Nitroolefins synthesis intermediates

The total syntheses of the potent glycosidase inhibitors (+)-castanospermine, (+)-6-epicas-tanosperimine, (+)-australine, and (+)-3-epiaustraline have been reported. These four natural products are derived from a single common intermediate, the nitroso acetal (as shown in Scheme 8.43), which is created in the key step by the asymmetric tandem [4+2]/[3+2] cycloaddition between silaketal nitroolefin and chiral vinyl ether.182 The strategy of the synthesis is outlined in Scheme 8.43. Scheme 8.44 presents a total synthesis of (+)-castanosperimine and (+)-6-epi-castanosperimine from the common intermediate prepared by tandem [4+2]/[3+2] cycloaddition. 

Nitroolefins are attractive alternative acceptors to enones. In 1999, Barnes and Ji reported an efficient catalyst system for reaction of nitroolefins with 1,3-dicarbonyl compounds with high enantioselectivity (up to 97% ee Scheme 19) [22], Using this method, a highly functionalized nitro compound 38, an important intermediate in the synthesis of an endothelin-A antagonist, was prepared on a large scale in 88 % ee. In this case, the formation of a chiral Mg enolate as a reactive intermediate was proposed. 

The synthesis of the bisbenzannelated spiroketal core of the y-rubromycins was achieved by the research team of C.B. de Koning." The key step was the Nef reaction of a nitroolefin, which was prepared by the Henry reaction between an aromatic aldehyde and a nitroalkane. The nitroolefin was a mixture of two stereoisomers, and it was subjected to catalytic hydrogenation in the presence of hydrochloric acid. The hydrogenation accomplished two different tasks it first converted the nitroalkene to the corresponding oxime and removed the benzyl protecting groups. The oxime intermediate was hydrolyzed to a ketone that underwent spontaneous spirocyclization to afford the desired spiroketal product. 

There have been a number of investigations involving the study of nitroolefins as useful intermediates in the synthesis of energetic materials. A characteristic of many of them is a large twist about the double bond. Interest in the structural characteristics that accompany the rotation motivates a discussion of details. As would be expected, the rotation out of the normal planar conformation is associated with spatial crowding. Rgure 14 illustrates some of the largest out-of-plane rotations that have been measured and, in one case, calculated for crowded ethylenes [25j. 

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