Sauers et al.
112.2, 118.5, 141.5, 143.0, 145.7, 145.8, 147.8, 154.1; MS (EI)
m/z 239 [M+] (27), 196 [M+ - C3H8] (100), 167 (20), 141 (5), 95
(3). (R)-5,6-Furan (4b). Same experimental procedure as 4a,
except that (1R)-pinocarvone (made from (S)-(-)-R-pinene)31
was used in place of the (1R)-(-)-myrtenal listed above: yield
29 g (52%); dark brown oil; 1H NMR (400 MHz, CDCl3) δ 0.64
(s, 3H), 1.26 (d, J ) 9.5 Hz, 1H), 1.38 (s, 3H), 2.34-2.36 (m,
1H), 2.62-2.68 (m, 1H), 2.73 (t, J ) 5.6 Hz, 1H), 3.13 (d, J )
2 Hz, 2H), 6.47 (dd, J1 ) 1.8 Hz, J2 ) 3.4 Hz, J3 ) 5.1 Hz,
1H), 6.93 (d, J ) 2.9 Hz, 1H), 7.19 (d, J ) 7.8 Hz, 1H), 7.35 (d,
J ) 7.8 Hz, 1H), 7.47 (d, J ) 1.2 Hz, 1H); 13C NMR (125 MHz,
CDCl3) δ 21.6, 26.3, 32.2, 36.9, 39.8, 40.4, 46.7, 107.5, 112.0,
115.8, 133.8, 140.8, 142.9, 147.0, 154.2, 157.2; MS (EI) m/z 239
[M+] (60), 224 (50), 210 (20), 196 (100), 167 (18) 128 (8), 105
(7), 77 (7).
(m, 1H), 2.71-2.80 (m, 1H), 2.86 (t, J ) 5.7 Hz, 1H), 3.20 (d,
J ) 2.9 Hz, 2H), 7.36 (d, J ) 7.6 Hz, 1H), 7.69 (d, J ) 7.6 Hz,
1H), 10.0 (s, 1H); 13C (125 MHz, CDCl3) δ 21.5, 26.2, 31.8, 36.6,
39.7, 40.2, 47.2, 120.0, 133.8, 147.9, 150.9, 158.2, 193.5; MS
(EI) m/z 200 [M+ - H] (25), 186 (26), 158 (100), 130 (34), 77
(10).
(R)-4,5-Pyridoin (7a). A solution of 2a (3.1 g, 1.55 × 10-2
mol) in pyridine (19 mL) was heated to 100 °C. Sodium cyanide
was added (0.21 g, 4.25 × 10-3 mol), and the resulting mixture
was stirred at 100 °C for 0.5 h. To this solution was added
water (6 mL), and the mixture was stirred at 100 °C for 0.5 h.
The mixture was then cooled to 0 °C and stirred for 1-1.5 h.
The formed precipitate was filtered and washed with cold
methanol (5 mL): yield 1.7 g (56%); orange crystalline solid;
1H NMR (400 MHz, acetone-d6) δ 0.68 (s, 6H), 1.24 (d, J )
9.62 Hz, 2H), 1.44 (s, 6H), 2.32-2.38 (m, 2H), 2.74-2.80 (m,
3H), 2.92 (t, J ) 5.46 Hz, 2H), 3.12 (d, J ) 2.37 Hz, 4H), 7.66
(s, 2H), 8.12 (s, 2H), 13.1 (wide s, exchangeable H); 13C (125
MHz, CDCl3) δ 20.9, 21.0, 25.4, 25.6, 31.2, 31.8, 32.8, 33.0,
38.9, 39.3, 40.0, 40.2, 44.6, 44.9, 118.5, 121.2, 140.8, 142.0,
146.2, 146.8, 148.3, 155.4, 197.7; MS (EI) m/z 402 [M+] (56),
343 (21), 202 (34), 158 (100), 130 (69), 103 (21), 77 (76). (R)-
5,6-Pyridoin (7b): yield 3.3 g (53%); yellow crystalline solid;
1H NMR (400 MHz, acetone-d6) δ 0.66 (s, 6H), 1.30 (d, J )
9.6, 2H), 1.42 (s, 6H), 2.30-2.40 (m, 2H), 2.73-2.82 (m, 3H),
2.86 (t, J ) 5.6 Hz, 2H), 3.11 (d, J ) 2.4 Hz, 4H), 7.50 (d, J )
8.0 Hz, 2H), 7.54 (d, J ) 7.8 Hz, 2H), 12.9 (s, 1H); 13C (125
MHz, CDCl3) δ 20.8, 25.6, 32.0, 35.8, 39.8, 40.3, 46.4, 95.0,
134.9; MS (EI) m/z 402 [M+] (55), 372 (40), 329 (50), 301 (20),
276 (10), 224 (5), 202 (37), 172 (100), 158 (90), 145 (29), 130
(91), 103 (42), 91 (26), 77 (58), 69 (38).
