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

322 NITRONES: NOVEL STRATEGIES IN SYNTHESIS
Table 2.19 γ-Hydroxy-α-amino acids and lactones derived from cycloadducts 491
a–c
Cycloadduct
491a
491b
491c
Lactone
(method; a yields b )
Ph
O
O
NH3Cl
494 a (A; 68%, 99%)
PhBu t- p
O
O
NH3Cl
494 b (A; 83%, 99%)
Cy
O
O
NH3Cl 494 c (B; 87%, 99%)
O
O
a-amino acid
(yield c )
O
+
NH3 OH
495 a (75%)
O
O
NH3OH
Ph
495 b (50%)
O
495 c (62%)
p -Bu t Ph
Cy
NH3 OH
aMethod A: (1) Zn/HOAc/AC2O; (2) K2CO3/MeOH; (3) 6N HCl, reflux.
Method B: (1) Pd/C, ammonium formate/MeOH; (2) 6N HCl, reflux.
bamino alcohol, lactone.
cAfter basic hydrolysis, neutralization, ion exchange chromatography,
and lyophilization.
Me
(EtO)2(O)P
+
N
O
+
R
−
toluene
60°C
−
−
−
+
Me
(EtO) 2(O)P
+
N
O
R
Me
(EtO) 2(O)P
496 497 498
Scheme 2.241
Cycloaddition of nitrone (508) to allyl alcohol at ambient temperature gave
a mixture of four cycloadducts in a 23:5:4:1 ratio (Scheme 2.244). All of the
adducts (509) are derived from the regiochemical approach opposite to the intramolecular
pathway (Fig. 2.35). Formation of the cycloadduct in the intramolecular
cycloaddition reaction is ascribed to a high preference for an endo-syn transition
state, due to the constraint imposed by the short, three atom connecting chain
(116). The major product in the intermolecular cycloaddition reaction was the
exo-anti –(509) adduct (Scheme 2.244 and Fig. 2.35).
+
N
O
R