3.2.1. General Experiment for the Preparation of Chloroketals (12–15)
A stirred solution of chloroketone
8–
11, 2,2-dimethyl-1,3-propanediol (1.0 or 1.2 equiv) and
p-TsOH·H
2O (0.023 equiv) in cyclohexane (c = 0.7 M) was refluxed in a round bottom flask equipped with a Dean–Stark apparatus. After the indicated time, the mixture was cooled to RT and solvent was evaporated in vacuo (bath temperature 50–55 °C, pressure 30–50 mbar) and the resulting oil dissolved in Et
2O. The ethereal solution was sequentially washed with sat. aq. NaHCO
3 soln., water and brine, dried (MgSO
4) and concentrated in vacuo (35 °C, 30 mbar). The obtained crude product was further used as such or purified either by bulb-to-bulb vacuum distillation (Kugelrohr) or FLC to furnish a corresponding chloroketal
12–
15. The structural characterization (
1H-NMR,
13C-NMR spectra) of the new compound are presented in
Supplementary Materials.
2-(1-Chloroethyl)-2,5,5-trimethyl-[1,3]dioxane (12)
Prepared accordingly to Ref. [
30]: commercial 3-chlorobutanone
8 (5.86 mL, 56 mmol), 2,2-dimethyl-1,3-propanediol (5.87 g, 56 mmol),
p-TsOH·H
2O (246 mg, 1.3 mmol), cyclohexane (81 mL), reflux (100 °C), 17 h, concentrated in vacuo (50 °C, 30 mbar), Et
2O (61 mL), NaHCO
3 (37 mL), water (37 mL), brine (37 mL), crude chloroketal
12 (9.79 g, 90%) as yellow oil; R
f (hexanes/AcOEt 5:1) 0.74; δ
H (300 MHz, CDCl
3) 4.14 (q,
J = 6.8 Hz, 1H, CHCl), 3.61 (dd,
J = 11.5, 8.9 Hz, 2H, OCH
2), 3.52–3.40 (m, 2H, OCH
2), 1.53 (d,
J = 6.8 Hz, 3H, Me), 1.46 (s, 3H, Me), 1.08 (s, 3H, Me
2), 0.85 (s, 3H, Me
2). NMR spectrum fully corresponds to the literature data [
30];
m/z (ESI) 157.2 (100, M-Cl
+), 158.0 (9%), 175.2 (76, M-Cl+H
2O
+), 176.0 (8%), t
R = 2.34 min.
2-(1-Chloroethyl)-2-ethyl-5,5-dimethyl-[1,3]dioxane (13)
2-Chloropentan-3-one
9 (2.73 g, 23 mmol, prepared accordingly to Ref. [
34]), 2,2-dimethyl-1,3-propanediol (2.36 g, 23 mmol),
p-TsOH·H
2O (99 mg, 0.52 mmol), cyclohexane (32.6 mL), reflux (130 °C), 27 h, concentrated in vacuo (50 °C, 45 mbar), Et
2O (40 mL), NaHCO
3 (30 mL), water (30 mL), brine (30 mL), FLC (176 g SiO
2, Hex: Et
2O 12:1, 650 mL), pure chloroketal
13 (2.41 g, 51%) as colourless oil; R
f (hexanes/AcOEt 6:1) 0.67; ν
max (ATR) 2956, 2869, 1469, 1396, 1186, 1142, 1126, 1093, 1081, 1038, 1016, 957, 916 cm
−1; δ
H (600 MHz, CDCl
3) 4.35 (q,
J = 6.8 Hz, 1H, CHCl), 3.59 (d,
J = 11.5 Hz, 1H, OCH
2), 3.55 (d,
J = 11.5 Hz, 1H, OCH
2), 3.49 (d,
J = 11.5 Hz, 1H, OCH
2), 3.48 (d,
J = 11.5 Hz, 1H, OCH
2), 1.96 (m, 2H, CH
2), 1.55 (d,
J = 6.8 Hz, 3H, Me), 1.04 (s, 3H, Me
2), 0.93 (t,
J = 7.5 Hz, 3H, Me), 0.90 (s, 3H, Me
2); δ
C (151 MHz, CDCl
3) 100.1 (OC
q), 70.2 (2 × OCH
2), 56.5 (CHCl), 29.6 (C
q), 22.9 (Me
2), 22.5 (Me
2), 21.2 (CH
2), 18.7 (Me), 7.0 (Me);
m/z (ESI) 189.2 (100, M-Cl+H
2O
+), 190.0 (10%), 171.2 (95, M-Cl
+), 172.2 (8%), t
R = 2.96 min; HR-MS (HESI): M
+, found 170.1305. C
10H
18O
2 requires 170.1301.