(R)-4,5-Ester (6a). To a suspension of 4a (10 g, 0.418 mol)
and ammonium metavanadate (0.70 g, 5.98 × 10-3 mol) in
water (200 mL) was added concentrated nitric acid (132 mL),
and the mixture was stirred at reflux for 3-4 h. The water
and nitric acid were removed by distillation at 180 °C, with
vacuum applied at the very end of the distillation to ensure
dryness of the reaction mixture. Ethanol (80 mL) and sulfuric
acid (20 mL) were added to the reaction flask, and the mixture
was stirred at reflux overnight. The reaction mixture was then
poured into hexanes (150 mL) and neutralized with an aqueous
solution of saturated sodium bicarbonate. The water layer was
extracted with hexanes (3 × 100 mL), and the combined
organic layers were then washed with water (3 × 100 mL),
dried over sodium sulfate and concentrated on a rotary
1
evaporator: yield 5.7 g (56%); brown oil; H NMR (400 MHz,
CDCl3) δ 0.60 (s, 3H), 1.19 (d, J ) 9.7 Hz, 1H), 1.40-1.45 (m,
6H), 2.32 (quint, J1 ) 2.9 Hz, J2 ) 5.6 Hz, J3 ) 8.6 Hz, J4 )
11.5 Hz, 1H), 2.66-2.74 (m, 1H), 2.88 (t, J ) 5.4 Hz, 1H), 3.01
(d, J ) 2.8 Hz, 2H), 4.45 (q, J1 ) 6.5 Hz, J2 ) 7.1 Hz, J3 ) 7.7
Hz, 2H), 7.91 (s, 1H), 8.26 (s, 1H); 13C (125 MHz, CDCl3) δ
14.6, 21.5, 26.1, 31.7, 33.0, 39.2, 40.1, 44.9, 61.9, 124.8, 145.8,
146.6, 146.7, 146.8, 166.0. MS (EI) m/z 244 [M+ - H] (23), 202
(90), 223 (45), 173 (95), 156 (100), 129 (87), 91 (45), 77 (73).
(R)-5,6-Ester (6b): yield 4.8 g (47%); brown oil; 1H NMR (400
MHz, CDCl3) δ 0.60 (s, 3H), 1.23 (d, J ) 9.7 Hz, 1H), 1.36 (t,
J ) 6.4 Hz, 3H), 1.38 (s, 3H), 2.33-2.39 (m, 1H), 2.63-2.71
(m, 1H), 2.80 (t, J ) 5.7 Hz, 1H), 3.19 (d, J ) 2.9 Hz, 2H),
4.38-4.48 (m, 2H), 7.29 (d, J ) 7.7 Hz, 1H), 7.82 (d, J ) 7.46
Hz, 1H); 13C (125 MHz, CDCl3) δ 14.6, 21.5, 26.2, 31.8, 36.9,
39.6, 40.2, 47.0, 61.9, 122.8, 133.6, 145.8, 146.5, 157.9, 165.9;
MS (EI) m/z 245 [M+ - H] (5), 230 (4), 216 (7), 200 (30), 186
(37), 170 (39), 158 (100), 141 (27), 128 (79), 117 (23), 103 (24),
84 (22), 77 (68), 69 (40).
(R)-4,5-PTPPZ. A mixture of 7a (0.39 g, 9.69 × 10-4 mol)
and ammonium acetate (2.0 g, 2.56 × 10-2 mol) was heated
without solvent at 180 °C for 1 h. The liquid mixture was then
cooled to room temperature, and methanol was added (∼5 mL).
