Novel stereoselective synthesis of 2,3-dihydro-1H-benzo[f]chromen-3-amine derivatives through a one-pot three-component reaction

Article abstract of DOI:10.1016/j.tetasy.2011.08.007

A short and stereoselective novel synthesis of benzo[f]chromen-3-amine derivatives in good yields, through a three-component aromatic Betti type reaction under solvent free conditions is reported. The spontaneous reaction occurs in the absence of acid cat

Full text of DOI:10.1016/j.tetasy.2011.08.007

Tetrahedron: Asymmetry 22 (2011) 1542–1547
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Novel stereoselective synthesis of
2,3-dihydro-1H-benzo[f]chromen-3-amine derivatives through a one-pot three-
component reaction
⇑
Cristina Cimarelli, Davide Fratoni, Gianni Palmieri
School of Science & Technology, University of Camerino, v. S.Agostino 1, 62032 Camerino, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
A short and stereoselective novel synthesis of benzo[f]chromen-3-amine derivatives in good yields,
through a three-component aromatic Betti type reaction under solvent free conditions is reported. The
spontaneous reaction occurs in the absence of acid catalysts. The use of chiral 1-phenylethylamine or
Received 18 July 2011
Accepted 9 August 2011
Available online 15 September 2011
a
,b-unsaturated aldehydes allowed us to prepare enantiopure benzo[f]chromen-3-amine derivatives
with good stereoselectivity. Conformational analysis compared with the 1H NMR data of the products
obtained, allowed us to the determine the absolute configuration, which was also confirmed by X-ray
analysis.
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
of 2-naphthol with trans-cinnamaldehyde, affords 1-phenyl-1H-
naphtho[2,1-b]pyran as the main product rather than 1-phenyl-
New methods for the stereoselective aminoalkylation of elec-
tron-rich aromatic compounds are of great interest. The Mannich
reaction is one of the most important multi-component reactions
of aminoalkylation in organic synthesis.1–3 At the beginning of
the 20th century, Betti reported the synthesis of 1-aminoalkyl-2-
naphthols, a reaction that is very important because a C–C bond
is formed under mild experimental conditions.4–9 Although a vari-
ety of methods for the aminoalkylation of electron-rich aromatic
compounds are available,10,11 new, mild and direct approaches that
are stereoselective enough to allow the preparation of single dia-
stereoisomers are of increasing interest. We have found that a
straightforward and stereoselective synthesis of aminoalkyl naph-
thols can be performed by a Betti reaction using enantiopure
amines and other inexpensive reagents.12,13 The aminoalkyl naph-
thols obtained with this methodology, in typically good yield and
high enantiomeric purity, are effective catalysts in the enantiose-
lective alkylation of aldehydes.12–17 With the aim of exploring
the synthetic possibilities of this reaction we have studied a con-
2,3-dihydro-1H-naphtho[2,1-b]pyran-3-ol. This can be used to ob-
tain amino derivatives by reaction with amines in the absence of a
catalyst.24
However, to the best of our knowledge, the previously reported
synthetic procedures were generally complicated and did not give
satisfactory yields, also we were unable to find a report on the
asymmetric synthesis of 2,3-dihydro-1H-benzo[f]chromen-3-
amine derivatives.
2. Results and discussion
Herein we report the results of the diastereoselective synthesis
of 2,3-dihydro-1H-benzo[f]chromen-3-amine 3a–g through
three-component Betti type one-pot reaction from b-naphthol,
,b-unsaturated aldehydes 1 and amines 2 under solvent free con-
a
a
ditions (Table 1). On the basis of our previous experience and of lit-
erature reports,16,17 only electron-rich naphthols and phenols can
take part in this spontaneous reaction to afford the desired adduct
without the use of an acid catalyst. We limited our research to 2-
naphthol for practical reasons.
