Benzyl (-)-glycidyl ether

Under an argon atmosphere, to a suspension of NaH (179 mg, 4.10 mmol, 55percent in oil) in THF (2 mL) were sequencially added a solution of (S)-glycidol (S1, 200 mg, 2.70 mmol) in THF (4 mL), and benzyl bromide (0.340 mL, 2.86 mmol) at 0 °C. After the mixture was stirred for 19 h under reflux, the reaction was quenched with 0.1 M phosphate buffer (pH 6.5). The products were extracted with AcOEt (x3), and the combined organic layer was washed with brine, then dried over Na(R, R)-N, N-Bis-(3, 5-di-tert-butylsalicyclidene)-1, 2-cyclohexanesanediaminocobalt (II) (0.029 g, 0.05 mmol) was added to a mixture of 2-((benzyloxy)methyl)oxirane (1.63 g, 9.91 mmol), AcOH (0.011 mL, 0.198 mmol) and THF (0.15mL). The mixture was cooled to 0 °C and treated with H0.5 mole of racemic 1, 2-epoxy compounds were added with 0.4 mole percent of the catalyst prepared in Preparation [(1-RR)-(Dibenzoyl-LTA) ] (or Preparation [ (1-SS) - (Dibenzoyl- DTA)]) and cooled down to 5 To a stirred solution of(S)-glycidol (5 g, 67.5 mmol) and benzyl chloride (13 g) in DMF (40 mL) cooled at 0 °C was added a powder of NaH (2.4 g) slowly for 10 minutes. The mixture wasstirred at 0 °C for 1 h and then at room temperature for 3 h. After the reactionvessel was cooled to 0 C, the mixture was treated carefully with droplets ofmethanol (2 mL) and stirred for 2 h at room temperature. The mixture was pouredinto aqueous sat. NaCl solution (100 mL) and extracted three times with a mixtureof ethyl acetate and toluene (1:10, 60 mL). The extracts were combined, washedwith NaCl aq. solution three times, dried over MgSO4, and evaporated underdiminished pressure to give I [(R)-3-O-benzyl-glycidol, CAS:14618-80-5] as a crudesyrup (11 g), which was used in the following reaction without purification.A mixture of 2-(benzyloxymethyl)-oxirane 2 (10.00 g, 61 mmol) and (S, S)-salen Co(III)OAc complex-A (0.09 g, 0.14 mmol) was vigorously stirred for 15 min, then cooled to 0 °C, and water added (0.6 mL, 34 mmol) over a period of 15 min through a micro-syringe. The reaction mixture was stirred at room temperature for 20 h, and then additional (S, S)-salen Co(III)OAc complex-A (0.09 g, 0.14 mmol) was added and stirring was continued for an additional 10 h. The reaction mixture was diluted with ethyl acetate, dried over NaA mixture of epoxide 2 (10.00 g, 61 mmol) and (S, S)-Salen Co(III)-(OAc) complex-A (0.09 g, 0.14 mmol) was stirred vigorously for 15min then cooled to 0 °C. H2O (0.6 mL, 34 mmol) was added from a micro syringe over 15 min, and the resulting mixture was stirred at r.t. for 20 h. Additional (S, S)-Salen Co(III)-(OAc) complex-A (0.09g, 0.14 mmol) was then added, and stirring was continued for a further 10 h. The resulting mixture was diluted with EtOAc (30 mL), dried (Na2SO4), and concentrated under reduced pressure. The residue was purified by column chromatography [silica gel, PE–acetone (95:5)]; the less-polar epoxide (R)-3a eluted first, followed by diol (S)-3b.(R)-3a Colorless oil; yield: 4.6 g (46percent); [α]D22 –7.9 (c 0.4, EtOH) {Lit.14[α]D22 –5.8 (c 0.4, EtOH)}. Chiral HPLC: column: CHIRALCEL OD-H (250 × 4.6 mm); eluent: hexane–i-PrOH (90:10); flow rate: 0.5 mL/min; detector: 220nm [(S)-isomer: tR= 15.20 min; (R)-isomer: tR= 16.46 min]; ee >99percent. IR (CHCl3): 3418, 3020, 2401, 1719, 1603, 1523, 1495, 1421, 1216, 1094, 929, 669 cm–1. 1H NMR (200 MHz, CDCl3): δ H= 2.61 (dd, J= 5.1, 2.7 Hz, 1 H), 2.80 (dd, J= 5.3, 4.2 Hz, 1 H), 3.15–3.23 (m, 1 H), 3.44 (dd, J=11.3, 5.8 Hz, 1 H), 3.77 (dd, J= 11.4, 3.0 Hz, 1 H), 4.60 (s, 2 H), 7.28–7.37 (m, 5 H). 13C NMR (50 MHz, CDCl3): δ C= 137.8 (C), 128.4 (CH, 2 C), 127.7(CH, 3 C), 73.3 (CH2), 70.7 (CH2), 50.8 (CH), 44.2 (CH2).MS: m/z = 187 [M + Na]+. [(S)-3b] Colorless oil; yield: 4.7 g (43percent); [α]D22 –2.3 (c 6.5, CHCl3) {Lit.15[α]D22 –3.6 (c 6.6, CHCl3)}. IR (CHCl3): 3434, 3020, 1600, 1495, 1215, 1045, 1029, 929, 697cm–1. 1H NMR (200 MHz, CDCl3): δ H= 2.73 (t, J= 5.8 Hz, 1 H, OH), 3.13 (d, J= 5 Hz, 1 H, OH), 3.52 (dd, J= 5.4, 2.6 Hz, 2 H), 3.57–3.68 (m, 2 H), 3.82–3.92 (m, 1 H), 4.54 (s, 2 H), 7.28–7.39 (m, 5 H, Ph). 13C NMR (50 MHz, CDCl3): δ C= 137.6 (C), 128.4 (CH, 2 C), 127.8(CH, 3 C), 73.5 (CH2), 71.6 (CH2), 70.7 (CH), 63.9 (CH2).

Used in the preparation of lactone fragments of compadine and lovastatin. 1 Preparation of cis-1,3-polyol, 2 dideoxy nucleoside 3 and spiroacetal cyanohydrin chiral.

Molecular Weight:164.20
XLogP3:1.3
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:4
Exact Mass:164.083729621
Monoisotopic Mass:164.083729621
Topological Polar Surface Area:21.8
Heavy Atom Count:12
Complexity:130
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes