Dimethyl Sulfoxide → (R)-4-((2S,6R)-6-(((2S,6R)-6-((E)-3-((2S,6S)-6-((2R,3R)-3-(benzyloxymethoxy)-2-(tert-butyldimethylsilyloxy)butyl)-2-methoxy-3-oxo-tetrahydro-2H-pyran-2-yl)-3-methylbut-1-enyl)-4-methylene-tetrahydro-2H-pyran-2-yl)methyl)-4-methylene-tetrahydro-2H-pyran-2-yl)-3-(4-methoxybenzyloxyl)butanal

HRID 509211Notes

Reaction equation

HRID 509211 reaction equation
[CH2:1]([O:8][CH2:9][O:10][C@H:11]([CH3:66])[C@H:12]([O:58][Si:59]([C:62]([CH3:65])([CH3:64])[CH3:63])([CH3:61])[CH3:60])[CH2:13][C@H:14]1[O:19][C@:18]([C:22]([CH3:56])(/[CH:24]=[CH:25]/[C@H:26]2[CH2:31][C:30](=[CH2:32])[CH2:29][C@@H:28]([CH2:33][C@H:34]3[CH2:39][C:38](=[CH2:40])[CH2:37][C@@H:36]([CH2:41][C@@H:42]([O:46][CH2:47][C:48]4[CH:53]=[CH:52][C:51]([O:54][CH3:55])=[CH:50][CH:49]=4)[CH2:43][CH2:44][OH:45])[O:35]3)[O:27]2)[CH3:23])([O:20][CH3:21])[C:17](=[O:57])[CH2:16][CH2:15]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.CS(C)=O>C(Cl)Cl>[CH2:1]([O:8][CH2:9][O:10][C@H:11]([CH3:66])[C@H:12]([O:58][Si:59]([C:62]([CH3:65])([CH3:64])[CH3:63])([CH3:61])[CH3:60])[CH2:13][C@H:14]1[O:19][C@:18]([C:22]([CH3:56])([CH3:23])/[CH:24]=[CH:25]/[C@@H:26]2[O:27][C@H:28]([CH2:33][C@@H:34]3[O:35][C@H:36]([CH2:41][C@@H:42]([O:46][CH2:47][C:48]4[CH:49]=[CH:50][C:51]([O:54][CH3:55])=[CH:52][CH:53]=4)[CH2:43][CH:44]=[O:45])[CH2:37][C:38](=[CH2:40])[CH2:39]3)[CH2:29][C:30](=[CH2:32])[CH2:31]2)([O:20][CH3:21])[C:17](=[O:57])[CH2:16][CH2:15]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 679Dimethyl SulfoxideHCID 81531DiisopropylethylamineHCID 131733238(2S,6S)-6-((2R,3R)-3-(benzyloxymethoxy)-2-(tert-butyldimethylsilyloxy)butyl)-2-((E)-4-((2R,6S)-6-(((2R,6S)-6-((S)-4-hydroxy-2-(4-methoxybenzyloxyl)butyl)-4-methylene-tetrahydro-2H-pyran-2-yl)methyl)-4-methylene-tetrahydro-2H-pyran-2-yl)-2-methylbut-3-en-2-yl)-2-methoxy-dihydro-2H-pyran-3(4H)-one

