Spectral Data 175

Chapter 6. Diastereoselective Synthesis of Substituted Dihydropyrans

6.6 Spectral Data 175

Ethyl 3-hydroxy-3,5-dimethylhex-5-enoate (25a):

Colourless oil (1.53 g, 82%); ¹H NMR (400 MHz, CDCl3): δ 1.27 (s, 3 H), 1.29 (t, J = 7.2 Hz, 3 H), 1.85 (t, J = 1.2 Hz, 3 H), 2.27 (brs, 2 H), 2.43 (d, J = 15.6 Hz, 1 H), 2.56 (d, J = 15.6 Hz, 1 H), 3.68 (brs, 1 H), 4.19 (q, J = 7.2 Hz, 2 H), 4.70-4.74 (m, 1 H), 4.89-4.92 (m, 1 H); ¹³C NMR (100 MHz, CDCl3): δ 14.1, 24.5, 27.3, 44.8, 49.6, 60.5, 71.1, 115.0, 142.4, 173.1; IR (Neat) 3482, 2980, 2935, 1716, 1642, 1374, 1190, 1095, 1031 cm^-1. HRMS (APCI) cald. for C10H18O3 (M+H)⁺ requires 187.1334; found 187.1328.

Ethyl 3-ethyl-3-hydroxy-5-methylhex-5-enoate (25b):

Colourless oil (1.6 g, 80%); ¹H NMR (400 MHz, CDCl3): δ 0.92 (t, J = 7.2 Hz, 3 H), 1.28 (t, J = 7.2 Hz, 3 H), 1.55-1.63 (m, 2 H), 1.85 (s, 3 H), 2.22 (d, J = 13.6 Hz, 1 H), 2.28 (d, J = 13.6 Hz, 1 H), 2.44 (d, J = 15.6 Hz, 1 H), 2.52 (d, J = 15.6 Hz, 1 H), 3.64 (brs, 1 H), 4.18 (q, J = 7.2 Hz, 2 H), 4.72 (brs, 1 H), 4.90 (brs, 1 H); ¹³C NMR (100 MHz, CDCl3): δ 8.4, 14.3, 24.7, 32.8, 42.3, 46.8, 60.8, 73.6, 115.2, 142.7, 173.7; IR (Neat) 3504, 2977, 2940, 1715, 1642, 1372, 1186, 1095, 1029 cm^-1. HRMS (APCI) cald. for C11H20O3 (M+H)⁺ requires 201.1490; found 201.1486.

Ethyl 2-((2R*,6R*)-5,6-dihydro-2,4-dimethyl-6-phenyl-2H-pyran-2-yl)acetate (27a):

Colourless oil (214 mg, 78 %); ¹H NMR (400 MHz, CDCl3): δ 1.27 (t, J = 7.2 Hz, 3 H), 1.41 (s, 3 H), 1.74 (s, 3 H), 2.01 (dd, J

= 16.8 and 3.2 Hz, 1 H), 2.13 (dd, J = 16.8 and 10.4 Hz, 1 H), 2.59 (d, J = 13.6 Hz, 1 H), 2.65 (d, J = 13.6 Hz, 1 H), 4.10-4.18 (m, 2 H), 4.71 (dd, J = 10.4 and 3.2 Hz, 1 H), 5.55 (brs, 1 H), 7.26-7.29 (m, 1 H), 7.32-7.36 (m, 2 H), 7.38-7.42 (m, 2 H); ¹³C NMR (100 MHz, CDCl3): δ 14.4, 23.1, 25.2, 37.9, 47.6, 60.2, 70.8, 74.5, 126.0, 126.2, 127.4, 128.4, 131.7, 143.1, 170.7; IR (Neat) 2971, 2927, 1734, 1674, 1450, 1367, 1211, 1094, 1076, 752, 699 cm^-1. HRMS (APCI) cald. for C17H22O3 (M+H)⁺ requires 275.1647; found 275.1642.

