PAPER
Synthesis of a-Substituted Dihydropyrans
3617
IR (paraffin): 1280, 1220, 1105, 1080, 1055, 1015, 990, 970, 900,
815, 650 cm–1.
2), 71.2 (C-1¢), 104.2 (C-5), 129.1 (ArCH), 129.3 (ArCH), 135.2 (Ar),
144.2 (Ar or C-6), 146.2 (C-6 or Ar).
1H NMR (CDCl3, 300 MHz): d = 1.65–1.72 (m, 2 H, H-3), 1.90–
1.97 (m, 2 H, H-4), 2.44 (s, 3 H, ArCH3), 2.56–2.67 (m, 1 H, H-2¢a),
2.71–2.79 (m, 1 H, H-2¢b), 3.48 (dd, J = 11.3, 4.1 Hz, 1 H, H-1¢),
3.68–3.74 (m, 1 H, H-2a), 3.79–3.86 (m, 1 H, H-2b), 4.67 (t, J = 4.1
Hz, 1 H, H-5), 5.05 (br d, J = 10.3 Hz, 1 H, H-4¢a), 5.11 (dd,
J = 16.5, 2.6 Hz, 1 H, H-4¢b), 5.67 (ddt, J = 16.5, 10.3, 7.2 Hz, 1 H,
H-3¢), 7.31 (d, J = 8.2 Hz, 2 H, Ar), 7.74 (d, J = 8.2 Hz, 2 H, Ar).
13C NMR (CDCl3, 75.5 MHz): d = 20.4 (C-4), 21.6 (ArCH3), 21.7
(C-3), 29.7 (C-2¢), 66.3 (C-2), 70.5 (C-1¢), 104.7 (C-5), 117.9 (C-
4¢), 129.2 (ArCH), 129.3 (ArCH), 133.2 (C-3¢), 134.9 (Ar), 144.4 (Ar
or C-6), 145.6 (C-6 or Ar).
MS (EI): m/z = 308 (M, 3%).
Anal. Calcd for C17H24O3S: C, 66.2; H, 7.8. Found: C, 65.9; H, 8.1.
3,4-Dihydro-6-[2¢-methyl-1¢-(p-toluenesulfonyl)-1¢-propyl]-2H-
pyran (3f)
Colourless prisms; yield: 60%; mp 58–61 °C.
IR (paraffin): 1660, 1355, 1285, 1225, 1130, 1110, 1080, 1055,
1015, 910, 810, 790, 650 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.02 (d, J = 7.2 Hz, 3 H,
CHCH3a), 1.25 (d, J = 7.2 Hz, 3 H, CHCH3b), 1.50–1.57 (m, 2 H,
H-3), 1.69–1.93 (m, 2 H, H-4), 2.42 (s, 3 H, ArCH3), 2.46–2.55 (m,
1 H, H-2¢), 3.23 (d, J = 9.2 Hz, 1 H, H-1¢), 3.59–3.75 (m, 2 H, H-2),
4.60 (t, J = 4.1 Hz, 1 H, H-5), 7.28 (d, J = 8.2 Hz, 2 H, Ar), 7.75 (d,
J = 8.2 Hz, 2 H, Ar).
MS (EI): m/z = 293 (M + 1, <1%).
Anal. Calcd for C16H20O3S: C, 65.7; H, 6.9. Found: C, 65.9; H, 7.1.
3,4-Dihydro-6-[1¢-(p-toluenesulfonyl)ethyl]-2H-pyran (3c)
13C NMR (CDCl3, 75.5 MHz): d = 20.2 (C-4), 21.0 (CHCH3a), 21.5
(C-3), 21.6 (ArCH3), 21.8 (CHCH3b), 27.1 (C-2¢), 66.1 (C-2), 77.4
(C-1¢), 104.1 (C-5), 128.9 (ArCH), 129.1 (ArCH), 136.4 (Ar), 143.9
(Ar or C-6), 147.1 (C-6 or Ar).
Pale yellow oil; yield: 83%.