1-Chloro-8,8-dimethyl-6,10-dioxaspiro [4.5] decane (14)
Commercial 2-chlorocyclopentanone 10 (755 µL, 7.5 mmol), 2,2-dimethyl-1,3-propanediol (943 mg, 9.1 mmol), p-TsOH·H2O (33 mg, 0.17 mmol), cyclohexane (11 mL), reflux (128 °C), 4.5 h, concentrated in vacuo (50 °C, 50 mbar), Et2O (15 mL), NaHCO3 (6 mL), water (6 mL), brine (6 mL), FLC (41 g SiO2, Hex: AcOEt 6:1, 270 mL), pure chloroketal 14 (1.27 g, 82%) as colourless oil; Rf (hexanes/AcOEt 5:1) 0.67; νmax (ATR) 2954, 2867, 1472, 1396, 1337, 1207, 1144, 1112, 1076, 1016, 837 cm−1; δH (300 MHz, CDCl3) 4.39–4.34 (m, 1H, CHCl), 3.55–3.45 (m, 4H, 2 × OCH2), 2.29–1.60 (m, 6H, 3xCH2), 1.00 (s, 3H, Me2), 0.98 (s, 3H, Me2); δC (151 MHz, CDCl3) 107.6 (OCq), 72.3 (OCH2), 72.1 (OCH2), 60.7 (CHCl), 32.9 (CH2), 31.1 (CH2), 30.0 (Cq), 22.4 (Me2), 22.3 (Me2), 18.6 (CH2); HR-MS (HESI): M+, found 204.0913. C10H17ClO2 requires 204.0912.
7-Chloro-3,3-dimethyl-1,5-dioxaspiro[5.5]undecane (15)
Commercial 2-chlorocyclohexanone
11 (860 µL, 7.5 mmol), 2,2-dimethyl-1,3-propanediol (942 mg, 9.0 mmol),
p-TsOH·H
2O (33 mg, 0.17 mmol), cyclohexane (10.9 mL), reflux (160 °C), 10 h, concentrated in vacuo (55 °C, 50 mbar), Et
2O (20 mL), NaHCO
3 (5 mL), water (5 mL), brine (5 mL), bulb-to-bulb distillation (175–180 °C, 27 mbar), pure chloroketal
15 (1.43 g, 87%) as yellow oil.; R
f (hexanes/AcOEt 5:1) 0.67; ν
max (ATR) 2942, 2864, 1472, 1446, 1395, 1364, 1215, 1167, 1112, 1111, 1096, 1016, 965, 804 cm
−1; δ
H (600 MHz, CDCl
3) 4.23–4.18 (m, 1H, CHCl), 3.62 (d,
J = 11.4 Hz, 1H, OCH
2), 3.58 (d,
J = 11.5 Hz, 1H, OCH
2), 3.52 (dd,
J = 11.4, 1.8 Hz, 1H, OCH
2), 3.45 (dd,
J = 11.4, 1.8 Hz, 1H, OCH
2), 2.33–2.23, 2.07–2.00, 1.96–1.88, 1.76–1.68 (4xm, 4 × 1H, 2 × CH
2), 1.57–1.37 (m, 4H, 2 × CH
2), 1.12 (s, 3H, Me
2), 0.87 (s, 3H, Me
2).
1H NMR spectrum fully corresponds the literature data [
35]; δ
C (151 MHz, CDCl
3) 97.2 (OC
q), 70.3 (OCH
2), 69.8 (OCH
2), 61.6 (CHCl), 32.0 (C
q, CH
2), 30.0 (CH
2), 27.4 (CH
2), 22.8 (Me
2), 22.4 (Me
2), 21.6 (CH
2); HR-MS (HESI): M
+, found 218.1071. C
11H
19ClO
2 requires 218.1068.
3.2.2. General Experiment for the Preparation of Alkene Ketals (16–19, 25)
To a stirred solution of potassium hydroxide (11 eq.) in ethylene glycol was added to chloroketal 12–15 at 120 °C and the reaction mixture was heated at 160 °C for 7–23 h. After cooling to RT, water was added and extracted with Et2O. The organic phase was washed with water and brine, dried (MgSO4) and concentrated in vacuo (35 °C, 30–200 mbar). The crude product was purified either by bulb-to-bulb vacuum distillation (Kugelrohr) or FLC to furnish a corresponding ketal 16–19, 25.
