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A. C. Spivey et al. / Tetrahedron 60 (2004) 4513–4525
for 24 h. After cooling the mixture was dissolved in EtOAc
then washed with 1 M K2CO3 and water. The organic
extracts were then dried using MgSO4, filtered, and con-
centrated in vacuo. Purification by flash chromatography
eluting with petrol/CH2Cl2 (6/4)!CH2Cl2 gave:
6.73 (1H, d, J¼6.0 Hz), 7.24–7.38 (4H), 7.72–7.77 (2H),
8.07 (1H, s), 8.13 (1H, d, J¼6.0 Hz), 9.34 (1H, s); dC
(63 MHz) 13.7 (2£CH3), 20.1 (2£CH2), 29.3 (2£CH2), 51.4
(2£CH2), 111.2 (CH), 118.6 (Cq), 119.5 (CH), 120.3 (Cq),
123.0 (CH), 124.7 (CH), 126.3 (CH), 128.0 (CH), 128.8
(Cq), 129.6 (CH), 133.4 (Cq), 148.0 (CH), 152.8 (Cq), 154.0
(CH), 155.2 (Cq); m/z (EIþ) (rel intensity) 348 (30, Mþ), 305
(100); HRMS calculated for C23H28N2O 348.220, found
348.220.
3,5-Dibromo(pyridine-4-yl)di-n-butylamine 2f (550 mg,
1.51 mmol, 50%) as a yellow oil. Rf 0.38 (CH2Cl2); nmax
/
cm21 (CHCl3) 2957, 1547, 1454; dH (CDCl3, 400 MHz)
0.83 (6H, t, J¼7.0 Hz), 1.16–1.46 (8H), 3.21 (4H, t, J¼
7.0 Hz), 8.47 (2H, s); dC (100 MHz) 13.9 (2£CH3), 20.2
(2£CH2), 30.8 (2£CH2), 52.0 (2£CH2), 121.9 (2£Cq), 152.1
(2£CH), 154.5 (Cq); m/z (EIþ) (rel intensity) 362, 364, 366
(1:2:1, 10, Mþ), 321 (100), 265 (55); HRMS calculated for
C13H20N2Br729 361.999, found 362.000.
4.2.15. Trifluoromethanesulfonic acid-1-(4-di-n-butyl-
aminopyridin-3-yl)napthalen-2-yl ester 5f. To a solution
of naphthol 4f (160 mg, 0.46 mmol) in pyridine (4 mL)
at 0 8C was slowly added triflic anhydride (93 mL,
0.55 mmol). The reaction mixture was stirred at 0 8C for
4 h and then concentrated in vacuo. The residue was then
partitioned between CH2Cl2 and water, the organic extracts
were then dried using MgSO4, filtered, and concentrated in
vacuo. Purification by flash chromatography eluting with
CH2Cl2/EtOAc (6/4) gave triflate 5f (209 mg, 0.44 mmol,
95%) as an orange oil. Rf 0.61 (EtOAc); nmax/cm21 (CHCl3)
2960, 1582, 1421, 1215, 1142; dH (CDCl3, 250 MHz) 0.62
(6H, t, J¼7.2 Hz), 0.81 (4H, m), 1.12 (4H, m), 2.80 (4H, m),
6.82 (1H, d, J¼6.0 Hz), 7.45–7.60 (3H), 7.79 (1H, d, J¼
7.6 Hz), 7.94 (2H, t, J¼8.2 Hz), 8.13 (1H, s), 8.37 (1H, d,
J¼6.0 Hz); dC (63 MHz) 13.5 (2£CH3), 19.9 (2£CH2), 29.4
(2£CH2), 51.5 (2£CH2), 111.7 (CH), 117.1 (Cq), 118.3
(CF3, q, J¼315 Hz), 119.5 (CH), 126.6 (CH), 127.2 (CH),
127.8 (CH), 128.3 (CH), 129.6 (Cq), 130.3 (CH), 132.8 (Cq),
132.9 (Cq), 144.9 (Cq), 150.0 (CH), 153.6 (CH), 155.7 (Cq);
m/z (EIþ) (rel intensity) 480 (20, Mþ), 437 (60), 287 (100);
HRMS calculated for C24H27N2O3F3S 480.170, found
480.170.
3,5-Dibromo(pyridine-4-yl)-n-butylamine
0.33 mmol, 11%) as a yellow oil. Rf 0.14 (CH2Cl2);
max/cm21 (CHCl3) 2958, 1561, 1496; dH (CDCl3,
(101 mg,
n
250 MHz) 0.94 (3H, t, J¼7.0 Hz), 1.40 (2H, m), 1.58 (2H,
m), 3.65 (2H, q, J¼7.0 Hz), 4.70 (1H, s), 8.28 (2H, s); dC
(63 MHz) 13.7 (CH3), 19.8 (CH2), 33.0 (CH2), 46.1 (CH2),
108.2 (2£Cq), 149.0 (Cq), 151.2 (2£CH); m/z (EIþ) (rel
intensity) 306, 308, 310 (1:2:1, 35, Mþ), 265 (100); HRMS
calculated for C9H12N2Br729 305.937, found 305.938.
