 (s), 130.4
(s), 130.0 (d, 2 C), 128.4 (d, 4 C), 127.3 (d), 127.2 (d), 125.8 (d, 4
C), 114.1 (d, 2 C), 113.6 (s), 74.2 (d), 74.0 (d), 56.6 (d), 55.2 (q),
50.0 (t), 36.3 (t), 35.1 (t), 30.0 (t), 29.2 (t); MS m/z 419 (M+, 1),
121 (100); IR (CDCl3) 3614 cm-1. Anal. Calcd for C27H33NO3:
C, 77.29; H, 7.93; N, 3.34. Found: C, 77.11; H, 8.10; N, 3.15.
(1R,7R)-(+)-1,7-Dip h en yl-4-[N-((4-a cet yloxyp h en yl)m e-
th yl)a m in o]h ep ta n e-1,7-d iol (5d ). As reported for 5a , but in
the workup, NaHCO3 is added to adjust pH 7. Starting from 4a
(434 mg, 1.45 mmol) and p-acetyloxybenzaldehyde (228 µL, 1.62
(3S,4S,5S,7a R)-(-)-3,5-Dip h en yl-4-[(4-m et h oxyp h en yl)-
m eth yl]p yr r olizid in iu m Ch lor id e (6c). Prepared and purified
as reported for 6a . Starting from 5c (298 mg, 0.71 mmol), pure
6c (203 mg, 68%) was obtained, after chromatography (CH2Cl2-
MeOH, 20:1, Rf 0.12), as a white solid: mp 118-119 °C; [R]25
D
1
-112.8 (c 1.10, CHCl3); H NMR (CDCl3) δ 8.07 (d, J ) 8.8 Hz,
2 H), 7.58 (m, 4 H), 7.20 (m, 2 H), 7.00 (m, 4 H), 6.54 (d, J ) 7.7
Hz, 2 H), 5.69 (m, 1 H), 5.57 (d, J ) 16.0 Hz, 1 H), 5.06 (dd, J )
12.8, 4.7 Hz, 1 H), 4.70 (dd, J ) 13.1, 5.1 Hz, 1 H), 3.90 (m, 1
H), 3.83 (s, 3 H), 3.56 (d, J ) 16.0 Hz, 1 H), 2.87-2.58 (m, 2 H),
2.20-1.90 (m, 3 H), 1.75 (m, 1 H), 1.22 (m, 1 H); 13C NMR
(CDCl3) δ 160.5 (s), 135.0 (d, 2 C), 131.3 (d, 2 C), 130.9 (d, 2 C),
130.0 (s), 129.9 (s), 129.9 (d) 129.7 (d, 2 C), 129.3 (d), 129.0 (d,
2 C), 120.1 (s), 114.3 (d, 2 C), 78.1 (d), 77.2 (d), 71.9 (d), 61.9 (t),
55.0 (q), 31.1 (t), 30.9 (t), 27.6 (t), 27.1 (t); MS m/z 419 (M+, 1),
121 (100). Anal. Calcd for C27H30NOCl: C, 77.22; H, 7.20; N,
3.34. Found: C, 77.48; H, 7.47; N, 3.17.
mmol), pure 5d (597 mg) was obtained as
a low-melting
1
compound in 92% yield: [R]25 +32.5 (c 0.27, CHCl3); H NMR
D
(CDCl3) δ 7.40-7.15 (m, 12 H), 7.02 (m, 2 H), 4.63 (m, 2 H),
3.72 (AB system, J ) 12.9 Hz, 2 H), 2.65 (m, 1 H), 2.27 (s, 3 H),
1.90-1.40 (m, 8 H); 13C NMR (CDCl3) δ: 169.6 (s), 149.9 (s),
145.2 (s), 145.0 (s), 136.6 (s), 129.6 (d, 2 C), 128.4 (d, 4 C), 127.2
(d, 2 C), 125.8 (d, 4 C), 121.8 (d, 2 C), 74.3 (d), 74.1 (d), 56.8 (d),
50.4 (t), 36.3 (t), 35.2 (t), 30.4 (t), 29.6 (t), 21.1 (q); MS m/z 447
(M+, 1), 107 (100); IR (CDCl3) 3612, 1755 cm-1. Anal. Calcd for
C
28H33NO4: C, 75.14; H, 7.43; N, 3.13. Found: C, 75.43; H, 7.62;
N, 3.04.