2,5,5-Trimethyl-2-vinyl-[1,3]dioxane (16)
KOH (31.72 g, 0.57 mol), ethylene glycol (68 mL), chloroketal
12 (9.76 g, 51 mmol), 23 h, water (340 mL), Et
2O (3 × 150 mL), water (110 mL), brine (110 mL), concentrated in vacuo (35 °C, 30 mbar), bulb-to-bulb vacuum distillation (80–95 °C, 27 mbar), ketal
16 (4.76 g, 60%) as colourless oil; R
f (hexanes/AcOEt 5:1) 0.72; δ
H (300 MHz, CDCl
3) 5.76 (dd,
J = 17.8, 10.8 Hz, 1H, C
H=CH
2), 5.38 (dd,
J = 13.6, 1.5 Hz, 1H, CH=C
H2), 5.33 (dd,
J = 6.6, 1.5 Hz, 1H, CH=C
H2), 3.58 (d,
J = 10.6 Hz, 2H, OCH
2), 3.32 (dt,
J = 11.1, 1.2 Hz, 2H, OCH
2), 1.40 (s, 3H, Me), 1.17 (s, 3H, Me
2), 0.70 (s, 3H, Me
2). NMR spectrum is in accordance with the literature data [
30].
2-Ethyl-5,5-dimethyl-2-vinyl-[1,3]dioxane (17)
KOH (7.46 g, 0.13 mol), ethylene glycol (16 mL), chloroketal 13 (2.46 g, 12 mmol), 21 h, water (200 mL), Et2O (3 × 80 mL), water (80 mL), brine (80 mL), concentrated in vacuo (35 °C, 200 mbar), FLC (112 g SiO2, DCM, 400 mL), ketal 17 (1.44 g, 71%) as colourless oil; Rf (DCM) 0.54; νmax (ATR) 2952, 2870, 1471, 1403, 1395, 1363, 1179, 1154, 1085, 955, 914 cm−1; δH (600 MHz, CDCl3) 5.66 (dd, J = 17.7, 11.0 Hz, 1H, CH=CH2), 5.40 (dd, J = 11.0, 1.6 Hz, 1H, CH=CH2), 5.33 (dd, J = 17.8, 1.6 Hz, 1H, CH=CH2), 3.61 (d, J = 11.0 Hz, 2H, OCH2), 3.32 (d, J = 11.2 Hz, 2H, OCH2), 1.65 (q, J = 7.5 Hz, 2H, CH2), 1.17 (s, 3H, Me2), 0.92 (t, J = 7.5 Hz, 3H, Me), 0.69 (s, 3H, Me2); δC (151 MHz, CDCl3) 137.4 (CH=CH2), 119.0 (CH=CH2), 100.5 (OCq), 71.5 (2 × OCH2), 34.5 (CH2), 30.2 (Cq), 22.8 (Me2), 22.0 (Me2), 7.1 (Me); m/z (ESI) 171.2 (82, M+H+), 172.2 (8%), tR = 2.89 min; HR-MS (HESI): M+, found 170.1310. C10H18O2 requires 170.1301.
8,8-Dimethyl-6,10-dioxaspiro[4.5]dec-1-ene (18)
KOH (3.88 g, 69 mmol), ethylene glycol (8.3 mL), chloroketal 14 (1.27 g, 6.2 mmol), 7 h, water (90 mL), Et2O (3 × 50 mL), water (50 mL), brine (50 mL), concentrated in vacuo (35 °C, 30 mbar), bulb-to-bulb vacuum distillation (125–130 °C, 28 mbar), ketal 18 (0.62 g, 60%) as yellow oil; Rf (hexanes/AcOEt 6:1) 0.51; νmax (ATR) 2952, 2855, 1473, 1395, 1363, 1203, 1141, 1129, 1088, 1048, 1036, 955, 908, 894 cm−1; δH (600 MHz, CDCl3) 6.16 (dt, J = 5.8, 2.2 Hz, 1H, CH=CH2), 6.10 (dt, J = 5.9, 2.4 Hz, 1H, CH=CH2), 3.59 (d, J = 11.3 Hz, 2H, OCH2), 3.53 (d, J = 11.3 Hz, 2H, OCH2), 2.42 (dt, J = 7.5, 6.7, 2.3 Hz, 2H, CH2), 2.14–2.11 (m, 2H, CH2), 1.01 (s, 3H, Me2), 0.98 (s, 3H, Me2); δC (151 MHz, CDCl3) 136.9 (CH=CH2), 128.9 (CH=CH2), 111.9 (OCq), 72.5 (2 × OCH2), 33.4 (CH2), 30.0 (Cq), 29.6 (CH2), 22.6 (Me2), 22.4 (Me2); HR-MS (HESI): M+, found 168.1144. C10H16O2 requires 168.1145.