Ethyl 2-((2R*,6R*)-5,6-dihydro-2,4-dimethyl-6-p-tolyl-2H-pyran-2-yl)acetate (27b):

Colourless oil (236 mg, 82%); ¹H NMR (400 MHz, CDCl3): δ 1.27 (t, J = 7.2 Hz, 3 H), 1.40 (s, 3 H), 1.73 (s, 3 H), 1.97 (dd, J = 16.8 and 3.2 Hz, 1 H), 2.12 (dd, J = 16.8 and 10.8 Hz, 1 H), 2.33 (s, 3 H), 2.58 (d, J = 13.6 Hz, 1 H), 2.63 (d, J = 13.6 Hz, 1 H), 4.10-4.18 (m, 2 H), 4.67 (dd, J = 10.8 and 3.2 Hz, 1 H), 5.54 (brs, 1 H), 7.15 (d, J = 8.0 Hz, 2 H), 7.28 (d, J = 8.0 Hz, 2 H); ¹³C NMR (100 MHz,

OH

CO₂Et

OH

CO₂Et

O CO₂Et

O CO₂Et H₃C

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CDCl3): δ 14.4, 21.2, 23.1, 25.1, 37.9, 47.6, 60.1, 70.7, 74.5, 126.0, 126.2, 129.0, 131.7, 136.9, 140.1, 170.7; IR (Neat) 2973, 2926, 1734, 1687, 1446, 1367, 1215, 1089, 1033, 808, 716 cm^-1. HRMS (APCI) cald. for C18H24O3 (M+H)⁺ requires 289.1803; found 289.1790.

Ethyl 2-((2R*,6R*)-6-(4-bromophenyl)-5,6-dihydro-2,4-dimethyl-2H-pyran-2- yl)acetate (27c):

Colourless oil (230 mg, 65%); ¹H NMR (400 MHz, CDCl3): δ 1.26 (t, J = 7.2 Hz, 3 H), 1.39 (s, 3 H), 1.74 (s, 3 H), 1.98 (dd, J = 16.4 and 3.6 Hz, 1 H), 2.06 (dd, J = 16.4 and 10.4 Hz, 1 H), 2.56 (d, J = 13.6 Hz, 1 H), 2.63 (d, J = 13.6 Hz, 1 H), 4.09-4.18 (m, 2 H), 4.66 (dd, J = 10.8 and 3.2 Hz, 1 H), 5.54 (brs, 1 H), 7.27 (d, J = 8.4 Hz, 2 H), 7.46 (d, J = 8.4 Hz, 2 H); ¹³C NMR (100 MHz, CDCl3): δ 14.4, 23.1, 25.2, 37.8, 47.6, 60.3, 70.2, 74.6, 121.1, 126.3, 127.8, 131.5 (2C), 142.2, 170.6; IR (Neat) 2974, 2927, 1734, 1679, 1445, 1367, 1217, 1088, 1033, 815, 710 cm^-1. HRMS (APCI) cald.

for C17H21BrO3 (M+H)⁺ requires 353.0754; found 353.0742 (⁷⁹Br).

Ethyl 2-((2R*,6R*)-6-(4-chlorophenyl)-5,6-dihydro-2,4-dimethyl-2H-pyran-2- yl)acetate (27d):

Colourless oil (198 mg, 64%); ¹H NMR (400 MHz, CDCl3):

δ 1.26 (t, J = 7.2 Hz, 3 H), 1.39 (s, 3 H), 1.74 (s, 3 H), 1.97 (dd, J = 16.8 and 3.6 Hz, 1 H), 2.05 (dd, J = 16.4 and 10.4 Hz, 1 H), 2.58 (d, J = 13.6 Hz, 1 H), 2.63 (d, J = 13.6 Hz, 1 H), 4.08-4.18 (m, 2 H), 4.67 (dd, J = 10.4 and 3.6 Hz, 1 H), 5.54 (brs, 1 H), 7.28-7.34 (m, 4 H); ¹³C NMR (100 MHz, CDCl3): δ 14.4, 23.1, 25.2, 37.8, 47.6, 60.3, 70.2, 74.7, 126.3, 127.4, 128.5, 131.5, 133.0, 141.7, 170.7; IR (Neat) 2963, 2926, 1735, 1685, 1445, 1368, 1217, 1087, 1033, 817, 692 cm^-1. HRMS (APCI) cald. for C17H21ClO3 (M+H)⁺ requires 309.1257; found 309.1247 (³⁵Cl).

