Solvent-free asymmetric aminoalkylation of electron-rich aromatic compounds: Stereoselective synthesis of aminoalkylnaphthols by crystallization-induced asymmetric transformation

Article abstract of DOI:10.1021/jo0101205

Electron-rich aromatic compounds such as 2-naphthol give a faster and asymmetric 1-aminoalkylation with high yields when treated with (R)-1-phenylethylamine and aromatic aldehydes in solvent-free conditions. An asymmetric transformation of a second kind, probably induced by the preferential crystallization of one diastereomer, affords the straightforward and stereoselective synthesis of aminoalkylnaphthols. Mechanisms predictable for this asymmetric reaction are reported. The absolute configurations and the conformations of the unknown aminonaphthols are widely ascertained.

Full text of DOI:10.1021/jo0101205

J . Org. Chem. 2001, 66, 4759-4765
4759
Solven t-F r ee Asym m etr ic Am in oa lk yla tion of Electr on -Rich
Ar om a tic Com p ou n d s: Ster eoselective Syn th esis of
Am in oa lk yln a p h th ols by Cr ysta lliza tion -In d u ced Asym m etr ic
Tr a n sfor m a tion
Cristina Cimarelli,† Andrea Mazzanti,‡ Gianni Palmieri,*,† and Emanuela Volpini†
Dipartimento di Scienze Chimiche, Universita di Camerino, via s. Agostino 1, 62032 Camerino, Italy, and
Dipartimento di Chimica Organica “A.Mangini”, Universita degli Studi di Bologna, viale Risorgimento 4,
40136 Bologna, Italy
palmieri@camserv.unicam.it
Received J anuary 30, 2001
Electron-rich aromatic compounds such as 2-naphthol give a faster and asymmetric 1-aminoalky-
lation with high yields when treated with (R)-1-phenylethylamine and aromatic aldehydes in solvent-
free conditions. An asymmetric transformation of a second kind, probably induced by the preferential
crystallization of one diastereomer, affords the straightforward and stereoselective synthesis of
aminoalkylnaphthols. Mechanisms predictable for this asymmetric reaction are reported. The
absolute configurations and the conformations of the unknown aminonaphthols are widely
ascertained.
Sch em e 1. En a n tioselective Alk yla tion of
In tr od u ction
Ben za ld eh yd e Ca ta lyzed by th e Am in op h en ol
(R,R)-12a a n d th e Am in on a p h th ol (R,R)-3a
The search for new metal-catalyzed asymmetric reac-
tions has provided some fascinating insights into the
effects imposed on the metal catalysts by chiral ligands.
A practical consequence is the discovery of ligand-
accelerated catalysis (LAC).1 Thus, an existing catalyzed
process is improved by the addition of a specific ligand,
which leads to a faster “ligand-accelerated” reaction. The
concept is especially valuable in reactions catalyzed by
early transition metals.2
In previous work, we have found that a catalytic
amount of enantiopure aminophenol (R,R)-12a and ami-
nonaphthol (R,R)-3a considerably accelerates the addi-
tion of dialkylzincs to aldehydes, affording the corre-
sponding alcohols in good enantiomeric purity3 (see
Scheme 1). The precatalyst aminophenol (R,R)-12a is an
accessible compound generally obtained by stereoselec-
tive reduction of the corresponding 2-imidoylphenol.4 The
aminoalkylation of electron-rich aromatic compounds (the
aromatic Mannich reaction) is an alternative route to
aminonaphthol 3.5 Here, we report the results of our work
in the straightforward and stereoselective synthesis of
aminoalkylnaphthols (R,R)-3 (see Scheme 2).
Sch em e 2. Syn th esis of En a n tiop u r e
Am in oa lk yln a p h th ols (R,R)-3a -l by Solven t-F r ee
Asym m etr ic Ma n n ich Rea ction
Resu lts a n d Discu ssion
Electron-rich aromatic compounds as 2-naphthol give
1-aminoalkylation with high yields and dr when treated
with (R)-1-phenylethylamine and aromatic aldehydes (see
Scheme 2 and Table 1, entries 1-7). Less reactive
* To whom correspondence should be addressed. Fax: (+39) 0737
637345.
† Universita di Camerino.
‡ Universita degli Studi di Bologna.
(1) Berrisford, D. J .; Bolm, C.; Sharpless, K. B. Angew. Chem., Int.
Ed. Engl. 1995, 34, 1059-1070.
(2) Brunner, H. Synthesis 1988, 645-654.
(3) Palmieri, G. Tetrahedron: Asymmetry 2000, 11, 3361-3373.
(4) (a) Palmieri, G. Eur. J . Org. Chem. 1999, 805-811. (b) Cimarelli,
C.; Palmieri, G. Tetrahedron 1998, 54, 15711-15720.
1-naphthol and 8-quinolinol give 2- and 7-aminoalkyla-
tion, respectively, with moderate yields (see Scheme 2
and Table 1, entries 11, 12). The use of enantiopure
10.1021/jo0101205 CCC: $20.00 © 2001 American Chemical Society
Published on Web 06/19/2001

4760 J . Org. Chem., Vol. 66, No. 14, 2001
Cimarelli et al.
Ta ble 1. Ster eoselective Syn th esis of
o-Hyd r oxya r yla m in e (R,R)-3 by Ma n n ich Rea ction
Sch em e 3. Syn th esis of Am in on a p h th ols 3h ,i, 5a ,
Na p h th oxa zin es 6a a n d 7h , a n d Vin yln a p h th ol 11i
time yielda
entry
HO-Ar
R
(R,R)-3
(h)
(%)
drb
99
24
4.1
4.3
3.0
9.5
4.7
6.1
66
32
2.4
1.4
1
2
2-naphthol C6H5
2-naphthol 4-MeC6H4
(R,R)-3a
(R,R)-3b
8
8
14
7
14
20
30
12
24
28
8
93
72
66
72
86
54
62
41
45
48
50
44
3
4
2-naphthol 4-MeOC6H4 (R,R)-3c
2-naphthol 4-ClC6H4 (R,R)-3d
5
6
7
2-naphthol 3-NO2C6H4 (R,R)-3e
2-naphthol 1-naphthyl (R,R)-3f
2-naphthol 2-naphthyl (R,R)-3g
8
9
10
11
12
2-naphthol 1-hexyl
2-naphthol cyclohexyl
2-naphthol iPr
1-naphthol C6H5
8-quinolinol C6H5
(R,R)-3h
(R,R)-3i
(R,R)-3j
(R,R)-3k
(R,R)-3l
20
a
b
Yields of the pure isolated major diastereomer. The dr value
were determined by HPLC or by 1H NMR of the reaction mixture.