3,3-Dimethyl-1,5-dioxaspiro[5.5]undec-7-ene (19) and 3,3-Dimethyl-1,5-dioxaspiro[5.5]undec-8-ene (25)
KOH (2.86 g, 51 mmol), ethylene glycol (6.1 mL), chloroketal 15 (1.0 g, 4.6 mmol), 18.5 h, water (60 mL), Et2O (3 × 20 mL), water (20 mL), brine (20 mL), concentrated in vacuo (35 °C, 30 mbar), bulb-to-bulb vacuum distillation (145–155 °C, 27 mbar) to give a mixture of ketals 19:25 in ratio 5:1 determined by 1H NMR spectroscopy (0.69 g, 83%) as colourless oil; Rf (hexanes/AcOEt 5:1) 0.59.
Ketal (19): δH (600 MHz, CDCl3) 6.10 (dt, J = 10.4, 2.1 Hz, 1H, CH=CH2), 5.92 (dt, J = 10.3, 3.6 Hz, 1H, CH=CH2), 3.62 (d, J = 11.4 Hz, 2H, OCH2), 3.51 (d, J = 11.4 Hz, 2H, OCH2), 2.07–2.03 (m, 2H, CH2), 1.93–1.90 (m, 2H, CH2), 1.75–1.70 (m, 2H, CH2), 1.02 (s, 3H, Me2), 0.95 (s, 3H, Me2); δC (151 MHz, CDCl3) 132.1 (CH=CH2), 125.2 (CH=CH2), 95.1 (OCq), 70.4 (2 × OCH2), 32.0 (CH2), 30.1 (Cq), 25.6 (CH2), 22.8 (Me2), 22.6 (Me2), 19.3 (CH2); m/z (ESI) 183.0 (53, M+H+), 184.0 (7%), tR = 2.44 min.
Ketal (25): νmax (ATR) 3027, 2952, 2861, 1470, 1361, 1269, 1251, 1105, 1036, 1015, 845 cm−1; δH (600 MHz, CDCl3) 5.70–5.66 (m, 1H, CH=CH2), 5.58–5.54 (m, 1H, CH=CH2), 3.59 (d, J = 11.5 Hz, 2H, OCH2), 3.49 (d, J = 11.5 Hz, 2H, OCH2), 2.39–2.35 (m, 2H, CH2), 2.16–2.11 (m, 2H, CH2), 1.96 (t, J = 6.5 Hz, 2H, CH2), 1.03 (s, 3H, Me2), 0.92 (s, 3H, Me2); δC (151 MHz, CDCl3) 126.4 (CH=CH2), 123.4 (CH=CH2), 97.0 (OCq), 70.2 (2 × OCH2), 34.8 (CH2), 30.2 (Cq), 27.3 (CH2), 23.5 (CH2), 22.8 (Me2), 22.5 (Me2); HR-MS (HESI): M+, found 183.1316. C11H18O2 requires 182.1301.
3.2.4. General Experiment for the Preparation of Alcohols (20, 22, 23)
To a stirred solution of ketal 16–18, anhydrous THF was added dropwise to a solution of DIBAL in toluene (1.0 M, 3–5 equiv) at 0 °C over 5–10 min under Ar. The mixture was warmed to 50 °C and stirred for 2–4.5 d. The cooled mixture (ice) was quenched with sat. aq. soln. of Rochelle salt and water, Et2O was added and stirred for 2–5 h at RT. The layers were separated and the aqueous phase was extracted with Et2O. The combined organic layers were washed with brine and dried over MgSO4. The solvents were evaporated in vacuo (73 °C, 30 mbar). The crude product was purified either by bulb-to-bulb vacuum distillation (Kugelrohr) or FLC to furnish a corresponding alcohol 20, 22, 23.
