Nitrogen → (E)-4-((2S,6S)-6-((2R,3R)-3-(benzyloxymethoxy)-2-(tert-butyldimethylsilyloxy)butyl)-2-methoxy-3-oxo-tetrahydro-2H-pyran-2-yl)-4-methylpent-2-enal

HRID 509208Notes

Reaction equation

HRID 509208 reaction equation
[CH2:1]([O:8][CH2:9][O:10][C@H:11]([CH3:41])[C@H:12]([O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35])[CH2:13][C@H:14]1[O:19][C@:18]([C:22]([CH3:31])([CH3:30])/[CH:23]=[CH:24]/[C:25](=[O:29])SCC)([O:20][CH3:21])[C:17](=[O:32])[CH2:16][CH2:15]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C=CCCCC.N1C2C(=CC=CC=2)C=CC=1.N#N.C([SiH](CC)CC)C>CC(C)=O.[Pd].CC([O-])=O.CC([O-])=O.[Pb+2].CCOC(C)=O>[CH2:1]([O:8][CH2:9][O:10][C@H:11]([CH3:41])[C@H:12]([O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35])[CH2:13][C@H:14]1[O:19][C@:18]([C:22]([CH3:31])([CH3:30])/[CH:23]=[CH:24]/[CH:25]=[O:29])([O:20][CH3:21])[C:17](=[O:32])[CH2:16][CH2:15]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 5

HCID 947NitrogenHCID 7047QuinolineHCID 115971-HexeneHCID 12052TriethylsilaneHCID 131733236(E)-S-ethyl 4-((2S,6S)-6-((2R,3R)-3-(benzyloxymethoxy)-2-(tert-butyldimethylsilyloxy)butyl)-2-methoxy-3-oxo-tetrahydro-2H-pyran-2-yl)-4-methylpent-2-enethioate

Product 1

HCID 87214192(E)-4-((2S,6S)-6-((2R,3R)-3-(benzyloxymethoxy)-2-(tert-butyldimethylsilyloxy)butyl)-2-methoxy-3-oxo-tetrahydro-2H-pyran-2-yl)-4-methylpent-2-enalYield 91.1%

Reagents, catalysts & solvents 3

HCID 131709914Lindlars catalystCatalystHCID 180AcetoneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirring solution of thiolester 21 (219 mg, 0.360 mmol, 1.0 equiv) in acetone (5.2 mL), in a 25 mL pear shaped flask at rt, was added 1-hexene (450 μL, 3.60 mmol, 10.0 equiv), quinoline (21 μL, 0.180 mmol, 0.5 equiv), and Lindlar's catalyst (5% Pd/wt, Acros, 1.53 g, 0.719 mmol, 2.0 equiv). The flask was purged with N2, and triethylsilane (144 μL, 0.900 mmol, 2.5 equiv) was added dropwise via syringe over 1 min. The mixture stirred vigorously at rt for 40 min and was then diluted with EtOAc (10 mL). The reaction mixture was filtered through a pad of Celite®, and the solvent was removed under reduced pressure. Purification was accomplished using flash column chromatography with a 3×8.5 cm silica gel column, eluting with 15% EtOAc/hexanes, collecting 13×100 mm test tube fractions. The product containing fractions were concentrated under reduced pressure to provide pure aldehyde 6 (180 mg, 91%) as a clear colorless oil: Rf=0.54 (30% EtOAc/hexanes); [α]D20=+19.9 (c=0.67, CHCl3); 500 MHz 1H NMR (CDCl3) δ 9.45 (d, J=7.7 Hz, 1H), 7.29-7.19 (m, 6H), 5.99 (dd, J=16.1, 7.7 Hz, 1H), 4.72 (d, J=7.0 Hz, 1H), 4.69 (d, J=7.0 Hz, 1H), 4.55 (s, 2H), 4.15 (dddd, J=9.3, 9.3, 3.0, 3.0 Hz, 1H), 3.97 (ddd, J=9.2, 4.4, 2.2 Hz, 1H), 3.79-3.72 (m, 1H), 3.26 (s, 3H), 2.57-2.38 (m, 2H), 2.05-1.99 (m, 1H), 1.92-1.80 (m, 2H), 1.47 (ddd, J=14.0, 9.4, 3.4 Hz, 1H), 1.12 (s, 3H), 1.12 (s, 3H), 1.08 (d, J=6.2 Hz, 3H), 0.82 (s, 9H), 0.02 (s, 3H), 0.02 (s, 3H); 125 MHz 13C NMR (CDCl3) δ 206.1, 194.9, 164.8, 138.0, 130.2, 128.7, 128.0, 128.0, 103.3, 93.4, 75.2, 70.6, 69.6, 69.3, 53.3, 46.2, 37.8, 37.8, 31.2, 26.1, 22.5, 22.5, 18.3, 13.8, −3.8, −4.4; 125 MHz DEPT 13C NMR (CDCl3) CH3 δ 53.2, 26.1, 22.5 (×2), 13.8, −3.8, −4.5; CH2 δ 93.4, 69.6, 37.8, 37.7, 31.2; CH δ 194.9, 164.8, 130.2, 128.7, 128.0 (×2), 75.1, 70.6, 69.3; CH0 δ 206.1, 138.0, 103.3, 46.6, 18.3; IR (neat) 2955, 2932, 2888, 2857, 1726, 1691, 1630, 1472, 1381, 1361, 1256, 1114, 1043, 978, 920, 837, 810, 777 cm−1; LRMS (ESI) calcd for C30H48O7SiNa (M+Na) 571.3. found 571.2; HRMS (CI+) calcd for C36H63O7Si2 (M+TBS) 663.4112. found 663.4108.

Workup

  1. additionwas added dropwise via syringe over 1 min
  2. filtrationThe reaction mixture was filtered through a pad of Celite®
  3. customthe solvent was removed under reduced pressure
  4. customPurification
  5. washeluting with 15% EtOAc/hexanes
  6. customcollecting 13×100 mm test tube fractions
  7. additionThe product containing fractions
  8. concentrationwere concentrated under reduced pressure

Sources & evidence

ORD record
ord-2f41d38e4e3a4a12aa544b1900ced67e
Source dataset
uspto-grants-2015_08
Patent number
US09096550B2

Reaction notes

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