The reaction was performed at 70 °C for 12–72 h under solvent
free conditions and under an argon atmosphere. The reaction mix-
ture showed an increasing viscosity over time while the water pro-
duced by the condensation was separated. The use of Lewis acid
catalysts (LiClO4, BF3ꢀOEt2) did not give better results. The major
stereoisomers 3 can be obtained in enantiomerically pure form,
by flash chromatography and are stable for a long time with no epi-
merisation being observed.
densation that makes use of
a,b-unsaturated aldehydes.
In the literature, there are examples in which the 2-naphthol
promotes conjugate addition to a,b-unsaturated electrophilic mol-
ecules such as unsaturated ketoesters or dicyanoolefins.18,19 Some
synthetic approaches reported in the literature were found to be
most closely related to the present investigation.20–23 The reaction
⇑
Corresponding author. Tel.: +39 0737 402241; fax: +39 0737 637345.
E-mail address: gianni.palmieri@unicam.it (G. Palmieri).
0957-4166/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2011.08.007

C. Cimarelli et al. / Tetrahedron: Asymmetry 22 (2011) 1542–1547
1543
Table 1
Stereoselective synthesis of 2,3-dihydro-1H-benzo[f]chromen-3-amine 3a–g through a three-component Betti type reaction
4
O
H
5
OH
H
O
R
N
R
R2
6
3
R2
+
+
H2N
7
8
2
1
70 °C
R1
R1
10
1
2
3
9
1
2
1,3-trans-3, yielda (%)
(1S,3R)-3a, 47
drb
—
H
O
O
H2N
Ph
1
2
2a
1a
H
H2N
Ph
2b
(R⁄,R⁄)-3b, 42
76/24
81/19
Ph
1b
3
4
1b
1b
2a
2a
(1R,3R)-3c, 43
(1S,3S)-3c, 10
H
O
5
6
2b
2a
(1R⁄,2S⁄,3R⁄)-3d, 51
(1R,2S,3R)-3e, 51
82/18
84/16
Ph
1c
1c
O
H
E
(R)
7
8
2b
2a
(1R,2R,3S)-3f, 48
(1R,2R,3S)-3g, 42
68/23
59/41
(S)
1d
1d
a
Yield of the pure isolated diastereomers.
The dr values (1,3-trans/cis-3b,d,f and enantiopure 1,3-trans-3c,e,g major stereoisomers) were determined by 1H NMR of the crude reaction mixture.
b
3f,g, the cyclization of the respective intermediate C preferentially
takes place on the Si-face of the imine carbon atom, due to the asym-
metric induction from the (1R,5S)-6.6-dimethylbicyclo[3.1.1]hep-
tane system of the starting (1R)-(ꢁ)-myrtenal 1d to form
enantiopure (1R,2R,3S)-3f and (1R,2R,3S)-3g as the main products.
The cyclization occurs from the exo side of the bicyclic system, as
it is sterically less cumbersome.
3. Configuration attribution
Conformational analysis of the 1H NMR data of the products ob-
tained, allowed us to determine the relative and absolute configu-
rations, which were confirmed by X-ray analysis. With the help of
molecular modelling the most stable conformations of all possible
stereoisomers were found. Conformational analysis on all of the
possible diastereomers of products 3, through a preliminary con-
formational search, was carried out using a systematic search with
the MMFF molecular mechanics force field. All of the conforma-
tions within a 3 kcal/mol window were then optimized using
DFT at the B3LYP/6-31G⁄ level.25 On the basis of 3J values measured
by 1H NMR (reported in Table 2 for protons H-1, H-2 and H-3 and
the dihedral angle for these protons) as observed on the stable con-
formations, it was possible to assign the configuration of benzo-
chromenes 3, isolated as the main products and reported in
Table 2.