IR (neat): 1660, 1595, 1350, 1295, 1280, 1230, 1130, 1060, 1035,
1015, 905, 810, 770, 725, 650 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.47 (d, J = 7.2 Hz, 3 H, H-2¢),
1.65–1.73 (m, 2 H, H-3), 1.93–1.98 (m, 2 H, H-4), 2.43 (s, 3 H,
ArCH3), 3.61 (q, J = 7.2 Hz, 1 H, H-1¢), 3.68–3.75 (m, 1 H, H-2a),
3.77–3.84 (m, 1 H, H-2b), 4.71 (t, J = 3.8 Hz, 1 H, H-5), 7.31 (d,
J = 8.2 Hz, 2 H, Ar), 7.74 (d, J = 8.2 Hz, 2 H, Ar).
13C NMR (CDCl3, 75.5 MHz): d = 12.0 (C-2¢), 20.3 (C-4), 21.6
(ArCH3), 21.7 (C-3), 65.5 (C-1¢), 66.3 (C-2), 102.9 (C-5), 129.2
(ArCH), 129.3 (ArCH), 134.8 (Ar), 144.3 (Ar or C-6), 147.7 (C-6 or
Ar).
MS (EI): m/z = 294 (M, 1%).
Anal. Calcd for C15H22O3S: C, 63.8; H, 7.9. Found: C, 63.9; H, 7.9.
3,4-Dihydro-6-[(p-toluenesulfonyl)-[2H2]-methyl]-2H-pyran (6)
A solution of 2 (0.50 g, 2.0 mmol) in anhyd THF (30 mL) was
placed under argon and cooled to –78 °C. n-BuLi (0.8 mL of 1.95
M in hexanes, 1.56 mmol) was added dropwise, then the tempera-
ture was allowed to rise to 0 °C. After 15 min, the solution was
cooled to –78 °C and HMPA (1.74 mL, 10 mmol) was added drop-
wise, followed by D2O (1.0 mL, 50 mmol) which was added all at
once. The crude product was isolated as described for compound 3a
above, and purified by flash chromatography (20% EtOAc/light pe-
troleum) to give the title compound (0.30 g) as colourless prisms;
yield: 59%; mp 60–61 °C; (Lit.6 mp for 2: 56–58 °C).
MS (EI): m/z = 266 (M, <1%).
3,4-Dihydro-6-[2¢-phenyl-1¢-(p-toluenesulfonyl)ethyl]-2H-py-
ran (3d)
Colourless prisms; yield: 84%; mp 134–137 °C.
IR (paraffin): 2240, 2140, 1665, 1595, 1295, 1280, 1240, 1180,
1145, 1115, 1080, 1065, 1030, 930, 840, 805, 780, 750, 720, 705,
675 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.68–1.75 (m, 2 H, H-4), 1.96–
2.01 (m, s H, H-3), 2.44 (s, 3 H, ArCH3), 3.81 (t, J = 5.1 Hz, 2 H,
H-2), 4.73 (t, J = 3.8 Hz, 1 H, H-5), 7.33 (d, J = 8.2 Hz, Ar), 7.77
(d, J = 8.2 Hz, Ar).
13C NMR (CDCl3, 75.5 MHz): d = 20.2 (C-4), 21.4 (C-3), 21.5
(ArCH3), 61.6 (quintet, J = 21.4 Hz, CD2SO2), 66.3 (C-2), 104.5 (C-
5), 128.4 (ArCH), 129.3 (ArCH), 135.9 (Ar), 143.4 (Ar or C-6), 144.4
(C-6 or Ar).
IR (paraffin): 1280, 1225, 1120, 1080, 1060, 900, 860, 850, 815,
795, 740, 645 cm–1.
1H NMR (CDCl3, 300 MHz): d = 1.58–1.64 (m, 2 H, H-3), 1.78–
1.83 (m, 2 H, H-4), 2.45 (s, 3 H, ArCH3), 3.17 (br t, Jav = 12.8 Hz,
1 H, H-1¢), 3.36 (dd, J = 13.6, 3.3 Hz, 1 H, H-2¢a), 3.64 (dd,
J = 12.1, 3.3 Hz, 1 H, H-2¢b), 3.69–3.76 (m, 1 H, H-2a), 3.79–3.86
(m, 1 H, H-2b), 4.49 (t, J = 3.8 Hz, 1 H, H-5), 7.14–7.31 (m, 5 H,
C6H5), 7.33 (d, J = 8.2 Hz, 2 H, Ar), 7.79 (d, J = 8.2 Hz, 2 H, Ar).
