Rearrangement of a-Alkoxy-Substituted Allylic Esters

Ireland-Claisen Rearrangement of a-Alkoxy Substituted Allylic Esters 

Method A Synthesis of Methyl (R,S)-2-Methoxy-3-Methyl-4-Pentenoate (syn-17a) 

To a solution of LDA (3.9 mmol) in THF (25 mL) at -100 °C the ester 16a (0.50g, 3.5 mmol) was added in THF (6mL). After the reaction mixture had stirred for 1 h at -100 °C, there was added 1.0 mL of the supernatant from the centrifugation of a 1 1 mixture of MejSiCl and EtjN. The mixture was allowed to stir an additional 1 h at -100 °C, was then allowed to warm to 25 °C, and was stirred for 12 h. The solution was then poured into 5% aqueous NaOH (75 mL) and stirred for 10 min, and the aqueous layer was washed with ether. The aqueous phase was acidified with concentrated HCl at 0 °C and was extracted repeatedly with CHjCh. The combined extracts were dried (MgS04) and concentrated. The crude carboxylic acid was dis- 

Entry Subst. R R R R Method Yield [%] Ratio syn aitti Ref. 

To a solution of ester 16k (1.10 g, 6.96 mmol) in THF (40 mL) at -78 °C was added LDA (17.6mL, 0.5M in THF, 8.80mmol) over 30s. The reaction was stirred 1.5 min and trimethylsilyl chloride (2.60 mL, 20.5 mmol) was added. The reaction was held at -78 °C for 10 min and then was allowed to warm to 25 °C for 2 h. The reaction was quenched by addition of saturated aqueous NH4CI (8mL). The mixture was acidified with 5% HCl (8mL) and extracted with ether (3 x 25 mL). The organic fractions were treated with diazomethane, dried over MgSOi, and chromatographed on silica gel (30 1 hexane/ether) to yield a 40 1 mixture of syn-17k and owti-17k as a colorless oil (0.98 g, 89%). 

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