Ethyl 2-((2R*,6R*)-6-(4-fluorophenyl)-5,6-dihydro-2,4-dimethyl-2H-pyran-2-yl)acetate (27e):

Colourless oil (181 mg, 62%); ¹H NMR (400 MHz, CDCl3):

δ 1.26 (t, J = 7.2 Hz, 3 H), 1.40 (s, 3 H), 1.74 (s, 3 H), 1.98 (dd, J = 16.8 and 3.2 Hz, 1 H), 2.06-2.13 (dd, J = 16.8 and 10.8 Hz, 1 H), 2.58 (d, J = 13.6 Hz, 1 H), 2.64 (d, J = 13.6 Hz, 1 H), 4.09-4.18 (m, 2 H), 4.69 (dd, J = 10.8 and 3.6 Hz, 1 H), 5.54 (brs, 1 H), 7.02 (t, J

= 8.8 Hz, 2 H), 7.33-7.37 (m, 2 H); ¹³C NMR (100 MHz, CDCl3): δ 14.5, 23.1, 25.3, 38.0, 47.7, 60.3, 70.4, 74.7, 115.2 (d, J = 21.3 Hz), 126.3, 127.7 (d, J = 8.4 Hz), 131.6, 139.1,

O CO₂Et Br

O CO₂Et Cl

O CO₂Et F

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162.2 (d, J = 243.3 Hz), 170.7; ¹⁹F NMR (376 MHz, CDCl3/C6F6): δ -219.7-(-219.6) (m, 1 F); IR (Neat) 2977, 2930, 1734, 1685, 1511, 1444, 1368, 1223, 1086, 1033, 826, 774 cm^-1. HRMS (APCI) cald. for C17H21FO3 (M+H)⁺ requires 293.1553; found 293.1545.

Ethyl 2-((2R*,6R*)-5,6-dihydro-2,4-dimethyl-6-(4-nitrophenyl)-2H-pyran-2-yl)acetate (27f):

Colourless oil (198 mg, 62%); ¹H NMR (400 MHz, CDCl3): δ 1.27 (t, J = 7.2 Hz, 3 H), 1.41 (s, 3 H), 1.76 (s, 3 H), 2.02-2.09 (m, 2 H), 2.60 (d, J = 13.6 Hz, 1 H), 2.66 (d, J = 13.6 Hz, 1 H), 4.10-4.19 (m, 2 H), 4.82 (t, J = 7.2 Hz, 1 H), 5.57 (brs, 1 H), 7.56 (d, J = 8.8 Hz, 2 H), 8.20 (d, J = 8.8 Hz, 2 H); ¹³C NMR (100 MHz, CDCl3): δ 14.4, 23.0, 25.1, 37.6, 47.4, 60.3, 70.0, 74.8, 123.6, 126.4, 126.6, 131.1, 147.2, 150.6, 170.5; IR (Neat) 2975, 2928, 1733, 1605, 1521, 1446, 1374, 1212, 1091, 1032, 855, 749 cm^-1. HRMS (APCI) cald. for C17H21NO5 (M+H)⁺ requires 320.1498; found 320.1485.

Methyl 4-((2R*,6R*)-6-((ethoxycarbonyl)methyl-3,6-dihydro-4,6-dimethyl-2H-pyran- 2-yl)benzoate (27g):