1-phenylethylamine, very accessible in both the enan-
tiomeric forms, allows the preparation of both the enan-
tiopure aminonaphthols with moderate to high yields.
The reaction was performed in solvent-free conditions:
a mixture of naphthol, (R)-1-phenylethylamine, and the
aldehyde, in a molar ratio of 1.0:1.05:1.2, respectively,
was stirred and heated to 60 °C for the time required,
under inert atmosphere. It is possible to observe after
mixing the separation of some drops of water and, during
the course of the reaction, a rise of the reaction mixture
viscosity to obtain in some entries a final semisolid and
crystalline mass. When high dr were obtained, the pure
and crystalline major diastereomer could be isolated in
a simpler manner by dispersion of the crude reaction
mixture in a few milliliters of ethanol. In all cases, the
pure diastereomers were obtained without any workup
but by direct chromatographic separation of the crude
reaction mixture. All the unknown aminonaphthols 3a -l
prepared have been fully characterized by spectroscopic
methods.
With aliphatic aldehydes only (Table 1, entries 8-10),
a moderate conversion was observed, with the recovery
of a considerable amount of the starting 2-naphthol and
the formation of byproducts as the naphthoxazine 7h and
the 1-cyclohexylidenemethyl-2-naphthol 11i deriving from
elimination of the auxiliary amine (see Scheme 3a,b).
Contrary to that reported for the classical condition
adopted in the Betti reaction,5a-j in this case the forma-
tion of oxazine 7 was generally not observed, probably
because of a larger steric hindrance of the 1-phenylethyl-
amine with respect to benzylamine. In fact, when the
latter was used, the corresponding oxazine 6a was
isolated as byproduct (28% yield) together with the
aminonaphthol 5a 5f (57% yield, see Scheme 3c). The
oxazine 7 was obtained as a byproduct only when
heptaldehyde was used (7h ) and was not obtained with
the other aldehydes with major steric hindrance.
The reaction carried out in refluxing ethanol as solvent
(the classical conditions adopted for the aminoalkylation5)
is slow (85% conversion after 15 h, Vo ) 1.7 mM/min) if
compared with our reaction conditions, and the product
(R,R)-3a shows a moderate dr ) 1.3. Under our condi-
tions (absence of solvent), the reaction is quicker (Vo )
7.9 and 23.7 mM/min, respectively, at 20 and 60 °C);
moreover, an increase of the dr for (R,R)-3 from good to
high final value was observed, as reported in the Figure
1 and Table 1. Generally, the progress of the reaction is
1
followed by TLC and HPLC analysis. H NMR analysis
of the reaction mixture stopped at different times showed
the trends reported in Figure 1 for (R,R)-3a . Although
the reaction is faster in solvent-free conditions at 20 °C,
the asymmetric transformation in the initial mixture of
diastereomers takes place only at 60 °C. This is a typical
situation of “asymmetric transformation of second kind”
induced by the preferential crystallization of a diastere-
omer6 (see Scheme 4a).
The mechanisms theoretically predictable for this
asymmetric transformation are reported in Scheme 4.
The pathway A, assumed for the synthesis of the ami-
nonaphthol 3, can be theoretically reversible, allowing
the epimerization process, but has been experimentally
(5) (a) Arend, M.; Westermann, B.; Risch, N. Angew. Chem., Int.
Ed. 1998, 37, 1044-1070. (b) Tramontini, M. Synthesis 1973, 703-
775. (c) Tramontini, M.; Angiolini, L. Tetrahedron 1990, 46, 1791-
1837. (d) Heaney, H. Comprehensive Organic Synthesis; Trost, B. M.,
Ed.; Pergamon: Oxford, 1991; Vol. 2, p 953-973. (e) Betti, M. Organic
Syntheses; Wiley: New York, 1941; Collect. Vol. I, pp 381-383. (f)
Cardellicchio, C.; Ciccarella, G.; Naso, F.; Schingaro, E.; Scordari, F.
Tetrahedron: Asymmetry 1998, 9, 3667-3675. (g) Cardellicchio, C.;
Ciccarella, G.; Naso, F.; Perna, F.; Tortorella, P. Tetrahedron 1999,
55, 14685-14692. (h) Mohrle, H.; Miller, C.; Wendisch, D. Chem. Ber.
1974, 107, 2675-2682. (i) Burke, W. J .; Nasutavicus, W. A.; Weath-
erbee, C. J . Org. Chem. 1964, 29, 407-410. (j) Adamek, M.; Bobulova,
P.; Glask, S. Frantisek, G.; Kovacikova, A.; Novak, L.; Strouhal, F.
Czechosl. Patent 133091, 1969; Chem. Abstr. 1970, 73, 87933. (k) Burke,
W. J .; Kolbezen, M. J .; Stephens, C. W. J . Am. Chem. Soc. 1952, 74,
3601-3605. (l) Grumbach, H. J .; Arend, M.; Risch, N. Synthesis 1996,
883-887.

Stereoselective Synthesis of Aminoalkylnaphthols
J . Org. Chem., Vol. 66, No. 14, 2001 4761
Sch em e 4. Asym m etr ic Tr a n sfor m a tion of th e
Secon d Kin d In d u ced by th e P r efer en tia l
Cr ysta lliza tion of th e Dia ster eom er (R,R)-3a
[R*-NH2 ) (R)-1-P h en yleth yla m in e]
F igu r e 1. Conversion and dr observed in the solvent-free
synthesis of (R,R)-3a at 60 or 20 °C reaction temperature.
verified to be too slow for it: both the pure diastereomers
(R,R)- and (1S,1′R)-3a were stable for many days, also
at 60 °C. The pathways B and C are both possible, but
the second one has been experimentally found to be faster
and so preferentially followed (see Scheme 5). To ascer-
tain which is the way to product (R,R)-3a , some experi-
mental attempts were made on diastereomer (1S,1′R)-
3a . Product (1S,1′R)-3a has been refluxed in the presence
of a 4-fold excess of benzylamine, and it has scarcely
afforded product 5a (Scheme 5, reaction conditions ii).
In the presence of a 4-fold excess of benzaldehyde
(reaction conditions i), the same product interconverts
almost quantitatively in its diastereoisomer (R,R)-3a ,
while under the same conditions the transformation from
(R,R)-3a to (1S,1′R)-3a does not take place. In the
presence of benzaldehyde and benzylamine (reaction
conditions iii), product 5a is easily obtained from (1S,1′R)-
3a . All this experimental evidence, allows us to conclude
that path C is preferentially followed instead of path B.