(1R,7R)-(+)-1,7-Bis(2-m et h oxyp h en yl)-4-[N-((4-a cet yl-
(3S,4S,5S,7a R)-(-)-3,5-Dip h en yl-4-[(4-a cetyloxyp h en yl)-
m eth yl]p yr r olizid in iu m Ch lor id e (6d ). Prepared as reported
for 6a . Starting from 5d (300 mg, 0.67 mmol), pure 6d (234 mg,
78%) was obtained, after chromatography (CH2Cl2-MeOH, 20:
oxyp h en yl)m eth yl)a m in o]h ep ta n e-1,7-d iol (5e). As reported
for 5a , but in the workup NaHCO3 is added to adjust pH 7.
Starting from 4b (334 mg, 0.93 mmol) and p-acetyloxybenzal-
dehyde (147 µL, 1.04 mmol), pure 5e (425 mg) was obtained as
a low-melting compound in 90% yield: [R]25D +30.7 (c 0.21, CH2-
Cl2); 1H NMR (CDCl3) δ 7.40-7.30 (m, 3 H), 7.25-7.05 (m, 3
H), 7.00-6.75 (m, 6 H), 4.87 (m, 2 H), 3.80 (s, 3 H), 3.79 (m, 2
1, Rf 0.10), as a white solid: mp 122-123 °C; [R]25 -102.3 (c
D
0.27, CHCl3); 1H NMR (CDCl3) δ 8.14 (d, J ) 8.8 Hz, 2 H), 7.57
(m, 4 H), 7.20 (m, 2 H), 7.05 (m, 4 H), 6.54 (d, J ) 7.7 Hz, 2 H),
5.70 (m, 1 H), 5.66 (d, J ) 12.8 Hz, 1 H), 5.00 (dd, J ) 13.1, 4.7
Hz, 1 H), 4.71 (dd, J ) 13.5, 5.1 Hz, 1 H), 3.90 (m, 1 H), 3.50 (d,
J ) 12.8 Hz, 1 H), 2.90-2.55 (m, 2 H), 2.35-1.90 (m, 3 H), 2.29

1732 J . Org. Chem., Vol. 64, No. 5, 1999
Notes
(s, 3 H), 1.78 (m, 1 H), 1.22 (m, 1 H); 13C NMR (CDCl3) δ 168.8
(s), 151.9 (s), 134.9 (d, 2 C), 131.6 (d, 2 C), 131.3 (d), 131.1 (d, 2
C), 130.1 (s), 129.9 (d, 2 C), 129.8 (s), 129.7 (d), 128.1 (d, 2 C),
126.3 (s), 122.4 (d, 2 C), 78.7 (d), 77.9 (d), 72.6 (d), 61.7 (t), 31.3
(t), 30.9 (t), 27.8 (t), 27.3 (t), 20.9 (q); MS m/z 294 (21), 83 (100);
IR (CDCl3) 1762 cm-1. Anal. Calcd for C28H30NO2Cl: C, 75.07;
H, 6.75; N, 3.13. Found: C, 74.88; H, 6.92; N, 2.97.