3-(But-3-en-2-yloxy)-2,2-dimethylpropan-1-ol (20)
Ketal 16 (0.5 g, 3.2 mmol), THF (16 mL), 1M DIBAL in toluene (17.4 mL, 17.4 mmol, 5.5 equiv, 7 min), 50 °C, 44 h, sat. aq. Rochelle salt soln. (25 mL), water (5 mL), Et2O (150 mL), 5 h, Et2O (2 × 25 mL), brine (50 mL), bulb-to-bulb vacuum distillation (135–145 °C, 31 mbar), alcohol 20 (307 mg, 61%) as colourless oil; Rf (hexanes/AcOEt 5:1) 0.3; νmax (ATR) 3399 (OH), 2972, 2956, 2870, 1475, 1421, 1368, 1319, 1094, 1044, 991, 921 cm−1; δH (300 MHz, CDCl3) 5.70 (ddd, J = 17.3, 10.3, 7.1 Hz, 1H, CH=CH2), 5.17 (ddd, J = 14.6, 1.6, 1.0 Hz, 1H, CH=CH2), 5.12 (ddd, J = 7.6, 1.6, 1.0 Hz, 1H, CH=CH2), 3.82–3.71 (m, 1H, CH), 3.44 (s, 2H, CH2), 3.34 (d, J = 8.9 Hz, 1H, CH2), 3.16 (d, J = 8.8 Hz, 1H, CH2), 2.91 (brs, 1H, OH), 1.23 (d, J = 6.4 Hz, 3H, Me), 0.91 (s, 6H, Me2); δC (151 MHz, CDCl3) 140.0 (CH=CH2), 115.9 (CH=CH2), 78.2 (CH2), 77.8 (CH), 72.4 (CH2), 35.9 (Cq), 21.9 (Me2), 21.2 (Me); HR-MS (HESI): M+, found 158.1303. C9H18O2 requires 158.1301.
2,2-Dimethyl-3-(pent-1-en-3-yloxy)propan-1-ol (22)
Ketal 17 (0.8 g, 4.7 mmol), THF (23.5 mL), 1M DIBAL in toluene (25.9 mL, 25.9 mmol, 5.5 equiv, 5 min), 50 °C, 4.5 d, sat. aq. Rochelle salt soln. (42 mL), water (30 mL), Et2O (80 mL), 2 h, Et2O (2 × 40 mL), brine (80 mL), FLC (14.6 g SiO2, Hex/AcOEt 7:1, 180 mL), alcohol 22 (122 mg, 15%) as colourless oil; Rf (hexanes/AcOEt 5:1) 0.43; νmax (ATR) 3411 (OH), 2961, 2873, 1475, 1422, 1322, 1091, 1045, 993, 921 cm−1; δH (600 MHz, CDCl3) 5.64 (ddd, J = 17.2, 10.5, 7.5 Hz, 1H, CH=CH2), 5.20–5.14 (m, 2H, CH=CH2), 3.50 (dd, J = 13.6, 6.7 Hz, 1H, CH), 3.44 (d, J = 5.2 Hz, 2H, OCH2), 3.38 (d, J = 8.8 Hz, 1H, OCH2), 3.11 (d, J = 8.8 Hz, 1H, OCH2), 2.91 (t, J = 5.6 Hz, 1H, OH), 1.63–1.47 (m, 2H, CH2), 0.93 (s, 3H, Me), 0.90 (s, 3H, Me), 0.90 (t, J = 7.5 Hz, 3H, Me); δC (151 MHz, CDCl3) 138.6 (CH=CH2), 116.9 (CH=CH2), 83.5 (OCH), 78.4 (OCH2), 72.4 (OCH2), 36.0 (Cq), 28.3 (CH2), 21.9 (Me2), 9.6 (Me); HR-MS (HESI): M+, found 172.1463. C10H20O2 requires 172.1458.
3-(Cyclopent-2-enyloxy)-2,2-dimethylpropanol (23)
Ketal 18 (596 mg, 3.5 mmol), THF (17.7 mL), 1M DIBAL in toluene (10.6 mL, 10.6 mmol, 3 equiv, 10 min), 50 °C, 50 h, sat. aq. Rochelle salt soln. (13 mL), water (20 mL), Et2O (60 mL), 2 h, Et2O (2 × 30 mL), brine (60 mL), FLC (27.9 g SiO2, gradient elution Hex/AcOEt 8:1 (360 mL) → 1:1 (100 mL)), alcohol 23 (107 mg, 18%) as colourless oil; Rf (hexanes/AcOEt 5:1) 0.29; νmax (ATR) 3419 (OH), 2953, 2854, 1474, 1359, 1116, 1082, 1041 cm−1; δH (600 MHz, CDCl3) 6.02–5.99 (m, 1H, CH=CH), 5.82–5.79 (m, 1H, CH=CH), 4.53–4.50 (m, 1H, CH), 3.43 (s, 2H, OCH2), 3.32 (d, J = 8.7 Hz, 1H, OCH2), 3.29 (d, J = 8.7 Hz, 1H, OCH2), 2.91 (brs, 1H, OH), 2.50–2.43 (m, 1H, CH2), 2.28–2.22 (m, 1H, CH2), 2.16–2.09 (m, 1H, CH2), 1.77–1.70 (m, 1H, CH2), 0.91 (s, 6H, Me2); δC (151 MHz, CDCl3) 135.9 (CH=CH), 130.4 (CH=CH), 85.4 (CH), 78.1 (OCH2), 72.4 (OCH2), 35.9 (Cq), 31.0 (CH2), 29.6 (CH2), 22.0 (Me2); m/z (ESI) 169.2 (100, M-H+), 170.2 (10, M+), tR = 1.96 min; HR-MS (HESI): M+, found 170.1312. C10H18O2 requires 170.1301.
