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

280 NITRONES: NOVEL STRATEGIES IN SYNTHESIS
Table 2.15 Diastereoselective addition of vinyl reagents to nitrone BIGN 292
Lewis Yield
Entry M (eq) acid a Solvent (t 0 ) Time syn/anti b (%) c
1 MgBr (1.2) none THF (0 ◦ C) 1 h 76:24 86
2 MgBr (1.2) ZnBr2 Et2O (0 ◦ C) 1 h 53:47 84
3 MgBr (1.2) MgBr2 Et2O (0 ◦ C) 1 h 56:44 80
4 MgBr (1.2) Et2AlCl Et2O (0 ◦ C) 1 h 8:92 86
5 CeCl3 (1.2) none THF (−40 ◦ C) 2 h 58:42 74
6 CeCl3 (1.2) Et2AlCl THF (−40 ◦ C) 2 h 30:70 78
7 (CuLi)1/2 (1.0) none THF (−80 ◦ C) 2 h 70:30 80
8 (CuLi)1/2 (1.0) Et2AlCl THF (−80 ◦ C) 2 h 22:78 79
9 Li (1.5) none THF (−80 ◦ C) 15 min 35:65 90
10 Li (1.5) Et2AlCl Et2O (−80 ◦ C) 15 min 4:96 92
11 AlEt2 (1.1) none Et2O (−40 ◦ C) 2 h 52:48 86
12 AlEt2 (3.0) none Et2O (−40 ◦ C) 2 h 32:68 87
a Nitrone was precomplexed with 1.0 eq of the Lewis acid prior to the addition.
b Measured from the intensities of 1 H NMR signals.
c Determined on isolated mixtures of syn and anti adducts.
High stereoselective addition of vinylmagnesium bromide to L-tartaric acidderived
nitrone was used as a key step in the synthesis of ( + )-lentiginosine and
its structural analogs (653).
It was shown (654) that the sequence terminal alkyne hydrozirconation, Zr
to Zn exchange and addition to nitrones, is a good method to the stereoselective
synthesis of (E)-N-allylhydroxylamines, under mild conditions and in good
yield.
Another useful method for generating various N -allylhydroxylamines is the
reaction between vinyl boronic ester of pinacol and nitrone in the presence of
dimethylzinc (655).
Addition of lithium derivatives of acetylenides (Li—C≡C–CO2R) to chiral
nitrones proceeds with high stereoselectivity, giving α-acetylene substituted
hydroxylamines (410a,b) (656). This reaction has been successfully applied to
the synthesis of γ-hydroxyamino-α,β-ethylene substituted acids (411a,b), formed
in the reduction of (410) with Zn in the presence of acid (657, 658), and to chiral
5-substituted-3-pyrroline-2-ones (412a,b) (Scheme 2.184) (658).
Similar addition reactions of alkyl 3-lithiopropiolates to nitrones with subsequent
Raney Ni hydrogen reduction and amino group protection, led to the
synthesis of (S) and (R)-vigabatrin (659).
Addition of (trimethylsilyl)acetylides to chiral α-aminoalkyl- (413) and
α-alkoxyalkyl-(BIGN) (292) nitrones proceeds stereoselectively. Successive desilylation
(Bu4NF, THF) and transformation of the ethynyl group into carboxyl
(RuCl3-NaIO4) led to the synthesis of diastereomerically pure N -hydroxy-αamino
acids (414) andα-amino acids (415) (Scheme 2.185) (199, 202, 652,
660).