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

176 NITRONES: NOVEL STRATEGIES IN SYNTHESIS
CH3
CH 3CCH 2CCH 3
N
OH
164
NHOH
R 1
CH3CHO
O
N OH
166
H3C CH3
N+
CH3 N
O− OH
CH3
CH3 CH3CCH2C
N CH3
OH
+
N = C
−
O
165A 165B
+
O
Scheme 2.58
R 2
R 3
NH 4OAc
R 1
N
N
O
167
R 2
R3 −
R 1 = Ph, m-O 2NC 6H 4, p-O 2NC 6H 4, Me, CH=NOH
R 2 = Me, CH3(CH2)7, Pr, CH3(CH2)12
R 3 = Me, CH3(CH2)7, CH3(CH2)8, CH2Cl, EtOCOCH2,
HOCOCH 2CH2, Pr, CH3OCO(CH2)4
R 2 , R 3 = (CH 2) 5
Scheme 2.59
does not occur (323). It is noteworthy that such reactions also form secondary
hydroxylamine groups which can be oxidized to nitrones or nitroxyl groups (313).
Condensation of hydroxyamino-ketones (166) with ketones and ammonium
acetate leads to the formation of 2H -imidazole-1-oxides (167) (Scheme 2.59)
(324).
Addition of carbonyl oxide (169) to oximes (168) results in the formation of
(E)-N -(hydroperoxyalkyl) keto nitrones (170); the reaction involves a one-pot
step synthesis (Scheme 2.60) (325, 326).
2.2.2.3. Synthesis from Nitro Compounds Nitrones can be obtained in good
yields from the addition of benzyl and allyl Grignard reagents to aryl- and alkylnitro
compounds. This reaction proceeds chemoselectively; carbonyl groups and
other reactive electrophilic groups are not affected by the reaction conditions.
Double bond stereochemistry is determined by the nature of the employed Grignard
reagent. Benzylmagnesium halides give exclusively Z -isomers of nitrones
(173) and (174), whereas 2-butenylmagnesium chloride gives nonconjugated
Z-nitrones with the predominance of E-isomers in the conjugated nitrone (174)
(Scheme 2.61) (327–329). Ce(III) chloride facilitates the addition of Grignard
reagents to nitroalkanes. (330)
+
H
CH 3