Synthesis of 3-(P-Nitrophenyl)SulfonylOxy2- Keto Esters from alpha-Keto Esters and a Survey of Their Reactions as 1 2,3-Trifunctionalized Intermediates
Abstract
3-(P-Nitrophenyl)sulfonyloxy2-keto esters, 15, were efficiently prepared in good yields by electrophilic attack of bis(p-nitrobenzene sulfonyl)-peroxide (p-NBSP) on the electron rich carbon-carbon double bond of 1-carboethoxy-1- (trimethylsiloxy)- alkenes, 11. Silyl enol ethers 11 were prepared from alpha-keto esters in good to excellent yields by two methods that differed by the base used to remove the proton. Carbonyl reactions and substitution reactions of 15 were investigated. The carbonyl of 15 was found be very electrophilic, as demonstrated by the facile reaction of 15 with water to provide gem diol's 16. The mild reducing agent, sodium triacetoxyborohydride easily reduced 15 to give syn-3- P-NITROPHENYL) SULFONYLoxy2- hydroxy esters, 18 in good yields. The Felkin-Anh model was used to rationalize the stereoselectivity of the reduction reaction. Base-promoted, stereoselective ring closure of 18 provided cis-glycidic esters, cis-22, in good yields. Reactions of 15 with nucleophilic amines gave base-promoted decomposition. Due to the high reactivity of 15, the scope of the survey of reactions was limited to the reactions of 15b. Nucleophiles with a low pk(alpha) sub alpha, such as morpholine and azide ion, replaced the nosylate group of 15b to afford ethyl 3-morpholino-2-oxo-4-phenyl butanoate, 24, and ethyl 3-azido-2-oxo-4-phenylbutanoate, 30b, in good yields. Two sequences: reduction protection substitution, RPS, and substitution reduction protection, SRP, of 30b were evaluated. Both sequences provided ethyl 3-azido-2-carboethoxy-4-phenylbutancate, 34b. While more diastereoselective, the RPS sequence gave only modest yields of anti 34b, due to competing elimination reactions.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1996
- Accession Number
- ADA342608
Entities
People
- Mary C. Johnson
Organizations
- New Mexico State University