4.2.13. [3-(2-Benzyloxynaphthalen-1-yl)pyridine-4-yl]di-
n-butylamine 3f. To a solution of dibromide 2f (443 mg,
1.22 mmol) in toluene (12 mL) and ethanol (750 mL) was
added 2 M KOH (3 mL) followed by Pd(PPh3)4 (70 mg,
0.06 mmol) and 2-benzyloxy-1-naphthaleneboronic acid30
(406 mg, 1.46 mmol). The mixture was heated at 100 8C for
20 h with vigorous stirring, then cooled to RT and diluted
with water (25 mL). The phases were separated and
the aqueous phases extracted further with CH2Cl2. The
combined organic extracts were dried using MgSO4,
filtered, and concentrated in vacuo. Purification by flash
chromatography eluting with CH2Cl2!CH2Cl2/EtOAc
(1/1) gave benzyl ether 3f (263 mg, 0.6 mmol, 50%) as a
brown oil. Rf 0.22 (EtOAc); nmax/cm21 (CHCl3) 2956,
1582, 1497, 1267; dH (CDCl3, 250 MHz) 0.62 (6H, t,
J¼7.2 Hz), 0.82 (4H, m), 0.95–1.09 (2H), 1.16–1.31 (2H),
2.87 (4H, m), 5.16 (2H, s), 6.77 (1H, d, J¼6.0 Hz), 7.23–
7.42 (8H), 7.43–7.47 (1H), 7.77–7.86 (2H), 8.11 (1H, s),
8.34 (1H, d, J¼6.0 Hz); dC (63 MHz) 13.7 (2£CH3), 20.0
(2£CH2), 29.5 (2£CH2), 51.4 (2£CH2), 70.8 (CH2), 110.7
(CH), 114.9 (CH), 119.8 (Cq), 123.5 (Cq), 123.9 (CH), 125.6
(CH), 126.5 (CH), 126.8 (2£CH), 127.6 (CH), 127.9 (CH),
128.4 (2£CH), 129.3 (Cq), 129.4 (CH), 133.3 (Cq), 137.3
(Cq), 148.8 (CH), 153.1 (Cq), 153.7 (CH), 155.3 (Cq); m/z
(EIþ) (rel intensity) 439 (100, Mþ); HRMS calculated for
C30H55N2O 439.275, found 439.274.
4.2.16. (6)-Di-n-butyl-[3-(2-phenylnaphthalen-1-yl)pyri-
din-4-yl]amine 6f. To a solution of triflate 5f (100 mg,
0.21 mmol) in Et2O (2 mL) was added PdCl2(dppp) (6 mg,
0.01 mmol) followed by a solution of PhMgBr in hexanes
(1.65 M, 315 mL, 0.52 mmol). The resulting mixture was
heated at 40 8C for 20 h, then cooled to RT, diluted with
water, and extracted with CH2Cl2. The organic extracts
were then dried using MgSO4, filtered, and concentrated in
vacuo. Purification by flash chromatography eluting with
EtOAc/CH2Cl2 (1/1)!MeOH/EtOAc (1/9) gave (^)-biaryl
6f (65 mg, 0.16 mmol, 77%) as a white solid. Mp 92–94 8C.
Rf 0.40 (MeOH/EtOAc, 1/9); nmax/cm21 (CHCl3) 3054,
2957, 1583, 1494; dH (CDCl3, 250 MHz) 0.55 (6H, t, J¼
6.9 Hz), 0.61–0.77 (4H), 0.79–0.99 (4H), 2.48–2.60 (2H),
2.67–2.79 (2H), 6.45 (1H, d, J¼6.0 Hz), 7.08–7.20 (5H),
7.41–7.54 (2H), 7.56 (1H, s), 7.82–7.95 (3H), 8.16 (1H, s),
8.19 (1H, d, J¼6.0 Hz); dC (63 MHz) 13.5 (2£CH3), 19.9
(2£CH2), 29.2 (2£CH2), 51.2 (2£CH2), 111.1 (CH), 121.7
(Cq), 126.0 (CH), 126.5 (2£CH), 126.8 (CH), 127.6
(2£CH), 128.0 (CH), 128.2 (CH), 128.4 (CH), 129.6
(2£CH), 132.3 (Cq), 133.2 (Cq), 134.1 (Cq), 138.9 (Cq),
141.5 (Cq), 148.4 (CH), 154.0 (CH), 154.7 (Cq); m/z (EIþ)
(rel intensity) 408 (25, Mþ), 365 (100); HRMS calculated
for C29H32N2 408.257, found 408.256.
4.2.14. 1-(4-Di-n-butylaminopyridin-3-yl)naphthalene-2-
ol 4f. To a solution of benzyl ether 3f (263 mg, 0.60 mmol)
in ethanol (20 mL) was added 10% Pd/C (80 mg). The
reaction mixture was stirred under H2 at atmospheric
pressure and RT for 18 h. The mixture was then passed
through a pad of Celitew and concentrated in vacuo to give
naphthol 4f (159 mg, 0.46 mmol, 78%) as a white foam. Rf
0.20 (MeOH/EtOAc, 9/1); nmax/cm21 (CHCl3) 3049, 3957,
1593, 1504, 1345; dH (CDCl3, 250 MHz) 0.66 (6H, t, J¼
7.8 Hz), 0.91 (4H, m), 1.24 (4H, m), 2.94 (4H, t, J¼7.8 Hz),
4.2.17. (2)-(Sa) and (1)-(Ra)-Di-n-butyl-[3-(2-phenyl-
naphthalen-1-yl)pyridin-4-yl]amine 6f. CSP-HPLC con-
ditions: Chiralcel OD (1 cm£25 cm); hexanes/EtOAc/
Et2NH, 85/14.4/0.6; 3 mL min21; 25 8C; UV detection at