This pathway C can pass through two alternative inter-
mediates, both theoretically possible: 8a 2, which under-
goes the reversible cycloaddition [pathway C1, followed
in the reaction conditions i and iii, Scheme 5, affording
(R,R)-3a and 5a , respectively] or necessarily through the
spiroazetidine intermediate 10 [pathway C2, followed in
the reaction conditions iv, Scheme 5, with formation of
(R,R)-3b]. It is noteworthy that the difference in the heat
of formation of the diastereomer (R,R)- and (1S,1′R)-3a
(0.41 kcal/mol) is too low to justify the high dr obtained
even at 60 °C. Therefore, an asymmetric transformation
of the second kind induced by the preferential crystal-
lization of a diastereomer may be assumed. None of the
aminonaphthols (R,R)-3a -l gives a spontaneous asym-
metric transformation when dissolved in ethanol or
chloroform as we have previously observed in the case
of the comparable aminophenol (1S,1′R)-12b, which gives
a spontaneous epimerization to (R,R)-12b (dr ) 7) when
dissolved in chloroform (see Scheme 6). The crystals of
starting pure aminophenol (1S,1′R)-12b can again be
obtained by slow evaporation of the solvent, and this
phenomenon can be observed for many of the cycles
(unpublished results). The intermediate 13, sterically less
hindered than the comparable 8a , can be hypothesized
as the intermediate of this asymmetric transformation
(pathway B, Scheme 4). Because of the lesser steric
hindrance, any spontaneous epimerization was observed
when aminophenols (R,R)- and (1S,1′R)-12a were dis-
solved in chloroform (see Scheme 6).
Ster eoch em istr y
(6) (a) Harris, M. M. The Study of Optically Labile Compounds. Prog.
Stereochem. 1958, 2, 157. (b) J acques, J .; Collet, A.; Wilen, S. H.
Enantiomers, Racemates and Resolutions; Wiley: New York, 1981, p
374. (c) Buchanan, C.; Graham, S. H. J . Chem. Soc. 1950, 500-507.
(d) Eliel, E. Stereochemistry of Carbon Compounds; McGraw-Hill: New
York, 1962, p 63. (e) Mason, S. F. Molecular Optical Activity and the
Chiral Discriminations; Cambridge University Press: Cambridge, UK,
1982; p 208.
The stereochemistry of the unknown aminonaphthols
3a -l was attributed on the basis of the following con-
siderations. In all the aminonaphthols 3a -l, the HN of
one diastereoisomers is shifted upfield by 0.24-0.57 ppm
than the other (see Figure 5 in the Supporting Informa-

4762 J . Org. Chem., Vol. 66, No. 14, 2001
Cimarelli et al.
Sch em e 5. Asym m etr ic Tr a n sfor m a tion of
(1S,1′R)-3a to (R,R)-3a a n d to (R,R)-3b a n d 5a in
th e Solven t-F r ee Rea ction a
F igu r e 2. More stable conformations of aminonaphthols
(R,R)- and (1S,1′R)-3a (PM3 semiempirical minimization).
a
Reagents: (i) 4 equiv of Ph-CHO, 60 °C, 6 h; (ii) 4 equiv of
Bn-NH2, 60 °C, 6 h; (iii) 4 equiv of Ph-CHO, 4 equiv of Bn-NH2,
60 °C, 6 h; (iv) 4 equiv of p-Tol-CHO, 60 °C, 6 h.
Sch em e 6. Asym m etr ic Tr a n sfor m a tion of
Secon d Kin d In d u ced by th e P r efer en tia l
Cr ysta lliza tion of th e Dia ster eom er (1S,1′R)-12b
[R*-NH2 ) (R)-1-P h en yleth yla m in e]
tion). This trend can be easily rationalized by observing
that in the more stable conformations of the possible two
diastereoisomers, obtained with PM3 semiempirical mini-
mization,7 the phenyl group of the auxiliary amine exer-
cises a shielding magnetic anisotropy on the proton HN
at the new stereogenic center in the (R,R) diastereo-
1
isomer (see Figure 2). NOE H NMR experiments were
carried out on oxazines (R,R)- and (1S,1′R)-4a and on
aminonaphthols (R,R)- and (1S,1′R)-3f to have experi-
mental confirmation of configurations and conformations
of aminonaphthol 3. The structural assignments of the
two diastereoisomers of 4a (see Figure 3) were achieved
F igu r e 3. More stable conformations of naphthoxazines (R,R)-
and (1S,1′R)-4a (PM3 semiempirical minimization) and some
sections of the 1H NMR spectrum with the respective NOE
experiments (Me irradiation).
1
by NOE H NMR experiments (see Figure 3).8 Inversion
of the Me lines of (1S,1′R)-4a enhances HN and the
geminal HC. The same experiment applied to (R,R)-4a
enhances HA and the geminal HC. A negative effect is
(7) Semiempirical PM3 calculations were performed with the Spar-
tan 5.0.3, Wavefunction, Inc., 18401 Von Karmen Ave., No. 370, Irvine,
CA 92715.

Stereoselective Synthesis of Aminoalkylnaphthols
J . Org. Chem., Vol. 66, No. 14, 2001 4763
Ta ble 2. Dista n ce Ra tio Obta in ed fr om Sp ectr a l Da ta
(NOE 1H NMR) a n d Th eor etica l Ca lcu la tion s (P M3
Min im iza tion Molecu la r Mod elin g) for th e Dia ster eom er s
(R,R)- a n d (1S,1′R)-4a
(R,R)-4a
(1S,1′R)-4a
target peak
Me
ratio
NOE ratio calcd NOE ratio calcd
1.04
1.69
1.76
1.04
1.60
1.68
>2a
∼2a
1.86
1.77
0.96
1.77
1.03
6 H / H
x
C
A
N
6 H / H
Me
x
A
6 H /H
Me
0.94
x
C
N
6 H / H
Me
1.88
1.00
x
N
B
B
A
B
B
6 H / H
Me
x
N
6 H / H
CH(Me)
CH(Me)
CH(Me)
CH(Me)
CH(Me)
CH(N)
CH(N)
CH(N)
1.43
1.16
1.66
1.33
1.16
1.54
x
N
6 H / H
F igu r e 4. X-ray crystal structure of syn-(R,R)-3f.