13C NMR (CDCl3, 75.5 MHz): d = 20.3 (C-4), 21.6 (ArCH3 and C-
3), 31.1 (C-2¢), 66.2 (C-2), 72.6 (C-1¢), 105.5 (C-5), 126.6 (ArCH),
128.3 (ArCH), 129.0 (ArCH), 129.2 (ArCH), 134.9 (Ar), 137.2 (Ar),
144.4 (Ar or C-6), 145.0 (C-6 or Ar).
MS (EI): m/z (%) = 255 (M + 1, 10), 254 (M, 11).
MS (EI): m/z = 342 (M, 1%).
Anal. Calcd for C13H14D2O3S: C, 61.4; H, 6.4. Found: C, 61.0; H,
6.2.
Anal. Calcd for C20H22O3S: C, 70.1; H, 6.5. Found: C, 69.9; H, 6.8.
3,4-Dihydro-6-[4¢-(p-toluenesulfonyl)oct-1¢-en-4¢-yl]-2H-pyran
(4c)
The second alkylation was performed according to the standard
method above, except that 1.1 equiv of n-BuLi was used. Alkylation
of the anion prepared from 3e with allyl bromide; yield: 90%. Al-
kylation of the anion prepared from 3b with n-butyl bromide; yield:
82%; colourless prisms; mp 71–73 °C.
3,4-Dihydro-6-[1¢-(p-toluenesulfonyl)-1¢-pentyl]-2H-pyran (3e)
Colourless prisms; yield: 70%; mp 74–76 °C.
IR (paraffin): 1360, 1280, 1230, 1210, 1140, 1110, 1060, 1020, 905,
800, 755, 730, 655 cm–1.
1H NMR (CDCl3, 300 MHz): d = 0.88 (t, J = 7.2 Hz, 3 H, H-5¢),
1.26–1.34 (m, 4 H, H-3¢ and H-4¢), 1.66–1.72 (m, 3 H, H-3 and H-
2¢a), 1.81–1.88 (m, 1 H, H-2¢b), 1.92–1.98 (m, 2 H, H-4), 2.44 (s, 3
H, ArCH3), 3.41 (dd, J = 11.8, 3.6 Hz, 1 H, H-1¢), 3.68–3.75 (m, 1
H, H-2a), 3.78–3.85 (m, 1 H, H-2b), 4.68 (t, J = 4.1 Hz, 1 H, H-5),
7.30 (d, J = 8.2 Hz, 2 H, Ar), 7.74 (d, J = 8.2 Hz, 2 H, Ar).
IR (paraffin): 1600, 1285, 1220, 1140, 1120, 1075, 1060, 1000, 910,
850, 810, 765, 725, 705, 650 cm–1.
1H NMR (CDCl3, 300 MHz): d = 0.89 (t, J = 7.1 Hz, 3 H, H-8¢),
1.21–1.37 (m, 3 H, H-6¢a and H-7¢), 1.46–1.56 (m, 1 H, H-6¢b),
1.60–1.68 (m, 2 H, H-3), 1.86 (td, J = 13.9, 3.7 Hz, 1 H, H-5¢a), 1.99
(td, J = 6.4, 4.0 Hz, 2 H, H-4), 2.05 (ddd, J = 13.9, 11.7, 4.5 Hz, 1
13C NMR (CDCl3, 75.5 MHz): d = 13.8 (C-5¢), 20.4 (C-4), 21.6
(ArCH3), 21.8 (C-3), 22.3 (C-4¢), 25.0 (C-3¢), 28.9 (C-2¢), 66.3 (C-
Synthesis 2005, No. 20, 3613–3619 © Thieme Stuttgart · New York