For all the examples in Table 1, the 1,3-trans-3a–g diastereomers
reported, are thermodynamically more stable and prevail quantita-
tively over the 1,3-cis-3b,d,f or 1,3-trans-3a,c,e,g diastereomers. In
enantiopure compounds 1,3-trans-3a,c,e, the prevailing stereoiso-
mer had an (R)-configuration at the C-3 carbon atom. The cyclization
of intermediate C takes place onto the Re-face of the imine carbon
atom, leading to the formation of the thermodynamically more sta-
ble benzochromenes 3 (Scheme 1). However, for benzochromenes
The (1R,2S,3R)-configuration was determined by 1H NMR for the
major stereoisomer of the benzochromene 3e and confirmed by X-
ray analysis26 (see Fig. 1). The molecular modelling structure calcu-
lated for (1R,2S,3R)-3e was almost identical to that of the X-ray
structure. The dihedral angles (78.13° and 58.61°) measured for
the solid compound in the crystalline form, were in agreement
with the estimated values made on the basis of the 3J coupling con-
stants measured by 1H NMR spectroscopy in CDCl3 solution (2.9
and 1.8 Hz, respectively).
A mechanistic hypothesis is depicted in Scheme 1. Mixing alde-
hydes 1 and amines 2 caused an immediate exothermic reaction to
take place, which afforded the corresponding imine, as evidenced
by the formation of drops of water in the reaction flask.27,28 After
the addition of naphthol, it was assumed that an aldimonium type
complex A was formed through protonation of the imine nitrogen
by 2-naphthol, in which the reactivity of both the electrophilic
imonium carbon atom and the nucleophilic carbon atom at the
1-position of 2-naphthol are activated.

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C. Cimarelli et al. / Tetrahedron: Asymmetry 22 (2011) 1542–1547
Table 2
The 1H NMR chemical shift, the multiplicity and 3J (in brackets) are reported
3a
H-1
H-2
H-3
H
(R)
O
N
Ph
(R)
1
2
4.64, m
3.48–3.71, m
4.75, dd (6.6, 1.5)
(S)
(1S,3R)-3a
H
N
O
(R)
Ph
4.16, dd (4.2, 3.5)
2.02, ddd (15.3, 4.8, 2.1)
2.50, ddd (15.3, 10.9, 3.5)
4.65, dd (10.9, 2.0)
(R)
Ph
(R*,R*)-3b
H
N
O
(R)
Ph
3
3.78, dd (9.2, 3.5)
2.02, dt (15.3, 3.2)
2.35 dt (15.3, 9.8)
4.87, dd (10.2, 3.1)
(S)
Ph
(1S*,3R*)-3b
H
N
(R)
O
(R)
Ph
4
5
4.72, dd (4.8, 3.7)
2.10–2.40, m
4.66, dd (8.4, 3.6)
(R)
Ph
(1R,3R)-3c
H
N
(R)
O
Ph
(S)
4.72, dd (3.7, 2.0)
2.22, ddd (13.2, 10.0, 4.2)
2.31, dt (13.2, 2.0)
4.98, dd (9.7, 2.0)
(S)
Ph
(1S,3S)-3c
H
N
O
Ph
(R)
(S)
(R)
6
7
4.43, d (2.2)
2.40, qt (7.0, 2.1)
4.85, d (2.0)
Ph
(1R*,2S*,3R*)-3d
H
N
O
Ph
(R)
(R)
(S)
4.25, d (6.8)
2.34, sext (7.0)
4.58, d (7.0)
Ph
(1S*,2R*,3R*)-3d
H
N
(R)
O
Ph
(R)
(S)
(R)
8
9
4.28, d (2.9)
2.16, qdd (7.0, 2.9, 1.8)
4.54, d (1.8)
Ph
(1R,2S,3R)-3e
H
N
(R)
O
Ph
(S)
(R)
(S)
4.45, d (2.0)
2.39, qt (7.0, 1.7)
5.01, d (1.6)
Ph
(1S,2R,3S)-3e

C. Cimarelli et al. / Tetrahedron: Asymmetry 22 (2011) 1542–1547
1545
Table 2 (continued)
3a
H-1
H-2
—
H-3
H
N
O
Ph
(S)
(R)
(R)
10
(S)
3.78, td (10.1, 1.8)
4.77, d (0.8)
(S)
(1R,2R,3S)-3f
H
N
O
(R) Ph
(S)
(R)
(R)
(S)
11
3.88, t (9.7)
—
4.28, d (2.9)
(S)
(1R,2R,3S)-3g
a
The configurations was determined on the basis of the 3J values observed for the H-1, H-2, H-3 protons of the isolated 2,3-dihydro-1H-benzo[f]chromen-3-amine 3.