x
A
6 H / H
1.00
1.13
1.13
1.37
1.20
1.60
1.03
1.07
1.04
1.32
1.11
1.49
conformational analysis (PM3 minimization)7 (see Figure
6 in the Supporting Information). Inversion of the Me
lines of (1S,1′R)-3f enhances HN.
x
N
6 HMe/ HN
6 HMe/ HB
x
x
Finally, to confirm the structures of aminonaphthols
3a -l, an X-ray study on the (R,R)-3f was carried out
(Figure 4). The X-ray structure is very similar to that
obtained by molecular modeling (see Figure 6 in the
Supporting Information), showing a strong hydrogen
bond between OH and N atom, which gives rigidity to
the structure and makes it suitable for NOE experiments,
without the need to cyclize the aminonaphthol 3 to the
corresponding naphthoxazine 4. In addition, X-ray stud-
ies confirm the syn-(R,R)-3f structure as more stable than
the anti conformations as previously calculated (see
Figure 6 in the Supporting Information). This preferred
conformation rationalizes the particularly downfield
chemical shift [6.80 and 6.31 ppm, respectively, for the
(1S,1′R)- and (R,R)-3f] observed for the benzylic hydrogen
atom HN, which suffers the deshielding effect of the two
syn-naphthyl groups surrounding it.
6 H / H
x
C
A
6 HMe/ HC
6 HMe/ HA
x
x
a
The DPFGSE NOE sequence can reveal NOE effects of about
0.1%.8
detected over HB, and a very little effect is detected for
HN. Detailed experimental and theoretical distance ratios
are reported in Table 2. The NOE constraints obtained
for the two prepared diastereomers (R,R)- and (1S,1′R)-
4a (see Table 2) are consistent with the calculated
structure (PM3 minimization), respectively, for (R,R)- and
(1S,1′R)-4a .7 Assignment of HA and HB was possible
4
because of the J coupling with HN that is observable in
six-membered cycles only when the “W” path is avail-
4
able.9 The J is observable in the (R,R)-4a isomer on HA
(J ) 1.9 Hz) and in the (1S,1′R)-4a on HB (J ) 2.1 Hz).
As observed for aminonaphthols 3a -l, the large shift
to high field of the HN signal in the spectrum of the (R,R)-
4a isomer with respect to (1S,1′R)-4a (∆δ ) 0.55 ppm)
and of HB, which assumes in the (1S,1′R)-4a the equiva-
lent position of HA in (R,R)-4a (∆δ ) 0.70 ppm, see Figure
3), can be understood on the basis of the position of these
hydrogens, which are more or less axial with respect to
the phenyl group of the auxiliary amine. This feature is
known to move significantly upfield the chemical shifts
of the hydrogens involved and has already been used as
a diagnostic tool to assign the stereochemistry in other
compounds of this kind.10 These findings demonstrate
that the strong intermolecular hydrogen bond forces the
aminonaphthols 3a -l to assume a conformation very
similar to that of the naphthoxazine 4a .
Con clu sion
In summary, a straightforward and stereoselective
synthesis of aminoalkylnaphthols (R,R)-3a -l, which are
useful chiral ligands for metal-catalyzed asymmetric re-
actions, is reported. This solvent-free very simple syn-
thetic methodology, through an asymmetric aminoalky-
lation of electron-rich aromatic compounds, shows a
phenomenon of crystallization-induced asymmetric trans-
formation. The absolute configurations and conforma-
tions of the products are determined by molecular
1
modeling, NOE H NMR experiments, and X-ray crystal-
lography.
Exp er im en ta l Section
Gen er a l P r oced u r e for th e Syn th esis of Am in oa lk yl-
n a p h th ol (R,R)-3. In the following typical procedure, a
mixture of 2-naphthol (0.72 g, 5.0 mmol), benzaldehyde (0.64
g, 6.00 mmol), and (R)-(+)-1-phenylethylamine (0.64 g, 5.25
mmol) was stirred at 60 °C for 8 h under nitrogen atmosphere.
Following the progress of the reaction by TLC and 1H NMR,
it was seen that the formation of the product occurs during
the first 4 h but the initial dr of (R,R)-3a (2.6 at 2 h) increases
over time (99 at 8 h) with the formation of a solid and
crystalline reaction mixture. The reaction mixture was dis-
persed at room temperature with EtOH (5 mL). The white
crystals separated were collected and washed with EtOH (3
× 3 mL). The crystalline white residue, purified by crystal-
lization from EtOAc/hexane, gives the pure (R,R)-3a (1.64 g,
4.65 mmol, yield 93%). The same procedure was used for
Structural assignment of the two diastereomers (R,R)-
and (1S,1′R)-3f was analogously achieved through NOE
1H NMR experiments, validating the results obtained by
(8) Stott, K.; Stonehouse, J .; Keeler, J .; Hwang, T.-L.; Shaka, A. J .
J . Am. Chem. Soc. 1995, 117, 4199-4200.
(9) Barfield, M.; Chakrabarti, D. Chem. Rev. 1969, 6, 757-778.
(10) Harada, N.; Watanabe, M.; Kuwahara, S.; Sugio, A.; Kasai, Y.;
Ichikawa, A. Tetrahedron: Asymmetry 2000, 11, 1249-1253.
(11) Since with the DPFGSE sequence it is intrinsically difficult to
obtain the NOE percentage enhancements value, the standard NOE-
difference sequence was used to find the value of the largest NOE
peaks, and the other values were scaled by calculations. See also:
Claridge, T. D. W. In High-resolution NMR techniques in Organic
Chemistry; Pergamon Press: New York, pp 320-322.

4764 J . Org. Chem., Vol. 66, No. 14, 2001
Cimarelli et al.
1-naphthol and 8-quinolinol. At the end of the reaction time,
the pure aminoalkylnaphthol (R,R)-3 can be isolated by flash
chromatography directly from the reaction mixture without
further workup. The characterization of the newly prepared
aminonaphthols 3a -l follows. Where only the major diaster-
s, 1 H), 3.96 (q, 1 H, J ) 6.7 Hz), 5.82 (s, 1 H), 7.05-7.80 (m,
15 H), 13.80 (br s, 1 H).
1-[(R)-(3-Nit r op h en yl)[[(1′R)-1′-p h en ylet h yl]a m in o]-
m eth yl]-2-n a p h th ol [(R,R)-3e]: yellow crystals; mp 154-157
°C (EtOH); [R]20D -215.1° (c 1.7, CHCl3); IR (Nujol) νmax 1621,
1529, 1350, 1235, 749 cm-1; 1H NMR (300 MHz, CDCl3) δ 1.55
(d, 3 H, J ) 6.9 Hz), 2.30 (br d, 1 H), 3.90-4.05 (m, 1 H), 5.56
(s, 1 H), 7.1-8.3 (m, 15 H), 13.30 (br s, 1 H); 13C NMR (75
MHz, CDCl3) δ 23.4, 57.1, 59.9, 112.4, 120.7, 121.0, 123.6,
127.0, 127.1, 128.4, 128.7, 129.3, 129.4, 130.6, 132.7, 134.7,
143.0, 143.6, 149.1, 157.8. Anal. Calcd for C25H22N2O3 (398.5):
C, 75.48; H, 5.39; N, 7.15. Found: C, 77.64; H, 5.79; N, 3.74.
