.alpha.-Methoxylation of Unsaturated Carbonyl Compounds

Synthesis of (E)‐4‐Bromo‐3‐methoxybut‐3‐en‐2‐one, the Key Fragment in the Polyhydroxylated Chain Common to Oscillariolide and Phormidolides A–C

“…For this purpose, the target compound is the ( E )‐4‐bromo‐3‐methoxybut‐3‐en‐2‐one ( E )‐ 1 as a single isomer. There are few publications reporting the synthesis of bromoenolether ketones and generally they report the undesired Z isomer . Therefore, tremendous efforts have been necessary to develop a suitable strategy that delivers the desired and key compound ( E )‐ 1 .…”

“…Interestingly, Feuerer and Severin described the synthesis of 3‐(benzyloxy)‐4‐bromo‐3‐buten‐2‐one as an isomeric mixture ( E / Z =10:1) . Therefore, their methodology was tested by replacing the benzylic alcohol with methanol (Scheme ).…”

“…Gil tones and generally they report the undesired Z isomer. [9,10] Therefore, tremendous efforts have been necessary to develop asuitable strategy that delivers the desired and keycompound (E)-1. The first attempted methodology was at hree-step procedure based on the transformation of bromopyruvic acid into the dimethyl acetal-methyl esther 2 [11] followed by reaction with MeLi at low temperature to give ketone 3.T he final step was the elimination of methanolu nder acidic conditions to give compound 1 (Scheme 1).…”

“…Interestingly,F euerer and Severind escribed the synthesis of 3-(benzyloxy)-4-bromo-3-buten-2-one as an isomeric mixture (E/Z = 10:1). [10] Therefore, their methodology was tested by replacing the benzylic alcohol with methanol (Scheme1). Bromohydrazone 4 was subjected to ao ne-pot-five-transformation sequence in which the first steps were bromination and elimination leadingt ot he formationo ft he corresponding intense red ene-azo compound I1.T hen, methanol addition in acidic media delivered the dibromo-methoxy intermediate I2.F inally, hydrolysis and DBU-promoted HBr elimination afforded again BMK (Z)-1 in a7 1% yield relative to 4.N MR spectroscopy data matched the previously characterized Z isomer.…”

Some Synthetic Uses of Double‐Bonded Functional Groups

“…This reaction can be readily brought about by formation of a hydrazone followed by treatment with bromine and then NaHCO 3 , and then aqueous acid and finally DBU (equation 48) 192 . Using a different hydrazone reagent, or by the initial formation of semicarbazones,ˇ-substitution is also possible 193,194 .…”