Me
Ph
H
Me
H
O
N
Ph
O
N
Me
Ph
Me
A
B
Ph
Me
Ph
H
N
O
(1R,2S,3R)-3e
Me
Ph
C
Scheme 1. The mechanistic hypothesis for the Mannich type diastereoselective
aminoalkylation.
Figure 2. A more stable conformation for the aldimonium ion A resulting from the
condensation of -methyl-trans-cinnamaldehyde 1c and (R)-1-phenylethylamine
a
2a, with the LUMO, more developed on the imonium- and b-carbon atoms and
exceeding the isodensity surface.
a,b-unsaturated imonium ion, which is sterically less hindered, to
form the intermediate B. This intermediate isomerizes to the ther-
modinamically more stable intermediate C, which then cyclizes to
(1R,2S,3R)-3e.
In the literature there has already been reported an example in
which trans-cinnamaldehyde is placed to react with 2-naphthol
and (R)-1-phenylethylamine (mediated by lithium perchlorate) to
form compound 4 (Scheme 2). That is the result of a Mannich reac-
tion on the imino carbon atom (a description of the spectroscopic
data of this compound is not reported).29
This is in contrast to our results, where the formation of com-
pound 3c, resulting from conjugate addition and then successive
cyclization, was observed.
Figure 1. X-ray structure of the benzo[f]chromen-3-amine (1R,2S,3R)-3e major
diastereomer.
Next, the conjugate addition of 2-naphthol to the b-carbon
atom of the
(R)-1-phenylethylamine was used, the immonium ion intermedi-
ate derived from -methyl-trans-cinnamaldehyde, took the shape
as shown in Figure 2 where the LUMO molecular orbital is more
developed on the imonium- and b-carbon atoms. The chiral group
on the nitrogen atom induces the stereoselective attack of the Re-
face of the b-naphthol onto the Si-face of the b-carbon atom of the
a
,b-unsaturated imonium ion took place.18,19 When
4. Conclusion
a
In conclusion, we have reported on a short and stereoselective
synthesis of benzo[f]chromen-3-amine derivatives obtained in
good yields, through a three-component aromatic Betti type reac-
tion under solvent free conditions. The use of chiral 1-phenylethyl-
amine or
a
,b-unsaturated aldehydes [(1R)-(ꢁ)-myrtenal] allows to

1546
C. Cimarelli et al. / Tetrahedron: Asymmetry 22 (2011) 1542–1547
H
N
O
OH
H
N
(R)
O
Ph
H
(R)
Ph
LiClO4
(R)
+ 1b
+ 2a
4
Ph
Ph
(1R,3R)-3c
Scheme 2.
prepare enantiopure benzo[f]chromen-3-amine derivatives, with
good stereoselectivity. Conformational analysis compared with
1H NMR data of the products obtained, allows the attribution of
the absolute configuration, also confirmed by X-ray analysis.
(dd, 1H, J = 10.9, 2.0 Hz, H-3), 7.00–7.85 (m, 16H); 13C NMR
(100 MHz, CDCl3) d 40.2, 52.1, 55.3, 61.2, 115.1, 120.0, 120.6,
126.4, 126.9, 127.3, 127.6, 128.3, 128.7, 128.8, 129.0, 129.1,
129.2, 132.2, 138.7, 139.9, 142.1, 156.9. Anal. Calcd for C26H23NO
(365.47): C, 85.45; H, 6.34; N, 3.83. Found: C, 85.53; H, 6.49; N,
3.56.
5. Experimental
5.2.1.2.