1-[(S )-(3-Nit r op h e n yl)[[(1′R )-1′-p h e n yle t h yl]a m in o]-
m eth yl]-2-n a p h th ol [(1S,1′R)-3e]: yellow crystals; mp 156-
1
eomers were obtained pure by chromatography, the H NMR
signals for the minor diastereomers were deduced from the
spectra of the crude reaction mixtures or from enriched
chromatographic fractions.
1-[(R)-P h en yl[[(1′R)-1′-p h en ylet h yl]a m in o]m et h yl]-2-
n a p h th ol [(R,R)-3a ]: colorless crystals; mp 155-156 °C
(AcOEt-hexane); [R]20D -220.7° (c 2.1, CHCl3); IR (Nujol) νmax
3271, 1621, 1238, 1077, 743, 696 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 1.52 (d, 3 H, J ) 6.9 Hz), 2.35 (br s, 1 H), 3.92 (q, 1
H, J ) 6.9 Hz), 5.47 (s, 1 H), 7.15-7.83 (m, 16 H), 13.70 (br s,
1 H); 13C NMR (75 MHz, CDCl3) δ 23.0, 56.7, 60.3, 113.1, 120.1,
121.1, 122.4, 126.4, 126.7, 127.7, 127.9, 128.0, 128.7, 128.8,
129.0, 129.1, 129.8, 132.6, 141.5, 143.1, 157.3; MS (70 eV) 232
(M+ - 121, 38), 231 (100), 202 (23), 116 (21). Anal. Calcd for
160 °C (EtOH); [R]20 ) +156.9° (c 1.9, CHCl3); 1H NMR (300
D
MHz, CDCl3) δ 1.6 (d, 3 H, J ) 6.7 Hz), 2.27 (br s, 1 H), 3.96
(q, 1 H, J ) 6.7 Hz), 5.95 (s, 1 H), 7.10-8.30 (m, 15 H), 12.75
(br s, 1 H).
1-[(R)-(1-Na p h th yl)[[(1′R)-1′-p h en yleth yl]a m in o]m eth -
yl]-2-n a p h th ol [(R,R)-3f]: colorless crystals; mp 195-197 °C
C
25H23NO (353.5): C, 84.95; H, 6.56; N, 3.96. Found: C, 85.21;
H, 6.37; N, 3.77.
(CH2Cl2-hexane); [R]20 -484.73° (c 2.1, CHCl3); IR (Nujol)
D
1-[(S)-P h en yl[[(1′R)-1′-p h en ylet h yl]a m in o]m et h yl]-2-
n a p h th ol [(1S,1′R)-3a ]: colorless crystals; mp 139-141 °C
(AcOEt-hexane); [R]20D +168.53° (c 3.0, CHCl3); IR (Nujol) νmax
νmax 3307, 1621, 1238, 822, 779, 752, 700 cm-1; 1H NMR (300
MHz, CDCl3) δ 1.54 (d, 3 H, J ) 6.9 Hz), 2.22 (br d, 1 H, J )
11.1), 3.97 (br dq, 1 H, J ) 11.1, 6.9), 6.31 (s, 1 H), 6.90-7.90
(m, 18 H), 13.70 (br s, 1 H); 13C NMR (75 MHz, CDCl3) δ 21.6,
55.5, 56.5, 113.2, 120.0, 121.0, 121.7, 122.5, 125.6, 126.0, 126.6,
126.7, 127.0, 127.6, 128.3, 128.7, 128.77, 128.8, 128.9, 129.3,
129.8, 130.2, 132.8, 134.1, 135.3, 142.1, 158.1. Anal. Calcd for
1
3265, 1615, 1240, 1070 cm-1; H NMR (300 MHz, CDCl3): δ
1.62 (d, 3 H, J ) 6.7 Hz), 2.35 (br s, 1 H), 4.01 (q, 1 H, J ) 6.7
Hz), 5.92 (s, 1 H), 7.15-7.80 (m, 16 H), 13.70 (br s, 1 H); 13C
NMR (75 MHz, CDCl3) δ 21.6, 56.0, 60.7, 114.9, 120.8, 121.5,
122.9, 127.0, 127.1, 128.1, 128.4, 128.5, 129.2, 129.4, 129.5,
C
29H25NO (403.5): C, 86.32; H, 6.24; N, 3.47. Found: C, 86.29;
129.6, 130.2, 132.8, 141.9, 143.5, 157.2. Anal. Calcd for C25H23
NO (353.5): C, 84.95; H, 6.56; N, 3.96. Found: C, 85.18; H,
6.42; N, 3.72.
