Level 1 – Case 8
Addition of Hydroxylamines to D D E E-Unsaturated
Esters
Key point: Isotopic labeling.
Concerted versus polar mechanism
Ph
OEt
O
MeNHOH.HCl
MeOH
MeONH 2 .HCl
MeOH
O
N
Ph
Me
O
No reaction
Addition of Hydroxylamines to D D E E-Unsaturated Esters
Hydroxylamine derivatives are known to efficiently add to DE-unsaturated esters
and lactones in a conjugated fashion. However, when the reaction was tested with
ethyl (E)-cinnamate 1, different results were obtained depending on the reagent
employed. Thus, the reaction of 1 with N-methylhydroxylamine yielded the isoxaN N
zolidinone 2, whereas no reaction took place (the starting material was recovered
unaltered) when O-methylhydroxylamine was used (Scheme 8.1).
Ph
O E t
O
MeNHOH.HCl
MeOH
MeOH
MeONH 2 .HCl
O
N
O
Ph
Me 2
1
Scheme 8.1
Propose a reasonable mechanism to explain the formation of the cyclization product 2 and justify the lack of reactivity when O-methylhydroxylamine is used.
Addition of Hydroxylamines to D D E E-Unsaturated
Esters
Key point: Isotopic labeling.
Concerted versus polar mechanism
Ph
OEt
O
MeNHOH.HCl
MeOH
MeONH 2 .HCl
MeOH
O
N
Ph
Me
O
No reaction
Addition of Hydroxylamines to D D E E-Unsaturated Esters
Hydroxylamine derivatives are known to efficiently add to DE-unsaturated esters
and lactones in a conjugated fashion. However, when the reaction was tested with
ethyl (E)-cinnamate 1, different results were obtained depending on the reagent
employed. Thus, the reaction of 1 with N-methylhydroxylamine yielded the isoxaN N
zolidinone 2, whereas no reaction took place (the starting material was recovered
unaltered) when O-methylhydroxylamine was used (Scheme 8.1).
Ph
O E t
O
MeNHOH.HCl
MeOH
MeOH
MeONH 2 .HCl
O
N
O
Ph
Me 2
1
Scheme 8.1
Propose a reasonable mechanism to explain the formation of the cyclization product 2 and justify the lack of reactivity when O-methylhydroxylamine is used.