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

258 NITRONES: NOVEL STRATEGIES IN SYNTHESIS
R 1
R
O
−
N
O R 2
Li R 2
357
O
+ N
Bu t
+
R 3
R
R 1
NH
O
O
N
Bu t
O R2
R = R 1 = Me; R = H, R 1 = i Pr; R 2 = Me, Et, Ph;
R 2 + R 2 = −(CH2)5; R 3 = Ph, p-MeOC6H4, p-ClC6H4;
R 3
R 2
O
O N
Bu t
358 359
Scheme 2.156
HO
R 2
O R2
R 3
R 2
O
O HN
ee>99%
Oxazolinyl-oxiranyllithiums (357) prepared from optically pure oxazolinyloxiranes
react with nitrones diastereo and enantioselectively to give almost optically
pure diazadispiroundecanes (358). These are appropriate candidates for the conversion
to α-epoxy-β-amino acids (360) in view of the lability of the N–O bond
of the isoxazolidinones (359) (Scheme 2.156) (590–596).
Nucleophilic addition of metallated heterocyclic derivatives to N -tetrahydropyranyl
(THP) protected nitrones (361) makes it possible to synthesize α-branched
hydroxylamines (362) (Table 2.13) (597).
2.6.6.1.3. Addition of 2-Alkyl-2-Oxazolines All of the above mentioned reactions
of nucleophilic addition of nitrones give the corresponding hydroxylamines.
In this chapter, the reactions of nitrones and nucleophiles and their conversions
to compounds of other structures are considered.
Lithiated 2-alkyl-4,5-dihydro-1,3-oxazoles (363) react with nitrones in high
stereoselectivity to give initially 1,6-dioxa -2,9-diazaspiro [4.4] nonane (364).
Upon further treatment with oxalic acid it is quantitatively converted to 4,4dimethyl-2-(1-methyl-2-phenylvinyl)-4,5-dihydro-1,3-oxazole
(365) (diastereomeric
mixture: E/Z = 9:1) with elimination of tert-buthylhydroxylamine (Scheme
2.157) (598, 599).
Lithiated 2-(chloromethyl)- and 2-(1-chloroethyl)-4,5-dihydro-1,3-oxazoles
(366) and (367) behave in a different way. The reaction of (366) with nitrones
leads stereoselectively to 2-[(Z )-alkenyl]-4,5-dihydro-1,3-oxazoles (368a) and
(368b) (Scheme 2.158), while the 2-(1-chloroethyl)-derivative (367) gives
360
R 2
R 3
Bu t