Colourless oil (226 mg, 68%); ¹H NMR (400 MHz, CDCl3): δ 1.27 (t, J = 7.2 Hz, 3 H), 1.41 (s, 3 H), 1.75 (s, 3 H), 1.99-2.10 (m, 2 H), 2.60 (d, J = 13.6 Hz, 1 H), 2.66 (d, J = 13.6 Hz, 1 H), 3.91 (s, 3 H), 4.10-4.19 (m, 2 H), 4.77 (dd, J = 10.0 and 4.0 Hz, 1 H), 5.55 (brs, 1 H), 7.46 (d, J = 8.4 Hz, 2 H), 8.01 (d, J = 8.4 Hz, 2 H); ¹³C NMR (100 MHz, CDCl3): δ 14.4, 23.1, 25.1, 37.7, 47.5, 52.1, 60.3, 70.4, 74.6, 125.9, 126.3, 129.1, 129.8, 131.4, 148.4, 167.1, 170.6; IR (Neat) 2953, 2927, 1725, 1613, 1436, 1368, 1278, 1090, 1033, 768, 704 cm^-1. HRMS (APCI) cald. for C₁₉H₂₄O₅ (M+H)⁺ requires 333.1702; found 333.1692.

Ethyl 2-((2R*,6S*)-5,6-dihydro-2,4-dimethyl-6-propyl-2H-pyran-2-yl)acetate (27h):

Colourless oil (216 mg, 90%); ¹H NMR (400 MHz, CDCl3): δ 0.91 (t, J = 7.2 Hz, 3 H), 1.24 (t, J = 7.2 Hz, 3 H), 1.30 (s, 3 H), 1.35-1.43 (m, 2 H), 1.45-1.54 (m, 2 H), 1.62-1.72 (m, 4 H), 1.82 (dd, J = 16.0 and 10.8 Hz, 1 H), 2.49 (brs, 2 H), 3.61-3.66 (m, 1 H), 4.11 (q, J = 7.2 Hz, 2 H), 5.45 (brs, 1 H); ¹³C NMR (100 MHz, CDCl3): δ 14.2, 14.4, 18.7, 23.2, 24.6, 35.6, 38.0, 47.7, 60.1, 68.2, 73.6, 126.4, 131.7, 170.8; IR (Neat) 2961, 2930, 2873, 1736, 1678, 1456, 1370, 1216, 1081, 1034, 825 cm^-1. HRMS (APCI) cald. for C14H24O3 (M+H)⁺ requires 241.1803; found 241.1794.

O CO₂Et O₂N

O CO₂Et MeO₂C

O CO₂Et

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Ethyl 2-((2R*,6R*)-6-cyclohexyl-5,6-dihydro-2,4-dimethyl-2H-pyran-2-yl)acetate (27i):

Colourless oil (236 mg, 84%); ¹H NMR (400 MHz, CDCl3): δ 0.93-1.04 (m, 2 H), 1.11-1.21 (m, 2 H), 1.24 (t, J = 7.2 Hz, 3 H), 1.28 (s, 3 H), 1.34-1.42 (m, 2 H), 1.65-1.76 (m, 7 H), 1.83-1.96 (m, 3 H), 2.47 (brs, 2 H), 3.33-3.38 (m, 1 H), 4.06-4.15 (m, 2 H), 5.43 (brs, 1 H); ¹³C NMR (100 MHz, CDCl3): δ 14.4, 23.4, 24.4, 26.2, 26.3, 26.8, 28.5, 29.1, 32.6, 42.5, 47.7, 60.1, 72.6, 73.5, 126.5, 131.8, 170.9; IR (Neat) 2967, 2925, 2852, 1736, 1679, 1449, 1367, 1216, 1097, 1034, 833 cm^-1. HRMS (APCI) cald. for C17H28O3

(M+H)⁺ requires 281.2116; found 281.2112.

Ethyl 2-((2R*,6S*)-5,6-dihydro-6-isobutyl-2,4-dimethyl-2H-pyran-2-yl)acetate (27j):

Colourless oil (219 mg, 86%); ¹H NMR (400 MHz, CDCl3): δ 0.89 (d, J = 6.4 Hz, 3 H), 0.90 (d, J = 6.4 Hz, 3 H), 1.24 (t, J = 7.2 Hz, 3 H), 1.31 (s, 3 H), 1.44-1.52 (m, 2 H), 1.65-1.72 (m, 4 H), 1.78-1.86 (m, 2 H), 2.48 (brs, 2 H), 3.67-3.74 (m, 1 H), 4.12 (q, J = 7.2 Hz, 2 H), 5.45 (brs, 1 H); ¹³C NMR (100 MHz, CDCl₃): δ 14.4, 22.4, 23.3, 23.4, 24.5 (2C), 36.2, 45.1, 47.7, 60.2, 66.6, 73.6, 126.5, 131.8, 171.0; IR (Neat) 2957, 2927, 2867, 1736, 1654, 1458, 1369, 1215, 1086, 1034, 971 cm^-1. HRMS (APCI) cald. for C15H26O3 (M+H)⁺ requires 255.1960; found 255.1954.