3.2.5. Preparation of Alcohol (24)
To a cooled mixture of ketals 19 + 25 (5:1, 754 mg, 4.1 mmol) in anhydrous THF (20.7 mL) 1M solution of DIBAL in toluene (18.6 mL, 18.6 mmol, 4.5 equiv) was added dropwise at 0 °C over 5 min under Ar. The mixture was warmed to 50 °C and stirred for 88 h. The cooled mixture (ice) was quenched with sat. aq. soln. of Rochelle salt (30 mL) and water (15 mL), diluted with Et2O (70 mL) and stirred for 2.5 h at RT. The layers were separated and the aqueous phase was extracted with Et2O (2 × 35 mL). The combined organic layers were washed with brine (70 mL) and dried over MgSO4. The solvents were evaporated in vacuo (73 °C, 30 mbar). The crude material was purified by FLC (31 g SiO2, gradient elution DCM/iPrOH 70:1 (213 mL) → 35:1 (36 mL)) to furnish desired alcohol 24 (303 mg, 48%) and unreacted ketal 25 (75 mg) as colourless oils.
3-(Cyclohex-2-enyloxy)-2,2-dimethylpropanol (24): Rf (DCM/iPrOH 70:1) 0.19; νmax (ATR) 3426 (OH), 3026, 2934, 2865, 1474, 1393, 1080, 1045, 947, 898, 725 cm−1; δH (300 MHz, CDCl3) 5.84–5.81 (dtd, J = 10.1, 3.5, 1.2 Hz, 1H, CH=CH), 5.74 (ddt, J = 10.1, 3.2, 2.0 Hz, 1H, CH=CH), 3.83–3.75 (m, 1H, CH), 3.44 (d, J = 3.8 Hz, 2H, OCH2), 3.38 (d, J = 8.7 Hz, 1H, OCH2), 3.33 (d, J = 8.6 Hz, 1H, OCH2), 2.99 (brs, 1H, OH), 2.10–1.45 (m, 6H, 3 × CH2), 0.92 (s, 6H, Me2); δC (151 MHz, CDCl3) 131.0 (CH=CH), 127.3 (CH=CH), 78.1 (OCH2), 73.5 (CH), 72.4 (OCH2), 36.0 (Cq), 28.2 (CH2), 25.1 (CH2), 21.9 (Me2), 19.1 (CH2); m/z (ESI) 105.2 (100%), 185.2 (58, M+H+), 186.2 (10%), tR = 3.13 min; HR-MS (HESI): M+, found 184.1445. C11H20O2 requires 184.1458.
3.2.6. General Experiment for the Preparation of Aldehydes (3–7)
To a solution of alcohol 20–24 in anhydrous DCM Dess–Martin periodinane (DMP, 1.10–1.25 equiv) and NaHCO3 (0.27 equiv) was added under Ar. The mixture was stirred for 2–6 h at RT and quenched with sat. aq. NaHCO3 soln. followed by addition of sat. aq. Na2S2O3 soln. and the stirring continued until all solids dissolved (1–4 h). The layers were separated, the aqueous layer was extracted with DCM and the combined organic layers were washed with brine and dried over MgSO4. The solvent was removed in vacuo (40 °C, 100–200 mbar) and residue was purified by either FLC or PTLC to furnish corresponding aldehyde 3–7.
