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

90 NITRILE OXIDES
TBSO H
Me
NOH
TBS = t-BuMe 2Si
+
Me OH
Me
i-PrOH (3 eq.)
EtMgBr (3 eq.)
CH2Cl2, 0°C - r.t.
Scheme 1.53
TBSO
N
O
Me Me
417
Macrocycles containing isoxazoline or isoxazole ring systems, potential receptors
in host–guest chemistry, have been prepared by multiple (double, triple or
quadruple) 1,3-dipolar cycloadditions of nitrile oxides, (prepared in situ from
hydroxamoyl chlorides) to bifunctional calixarenes, ethylene glycols, or silanes
containing unsaturated ester or alkene moieties (453). This one-pot synthetic
method has been readily extended to the preparation of different types of macrocycles
such as cyclophanes, bis-calix[4]arenes and sila-macrocycles. The ring
size of macrocycles can be controlled by appropriate choices of the nitrile oxide
precursors and the bifunctional dipolarophiles. Multiple cycloadditive macrocyclization
is a potentially useful method for the synthesis of macrocycles.
Enantiomerically pure isoxazolines 417 have been prepared (Scheme 1.53)
via the stereo- and regioselective cycloaddition of chiral nitrile oxides and allylic
alcohols (454). By ring opening with Et3SiCl followed by imine hydrolysis with
Raney nickel/B(OH)3, isoxazolines 417 were converted with stereo integrity to
the respective hydroxy ketones, the latter being used as polyketide building
blocks. This method has been used to prepare an isoxazoline analog of erythronolide
A seco acid. A new procedure for the selective reduction of conjugated
Δ 2 -isoxazolines to unsaturated β-hydroxy ketones has been described. The use of
SmI2 as the reducing agent and B(OH)3 to hydrolyze the resulting imine results
in a mild, convenient, and chemoselective protocol for this otherwise difÞcult
transformation. It complements the existing methodology for the preparation of
β-hydroxy ketones via nitrile oxides (455).
Intramolecular cycloaddition of nitrile oxides, prepared from 1,2-isopropylidene-protected
ether-linked oligo-pentoses leads to the diastereoselective formation
of chiral isoxazolines fused to 10–16-membered oxa-cycles (456).
A rapid access to carbocyclic nucleosides, containing a fused isoxazoline ring
has been proposed, starting from cyclopentadiene. The route involves a hetero
Diels–Alder cycloaddition reaction of nitrosocarbonylbenzene followed by
a 1,3-dipolar cycloaddition of nitrile oxides, cleavage of the N–O tether and
transformation of the heterocyclic aminols into nucleosides via construction of
purine and pyrimidine heterocycles (457).
1.4.1.3. Syntheses of Natural Products and Related Compounds 1,3-Dipolar
cycloaddition reactions of nitrile oxides in the synthesis of natural products and
their analogs has been the subject of a recent review (458).
OH
Me