Ethyl 2-((2R*,6R*)-2-ethyl-5,6-dihydro-4-methyl-6-phenyl-2H-pyran-2-yl)acetate (27k):

Colourless oil (213 mg, 74%); ¹H NMR (400 MHz, CDCl3): δ 0.93 (t, J = 7.2 Hz, 3 H), 1.26 (t, J = 7.2 Hz, 3 H), 1.64-1.72 (m, 1 H), 1.76 (s, 3 H), 1.77-1.86 (m, 1 H), 2.01 (dd, J = 16.8 and 3.2 Hz, 1 H), 2.09-2.18 (dd, J = 16.8 and 10.8 Hz, 1 H), 2.56 (d, J = 13.6 Hz, 1 H), 2.63 (d, J = 13.6 Hz, 1 H), 4.06-4.17 (m, 2 H), 4.68 (dd, J = 10.4 and 3.2 Hz 1 H), 5.59 (brs, 1 H), 7.24-7.28 (m, 1 H), 7.32-7.36 (m, 2 H), 7.38-7.42 (m, 2 H); ¹³C NMR (100 MHz, CDCl3): δ 8.3, 14.5, 23.3, 30.7, 37.7, 44.2, 60.2, 70.8, 76.8, 125.7, 126.1, 127.4, 128.4, 132.2, 143.3, 171.1; IR (Neat) 2970, 2927, 2854, 1734, 1676, 1450, 1369, 1207, 1095, 1031, 752, 698 cm^-1. HRMS (APCI) cald. for C18H24O3 (M+H)⁺ requires 289.1803; found 289.1794.

Ethyl 2-((2R*,6R*)-2-ethyl-5,6-dihydro-4-methyl-6-p-tolyl-2H-pyran-2-yl)acetate (27l):

Colourless oil (242 mg, 80%); ¹H NMR (400 MHz, CDCl3): δ 0.92 (t, J = 7.2 Hz, 3 H), 1.26 (t, J = 7.2 Hz, 3 H), 1.63-1.72 (m, 1 H), 1.75 (s, 3 H), 1.77-1.84 (m, 1 H), 1.98 (dd, J = 16.8 and 3.2 Hz, 1 H), 2.09-2.17 (dd, J = 16.8 and 10.4 Hz, 1 H), 2.34 (s, 3 H), 2.55 (d, J =

O CO₂Et

O CO₂Et

O CO₂Et

TH-1119_08612204

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O CO₂Et H₃C

O CO₂Et

13.6 Hz, 1 H), 2.61 (d, J = 13.6 Hz, 1 H), 4.07-4.17 (m, 2 H), 4.64 (dd, J = 10.4 and 3.2 Hz, 1 H), 5.58 (brs, 1 H), 7.15 (d, J = 7.6 Hz, 2 H), 7.28 (d, J = 8.0 Hz, 2 H); ¹³C NMR (100 MHz, CDCl3): δ 8.3, 14.5, 21.3, 23.3, 30.7, 37.7, 44.2, 60.2, 70.7, 76.7, 125.7, 126.1, 129.1, 132.2, 137.0, 140.3, 171.1; IR (Neat) 2969, 2926, 2856, 1734, 1679, 1445, 1368, 1206, 1088, 1033, 809, 668 cm^-1. HRMS (APCI) cald.

for C19H26O3 (M+H)⁺ requires 303.1960; found 303.1948.

