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

602 NITRONATES
Most studies and approaches concern the synthesis and transformations of
enantiomerically pure six-membered cyclic nitronates. (This problem was
considered in Sections 3.2.1.2.2.2 and 3.4.3.5)
Chiral LA are rarely used in the construction of chiral six-membered cyclic
nitronates by the Diels-Alder reaction of oleÞns with α-nitoralkenes (96, 158), in
spite of the potential efÞciency of the process. Apparently, this is associated with
the absence of known common features of the process and, as a consequence, with
the necessity to perform special investigations for optimization in each particular
case.
Two research groups examined the approach to the synthesis and the use of
six-membered cyclic nitronates by introducing chiral inductors into the molecule
of the starting α-nitroalkene. (Here, it is incorrect to use the term auxiliaries
because the chiral fragment is not eliminated and is involved in the target
product.)
The synthesis of chiral α-nitroalkenes (296) from galactose was documented
(157) (Scheme 3.180).
Then the highly enantioselective synthesis of the optically pure diastereomers
of nitronates (297) was carried out (endo approach, Re-face attack of (296)).
Storage of the latter compound in ethanol in the presence of an excess of vinyl
ethyl ether afforded optically active nitroso acetals (298) in good yield. Upon
storage, compound (298) underwent a rearrangement accompanied by cleavage
of the N–O bond to give enantiomerically pure isoxazoline (299) serving as a
convenient building block for asymmetric syntheses.
The synthesis of nitronates (297) in the presence of electron-deÞcient oleÞns
(398) produces optically pure nitroso acetals (300) with high optical purity. Interestingly,
the use of ethanol as the solvent in the (296→298) reaction leads to a
substantial increase in de compared to CH2Cl2 (157).
Another research group (147) studied the reaction of vinyl ethyl ether with
optically pure α-nitrooleÞn (302) giving rise to enantiomerically pure nitronate
(303). The reaction of the latter with an excess of the oleÞn gradually produces
nitroso acetal (304) (Scheme 3.181).
The optical purity of compound (304) is due to the high facial preference of
the attack of the oleÞn on nitronate (303) from the distal side with respect to
the substituents at the C-4 and C-6 atoms. ModiÞcations of nucleotides provide
a promising approach to the synthesis of new anti-HIV drugs.
The asymmetric synthesis of six-membered cyclic nitronates with the use of
dipolarophiles containing auxiliaries was studied in more detail. Chiral vinyl
ethers are most commonly used for this purpose. This process is schematically
shown in Scheme 3.182.
It should be noted that the reactions (306→307) and (307→308) can be either
inter- or intramolecular, and that the number of substituents attached to the C,C
double bond in the oleÞn can also be varied.
Denmark (442, 443) studied extensively various alcohols (305) with the aim
of using these compounds as auxiliaries in the process shown in Scheme 3.182
(141, 442) and demonstrated that enantiomers of alcohols (305a) and (305b) are