(1S⁄,3R⁄)-N-Benzyl-2,3-dihydro-1-phenyl-1H-benzo[f]
5.1. General methods
chromen-3-amine (1S⁄,3R⁄)-3b. 1H NMR (200 MHz, CDCl3) d
1.74 (br s, 1H), 2.02 (dt, 1H, J = 15.3, 3.2 Hz, H-2a), 2.35 (dt, 1H,
J = 15.3, 9.8 Hz, H-2b), 3.54 (d, 1H, J = 12.9 Hz), 3.65 (d, 1H,
J = 12.9 Hz), 3.78 (dd, 1H, J = 9.2, 3.5 Hz, H-1), 4.87 (dd, 1H,
J = 10.2, 3.1 Hz, H-3), 7.00–7.85 (m, 16H).
1H and 13C NMR spectra were recorded at 200 or 400 MHz and
50 or 100 MHz, respectively. Chemical shifts are given in ppm
downfield from Me4Si in a CDCl3 solution. Coupling constants are
given in Hertz. IR spectra were recorded using a FTIR apparatus.
Optical rotations were measured in a 1 dm cell at 20 °C. All melting
points are uncorrected. In cases where only the major diastereo-
mer was obtained in its pure form, the 1H NMR signals for the min-
or diastereomer were deduced from the spectra of the crude
reaction mixture or from enriched chromatographic fractions.
5.2.2. (1R,3R)-2,3-Dihydro-1-phenyl-N-((R)-1-phenylethyl)-1H-
benzo[f]chromen-3-amine (1R,3R)-3c
Oil; ½a 2D0
ꢂ
¼ þ178:0 (c 0.31, CHCl3); IR (neat) mmax 3225, 2921,
1621, 1498, 1134, 841 cmꢁ1
;
1H NMR (400 MHz, CDCl3) d 1.50 (d,
3H, J = 6.4 Hz), 2.05 (br s, 1H), 2.10–2.40 (m, 2H, H-2a,b), 4.56 (q,
1H, J = 6.4 Hz), 4.66 (dd, 1H, J = 8.4, 3.6 Hz, H-3), 4.72 (dd, 1H,
J = 4.8, 3.7 Hz, H-1), 6.96–7.80 (m, 16H); 13C NMR (100 MHz,
CDCl3) d 25.4, 37.6, 38.9, 53.6, 81.4, 119.4, 123.1, 123.4, 126.3,
126.6, 126.9, 127.0, 127.3, 127.6, 128.2, 128.5, 128.7, 128.8,
5.2. General procedure for the preparation of 2,3-dihydro-1H-
benzo[f]chromen-3-amine derivatives 3a–g
Amine 2a–d (5.0 mmol) was added to aldehyde 1a–d
(5.0 mmol) at 0 °C and the resultant mixture stirred for 30 min.
The oil was dissolved in DCM and the resulting solution dried
(MgSO4). After filtration, the solvent was removed under reduced
pressure. To the resulting oil was added 2-naphthol (0.72 g,
5.0 mmol) and the mixture was stirred and left to stand, under ar-
gon, under solvent free conditions at 70 °C for the time required
(12–72 h, monitored by TLC). Analogous yields were obtained
when a mixture of 2-naphthol (0.72 g, 5.0 mmol), aldehyde 1a–d
(5.0 mmol) and amine 2a–d (5.0 mmol) was stirred and left to
stand, under argon, under solvent free conditions at 70 °C for the
time required (12–72 h, without the elimination of condensation
water). Aminoalkylnaphthols 3a–g were separated and purified
by flash chromatography (on silica gel, hexane–ethyl acetate,
95:5 to 70:30, v/v) directly from the reaction mixture, without
any work-up.
129.2, 129.3, 132.9, 138.6, 145.8. Anal. Calcd for
C27H25NO
(379.49): C, 85.45; H, 6.64; N, 3.69. Found: C, 85.68; H, 6.51; N,
3.47.
