Acrylates alkyl nitronates

The number of investigations on the enantioselective dipolar cycloaddition of nitronates is still rather limited. In the case of simple alkyl nitronates, the facial selectivity is controlled solely by the steric environment about the two faces of the chiral unit. For example, the reaction of steroid dipolarophile 270 proceeds with the nitronate approaching the Re face of the alkene (Eq. 2.23) (234). The facial selectivity is controlled by the C(19) methyl group, which blocks the Si face of the dipolarophile. Similarly, exposure of 279 to ethyl acrylate at 40 °C for 24 h, provides a single nitroso acetal (Scheme 2.21) (242). The facial selectivity is presumed to arise from steric shielding by the menthol group, however the full stereostructure has not been established. 

Reductive coupling of the corresponding nitrones with alkyl acrylate is the key step in the short synthetic route of the selective and irreversible GABA inhibitor of amino transferase (S)-vigabatine (534) and of polyhydroxy pyrrolizidine alkaloid (+ )-hyacinthacine A2 (535). 

To carry out 1,3-dipolar cycloadditions with alkyl acrylates, nitrones of various structures such as ferrocenylnitrones (141), nitrones derived from chiral amino acids (210), L-serine-derived nitrones (660) and N -substituted C -phosphorylated nitrones (263) have been used. 

Moreover, the reaction of 3-[( )-2-nitroeth-l-enyl]pyr-idine 157b with alkyl vinyl ethers 158 at a low pressure (8 kbar) afforded five-membered nitronates 163 that reacted with an activated alkene 164 (styrene, acrylates, or maleimides) to afford the corresponding five/five-membered bicyclic nitrosoacetals 165 in moderate yields (53-74%) as shown in Scheme 11.34. 

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