-
H, 6.23; N, 3.47. 1-[(S)-(1-Na p h th yl)[[(1′R)-1′-p h en yleth yl]-
a m in o]m eth yl]-2-n a p h th ol [(1S,1′R)-3f]: 1H NMR (300
MHz, CDCl3) δ 1.67 (d, 3 H, J ) 6.7), 2.20 (br s, 1 H), 4.20-
4.40 (m, 1 H), 6.80 (s, 1 H), 6.88-7.90 (m, 18 H), 13.20 (br s,
1 H).
1-[(R)-(4-Meth ylp h en yl)[[(1′R)-1′-p h en yleth yl]a m in o]-
m eth yl]-2-n a p h th ol [(R,R)-3b]: crystals; mp 132-134 °C
(hexane); [R]20 -191.9° (c 3.1, CHCl3); IR (Nujol) νmax 3309,
1-[(R)-(2-Na p h th yl)[[(1′R)-1′-p h en yleth yl]a m in o]m eth -
yl]-2-n a p h th ol [(R,R)-3g]: crystals; mp 154-157 °C (CH2Cl2-
D
1621, 1236, 1077, 744, 700 cm-1; H NMR (300 MHz, CDCl3)
1
δ 1.55 (d, 3 H, J ) 6.9 Hz), 2.31 (s, 3 H), 2.35 (br s, 1 H), 3.95
(br q, 1 H, J ) 6.9 Hz), 5.51 (s, 1 H), 7.07-7.80 (m, 15 H),
13.86 (br s, 1 H); 13C NMR (75 MHz, CDCl3) δ 21.6, 23.6, 57.2,
60.6, 113.9, 120.6, 121.7, 122.9, 126.9, 127.3, 128.2, 128.4,
129.2, 129.3, 129.5, 130.2, 130.3, 133.2, 138.3, 139.2, 143.7,
157.8. Anal. Calcd for C26H25NO (367.5): C, 84.98; H, 6.86; N,
3.81. Found: C, 84.87; H, 6.79; N, 3.75. 1-[(S)-(4-Meth yl-
p h e n yl)[[(1′R )-1′-p h e n yle t h yl]a m in o]m e t h yl]-2-n a p h -
th ol [(1S,1′R)-3b]: 1H NMR (300 MHz, CDCl3) δ 1.61 (d, 3 H,
J ) 6.7 Hz), 2.32 (s, 3 H), 2.35 (br s, 1 H), 3.98 (q, 1 H, J ) 6.7
Hz), 5.88 (s, 1 H), 7.0-7.80 (m, 15 H), 13.80 (br s, 1 H).
1-[(R)-(4-Meth oxyp h en yl[[(1′R)-1′-p h en yleth yl]a m in o]-
m eth yl]-2-n a p h th ol [(R,R)-3c]: colorless crystals; mp 109-
hexane); [R]20 -261.50° (c 2.3, CHCl3); IR (Nujol) νmax 3306,
D
1623, 1240, 1092, 820, 746, 668 cm-1
;
1H NMR (300 MHz,
CDCl3) δ 1.54 (d, 3 H, J ) 6.9 Hz), 2.38 (br d, 1 H, J ) 11.8
Hz), 3.97 (br dq, 1 H, J ) 11.8, 6.9 Hz), 5.63 (s, 1 H), 7.18-
7.86 (m, 18 H), 13.85 (br s, 1 H); 13C NMR (75 MHz, CDCl3) δ
23.5, 57.2, 61.0, 113.5, 120.6, 121.6, 122.9, 126.1, 126.6, 126.7,
127.0, 127.1, 127.3, 128.0, 128.5, 128.6, 128.9, 129.3, 129.5,
129.6, 130.3, 133.1, 133.5, 133.9, 139.4, 143.6, 157.9. Anal.
Calcd for C29H25NO (403.5): C, 86.32; H, 6.24; N, 3.47.
Found: C, 86.25; H, 6.21; N, 3.45. 1-[(S)-(2-Na p h th yl)[[(1′R)-
1′-p h en yleth yl]a m in o]m eth yl]-2-n a p h th ol [(1S,1′R)-3g]:
1H NMR (300 MHz, CDCl3) δ 1.64 (d, 3 H, J ) 6.7 Hz), 2.35
(br s, 1 H,), 4.15 (q, 1H, J ) 6.7 Hz), 6.07 (s, 1 H), 7.18-7.86
(m, 18 H), 13.80 (br s, 1 H).
112 °C (EtOH); [R]20 -190.4° (c 1.9, CHCl3); IR (Nujol) νmax
D
3307, 1511, 1215, 745 cm-1; 1H NMR (300 MHz, CDCl3) δ 1.51
(d, 3 H, J ) 6.8 Hz), 2.20 (br d, 1 H), 3.72 (s, 3 H), 3.90-4.00
(m, 1 H), 5.42 (s, 1 H), 6.75-7.85 (m, 15 H) 13.80 (br s, 1 H);
13C NMR (75 MHz, CDCl3) δ ) 23.0, 55.3, 56.6, 59.8, 113.6,
120.1, 121.1, 121.2, 122.6, 126.5, 126.7, 127.8, 128.0, 128.9,
129.0, 129.8, 129.9, 133.6, 143.0, 153.8, 157.0, 159.2. Anal.
Calcd for C26H25NO2 (383.5): C, 81.43; H, 6.57; N, 3.65.
Found: C, 81.58; H, 6.43; N, 3.72. 1-[(S)-(4-Meth oxyp h en yl-
[[(1′R)-1′-ph en yleth yl]am in o]m eth yl]-2-n aph th ol [(1S,1′R)-
1-[(1R)-1-[[(1′R)-1′-P h en yleth yl]a m in o]h ep tyl]-2-n a p h -
th ol [(R,R)-3h ]: oil; [R]20 -3.90° (c 1.0, CHCl3); IR (liquid
D
film) νmax 3306, 3060, 1622, 1467, 1378, 1120, 817, 745, 700
cm-1; 1H NMR (300 MHz, CDCl3) δ 0.78-1.92 (m, 17 H), 3.73
(q, 1 H, J ) 6.9 Hz), 4.38 (d d, 1 H, J ) 8.1, 5.4 Hz), 7.05-7.90
(m, 11 H), 13.10 (br s, 1 H); 13C NMR (75 MHz, CDCl3) δ )
14.6, 23.1, 23.5, 26.5, 29.4, 32.1, 35.4, 55.4, 56.0, 118.5, 120.3,
121.5, 122.8, 126.6, 127.1, 128.2, 129.3, 129.4, 129.5, 130.2,
133.1, 143.8, 156.9. Anal. Calcd for C25H31NO (361.5): C, 83.06;
H, 8.64; N, 3.87. Found: C, 83.16; H, 8.63; N, 3.86.
