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

276 NITRONES: NOVEL STRATEGIES IN SYNTHESIS
R1 +
N
O
−
R 2
R 3
OSiR 3
cat.
OR 4
R 1
N
R2 R3 CO2R4 OSiR3
Cat.: Ti-(S) - BINOL - 2ArOH or Ar(OH)2
R 1 = Ph, Bn, Bu t ; R 2 = H; R 3 = Ph, 2-Naphthyl
p-MeC 6H4, 3-Pyridyl, 3,4-(OCH2O)C6H3
Scheme 2.178
R 1
N
H
R2 R3 CO2H
products in excellent yield. α-Aryl-N-tert-butylnitrone reacted with ethyl trimethylsilylacetate
to yield the unexpected α,β-unsaturated ester ArCH = CHCO2
Et in a 100% E-form (639). The use of a chiral titanium complex, prepared
from Ti(O i Pr)4, BINOL, and tert-butylcatechol, directs the addition reaction of
silyl ketene acetals enantioselectively. Further transformations of adducts give
optically active β-amino acids (Scheme 2.178) (640).
Theoretical calculations at DFT level agree that the reactions of nitrones with
silyl ketene acetal proceeds via 1,3-dipolar cycloaddition followed by the transfer
of the silyl group, yielding an open-chain product (641).
Asymmetric syntheses of β- amino acids result from the addition of chiral
enolates (399) to nitrone (400) viaN -acyloxyiminium ion formation (642, 643).
Regioselective convergence is obtained in the reactions of chiral boron- and
titanium- enolates (399a,b), (401), and (402). This methodology was used in
preparing four stereoisomers of α-methyl-β-phenylalanine (403) in enantiomeric
pure form (Scheme 2.179) (644).
The addition of lithium or magnesium ester enolates to nitrones in THF at
78 ◦ CorinEt2O at−20 ◦ C, constitutes a direct synthesis of N -hydroxy-β-amino
acid esters (Scheme 2.180) (645).
The N -hydroxylamino compounds (404) and (405), obtained from the reaction
of tert-butyl acetate with 3,4-dihydroisoquinoline-N -oxide or 5,5-dimethylpyrroline-N
-oxide, when boiled in methylene chloride in the presence of
triphenylphosphine, carbon tetrachloride and triethylamine, are transformed to
(1,2,3,4- tetrahydroisoquinolin-1-ilidene) acetate (406) or (pyrrolidin-2-ilidene)
acetate (407) (Scheme 2.181) (645).
High diastereoselectivity occurs in the addition of lithiated methoxyallene to
chiral cyclic nitrones. The hydroxylamines obtained can be easily transformed
into derivatives of 1,2-oxazine hydroxylamine, which are products of a novel
[3 + 3] cyclization reaction (Scheme 2.182) (646, 647).
2.6.6.1.8. Reactions of Vinylation and Ethynylation Vinylation and ethynylation
of nitrones using vinyl (137, 202, 563, 564) and ethynyl (199, 213, 219)
organometalic reagents is a convenient method for synthesizing various
nitrogen-containing compounds such as α-amino aldehydes, α-amino acids, amino