Tetrahydrofuran → HCID 75587249, compound

HRID 416675Notes

Reaction equation

HRID 416675 reaction equation
C([Sn](CCCC)(CCCC)C1CCCC=C1)CCC.[Li][CH2:21][CH2:22][CH2:23][CH3:24].[CH3:25][C@@:26]12[O:34][C:32](=[O:33])[C@:31]1([C@@H:35]([OH:42])[C@@H:36]1[CH:41]=[CH:40][CH2:39][CH2:38][CH2:37]1)[NH:30][C:28](=[O:29])[C@@H:27]2[CH2:43][CH2:44][Cl:45].[CH2:46]1[CH2:50][O:49][CH2:48][CH2:47]1>[Cl-].[Cl-].[Zn+2].[Zn]>[Cl:45][CH2:44][CH2:43][CH:27]1[C:26]2([CH3:25])[C:31]([CH:35]([CH:36]3[CH2:37][CH2:38][CH2:39][CH:40]=[CH:41]3)[OH:42])([C:32](=[O:33])[O:34]2)[N:30]([CH2:24][C:23]2[CH:46]=[CH:47][C:48]([O:49][CH3:50])=[CH:21][CH:22]=2)[C:28]1=[O:29]

Participants

7

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 11068666Stannane, tributyl-2-cyclohexen-1-yl-HCID 11347535MarizomibHCID 178418339Butyllithium

Product 1

HCID 75587249HCID 75587249, compound

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 3007855ZincchlorideCatalyst

Conditions

Temperature
-78 °C

Procedure

A solution of tri-n-butyl-2-cyclohexenyltin (140 mg, 0.377 mmol) in THF (0.7 mL) was treated with n-BuLi (2.5 M in hexanes, 133 μL, 0.333 mmol) at −78° C. After 30 min, ZnCl2 (0.5 M in THF, 0.77 mL, 0.39 mmol) was added and following an additional 30 min, a solution of the crude aldehyde in THF (1.3 mL) was slowly added to the freshly prepared zinc reagent 46. The resulting mixture was stirred at −78° C. for 2.5 h, quenched with water and diluted with EtOAc (50 mL). The organic layer was washed with saturated NH4Cl and brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by flash chromatography (1:6 EtOAc/hexanes) to give a mixture of predominantly two diastereomers (12 mg, 33%, dr 3.5:1+trace minor diasts., 500 MHz 1H NMR) as a colorless oil which was carried directly to the next step without further characterization. The major diastereomer (±)-81 was confirmed to possess the correct relative stereochemistry following subsequent conversion to salinosporamide A (below): Rf=0.64 (40% EtOAc/Hexanes); IR (neat) 3467, 1828, 1692 cm−1; LRMS (ESI) Calcd. for C23H28ClNO5 [M+Li] 440, found 440.

Workup

  1. waitfollowing an additional 30 min
  2. customquenched with water
  3. additiondiluted with EtOAc (50 mL)
  4. washThe organic layer was washed with saturated NH4Cl and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography (1:6 EtOAc/hexanes)
  9. customto give
  10. additiona mixture of predominantly two diastereomers (12 mg, 33%, dr 3.5:1+trace minor diasts., 500 MHz 1H NMR) as a colorless oil which

Sources & evidence

ORD record
ord-861b3bf28b3b4441abb309372b4b7a6a
Source dataset
uspto-grants-2012_01
Patent number
US08088923B2

Reaction notes

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