was then dissolved in Et2O, and diethanolamine (205 µL) was
added. The resulting suspension was stirred for 2 h, filtered,
and concentrated. The residue was chromatographed, eluting
first with CH2Cl2 and then with CH2Cl2-MeOH, 20:1, to give
the 1:1 diastereomeric mixture 12 (215 mg, 68%) as a low-
melting solid (Rf 0.25): 1H NMR (CDCl3) δ 7.30-7.00 (m, 10 H
+ 10 H), 4.30 (m, 3 H + 3 H), 2.20-1.40 (m, 8 H + 8 H); 13C
NMR (CDCl3) δ 143.8 (s, 2 C + 2 C), 128.5 (d, 2 C + 2 C), 128.3
(d, 2 C + 2 C), 127.7 (d, 2 C + 2 C), 125.6 (d, 4 C + 4 C), 88.9
(d), 87.8 (d), 73.5 (d, 2 C), 73.0 (d, 2 C), 34.8 (t, 2 C), 34.6 (t, 2
C), 30.2 (t, 2 C), 29.6 (t, 2 C).
(3S,5R,7a R)- a n d (3S,5R,7a S)-3,5-Dip h en ylp yr r olizid in e
(13). Nitrodiol 12 (215 mg, 0.65 mmol) was subjected to the usual
hydrogenation over Raney-Ni, and as reported for the prepara-
tion of 5d , the resulting amine (170 mg) was transformed into
the corresponding p-acetyloxybenzylamine (79 mg, 31%): 1H
NMR (CDCl3) δ: 7.20-7.10 (m, 12 H + 12 H), 7.03 (d, J ) 8.4
Hz, 2 H + 2 H), 4.65 (m, 2 H + 2 H), 3.77 (s, 2 H), 3.69 (s, 2 H),
2.72 (m, 1 H), 2.60 (m, 1 H), 2.29 (s, 3 H + 3 H), 1.90-1.50 (m,
8 H + 8 H).
This secondary amine was then converted into the pyrroliz-
idinium salt according to the usual procedure, and the crude
reaction mixture (66 mg) was dissolved in MeOH (2 mL) and
treated with a solution of K2CO3 (120 mg) in H2O (2 mL). After
2 h, the usual workup afforded a crude oil that was chromato-
graphed, eluting first with CH2Cl2-MeOH, 20:1, and then with
MeOH, obtaining the 1:1 diastereomeric mixture 13 (26 mg, 68%)
as a pale yellow oil: 1H NMR (CDCl3) δ 7.40-6.70 (m, 10 H +
10 H), 3.91 (t, J ) 6.6 Hz, 2 H), 3.20 (t, J ) 7.6 Hz, 2 H), 2.81
(m, 1 H), 2.49 (m, 3 H), 2.30-1.50 (m, 8 H + 6 H);13C NMR
(CDCl3) δ 131.5 (s, 2 C), 130.5 (s, 2 C), 127.9 (d, 4 C), 127.8 (d,
4 C), 127.2 (d, 4 C), 126.8 (d, 4 C), 126.1 (d, 2 C), 126.0 (d, 2 C),
72.6 (d), 70.0 (d), 65.1 (d, 2 C), 65.0 (d, 2 C), 40.3 (d, 2 C), 35.7
(d, 2 C), 32.4 (d, 2 C), 26.2 (d, 2 C); MS m/z 263 (M+, 30), 104
(100); IR (CDCl3) 2872, 2794, 2713, 2650 cm-1 (Bohlmann
bands).