Ethyl 2-((2R*,6S*)-2,6-diethyl-5,6-dihydro-4-methyl-2H-pyran-2-yl)acetate (27m):

Colourless oil (212 mg, 88%); ¹H NMR (400 MHz, CDCl3): δ 0.90 (t, J = 7.6 Hz, 3 H), 0.95 (t, J = 7.6 Hz, 3 H), 1.23 (t, J = 7.2 Hz, 3 H), 1.41-1.65 (m, 3 H), 1.69 (s, 3 H), 1.70-1.85 (m, 3 H), 2.48 (brs, 2 H), 3.48-3.54 (m, 1 H), 4.07-4.15 (m, 2 H), 5.50 (brs, 1 H); ¹³C NMR (100 MHz, CDCl3): δ 8.0, 10.2, 14.5, 23.4, 29.0, 29.8, 35.4, 43.9, 60.2, 69.8, 75.7, 126.0, 131.9, 171.2; IR (Neat) 2965, 2929, 2878, 1735, 1676, 1463, 1378, 1208, 1074, 1037, 941 cm^-1. HRMS (APCI) cald. for C₁₄H24O3 (M+H)⁺ requires 241.1803; found 241.1798.

Ethyl 2-((2R*,6S*)-2-ethyl-6-hexyl-5,6-dihydro-4-methyl-2H-pyran-2-yl)acetate (27n):

Colourless oil (243 mg, 82%); ¹H NMR (400 MHz, CDCl3): δ 0.88 (t, J = 6.8 Hz, 3 H), 0.90 (t, J = 7.6 Hz, 3 H), 1.23 (t, J = 7.2 Hz, 3 H), 1.25-1.35 (m, 8 H), 1.37- 1.47 (m, 2 H), 1.51-1.62 (m, 2 H), 1.69 (s, 3 H), 1.71- 1.75 (m, 1 H), 1.78-1.85 (m, 1 H), 2.48 (brs, 2 H), 3.52-3.60 (m, 1 H), 4.10 (q, J = 7.2 Hz, 2 H), 5.50 (brs, 1 H); ¹³C NMR (100 MHz, CDCl3): δ 7.97, 14.3, 14.4, 22.8, 23.4, 25.7, 29.5, 29.7, 32.1, 35.8, 36.2, 43.8, 60.2, 68.4, 75.8, 126.0, 132.0, 171.2; IR (Neat) 2959, 2928, 2856, 1736, 1676, 1461, 1368, 1205, 1091, 1033, 869 cm^-1. HRMS (APCI) cald. for C18H32O3 (M+H)⁺ requires 297.2429; found 297.2418.

Ethyl 2-((2R*,6R*)-5,6-dihydro-6-isopropyl-2,4-dimethyl-2H-pyran-2-yl)acetate (31b):

Colourless oil (163 mg, 68%); ¹H NMR (400 MHz, CDCl3): δ 0.89 (d, J = 6.8 Hz, 3 H), 0.94 (d, J = 6.8 Hz, 3 H), 1.24 (t, J = 7.2 Hz, 3 H), 1.29 (s, 3 H), 1.64-1.72 (m, 5 H), 1.82-1.89 (m, 1 H), 2.48 (brs, 2 H), 3.30-3.36 (m, 1 H), 4.06-4.17 (m, 2 H), 5.44 (brs, 1 H); ¹³C NMR (100 MHz, CDCl3): δ 14.4, 18.2, 18.7, 23.4, 24.5, 32.4, 32.8, 47.7, 60.1, 73.4, 73.6, 126.5, 131.7, 171.0; IR (Neat) 2965, 2929, 1736, 1676, 1448, 1368, 1211, 1081, 1035, 841 cm^-1. HRMS (APCI) cald. for C14H24O3 (M+H)⁺ requires 241.1803; found 241.1794.