1
3c]: H NMR (300 MHz, CDCl3) δ 1.60 (d, 3 H, J ) 6.7 Hz),
2.20 (br s, 1 H) 3.74 (s, 3 H), 4.01 (q, 1 H, J ) 6.7 Hz), 5.84 (s,
1 H), 6.75-7.85 (m, 15 H) 13.80 (br s, 1 H).
1-[(1S)-1-[[(1′R)-1′-P h en yleth yl]a m in o]h ep tyl]-2-n a p h -
1
th ol [(1S,1′R)-3h ]: H NMR (300 MHz, CDCl3) δ 0.78-1.92
1-[(R)-(4-Ch lor op h en yl)[[(1′R)-1′-p h en yleth yl]a m in o]-
m eth yl]-2-n a p h th ol [(R,R)-3d ]: colorless crystals; mp 132-
(m, 17 H), 3.81 (q, 1 H, J ) 6.6 Hz), 4.90 (t, 1 H, J ) 6.6 Hz),
7.05-7.90 (m, 11 H), 13.10 (br s, 1 H). 1-[(R)-Cycloh exyl-
[[(1′R)-1′-p h en yleth yl]a m in o]m eth yl]-2-n a p h th ol [(R,R)-
140 °C (EtOH); [R]20 -192.0° (c 3.5, CHCl3); IR (Nujol) νmax
D
1619, 1271, 1090, 951, 831, 703 cm-1
;
1H NMR (300 MHz,
3i]: crystals; mp 158-161 °C (CH2Cl2-hexane); [R]20 -5.93°
D
CDCl3) δ 1.51 (d, 3 H, J ) 6.8 Hz), 2.25 (br s, 1 H), 3.88 (q, 1
H, J ) 6.8 Hz), 5.42 (s, 1 H), 7.05-7.80 (m, 15 H), 13.60 (br s,
1 H); 13C NMR (75 MHz, CDCl3) δ 23.5, 57.1, 60.1, 113.2, 120.6,
121.4, 123.1, 127.0, 127.1, 128.5, 129.2, 129.4, 129.5, 129.6,
129.7, 130.5, 132.9, 134.3, 140.4, 143.4, 157.7. Anal. Calcd for
(c 2.1, CHCl3); IR (Nujol) νmax 3293, 1621, 1456, 1377, 1092,
1
816, 742, 702 cm-1; H NMR (300 MHz, CDCl3) δ 0.90-1.28
(m, 6 H), 1.46 (d, 3 H, J ) 6.9 Hz), 1.50-1.90 (m, 5 H), 2.27
(br d, 1 H, J ) 10.7 Hz), 3.68 (br dq, 1 H, J ) 10.7, 6.9 Hz),
4.16 (d, 1 H, J ) 6.1 Hz), 7.00-7.80 (m, 11 H), 13.18 (s, 1 H);
13C NMR (75 MHz, CDCl3) δ 23.2, 26.1, 26.2, 26.3, 29.0, 30.5,
42.4, 55.3, 60.1, 114.6, 119.7, 121.7, 122.1, 125.9, 126.7, 127.6,
128.6, 128.7, 128.8, 129.0, 133.4, 143.4, 156.9. Anal. Calcd for
C
25H22ClNO (387.9): C, 77.41; H, 5.72; N, 3.61. Found: C,
77.64; H, 5.79; N, 3.74. 1-[(S)-(4-Ch lor op h en yl[[(1′R)-1′-
p h en yleth yl]a m in o]m eth yl]-2-n a p h th ol [(1S,1′R)-3d ]: 1H
NMR (300 MHz, CDCl3) δ 1.58 (d, 3 H, J ) 6.7 Hz), 2.25 (br
C
25H29NO (359.5): C, 83.52; H, 8.13; N, 3.90. Found: C, 83.36;

Stereoselective Synthesis of Aminoalkylnaphthols
J . Org. Chem., Vol. 66, No. 14, 2001 4765
H, 8.14; N, 3.91. 1-[(S)-cycloh exyl[[(1′R)-1′-p h en yleth yl]-
a m in o]m eth yl]-2-n a p h th ol [(1S,1′R)-3i]: 1H NMR (300
MHz, CDCl3) δ 0.90-1.28 (m, 6 H), 1.46 (d, 3 H, J ) 6.9 Hz),
1.50-1.90 (m, 5 H), 2.20-2.38 (m, 1 H), 3.85 (br q, 1 H, J )
6.9 Hz), 4.55 (bd, 1 H, J ) 6.2 Hz), 7.00-7.80 (m, 11 H), 13.18
(s, 1 H);
Gen er a l P r oced u r e for th e P r ep a r a tion of th e 2,3-
Dih yd r o-1H-n a p h th o[1,2-e][1,3]oxa zin e 4. To a solution of
aminonaphthol 3 (2 mmol) in THF (3 mL) was added 35%
aqueous formaldehyde (2.2 mmol). The solution was stirred
for 15 h at room temperature. Solvent was removed and the
residue dried under reduced pressure. The crude material was
purified by filtration through an SiO2 pad eluting with
CH2Cl2.
1-[(1R)-2-Meth yl-1-[[(1′R)-1′-ph en yleth yl]am in o]pr opyl]-
2-n a p h t h ol [(R,R)-3j]: crystals; mp 137-139 °C (CH2Cl2-
hexane), [R]20 -10.95° (c 2.0, CHCl3); IR (Nujol) νmax 3337,
D
(1R)-1-P h en yl-2-[(1′R)-1′-p h en yleth yl]-2,3-d ih yd r o-1H-
n a p h th o[1,2-e][1,3]oxa zin e [(R,R)-4a ]: crystals; mp 125-
128 °C (hexane); [R]20D -132.50° (c 3.2, CHCl3); IR (Nujol) νmax
1622, 1233, 950, 744 cm-1; 1H NMR (300 MHz, CDCl3) δ 1.57
(d, 3 H, J ) 6.6 Hz), 4.01 (q, 1 H, J ) 6.6 Hz), 4.96 (d, 1 H, J AB
) 11.0 Hz), 5.17 (dd, 1 H, J AB ) 11.0, 2.0 Hz), 5.23 (s, 1H),
7.00-7.80 (m, 16 H); 13C NMR (75 MHz, CDCl3) δ 22.1, 57.6,
59.6, 74.9, 112.6, 118.9, 119.0, 123.1, 123.6, 127.0, 127.6, 128.0,
128.3, 128.6, 129.0, 129.1, 129.4, 129.6, 133.4, 143.6, 145.9,
153.3; MS (70 eV) 232 (M+ - 133), 231 (100), 202 (23), 105
(83). Anal. Calcd for C26H23NO (365.5): C, 85.45; H, 6.34; N,
3.83. Found: C, 85.43; H, 6.36; N, 3.80.
3058, 1620, 1466, 1271, 815, 702 cm-1
;
