Dimethylformamide → HCID 178482623, compound

Participants

Reaction Conditions

Reaction Steps

A solution of (R,R)-19a (324 mg, 1.05 mmol) in t-BuOMe (2 mL) was cooled to −40° C., treated with i-PrLi (0.59 mL, 1.77 M, 1.05 mmol) and stirred for 20 min at that temperature. The solution was transferred by cannula to a mixture of 11.BF3 at −78° C. [prepared by addition of BF3.OEt2 (66 μL, 0.53 mmol) to a solution of 11 (115 mg, 0.50 mmol) in t-BuOMe (5 mL) at 0° C. and stirring for 10 min]. The resulting reaction mixture was allowed to warm slowly to −40° C. over 2 h and then held at that temperature for an additional hour. After cooling back to −78° C., DMF (96 μL, 1.25 mmol) was added and the mixture was allowed to warm to room temperature. The reaction mixture was diluted with Et2O and worked-up by addition of a saturated solution of aqueous NaHCO3. The aqueous layer was extracted with Et2O (2×10 mL) and the combined organic extract was washed with H2O (1×10 mL), saturated NaCl solution (1×10 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure on a rotary evaporator. Gradient flash column chromatography (95:5 then 90:10 CH2Cl2/Et2O) gave sequentially recovered starting material (11) and aldehyde 12d (71 mg, 55%); CSP HPLC analysis (Chiralpak AS-H; eluent: 80:20 hexanes/i-PrOH, 1.0 mL/min) determined the enantiomeric ratio (er) of 12d. The results for the various lithiating reagents, as well as the equivalents of the lithiating reagent used are shown in Table 2. As seen in Table 2, using 2.1 equivalents (lithiating reagent and ligand) of isopropyllithium resulted in the highest enantiomeric ratio of 12d.

Provenance & Evidence