1824
G. Ricci, R. Ruzziconi / Tetrahedron: Asymmetry 16 (2005) 1817–1827
3684, 3339 (broad), 3015, 2931–2852, 1591, 1413, 969,
704 cmꢀ1. Anal. Calcd for C27H25NO: C, 85.45; H,
6.64; N, 3.69. Found: C, 85.32; H, 6.71; N, 3.57. The
second eluted product (0.22 g, 30%) was assigned the
structure of (Rp,S)-(+)-(4-methyl-[2]paracyclo-[2](5,8)-
quinolinophan-2-yl)phenylcarbinol on the basis of its
spectral and analytical characteristics and by the
absence of any NOE between the protons of the phenyl
group and the aromatic protons overlying the hetero-
cyclic ring. (Rp,S)-5 (100% ee by HPLC analysis,
lytical properties and by the absence of any NOE
between the naphthyl protons and the aromatic protons
of cyclophane moiety. (Rp,S)-6 (100% ee by HPLC ana-
lysis, 0.46 · 25 cm CHIRACEL ODH column, 98:2 hex-
29
ane/isopropanol): mp 157–159 ꢁC; ½aꢂ ¼ þ245 (c 0.70,
D
1
CHCl3); H NMR (CDCl3, 400 MHz) d 8.27 (m, 1H),
7.89–7.82 (m, 2H), 7.49–7.42 (m, 4H), 7.00–6.86 (AB
system, JAB = 7.3 Hz, 2H), 6.86 (s, 1H), 6.60 (s, 1H),
6.51 (AB system, JAB = 8.4 Hz, 2H), 6.30 (broad s,
1H), 5.77 (d, J = 7.5 Hz, 1H), 5.51 (d, J = 7.5 Hz, 1H),
4.44–4.38 (m, 1H), 3.84 (dd, J = 13.9 and 9.2 Hz, 1H),
3.20–2.99 (m, 5H), 2.60–2.53 (m, 1H), 2.56 (s, 3H); 13C
NMR (CDCl3, 100 MHz) d 157.2, 147.8, 144.7, 139.4,
139.0, 138.4, 137.8, 137.3, 134.2, 133.9, 133.0, 132.5,
131.5, 131.3, 129.5, 128.8, 128.7, 128.3, 127.9, 126.7,
126.2, 125.6, 125.3, 124.5, 120.4, 73.5, 37.6, 35.2, 34.4,
32.0, 22.8; IR (CHCl3) mmax 3335 (broad), 3011, 2932–
2856, 1591, 1507, 1435, 965 cmꢀ1. Anal. Calcd for
C31H27NO: C, 86.68; H, 6.34; N, 3.26. Found: C,
86.51; H, 6.44; N, 3.17.
0.46 · 25 cm CHIRACEL ODH column, 98:2 hexane/
29
isopropanol): mp 98–99 ꢁC; ½aꢂ ¼ þ225 (c 1.0, CHCl3);
D
1H NMR d 7.39 (d, J = 7.7 Hz, 2H), 7.32 (t, J = 7.7 Hz,
2H), 7.26 (m, 1H), 6.94 (d, J = 7.2 Hz, 1H), 6.87 (s, 1H),
6.83 (d, J = 7.3 Hz, 1H), 6.49 (tight AB system
JAB = 8.5 Hz, 2H), 6.26 (broad s, 1H), 5.89 (s, 1H),
5.74 (d, J = 7.8 Hz, 1H), 5.48 (d, J = 7.6 Hz,
1H), 4.37–4.31 (m, 1H), 3.83 (dd, J = 14.0 and 9.3 Hz,
1H), 3.19–2.98 (m, 5H), 2.62 (s, 3H), 2.56 (dt, J = 13.0
and 9.1 Hz, 1H); 13C NMR d 156.7, 147.7, 144.6,
143.4, 139.3, 138.9, 137.7, 137.2, 133.9, 132.9, 132.5,
131.3, 129.4, 128.5, 128.3, 128.3, 127.8, 127.8, 127.3,
120.6, 74.8, 37.6, 35.2, 34.4, 32.0, 22.8; IR (CHCl3) mmax
3684, 3339 (broad), 3015, 2931–2852, 1591, 1413, 969,
704 cmꢀ1. Elem. Anal. Calcd for C27H25NO: C, 85.45;
H, 6.64; N, 3.69. Found: C, 85.39; H, 6.55; N, 3.56.
