Nitrile Oxides, Nitrones, and Nitronates in Organic Synthesis : Novel ...

438 NITRONATES
and E + are involved in the reaction, it is necessary to perform deprotonation
of the resulting cationic intermediate. If the third component of the triangle, the
anion, reacts with the neutral molecule of the electrophile E–X, elimination of
the leaving group X − from the coupling product is required to complete the
synthesis.
The relationships between the components of the Hantzsch triangle were considered
in-depth in the monograph 2 and references therein. Although the problem
of reactivity of ambident substrates has been studied over many years and from
different points of view, the complexity of the starting system and its numerous
reaction pathways do not allow one to reliably predict the results of O-alkylation
in each particular case, because it is necessary to take into account the rates
of numerous reversible and irreversible processes as well as the thermodynamic
factors responsible for the position of the equilibrium; it is necessary to take solvent
effects into consideration when estimating the thermodynamic factors. All
accumulated observations are approximated by several empirical rules included
in monographs 2 and 3.
Diazo compounds and oxonium salts are the most efÞcient alkylating agents in
the synthesis of alkyl nitronates. It is assumed that diazo compounds are inserted
into the O–H bond in the aci forms of the corresponding AN, whereas oxonium
salts generally react with AN anions.
3.2.1.1.1. Alkylation with Diazo Compounds Diazomethane or diazoethane are
commonly used as diazo compounds. The reactions of these alkylating agents
proceed smoothly only with AN containing electron-withdrawing groups (EWG)
adjacent to the α-C atom (4–6) (Scheme 3.3).
CH 2
EWG
H
EWG
NO2
O
N
OH
RCHN2
EWG
H
EWG = NO Ref.4
2 , CO2MeRef.4 , CNRef.4 , COMeRef.4 , PhRef.4 , CONMe2 Ref.4 ,
NC
p-NO 2-C 6H 4 Ref.4 , PhSO2 Ref.4 ,
Scheme 3.3
O
N R = H, Me
OCH2R Ref.5
MeON , N
NC
Ref.6