Slowly, the formed suspension was warmed in an oil bath until
the solution began to reflux and then cooled again to room
temperature. The precipitate was filtered and washed with
methanol. The product powder was recrystallized from a
dichloromethane/methanol (1:2) solution: yield 0.13 g (35%);
yellow crystalline solid; 1H NMR (400 MHz, CDCl3) δ 0.67 (s,
12H, H(12)), 1.22(d, J ) 9.5 Hz, 4H, H(9a)), 1.40 (s, 12H,
H(13)), 2.26-2.30 (m, 4H, H(8)), 2.64-2.71 (m, 4H, H(9b)), 2.79
(t, J ) 5.71 Hz, 4H, H(10)), 2.94-2.96 (m, 8H, H(7a,b)), 7.63
(s, 4H, H(6)), 7.96 (s, 4H, H(3)); 13C (125 MHz, CDCl3) δ 21.6,
26.3, 32.0, 33.1, 39.4, 40.3, 44.7, 109.2, 124.4, 142.3, 145.3,
150.2, 155.1; HRMS calcd for C52H56N6 + H 765.4566, found
[M + H]+ 765.4664. (R)-5,6-PTPPZ: yield 2.6 g (69%); yellow
(R)-4,5-Aldehyde (2a) A solution of 5a (5.2 g, 2.13 × 10-2
mol) in tetrahydrofuran (100 mL) was cooled to -78 °C, under
nitrogen. A lithium aluminum hydride solution (26 mL, 1 M
in diethyl ether, 2.56 × 10-2 mol) was then added slowly, and
the resulting solution was stirred at -78 °C for 1 h. Acetic
acid (11 mL) was added to the reaction mixture at -78 °C,
and the resulting solution was added to hexanes (300 mL).
The mixture was then poured into water (300 mL) and
extracted with hexanes (3 × 300 mL). The combined organic
layers were washed with water (2 × 100 mL), dried over
sodium sulfate, and concentrated on a rotary evaporator: yield
crystalline solid; H NMR (400 MHz, CDCl3) δ 0.64 (s, 12 H,
1
H(12)), 1.19 (d, J ) 9.5 Hz, 4H, H(9a)), 1.38 (s, 12H, H(13)),
2.23-2.38 (m, 4H, H(8)), 2.61-2.69 (m, 4H, H(9b)), 2.76 (t, J
) 5.5 Hz, 4H, H(10)), 2.84-2.89 (m, 8H, H(7a,b)) 7.25 (d, J )
7.5 Hz, 4H, H(4)), 7.64 (d, J ) 7.8 Hz, 4H, H(3)); 13C (125 MHz,
CDCl3) δ 21.7, 26.3, 32.3, 36.6, 39.6, 40.4, 46.7, 121.7, 133.3,
141.4, 149.9, 154.4, 155.8; HRMS calcd for C52H56N6 + H
765.4566, found [M + H]+ 765.4653.
For the (S) enantiomers of the compounds listed above, (R)-
(+)-R-pinene was used to make the (S)-enantiomers of myrte-
nal30 and pinocarvone,31 in place of the aforementioned (R)-
enantiomers of myrtenal and pinocarvone used to make (R)-
4,5-PTPPZ and (R)-5,6-PTTPZ, respectively.
X-ray Crystallographic Procedures. A Nonius Kap-
paCCD diffractometer was employed to collect X-ray data
using graphite-monochromated Mo KR radiation (λ ) 0.71073
Å). The data were processed using DENZO-SMN and
SCALEPACK,32 and the structures were solved by direct
methods and refined by full-matrix least-squares methods
using SHELXTL.33 The SQUEEZE/BYPASS34 procedure im-
ple
1
2.7 g (64%); reddish-orange oil; H NMR (400 MHz, CDCl3) δ
0.59 (s, 3H), 1.18 (d, J ) 9.8 Hz, 1H), 1.40 (s, 3H), 2.28-2.34
(m, 1H), 2.66-2.74 (m, 1H), 2.89 (t, J ) 5.4 Hz, 1H), 3.00 (d,
J ) 2.8 Hz, 2H), 7.73 (s, 1H), 8.28 (s, 1H), 9.98 (s, 1H); 13C
(125 MHz, CDCl3) δ 21.6, 26.1, 31.6, 33.1, 39.3, 40.0, 45.2,
121.4, 146.0, 147.0, 148.4, 152.0, 193.8; MS (EI) m/z 201 [M+]
(26), 170 (52), 158 (100), 141 (53), 130 (82), 117 (21), 103 (32),
89 (16), 83 (5), 77 (83), 69 (12). (R)-5,6-Aldehyde (2b): yield
1
3.6 g (85%); reddish-orange oil; H NMR (400 MHz, CDCl3) δ
0.62 (s, 3H), 1.32 (d, J ) 9.8 Hz, 1H), 1.43 (s, 3H), 2.40-2.45
(32) Otwinowski, Z.; Minor, W. Method Enzymol. 1997, 276, 307-
326.
(33) Sheldrick, G. M. SHELXTL Version 5.04. Siemens Analytical
X-ray Instruments, Madison, WI, 1996.
(30) Shibuya, K. Synthetic Commun. 1994, 24, 2923-2941.
(31) Mihelich, E. D.; Eickhoff, D. J. J. Org. Chem. 1983, 48, 4135-
4137.
8914 J. Org. Chem., Vol. 69, No. 25, 2004