5.2.3. (1S,3S)-2,3-Dihydro-1-phenyl-N-((R)-1-phenylethyl)-1H-
benzo[f]chromen-3-amine (1S,3S)-3c
Crystals mp 158–160 (hexane); ½a D20
ꢂ
¼ ꢁ67:8 (c 0.42, CHCl3); IR
(neat) mmax 3203, 2925, 1618, 1498, 1133, 837 cmꢁ1
;
1H NMR
(400 MHz, CDCl3) d 1.37 (d, 3H, J = 6.4 Hz), 2.15 (br s, 1H), 2.22
(ddd, 1H, J = 13.2, 10.0, 4.2 Hz, H-2a), 2.31 (dt, 1H, J = 13.2,
2.0 Hz, H-2b), 4.49 (q, 1H, J = 6.4 Hz), 4.72 (dd, 1H, J = 3.7, 2.0 Hz,
H-1), 4.98 (dd, 1H, J = 9.7, 2.0 Hz, H-3), 6.96–7.80 (m, 16H); 13C
NMR (100 MHz, CDCl3) d 22.9, 37.3, 39.0, 52.9, 81.0, 113.9, 119.4,
123.2, 123.5, 126.6, 126.7, 126.9, 127.3, 128.5, 128.6, 128.7,
128.8, 129.3, 129.5, 133.0, 146.0, 146.8, 153.5. Anal. Calcd for
C27H25NO (379.49): C, 85.45; H, 6.64; N, 3.69. Found: C, 85.62; H,
6.54; N, 3.52.
5.2.1. (1S,3R)-2,3-Dihydro-1-methyl-N-((R)-1-phenylethyl)-1H-
benzo[f]chromen-3-amine (1S,3R)-3a
Oil, ½a 2D0
ꢂ
¼ þ54:5 (c 2.41, CHCl3); IR (neat) mmax 3338, 1622,
5.2.3.1. (1R⁄,2S⁄,3R⁄)-N-Benzyl-2,3-dihydro-2-methyl-1-phenyl-
1H-benzo[f]chromen-3-amine (1R⁄,2S⁄,3R⁄)-3d. Crystals mp
183–186 °C (hexane); IR (Nujol) mmax 1598, 1508, 1229,
1599, 1397, 1139 cmꢁ1
;
1H NMR (200 MHz, CDCl3) d 1.32 (d, 3H,
J = 7.0 Hz), 1.48 (d, 3H, J = 6.2 Hz), 2.10 (br s, 1H), 3.48–3.71 (m,
2H, H-2), 4.56 (q, 1H, J = 6.2 Hz), 4.64 (m, 1H, H-1), 4.75 (dd, 1H,
J = 6.6, 1.5 Hz, H-3), 6.98–8.02 (m, 11H); 13C NMR (100 MHz,
CDCl3) d 22.8, 27.1, 35.8, 52.8, 53.3, 80.9, 119.3, 122.3, 123.0,
123.4, 126.4, 126.9, 127.2, 127.3, 128.6, 128.8, 129.2, 129.3,
132.1, 132.4. Anal. Calcd for C22H23NO (317.42): C, 83.24; H,
7.30; N, 4.41. Found: C, 83.46; H, 7.49; N, 4.22.
1215 cmꢁ1 1H NMR (200 MHz, CDCl3) d 1.14 (d, 3H, J = 7.0 Hz),
;
2.20 (br s, 1H), 2.40 (qt, 1H, J = 7.0, 2.1 Hz), 3.90 (d, 1H,
J = 12.8 Hz), 4.35 (d, 1H, J = 12.8 Hz), 4.43 (d, 1H, J = 2.2 Hz), 4.85
(d, 1H, J = 2.0 Hz), 7.05–7.83 (m, 16H); 13C NMR (100 MHz, CDCl3)
d 13.4, 39.6, 47.4, 50.5, 85.1, 112.8, 119.1, 119.6, 123.3, 123.6,
124.1, 126.6, 126.61, 128.50, 128.55, 128.66, 128.70, 128.7, 129.3,
129.8, 133.5, 146.0, 152.8. Anal. Calcd for C27H25NO (379.494): C,
85.45; H, 6.64; N, 3.69. Found: C, 85.63; H, 6.79; N, 3.46.
