Methanol → (1S,2S)-6,7-Dibromo-2-methoxy-5,8-dimethyl-1,2-dihydronaphthalen-1-ol

HRID 1060705Notes

Reaction equation

HRID 1060705 reaction equation
[Br:1][C:2]1[C:11]([Br:12])=[C:10]([CH3:13])[CH:9]=[C:8]2[C:3]=1[C:4]1(C)O[CH:7]2[CH:6]=[CH:5]1.[CH2:16]([OH:21])C(F)(F)F.[CH3:22][OH:23]>>[Br:1][C:2]1[C:3]([CH3:4])=[C:8]2[C:9](=[C:10]([CH3:13])[C:11]=1[Br:12])[C@H:22]([OH:23])[C@@H:5]([O:21][CH3:16])[CH:6]=[CH:7]2

Participants

4

Reactant 3

HCID 887MethanolHCID 64092,2,2-TrifluoroethanolHCID 226789125,6-Dibromo-4,7-dimethyl-1,4-epoxy-1,4-dihydronaphthalene

Product 1

HCID 59041080(1S,2S)-6,7-Dibromo-2-methoxy-5,8-dimethyl-1,2-dihydronaphthalen-1-olYield 79%

Procedure

To a flame dried round bottom flask, [Rh(COD)Cl]2 (1.5 mg, 0.0029 mmol), (R)-(S)-PPF-PtBu2 (3.2 mg, 0.0059 mmol) and 26 (195 mg, 0.59 mmol) were added followed by addition of trifluoroethanol (1.0 mL) and methanol (1.0 mL). The mixture was heated to reflux for 20 hours. The solvents were then removed in vacuo. The resulting solid was purified by flash chromatography (50% ethyl acetate in hexanes) to give 29 as a white crystalline solid (171.6 mg, 79%). The ee was determined to be 97% using HPLC analysis on a CHIRALCEL OD column, λ=486 nm. Retention times in 4% isopropanol in hexanes were 16.8 min (major) and 19.3 min. Rf=0.39 on silica gel (50% ethyl acetate:hexanes); mp 114-116° (Et2O); [α]25D =−197.1° (c=10.0, CHCl3); IR (KBr, cm−1) 3349 (s), 2901 (m), 1700 (w), 1532 (w), 1404 (m), 1258 (m), 1081 (s), 936 (s); 1H NMR (400 MHz, CDCl3) δ6.96-6.93 (1H, m), 6.23-6.19 (1H, m), 4.89 (1H, s), 3.96-3.90 (1H, m), 3.38-3.35 (3H, m), 2.61-2.57 (3H, m), 2.54 (3H, s), 1.82-1.54 (1H, m); 13C NMR (400 MHz, CDCl3) δ137.3, 134.4, 133.2, 129.7, 129.5, 129.0, 128.1, 125.3, 75.3, 66.6, 56.6, 21.0, 20.6. HRMS calcd for C13H16O2Br2 (M+): 361.9518. Found: 361.9335.

Workup

  1. customTo a flame dried round bottom flask
  2. temperatureThe mixture was heated
  3. temperatureto reflux for 20 hours
  4. customThe solvents were then removed in vacuo
  5. customThe resulting solid was purified by flash chromatography (50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-d76040d615a74e34b371e56ae19bf4b0
Source dataset
uspto-grants-2003_02
Patent number
US06525068B1

Reaction notes

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