1H NMR (300 MHz,
CDCl3) δ 0.74 (d, 3 H, J ) 7.0 Hz), 0.97 (d, 3 H, J ) 6.8 Hz),
1.47 (d, 3 H, J ) 6.8 Hz), 2.05-2.30 (m, 2 H), 3.60-3.80 (m, 1
H), 4.12 (d, 1 H, J ) 6.0 Hz), 7.00-7.90 (m, 11 H), 13.10 (br s,
1 H); 13C NMR (75 MHz, CDCl3) δ 18.8, 20.7, 23.6, 33.0, 56.18,
61.2, 115.2, 120.2, 122.0, 122.6, 126.4, 127.2, 128.1, 129.1,
129.2, 129.3, 129.6, 133.8, 143.8, 157.3. Anal. Calcd for C22H25
-
NO (319.4): C, 82.72; H, 7.89; N, 4.38. Found: C, 82.75; H,
7.88; N, 4.39. 1-[(1S)-2-Meth yl-1-[[(1′R)-1′-p h en yleth yl]-
am in o]pr opyl]-2-n aph th ol [(1S,1′R)-3j]: 1H NMR (300 MHz,
CDCl3) δ 0.75 (d, 3 H, J ) 7.1 Hz), 1.07 (d, 3 H, J ) 6.9 Hz),
1.50 (d, 3 H, J ) 6.8 Hz), 2.05-2.30 (m, 2 H), 3.60-3.80 (m, 1
H), 4.70 (d, 1 H, J ) 6.3 Hz), 7.00-7.90 (m, 11 H), 13.00 (br s,
1 H).
(1S)-1-P h en yl-2-[(1′R)-1′-P h en yleth yl]-2,3-d ih yd r o-1H-
n a p h th o[1,2-e][1,3]oxa zin e [(1S,1′R)-4a ]: crystals; mp 158-
160 °C (hexane); [R]20 +95.5° (c 1.2, CHCl3); IR (Nujol) νmax
D
2-[(R)-P h en yl[[(1′R)-1′-p h en ylet h yl]a m in o]m et h yl]-1-
1630, 1241, 950, 755 cm-1; 1H NMR (300 MHz, CDCl3) δ 1.58
(d, 3 H, J ) 6.5 Hz), 4.13 (q, 1 H, J ) 6.5 Hz), 4.46 (dd, 1 H,
J ) 10.6, 2.0), 4.68 (d, 1 H, J AB ) 10.6), 5.76 (s, 1 H), 7.10-
7.80 (m, 16 H); 13C NMR (75 MHz, CDCl3) δ 21.9, 54.6, 58.1,
76.0, 112.0, 118.8, 122.4, 123.1, 126.6, 127.1, 127.4, 127.8,
128.1, 128.5, 128.6, 128.9, 129.0, 129.3, 132.6, 143.4, 144.0,
152.7; MS (70 eV) 232 (M+ - 133,), 231 (100), 202 (26), 105
(80). Anal. Calcd for C26H23NO (365.5): C, 85.45; H, 6.34; N,
3.83. Found: C, 85.21; H, 6.46; N, 3.61.
n a p h th ol [(R,R)-3k ]: oil; [R]20 -118.87 (dr ) 4.6) (c 2.0,
D
1
CHCl3); IR (liquid film) νmax 3312, 1636, 1575, 1085, 803; H
NMR (300 MHz, CDCl3) δ 1.54 (d, 3 H, J ) 6.8 Hz), 2.40 (br
s, 1 H), 3.94 (br q, 1 H, J ) 6.8 Hz), 4.83 (s, 1 H), 6.88 (d, 1 H,
J ) 8.6 Hz), 7.10-8.00 (m, 15 H), 13.10 (br s, 1 H); 13C NMR
(75 MHz, CDCl3) δ 23.8, 56.7, 65.7, 116.9, 118.6, 119.2, 123.0,
125.4, 126.7, 127.1, 127.7, 127.8, 128.0, 128.3, 128.4, 129.4,
129.5, 134.4, 142.8, 143.7, 154.4. Anal. Calcd for C25H23NO
(353.5): C, 84.95; H, 6.56; N, 3.96. Found: C, 85.17; H, 6.42;
N, 3.74. 2-[(S)-P h en yl[[(1′R)-1′-ph en yleth yl]am in o]m eth yl]-
1-n a p h th ol [(1S,1′R)-3k ]: 1H NMR (300 MHz, CDCl3) δ 1.53
(d, 3 H, J ) 6.6 Hz), 2.40 (br s, 1 H), 3.85 (q, 1 H, J ) 6.6 Hz),
5.06 (s, 1 H), 6.72 (d, 1 H, J ) 8.6), 7.10-8.0 (m, 15 H), 13.10
(br s, 1 H).
Ack n ow led gm en t. Financial support from Minis-
tero dell’Universita` e della Ricerca Scientifica e Tecno-
logica, Rome, and the University of Camerino (National
Project “Stereoselezione in Sintesi Organica, Metodolo-
gie ed applicazioni”) is gratefully acknowledged. Thanks
are also due to the I.Co.C.E.A. Institute of CNR,
Bologna, for the use of the 400 MHz spectrometer and
to Dr. C. Femoni, University of Bologna, for the collec-
tion of the X-ray structures.
7-[(R)-P h en yl[[(1′R)-1′-ph en yleth yl]am in o]m eth yl]qu in -
olin -8-ol [(R,R)-3l]: oil; [R]20D -82.0 (c 1.6, CHCl3); IR (liquid
film) νmax 3368, 1600, 1502, 1374, 760 cm-1 1H NMR (300
;
MHz, CDCl3) δ 1.46 (d, 3 H, J ) 6.6 Hz), 2.40 (br s, 1H), 3.77
(q, 1 H, J ) 6.6 Hz), 4.93 (s, 1 H), 7.00-7.50 (m, 13 H), 8.05
(m, 1H), 8.95 (m, 1 H), 12.00 (br s, 1 H); 13C NMR (75 MHz,
CDCl3) δ 24.1, 56.2, 63.9, 118.2, 121.9, 127.1, 127.5, 127.9,
128.1, 128.2, 128.3, 129.1, 129.2, 129.3, 136.2, 140.2, 142.9,
144.2, 149.3, 153.4. Anal. Calcd for C24H22N2O (354.4): C,
81.33; H, 6.26; N, 7.90. Found: C, 81.42; H, 6.41; N, 7.78.
7-[(S)-P h en yl[[(1′R)-1′-p h en yleth yl]a m in o]m eth yl]qu in o-
lin -8-ol [(1S,1′R)-3l]: 1H NMR (300 MHz, CDCl3) δ 1.44 (d, 3
H, J ) 6.9 Hz), 2.40 (br s, 1H) 3.85 (q, 1H, J ) 6.9 Hz), 5.20
(s, 1H), 7.00-7.50 (m, 13 H), 8.00 (m, 1 H), 8.90 (m, 1 H), 12.00
(br s, 1 H).
Su p p or tin g In for m a tion Ava ila ble: General methods,
the characterization data of (1S,1′R)-4k , (R,R)-4k , 6a , 7h , and
11i, Figures 5 and 6, and the crystallographic data of syn-
(R,R)-3f are provided. This material is available free of charge
via the Internet at http://pubs.acs.org.
J O0101205