Product 1

HCID 131733239(R)-4-((2S,6R)-6-(((2S,6R)-6-((E)-3-((2S,6S)-6-((2R,3R)-3-(benzyloxymethoxy)-2-(tert-butyldimethylsilyloxy)butyl)-2-methoxy-3-oxo-tetrahydro-2H-pyran-2-yl)-3-methylbut-1-enyl)-4-methylene-tetrahydro-2H-pyran-2-yl)methyl)-4-methylene-tetrahydro-2H-pyran-2-yl)-3-(4-methoxybenzyloxyl)butanalYield 93.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirring solution of alcohol 22 (104 mg, 0.111 mmol, 1.0 equiv) in CH2Cl2 (1.1 mL), in a 10 mL rb flask at 0° C., was added diisopropylethylamine (135 μL, 0.775 mmol, 7.0 equiv) and DMSO (80 μL, 1.11 mmol, 10.0 equiv). The solution stirred at 0° C. for 5 min and SO3.Py (71 mg, 0.444 mmol, 4.0 equiv) was added in one portion. Stirring continued at 0° C. for 1.25 h, after which the reaction mixture was quenched by addition of saturated aqueous NaHCO3 solution (2 mL). The mixture stirred at room temperature for 10 min until effervescence was complete, and the phases were separated. The aqueous phase was extracted three times with CH2Cl2 (10 mL), and the combined organic phases were dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting residue was washed through a small plug of silica gel with 40% EtOAc/hexanes (100 mL), and the solvent was removed under reduced pressure to provide pure aldehyde 23 (96.4 mg, 93%) as a clear viscous oil: Rf=0.44 (30% EtOAc/hexanes); [α]D20=+4.8 (c=0.82, CHCl3); 500 MHz 1H NMR (CDCl3) δ 9.79 (t, J=2.4 Hz, 1H), 7.38-7.28 (m, 5H), 7.24 (d, J=8.8 Hz, 2H), 6.88 (d, J=8.8 Hz, 2H), 6.04 (d, J=15.6 Hz, 1H), 5.47 (dd, J=16.1, 6.3 Hz, 1H), 4.81 (d, J=6.8 Hz, 1H), 4.78 (d, J=6.8 Hz, 1H), 4.75-4.71 (m, 2H), 4.68 (s, 1H), 4.62 (s, 2H), 4.60 (s, 1H), 4.51 (d, J=10.7 Hz, 1H), 4.46 (d, J=10.7 Hz, 1H), 4.19 (m, 1H), 4.13-4.09 (m, 1H), 4.07 (ddd, J=9.0, 4.1, 2.4 Hz, 1H), 3.85-3.75 (m, 2H), 3.80 (s, 3H), 3.56-3.42 (m, 3H), 3.29 (s, 3H), 2.67-2.63 (m, 2H), 2.44 (dd, J=8.3, 6.3 Hz, 2H), 2.28-2.15 (m, 4H), 2.05-1.90 (m, 8H), 1.80 (ddd, J=14.2, 8.8, 2.4 Hz, 1H), 1.67 (ddd, J=14.2, 10.0, 4.2 Hz, 1H), 1.59 (ddd, J=13.8, 7.0, 5.3 Hz, 1H), 1.53 (ddd, J=13.7, 9.3, 3.9 Hz, 1H), 1.16 (d, J=6.3 Hz, 3H), 1.13 (s, 3H), 1.09 (s, 3H), 0.88 (s, 9H), 0.08 (s, 3H), 0.08 (s, 3H); 125 MHz 13C NMR (CDCl3) δ 207.5, 201.6, 159.5, 144.4, 144.3, 138.0, 137.2, 130.4, 129.6, 129.2, 128.6, 128.0, 127.9, 114.1, 109.1, 109.0, 104.0, 93.4, 79.3, 75.2, 75.1, 75.0, 75.0, 72.1, 71.6, 70.8, 69.9, 69.6, 55.5, 52.7, 49.4, 44.4, 42.9, 42.3, 41.3, 41.2, 40.9, 40.5, 38.2, 37.7, 30.6, 26.1, 23.1, 22.1, 18.3, 14.0, −3.8, −4.4; 125 MHz DEPT 13C NMR (CDCl3) CH3 δ 55.5, 52.7, 26.1, 23.1, 22.1, 14.0, −3.8, −4.4; CH2 δ 109.1, 109.0, 93.4, 72.2, 69.6, 49.4, 42.9, 42.4, 41.3, 41.2, 40.9, 40.5, 38.2, 37.7, 30.7; CH δ 201.7, 137.2, 129.6, 129.2, 128.6, 128.0, 127.9, 114.1, 79.3, 75.2, 75.1, 75.0, 71.6, 70.8, 69.9; CH0 δ 207.5, 159.5, 144.4, 144.3, 138.0, 130.4, 104.0, 44.4, 18.3; IR (neat) 2936, 2857, 1725, 1652, 1613, 1514, 1463, 1381, 1250, 1174, 1112, 1041, 892, 836 cm−1.

Workup

  1. additionSO3.Py (71 mg, 0.444 mmol, 4.0 equiv) was added in one portion
  2. stirringStirring
  3. waitcontinued at 0° C. for 1.25 h
  4. customafter which the reaction mixture was quenched by addition of saturated aqueous NaHCO3 solution (2 mL)
  5. stirringThe mixture stirred at room temperature for 10 min until effervescence
  6. customthe phases were separated
  7. extractionThe aqueous phase was extracted three times with CH2Cl2 (10 mL)
  8. dry with materialthe combined organic phases were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. washThe resulting residue was washed through a small plug of silica gel with 40% EtOAc/hexanes (100 mL)
  12. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-8afa149180444028ac79ba8e41943c68
Source dataset
uspto-grants-2015_08
Patent number
US09096550B2

Reaction notes

Loading…