Phosphate → (2R,3R)-3-[t-Butyldimethylsilyloxy)-2-methylhexanal

HRID 22074

Reaction equation

HRID 22074 reaction equation
[CH3:1][C@@:2]1([CH2:8][OH:9])[C@@H:4]([CH2:5][CH2:6][CH3:7])[O:3]1.CCN(C(C)C)C(C)C.[Si:19](OS(C(F)(F)F)(=O)=O)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20].P([O-])([O-])([O-])=O>C(Cl)Cl.CCOCC>[Si:19]([O:3][C@H:4]([CH2:5][CH2:6][CH3:7])[C@@H:2]([CH3:1])[CH:8]=[O:9])([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20]

Participants

7

Reactant 4

HCID 1061PhosphateHCID 81531DiisopropylethylamineHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 14959484(2R,3R)-2-Methyl-3-propyloxiranemethanol

Product 1

HCID 14959487(2R,3R)-3-[t-Butyldimethylsilyloxy)-2-methylhexanalYield 116.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-42 °C

Procedure

This is a representative procedure for the rearrangement of epoxy alcohols with trialkylsilyl trifluoromethanesulfonates. Epoxy alcohol 15 (74.3 mg, 0.4647 mmol) was dissolved in 4.0 ml of CH2Cl2, treated with 100 mg of 4 Å powdered molecular sieves, DIPEA (129 μl, 0.7419 mmol, 1.3 eq) and cooled to -42° C. TBSOTf (157.2 μl, 0.6849 mmol, 1.3 eq) was then added drop wise and stirred for 80 min at which time the solution was poured onto 20 ml of Et2O and shaken with 5 ml of pH 5.5 phosphate buffer. The layers were separated and the aqueous phase extracted with Et2O (2×5 ml ). The combined organic phases were washed with H2O (3×2 ml), 5% NaHCO3 (2×2 ml), brine (1×2 ml), dried over MgSO4 and the solvent evaporated to yield 132.0 mg of aldehyde 16 (slight contamination of silanol, 95%+yield). 1H NMR (CDCl3, 360. 134 MHz) δ:9.67 (1H, d, J=2.35 Hz), 3.89 (1H, q, J=5.40 Hz), 2.44 (1H, qdd, J=7.02, 5.40, 2.35 Hz), 1.5-1.3 (4H, m), 1.02 (3H, d, J=7.02 Hz), 0.86 (3H, t, J=7.31 Hz), 0.82 (9H, s), 0.01 (3H, s,), and -0.01 (3H, s). 13C NMR (CDCl1 90.55 MHz) δ:205.0, 73.2, 51.1, 37.0, 25.6, 18.01, 17.99, 14.2, 10.3, -4.3 , and -4.8. IR (thin film): 2959 (s), 2934 (s), 2859 (s), 1727 (s), 1472 (s), 1464 (s), 1362 (m), 1256 (s), 1125 (s), 1090 (s), 1074 (s), 1038 (s), 1007 (m), 889 (w), 837 (s), and 775 (s) cm-1. High resolution MS (m/z): 187.1161, calcd for C9H19O2Si 187.1154 (M-C4H9). [α]D =-18.4° (c=1.43, CH2Cl2). 1H NMR integration of δ 3.89 and the contaminating diastereomer at δ 3.89 and the contaminating diastereomer at δ 4.05 indicated a 20:1 ratio.

Workup

  1. additiontreated with 100 mg of 4 Å
  2. customThe layers were separated
  3. extractionthe aqueous phase extracted with Et2O (2×5 ml )
  4. washThe combined organic phases were washed with H2O (3×2 ml), 5% NaHCO3 (2×2 ml), brine (1×2 ml)
  5. dry with materialdried over MgSO4
  6. customthe solvent evaporated

Sources & evidence

ORD record
ord-2b4b558bcc844b5a87c62bab6fae111c
Source dataset
uspto-grants-1995_06
Patent number
US05426206

Linked notes

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