4.6. (Rp,S)-(+)- and (Rp,R)-(ꢀ)-2-Methyl-1-(4-methyl-
[2]paracyclo[2](5,8)quinolinophan-2-yl)propanol (Rp,S)-7
and (Rp,R)-7
The products were prepared from aldehyde (R)-4
(0.91 g, 3.0 mmol) as described above using isopropyl-
magnesium bromide as the alkylating reagent. Chroma-
tography of the crude product on silica gel (eluent, 7:3
petroleum ether/ethyl acetate) allowed the reduction
product 2-hydroxymethyl-4-methyl-[2]paracyclo-[2](5,8)-
quinolinophane (0.51 g, 56%) to be separated from the
diastereomeric mixture of the addition products. The
two diastereomeric adducts (0.24 g, 23%) were separated
by preparative HPLC on a 50 cm · 10mm WATER Del-
ta-pak, prepPak C18 column by eluting with 7:3 MeCN/
H2O mixture. The first eluted product (0.1 g, 9%) was
assigned the structure of (Rp,S)-(+)-2-methyl-1-(4-
methyl-[2]paracyclo[2](5,8)quinolino-phan-2-yl)propanol
according to the following spectroscopic and analytical
properties. (Rp,S)-7 (100% ee by HPLC analysis,
4.5. (Rp,R)-(ꢀ)- and (Rp,S)-(+)-(4-Methyl-[2]paracyclo-
[2](5,8)quinolinophan-2-yl)(naphth-1-yl)methanol,
(Rp,R)-6 and (Rp,S)-6
They were obtained in the same way as the above phe-
nylcarbinols except that 1-naphthylmagnesium bromide
was used as the Grignard reagent. The first eluted
product (0.14 g, 16%) was identified as (Rp,R)-(ꢀ)-(4-
methyl-[2]paracyclo[2](5,8)quinolinophan-2-yl)(naphth-1-
yl)carbinol on the basis of the following spectroscopic
and analytical characteristics and on the basis of the ob-
served NOE between the aromatic protons overlying the
heterocyclic ring and the b- and peri protons of the
naphthyl group. (Rp,R)-6 (100% ee by HPLC analysis,
0.46 · 25 cm CHIRACEL ODH column, 98:2 hexane/
0.46 · 25 cm CHIRACEL ODH column, 99:1 hexane/
29
27
isopropanol): mp 161–163 ꢁC; ½aꢂ ¼ ꢀ315 (c 0.50,
isopropanol): mp 182–184 ꢁC (from MeCN); ½aꢂ ¼
D
D
1
1
CHCl3); H NMR d 8.48 (m, 1H), 7.91 (m, 2H), 7.70
(dd, J = 7.1 and 1.0 Hz, 1H), 7.57–7.47 (m, 3H), 6.96–
6.80 (AB system, JAB = 7.3 Hz, 2H), 6.80 (s, 1H),
þ16 (c 0.50, CHCl3); H NMR d 7.01 (s, 1H), 6.91–
6.89 (AB system, JAB = 7.2 Hz, 2H), 6.46 (s, 2H), 5.71
(d, J = 7.8 Hz, 1H), 5.44 (d, J = 7.8 Hz, 1H), 5.14 (broad
s, 1H), 4.75 (d, J = 3.4 Hz, 1H), 4.24 (m, 1H), 3.85 (dd,
J = 13.9 and 9.3 Hz, 1H), 3.16 (dd, J = 12.8 and 10.1 Hz,
1H), 3.11–2.88 (m, 4H), 2.72 (s, 3H), 2.56 (dt, J = 13.0
and 9.1 Hz, 1H), 2.12 (m, 1H), 1.12 (d, J = 6.8 Hz,
3H), 0.67 (d, J = 6.8 Hz, 3H); 13C-NMR d 157.6,
148.0, 144.1, 139.4, 139.0, 137.7, 137.2, 133.7, 132.7,
132.5, 131.2, 129.2, 128.2, 127.8, 120.3, 76.4, 37.7,
35.3, 34.7, 34.4, 32.0, 23.0, 19.9, 15.4; IR (CHCl3) mmax
3374 (broad), 3022, 2967–2856, 1593, 1434, 1226,
1018 cmꢀ1. Anal. Calcd for C24H27NO: C, 83.44; H,
7.88; N, 4.05. Found: C, 83.28; H, 7.77; N, 4.10.
4
6.56–6.50 (AB system, JAB = 7.9 Hz, J = 1.7 Hz, 2H),
6.38 (s, 1H), 6.37 (broad s, 1H), 5.92 (dd, J = 7.8 and
1.6 Hz, 1H), 5.30 (dd, J = 7.8 and 1.6 Hz, 1H), 4.48–
4.40 (m, 1H), 3.79 (dd, J = 13.7 and 9.0 Hz, 1H), 3.29–
2.97 (m, 5H), 2.54 (s, 3H), 2.45 (dt, J = 12.8 and
9.0 Hz, 1H); 13C NMR d 157.3, 148.2, 144.5, 139.5,
138.7, 138.2, 138.0, 137.3, 134.4, 134.0, 133.1, 132.4,
131.6, 131.3, 129.3, 129.0, 128.9, 128.8, 128.8, 126.9,
126.1, 125.7, 125.4, 124.7, 120.6, 73.5, 37.7, 35.2, 34.6,
31.5, 23.0; IR (CHCl3) mmax 3340 (broad), 3049, 3021,
2931–2856, 1590, 1507, 1228, 965 cmꢀ1. Anal. Calcd
for C31H27NO: C, 86.68; H, 6.34; N, 3.26. Found: C,
86.39; H, 6.41; N, 3.21.
The second eluted product (72 mg, 7%) was identified as
(Rp,R)-(ꢀ)-2-methyl-1-(4-methyl-[2]paracyclo[2](5,8)quino-
linophan-2-yl)propanol on the basis of the following
spectroscopic and analytical properties and by the posi-
tive NOE between the protons of the isopropyl group
The second eluted product (0.34 g, 40%) was identified
as (Rp,S)-(+)-(4-methyl-[2]paracyclo[2](5,8)quinolino-
phan-2-yl)(naphth-1-yl)carbinol by its spectral and ana-