5.2.1.1.
chromen-3-amine (R⁄,R⁄)-3b. Oil; IR (neat) mmax 3227, 3061,
2923, 2848, 1621, 1453, 1269 cmꢁ1 1H NMR (200 MHz, CDCl3) d
(R⁄,R⁄)-N-benzyl-2,3-dihydro-1-phenyl-1H-benzo[f]-
;
5.2.3.2. (1S⁄,2R⁄,3R⁄)-N-Benzyl-2,3-dihydro-2-methyl-1-phenyl-
1H-benzo[f]chromen-3-amine
(200 MHz, CDCl3) d 1.28 (d, 3H, J = 7.0 Hz), 2.20 (br s, 1H), 2.34
(sext, 1H, J = 7.0 Hz), 4.03 (d, 1H, J = 13.5 Hz), 4.19 (d, 1H,
1.74 (br s, 1H), 2.02 (ddd, 1H, J = 15.3, 4.8, 2.1 Hz, H-2a), 2.50
(ddd, 1H, J = 15.3, 10.9, 3.5 Hz, H-2b), 3.55 (d, 1H, J = 12.8 Hz),
3.82 (d, 1H, J = 12.8 Hz), 4.16 (dd, 1H, J = 4.2, 3.5 Hz, H-1), 4.65
(1S⁄,2R⁄,3R⁄)-3d. 1H
NMR

C. Cimarelli et al. / Tetrahedron: Asymmetry 22 (2011) 1542–1547
1547
J = 13.5 Hz), 4.25 (d, 1H, J = 6.8 Hz), 4. 58 (d, 1H, J = 7.0 Hz), 7.05–
7.83 (m, 16H).
152.7. Anal. Calcd for C28H31NO (397.55): C, 84.59; H, 7.86; N,
3.52. Found: C, 84.43; H, 7.66; N, 3.34.
Acknowledgements
5.2.3.3. (1R,2S,3R)-2,3-Dihydro-2-methyl-1-phenyl-N-((R)-
1-phenylethyl)-1H-benzo[f]chromen-3-amine (1R,2S,3R)-
3e. Crystals mp 158–160 °C (hexane); ½a D20
ꢂ
¼ þ126:4 (c 0.41,
The financial support of this research by a grant from the Uni-
versity of Camerino and from MIUR is gratefully acknowledged.
CHCl3); IR (Nujol) mmax 1610, 1623, 1599, 851, 831 cmꢁ1
;
1H NMR
(400 MHz, CDCl3) d 1.11 (d, 3H, J = 7.0 Hz), 1.37 (d, 3H, J = 6.6 Hz),
2.16 (qdd, 1H, J = 7.0, 2.9, 1.8 Hz, H-2), 2.20 (br s, 1H), 4.28 (d,
1H, J = 2.9 Hz, H-1), 4.37 (q, 1H, J = 6.6 Hz), 4.54 (d, 1H, J = 1.8 Hz,
H-3), 6.80–7.80 (m, 16H); 13C NMR (100 MHz, CDCl3) d 13.3,
25.3, 39.9, 47.3, 54.0, 83.3, 113.2, 119.2, 123.1, 123.6, 126.3,
126.4, 126.9, 128.3, 128.4, 128.5, 128.6, 129.1, 130.3, 133.5,
144.3, 145.3, 150.1, 153.1. Anal. Calcd for C28H27NO (393.520): C,
85.46; H, 6.92; N, 3.56. Found: C, 85.59; H, 7.09; N, 3.42.
References
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5.2.3.4.