O CO₂Et

O CO₂Et

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Ethyl 2-((2R*,6R*)-6-benzyl-5,6-dihydro-2,4-dimethyl-2H-pyran-2-yl)acetate (31c):

Colourless oil (185 mg, 64%); ¹H NMR (400 MHz, CDCl3):

δ 1.24 (t, J = 7.2 Hz, 3 H), 1.29 (s, 3 H), 1.60-1.67 (m, 4 H), 1.84-1.91 (m, 1 H), 2.51 (brs, 2 H), 2.69 (dd, J = 13.6 and 6.8 Hz, 1 H), 2.95 (dd, J = 13.6 and 6.8 Hz, 1 H), 3.81-3.87 (m, 1 H), 4.11 (q, J = 7.2 Hz, 2 H), 5.42 (brs, 1 H), 7.20-7.30 (m, 5 H); ¹³C NMR (100 MHz, CDCl3): δ 14.4, 23.2, 24.7, 35.0, 42.5, 47.6, 60.2, 69.6, 74.0, 126.2, 126.4, 128.2, 129.6, 131.4, 138.8, 170.8; IR (Neat) 2974, 2927, 1734, 1674, 1453, 1369, 1214, 1086, 1032, 751, 700 cm^-1. HRMS (APCI) cald. for C18H24O3 (M+H)⁺ requires 289.1803; found 289.1797.

Ethyl 2-((2R*,6R*)-6-(4-chlorobenzyl)-5,6-dihydro-2,4-dimethyl-2H-pyran-2-yl)acetate (31d):

Colourless oil (194 mg, 60%); ¹H NMR (400 MHz, CDCl3): δ 1.23 (t, J = 7.2 Hz, 3 H), 1.29 (s, 3 H), 1.61- 1.68 (m, 4 H), 1.83-1.90 (m, 1 H), 2.51 (brs, 2 H), 2.68 (dd, J = 14.0 and 6.8 Hz, 1 H), 2.86 (dd, J = 14.0 and 6.8 Hz, 1 H), 3.81-3.88 (m, 1 H), 4.11 (q, J = 7.2 Hz, 2 H), 5.43 (brs, 1 H), 7.17 (d, J = 8.4, 2 H), 7.24 (d, J = 8.8 Hz, 2 H); ¹³C NMR (100 MHz, CDCl3): δ 14.4, 23.2, 24.6, 35.0, 41.7, 47.6, 60.3, 69.3, 74.0, 126.5, 128.3, 131.0, 131.3, 132.0, 137.4, 170.8; IR (Neat) 2972, 2927, 1734, 1676, 1492, 1369, 1214, 1091, 1033, 822, 798 cm^-1. HRMS (APCI) cald. for C18H23ClO3 (M+H)⁺ requires 323.1414; found 323.1404 (³⁵Cl).

Ethyl 2-((2R*,6R*)-6-(4-bromobenzyl)-5,6-dihydro-2,4-dimethyl-2H-pyran-2- yl)acetate (31e):

Colourless oil (228 mg, 62%); ¹H NMR (400 MHz, CDCl3): δ 1.23 (t, J = 7.2 Hz, 3 H), 1.25 (s, 3 H), 1.60- 1.68 (m, 4 H), 1.83-1.90 (m, 1 H), 2.49 (brs, 2 H), 2.67 (dd, J = 14.0 and 6.8 Hz, 1 H), 2.85 (dd, J = 14.0 and 6.8 Hz, 1 H), 3.80-3.88 (m, 1 H), 4.11 (q, J = 7.2 Hz, 2 H), 5.43 (brs, 1 H), 7.12 (d, J = 8.4, 2 H), 7.39 (d, J = 8.4 Hz, 2 H); ¹³C NMR (100 MHz, CDCl3): δ 14.4, 23.2, 24.6, 35.0, 41.7, 47.6, 60.2, 69.2, 74.0, 120.0, 126.5, 128.1, 131.2, 131.4, 137.9, 170.7; IR (Neat) 2973, 2927, 1734, 1674, 1488, 1369, 1213, 1073, 1033, 863, 820 cm^-1. HRMS (APCI) cald. for C18H23BrO3 (M+H)⁺ requires 367.0909; found 367.0892 (⁷⁹Br).