(3S,5S,7a S)-(-)-3,5-Dip h en ylp yr r olizid in e (7a ). To a solu-
tion of salt 6d (90 mg, 0.2 mmol) in MeOH (2.5 mL) was added
a solution of K2CO3 (160 mg, 1.16 mmol) in water (1.6 mL), and
the resulting suspension was left under stirring at room tem-
perature. After 2 h, 2 N HCl was added up to pH 1-1.5, and
the solution was extracted with Et2O (2 × 5 mL). To the aqueous
layer was then added K2CO3 (s) up to pH 9-10, followed by
extraction with chloroform (2 × 10 mL). The latter organic layer
was dried over Na2SO4, filtered, and evaporated to give pure 7a
(38 mg, 72%) as a white solid: mp 40-41 °C; [R]25 -78.5 (c
D
0.61, CHCl3); 1H NMR (CDCl3) δ 7.00 (m, 8 H), 6.89 (m, 2 H),
4.32 (m, 1 H), 4.02 (m, 1 H), 3.67 (dd, J ) 9.2, 6.3 Hz, 1 H),
2.25-1.90 (m, 4 H), 1.85-1.40 (m, 4 H); 13C NMR (CDCl3) δ 131.5
(s), 129.5 (s), 129.2 (d, 2 C), 127.6 (d, 4 C), 127.2 (d), 126.7 (d, 2
C), 125.9 (d), 66.4 (d), 64.5 (d), 66.2 (d), 37.8 (t), 33.3 (t), 31.4 (t),
28.6 (t); MS m/z 263 (M+, 44), 104 (100). Anal. Calcd for
C
19H21N: C, 86.65; H, 8.04; N, 5.32. Found: C, 86.81; H, 8.13;
N, 5.21.
(3S,5S,7a S)-(-)-3,5-Bis(2-m eth oxyp h en yl)p yr r olizid in e
(7b). Aminodiol 5e (99 mg, 0.195 mmol) was converted into crude
salt 6e (92 mg, 93%) as reported above. This was not purified
but used directly for the deprotection step performed as de-
scribed for 7a . Pyrrolizidine 7b (49 mg) was obtained as a low-
melting compound in 78% yield: [R]25 -57.2 (c 0.13, CHCl3);
D
1H NMR (CDCl3) δ 7.51 (d, J ) 7.0 Hz, 1 H), 7.31 (d, J ) 7.6 Hz,
1 H), 7.00-6.80 (m, 2 H), 6.74 (m, 2 H), 6.36 (d, J ) 8.0 Hz, 1
H), 6.23 (d, J ) 8.4 Hz, 1 H), 4.44 (m, 1 H), 4.14 (dd, J ) 10.3,
5.2 Hz, 1 H), 3.81 (m, 1 H), 3.43 (s, 3 H), 3.40 (s, 3 H), 2.25-
1.90 (m, 4 H), 1.60-1.30 (m, 4 H); 13C NMR (CDCl3) δ 158.2 (s),
155.8 (s), 128.3 (d, 2 C), 128.1 (d, 2 C), 120.0 (s), 119.7 (d), 119.1
(s), 118.8 (d), 108.8 (d, 2 C), 65.6 (d), 65.4 (d), 60.1 (d), 54.9 (q),
54.5 (q), 36.0 (t), 33.7 (t), 31.3 (t), 26.2 (t); MS m/z 323 (M+, 46),
91 (100). Anal. Calcd for C21H25NO2: C, 78.00; H, 7.79; N, 4.33.
Found: C, 78.39; H, 7.42; N, 4.08.
Ack n ow led gm en t. The authors thank Ministero
dell’Universita` e della Ricerca Scientifica e Tecnologica
(MURST) and Consiglio Nazionale delle Ricerche (CNR)
for financial support. E.G.O. thanks Universita` di
Firenze for a two-year postdoctoral fellowship. Dr.
Cristina Faggi, Mrs. Brunella Innocenti, and Mr. Sandro
Papaleo are acknowledged for their technical assistance.
(1S,4R,7R)- a n d (1S,4S,7R)-1,7-Dip h en yl-4-n itr oh ep ta n e-
1,7-d iol (12). To a solution of (+)-DIP-Cl (343 mg, 1.07 mmol)
in CH2Cl2 (5 mL) cooled at -25 °C was added a solution of 11
(313 mg, 0.96 mmol) in CH2Cl2 (2 mL), under stirring and N2
atmosphere. After 5 h, the solvent was evaporated and the
R-pinene removed under high vacuum (0.15 mbar). The residue
J O981946I