(1S,2R,3S)-2,3-Dihydro-2-methyl-1-phenyl-N-((R)-1-
phenylethyl)-1H-benzo[f]chromen-3-amine (1S,2R,3S)-3e. 1H
NMR (400 MHz, CDCl3) d 1.13 (d, 3H, J = 6.8 Hz), 1.33 (d, 3H,
J = 6.4 Hz), 2.25 (br s, 1H), 2.39 (qt, 1H, J = 7.0, 1.7 Hz, H-2), 4.43
(q, 1H, J = 6.4 Hz), 4.45 (d, 1H, J = 2.0 Hz, H-1), 5.01 (d, 1H,
J = 1.6 Hz, H-3), 6.80–7.80 (m, 16H).
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2775.
5.2.4. (1R,2R,3S)-3f
Crystals mp 121–124 °C (hexane); ½a D20
ꢂ
¼ þ31:2 (c 1.4, CHCl3);
1H NMR
IR (Nujol) mmax 3059, 1758, 1686, 1257, 1226 cmꢁ1
;
(200 MHz, CDCl3) d 1.03 (s, 3H), 1.28 (s, 3H), 1.40–1.49 (m, 1H),
1.77–1.99 (m, 2H), 2.06–2.50 (m, 3H), 2.78 (d, 2H, J = 9.9 Hz),
3.72 (d, 1H, J = 13.2 Hz), 3.78 (td, 1H, J = 10.1, 1.8 Hz), 3.80 (d, 1H,
J = 13.2 Hz); 4.77 (d, 1H, J = 0.8 Hz), 7.90–7.10 (m, 11H); 13C NMR
(50 MHz, CDCl3) d 20.8, 22.4, 25.0, 26.2, 35.9, 39.6, 40.4, 40.5,
47.0, 48.8, 90.8, 120.8, 123.6, 123.8, 126.2, 127.2 127.6, 128.4,
128.5, 128.6, 129.1, 130.7, 132.1, 139.6, 147.7. Anal. Calcd for
C27H29NO (383.53): C, 84.55; H, 7.62; N, 3.65. Found: C, 84.34; H,
7.76; N, 3.48.
23. Huang, P.-J. J.; Cameron, T. S.; Jha, A. Tetrahedron Lett. 2009, 50, 51–54.
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Kaishi 1989, 244–250.
25. Spartan’06, Wavefunction, Inc., Irvine, CA.
26. Crystallographic data for the benzo[f]chromen-3-amine (1R,2S,3R)-3e (major
5.2.5. (1R,2R,3S)-3g
Oil; ½a 2D0
ꢂ
¼ þ38:3 (c 1.6, CHCl3); IR (liquid film)
mmax 3361, 3258,
1622, 1542, 969 cmꢁ1
;
1H NMR (400 MHz, CDCl3) d 1.06 (s, 3H),
diastereomer). Formula:
C28H27NO Unit cell parameters: a 6.3704(5) b
8.9220(7) c 18.9245(15) b 91.4920(10) space group P21 have been deposited
with the Cambridge Crystallographic Data Center as supplementary material
with the deposition number CCDC 288236. This data can be obtained, free of
charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html.
1.37 (s, 3H), 1.51 (d, 3H, J = 6.6 Hz), 1.81–1.97 (m, 2H), 2.16–2.39
(m, 3H), 2.46 (br s, 1H), 2.64–2.86 (m, 2H), 3.88 (t, 1H, J = 9.7 Hz),
4.28 (d, 1H, J = 2.9 Hz), 4.57 (q, 1H, J = 6.6 Hz), 7.02–7.90 (m,
11H); 13C NMR (100 MHz, CDCl3) d 20.7, 22.3, 25.3, 26.1, 26.3,
27.6, 36.4, 39.6, 40.5, 40.7, 53.8, 89.4, 119.3, 123.4, 123.9, 126.1,
126.2, 126.8, 127.3, 127.5, 128.6, 129.0, 130.5, 132.3, 145.0,
27. Danks, T. N.; Thomas, S. E. J. Chem. Soc., Perkin Trans. 1 1990, 3, 761–765.
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J. Org. Chem. 1989, 54, 5736–5745.
29. Saidi, M. R.; Azizi, N. Tetrahedron: Asymmetry 2003, 14, 389–392.