O CO₂Et

O CO₂Et Cl

O CO₂Et Br

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Ethyl 2-((2R*,6R*)-6-(4-methylbenzyl)-5,6-dihydro-2,4-dimethyl-2H-pyran-2- yl)acetate (31f):

Colourless oil (194 mg, 64%); ¹H NMR (400 MHz, CDCl3): δ 1.24 (t, J = 7.2 Hz, 3 H), 1.29 (s, 3 H), 1.60- 1.67 (m, 4 H), 1.82-1.89 (m, 1 H), 2.32 (s, 3 H), 2.51 (brs, 2 H), 2.65 (dd, J = 13.6 and 6.8 Hz, 1 H), 2.92 (dd, J = 13.6 and 6.8 Hz, 1 H), 3.82- 3.89 (m, 1 H), 4.12 (q, J = 7.2 Hz, 2 H), 5.43 (brs, 1 H), 7.08 (d, J = 8.0, 2 H), 7.13 (d, J = 8.0 Hz, 2 H); ¹³C NMR (100 MHz, CDCl3): δ 14.4, 21.2, 23.2, 24.7, 35.0, 42.1, 47.7, 60.2, 69.7, 74.0, 126.4, 129.0, 129.5, 131.5, 135.6, 135.7, 170.9; IR (Neat) 2975, 2926, 1734, 1676, 1445, 1369, 1213, 1078, 1033, 807, 749 cm^-1. HRMS (APCI) cald. for C19H26O3

(M+H)⁺ requires 303.1960; found 303.1948.

Ethyl 2-((2R*,6R*)-2-ethyl-5,6-dihydro-6-isopropyl-4-methyl-2H-pyran-2-yl)acetate (31g):

Colourless oil (165 mg, 65%); ¹H NMR (400 MHz, CDCl₃): δ 0.89 (t, J = 7.6 Hz, 3 H), 0.90 (d, J = 7.2 Hz, 3 H), 0.96 (d, J = 7.2 Hz, 3 H), 1.23 (t, J = 7.6 Hz, 3 H), 1.50-1.61 (m, 2 H), 1.63-1.74 (m, 5 H), 1.80-1.87 (m, 1 H), 2.47 (brs, 2 H), 3.26-3.31 (m, 1 H), 4.05- 4.13 (m, 2 H), 5.50 (brs, 1 H); ¹³C NMR (100 MHz, CDCl3): δ 8.0, 14.4, 18.4, 18.9, 23.5, 29.7, 32.7, 33.1, 43.8, 60.1, 73.2, 75.7, 126.0, 131.9, 171.2; IR (Neat) 2963, 2928, 1735, 1685, 1449, 1368, 1207, 1073, 1033, 867 cm^-1. HRMS (APCI) cald. for C15H26O3 (M+H)⁺ requires 255.1960; found 255.1952.

Ethyl 2-((2R*,6R*)-6-cyclohexyl-2-ethyl-5,6-dihydro-4-methyl-2H-pyran-2-yl)acetate (31h):

Colourless oil (183 mg, 62%); ¹H NMR (400 MHz, CDCl3): δ 0.89 (t, J = 7.6 Hz, 3 H), 0.94-1.03 (m, 2 H), 1.12-1.19 (m, 2 H), 1.23 (t, J = 7.2 Hz, 3 H), 1.31-1.40 (m, 2 H), 1.48-1.57 (m, 2 H), 1.62-1.76 (m, 7 H), 1.81-1.88 (m, 2 H), 1.98-2.02 (m, 1 H), 2.47 (brs, 2 H), 3.28-3.34 (m, 1 H), 4.05-4.12 (m, 2 H), 5.49 (brs, 1 H); ¹³C NMR (100 MHz, CDCl3): δ 8.0, 14.5, 23.6, 26.3, 26.5, 26.9, 28.8, 29.4, 29.6, 32.9, 42.9, 43.8, 60.2, 72.5, 75.7, 126.1, 132.0, 171.3; IR (Neat) 2965, 2925, 1735, 1675, 1449, 1377, 1207, 1096, 1033, 844 cm^-1. HRMS (APCI) cald. for C18H30O3 (M+H)⁺ requires 295.2273; found 295.2265.

O CO₂Et H₃C

O CO₂Et

O CO₂Et

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