2-(4-chlorobut-2-ynoxy)oxane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-chloro-but-2-yn-1-ol (2.16 g, 20.66 mmol), 3,4-dihydro-2H-pyran (2.83 mL, 30.99 mmol, 1.5 eq), and pyridinium p-toluenesulfonate (528.0 mg, 0.21 mmol, 0.10 eq) in anhydrous dichloromethane (50 mL) was stirred at room temperature under N2 for 17 h. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (2×150 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated in vacuo to give 3.80 g (97.4%) of the desired product as clear oil. 1H NMR (400 MHz, CDCl3) δ ppm 4.80 (t, J=4.0 Hz, 1H), 4.39-4.22 (m, 2H), 4.19 (t, J=2.0 Hz, 2H), 3.88-3.80 (m, 1H), 3.57-3.51 (m, 1H), 1.89-1.70 (m, 2H), 1.68-1.50 (m, 4H). extracted with EtOAc (2×150 mL) The combined organic layers were washed with brine dried (Na2SO4) filtered evaporated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-chloro-but-2-yn-1-ol (2.16 g, 20.66 mmol), 3,4-dihydro-2H-pyran (2.83 mL, 30.99 mmol, 1.5 eq), and pyridinium p-toluenesulfonate (528.0 mg, 0.21 mmol, 0.10 eq) in anhydrous dichloromethane (50 mL) was stirred at room temperature under N2 for 17 h. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (2×150 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated in vacuo to give 3.80 g (97.4%) of the desired product as clear oil. 1H NMR (400 MHz, CDCl3) δ ppm 4.80 (t, J=4.0 Hz, 1H), 4.39-4.22 (m, 2H), 4.19 (t, J=2.0 Hz, 2H), 3.88-3.80 (m, 1H), 3.57-3.51 (m, 1H), 1.89-1.70 (m, 2H), 1.68-1.50 (m, 4H). extracted with EtOAc (2×150 mL) The combined organic layers were washed with brine dried (Na2SO4) filtered evaporated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-chloro-but-2-yn-1-ol (2.16 g, 20.66 mmol), 3,4-dihydro-2H-pyran (2.83 mL, 30.99 mmol, 1.5 eq), and pyridinium p-toluenesulfonate (528.0 mg, 0.21 mmol, 0.10 eq) in anhydrous dichloromethane (50 mL) was stirred at room temperature under N2 for 17 h. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (2×150 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated in vacuo to give 3.80 g (97.4%) of the desired product as clear oil. 1H NMR (400 MHz, CDCl3) δ ppm 4.80 (t, J=4.0 Hz, 1H), 4.39-4.22 (m, 2H), 4.19 (t, J=2.0 Hz, 2H), 3.88-3.80 (m, 1H), 3.57-3.51 (m, 1H), 1.89-1.70 (m, 2H), 1.68-1.50 (m, 4H). extracted with EtOAc (2×150 mL) The combined organic layers were washed with brine dried (Na2SO4) filtered evaporated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: THPO-CH2C≡CH was treated with 1.1 equivalents of n-BuLi in THF at -78° C. for 0.5 hours and then 1.4 equivalents of paraformaldehyde ((CH2O)n) Over the course of 12 hours, the reaction was allowed to rise to 25° C. and a product isolated in 84% yield. This product was then treated with 1.6 equivalents of P(oct)3 in CCl4 at 25° C. for six hours, yielding THPO-CH2C≡CCH2Cl in 85% yield. This compound was then treated with 1.0 equivalents NA2S.9H2O in EtOH:H2O (10:1) at 25° C. for 12 hours. The product, which was isolated in 47% yield, was then treated with acetic acid (AcOH):H2O:THF (7:3:10) at 25° C. for 12 hours. The resulting product, which was isolated in 64% yield, was then treated with 3.0 equivalents of mCPBA in methylene chloride for 2 hours yielding a compound having structure (2) (R3 =R5 =H, R2 =R4 =CH2OH) in 40% yield. Over the course of 12 hours to rise to 25° C. a product isolated in 84% yield