3-(But-3-en-2-yloxy)-2,2-dimethylpropan-1-al (3)
Alcohol 20 (163 mg, 1.03 mmol), DCM (10.3 mL), DMP (546 mg, 1.29 mmol, 1.25 equiv), NaHCO3 (24 mg, 0.28 mmol), 3 h, sat. aq. NaHCO3 soln. (8.4 mL), sat. aq. Na2S2O3 soln. (8.4 mL), 1 h, DCM (3 × 25 mL), brine (40 mL), evaporation in vacuo (40 °C, 200 mbar), FLC (8.5 g SiO2, DCM, 150 mL), aldehyde 3 (62 mg, 38%) as colourless oil; Rf (DCM) 0.5; νmax (ATR) 2974, 2932, 2871, 1729 (C=O), 1474, 1367, 1092, 992, 925, 910 cm−1; δH (600 MHz, CDCl3) 9.55 (s, 1H, CHO), 5.68 (ddd, J = 17.3, 10.3, 7.1 Hz, 1H, CH=CH2), 5.15 (dt, J = 17.2, 1.3 Hz, 1H, CH=CH2), 5.11 (dt, J = 10.3, 1.4 Hz, 1H, CH=CH2), 3.78–3.72 (m, 1H, CH), 3.46 (d, J = 9.3 Hz, 1H, CH2), 3.29 (d, J = 9.3 Hz, 1H, CH2), 1.19 (d, J = 6.4 Hz, 3H, Me), 1.06 (s, 6H, 2 × Me); δC (151 MHz, CDCl3) 205.7 (CHO), 140.1 (CH=CH2), 115.8 (CH=CH2), 77.6 (CH), 73.4 (CH2), 47.0 (Cq), 21.0 (Me), 19.0 (Me2); m/z (ESI) 157.2 (26, M+H+), 158.2 (3%), tR = 2.48 min; HR-MS (HESI): M+, found 156.1139. C9H16O2 requires 156.1145.
2,2-Dimethyl-3-(2-methyl-but-3-en-2-yloxy)propan-1-al (4)
Alcohol 21 (81 mg, 0.47 mmol), DCM (4.7 mL), DMP (219 mg, 0.52 mmol), NaHCO3 (11 mg, 0.13 mmol), 2.5 h, sat. aq. NaHCO3 soln. (3.8 mL, sat. aq. Na2S2O3 soln. (3.8 mL), 1 h, DCM (3 × 12 mL), brine (25 mL), evaporation in vacuo (40 °C, 200 mbar), FLC (6.3 g SiO2, Hexanes/Et2O 8:1, 180 mL), aldehyde 4 (31 mg, 39%) as colourless oil; Rf (hexanes/Et2O 8:1) 0.55; νmax (ATR) 2976, 1731 (C=O), 1361, 1150, 1080, 1002, 924 cm−1; δH (400 MHz, CDCl3) 9.52 (s, 1H, CHO), 5.75 (dd, J = 17.8, 10.6 Hz, 1H, CH=CH2), 5.12 (dd, J = 4.9, 1.2 Hz, 1H, CH=CH2), 5.08 (dd, J = 2.2, 1.2 Hz, 1H, CH=CH2), 3.28 (s, 2H, CH2), 1.22 (s, 6H, 2 × Me), 1.04 (s, 6H, 2 × Me); δC (100 MHz, CDCl3) 206.1 (CHO), 143.7 (CH=CH2), 113.9 (CH=CH2), 74.9 (OCq), 67.8 (CH2), 46.7 (Cq), 25.5 (Me2), 19.0 (Me2); HR-MS (HESI): M+, found 170.1309. C10H18O2 requires 170.1301.
2,2-Dimethyl-3-(pent-1-en-3-yloxy)propan-1-al (5)
Alcohol 22 (107 mg, 0.62 mmol), DCM (6.2 mL), DMP (328 mg, 0.77 mmol), NaHCO3 (14 mg, 0.17 mmol), 3 h, sat. aq. NaHCO3 soln. (5 mL), sat. aq. Na2S2O3 soln. (5 mL), 1.5 h., DCM (3 × 15 mL), brine (30 mL), evaporation in vacuo (40 °C, 100 mbar), FLC (8.8 g SiO2, Hexanes/Et2O 7:1, 80 mL), aldehyde 5 (48 mg, 46%) as colourless oil; Rf (hexanes/Et2O 5:1) 0.61; νmax (ATR) 2996, 1731, 1454, 1322, 1092, 924 cm−1; δH (600 MHz, CDCl3) 9.56 (s, 1H, CHO), 5.62 (ddd, J = 17.0, 10.6, 7.5 Hz, 1H, CH=CH2), 5.17–5.13 (m, 2H, CH=CH2), 3.50 (d, J = 9.3 Hz, 1H, OCH2), 3.51–3.46 (m, 1H, CH), 3.24 (d, J = 9.3 Hz, 1H, OCH2), 1.59–1.51 (m, 1H, CH2), 1.50–1.42 (m, 1H, CH2), 1.07 (s, 6H, 2 x Me), 0.86 (t, J = 7.4 Hz, 3H, Me); δC (151 MHz, CDCl3) 205.7 (CHO), 138.8 (CH=CH2), 116.7 (CH=CH2), 83.4 (CH), 73.7 (OCH2), 47.2 (Cq), 28.2 (CH2), 19.0 (Me2), 9.6 (Me); HR-MS (HESI): M+, found 170.1305. C10H18O2 requires 170.1301.
3-(Cyclopent-2-enyloxy)-2,2-dimethylpropan-1-al (6)
Alcohol 23 (87 mg, 0.51 mmol), DCM (5.1 mL), DMP (270 mg, 0.64 mmol), NaHCO3 (12 mg, 0.14 mmol), 2 h, sat. aq. NaHCO3 soln. (4.2 mL), sat. aq. Na2S2O3 soln. (4.2 mL), 2 h, DCM (3 × 13 mL), brine (30 mL), evaporation in vacuo (40 °C, 200 mbar), PTLC (Hexanes/Et2O 3:1), aldehyde 6 (19 mg, 22%) as colourless oil; Rf (hexanes/Et2O 3:1) 0.61; νmax (ATR) 2931, 2854, 1729 (C=O), 1359, 1116, 1087, 1043, 897, 731 cm−1; δH (600 MHz, CDCl3) 9.55 (s, 1H, CHO), 6.01–5.98 (m, 1H, CH=CH), 5.82–5.79 (m, 1H, CH=CH), 4.55–4.51 (m, 1H, CH), 3.44 (d, J = 9.2 Hz, 1H, OCH2), 3.42 (d, J = 9.2 Hz, 1H, OCH2), 2.48–2.41 (m, 1H, CH2), 2.28–2.21 (m, 1H, CH2), 2.14–2.07 (m, 1H, CH2), 1.75–1.68 (m, 1H, CH2), 1.07 (s, 6H, 2 × Me); δC (151 MHz, CDCl3) 205.8 (CHO), 135.7 (CH=CH), 130.5 (CH=CH), 85.4 (CH), 73.3 (OCH2), 47.0 (Cq), 31.1 (CH2), 29.4 (CH2), 19.1 (Me2); HR-MS (HESI): M+, found 168.1141. C10H16O2 requires 168.1145.
3-(Cyclohex-2-enyloxy)-2,2-dimethylpropan-1-al (7)
Alcohol 24 (150 mg, 0.81 mmol), DCM (8.1 mL), DMP (432 mg, 1.02 mmol), NaHCO3 (19 mg, 0.23 mmol), 5.5 h, sat. aq. NaHCO3 soln. (6.6 mL), sat. aq. Na2S2O3 soln. (6.6 mL), 3.5 h, DCM (3 × 20 mL), brine (30 mL), evaporation in vacuo (40 °C, 100 mbar), FLC (7.9 g SiO2, DCM, 180 mL), aldehyde 7 (89 mg, 60%) as colourless oil; Rf (DCM) 0.56; νmax (ATR) 2933, 2865, 1729 (C=O), 1474, 1395, 1084, 948, 895, 726 cm−1; δH (600 MHz, CDCl3) 9.57 (s, 1H, CHO), 5.85–5.81 (m, 1H, CH=CH), 5.73–5.69 (m, 1H, CH=CH), 3.82–3.77 (m, 1H, CH), 3.50 (d, J = 9.1 Hz, 1H, OCH2), 3.46 (d, J = 9.1 Hz, 1H, OCH2), 2.06–1.99 (m, 1H, CH2), 1.97–1.90 (m, 1H, CH2), 1.82–1.76 (m, 1H, CH2), 1.75–1.68 (m, 1H, CH2), 1.65–1.58 (m, 1H, CH2), 1.55–1.48 (m, 1H, CH2), 1.08 (s, 3H, Me), 1.07 (s, 3H, Me); δC (151 MHz, CDCl3) 205.8 (CHO), 130.8 (CH=CH), 127.5 (CH=CH), 73.6 (CH), 73.3 (OCH2), 47.1 (Cq), 28.1 (CH2), 25.2 (CH2), 19.2 (CH2), 19.1 (Me2); HR-MS (HESI): M+, found 182.1302. C11H18O2 requires 182.1301.