Tandem Cycloaddition of Nitroalkenes

1 Inter [4+2]/inter [3+2] The tandem intermolecular [4+2]/intermolecular [3+2] cycloadditions create bicyclic nitroso acetals with up to six stereogenic centers, which can be controlled by the choice of the stereochemistry of each component and the Lewis acids. The nitronate derived from 2-nitrostyrene and 1-trimethylsilyloxycyclohexene reacts with methyl acrylate to give the nitroso acetal in good yield and high diastereoselectivity (Eq. 8.107).154 

However, a-substituted dipolarophiles give poor selectivity and P-substituted dipolarophiles such as methyl crotonate fail to react. 

High-pressure promoted tandem [4+2]/[3+2] cycloadditions of nitrostyrenes with enol ethers has been reported, which do not require the Lewis acids. The products are converted into 

Asymmetric tandem cycloaddition of a chiral carbohydrate nitroalkene with ethyl vinyl ether in the presence of electron-withdrawing alkenes produces a facile assembly of bicyclic systems, which can further be selectively cleaved to give homologated carbohydrates (Eq. 8.110).176 

2 Intra [4+2]/inter [3+2] This type of tandem reaction using nitroalkenes has not 

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SCHEME 16.77 Tandem cycloaddition of nitroalkene 394 and hydrogenolysis of the resulting... 

The tandem cycloaddition of nitroalkene 394 (Scheme 16.77) produces a tetracyclic nitroso acetal 397 with up to six new stereogenic centers in just two steps. Hydrogenolysis reveals a bicyclic amino diol 398, which may react further, for example, forming tetracyclic lactam 399. AU of the six newly formed stereogenic centers may potentially remain in the hydrogenolysis products, such as 398. It is this dramatic increase in complexity that makes the tandem, double-intramolecular nitroalkene cycloaddition so attractive. 

The tandem cycloaddition of nitroalkenes is a very complex process consisting of a number of elementary reactions. Multiple bonds, stereogenic centers, and rings are created. The connection between the starting materials and the final product is often not obvious. To simplify the retrosynthetic analysis, summary charts (e.g.. Figure 16.8) for most of the modes of the tandem cycloaddition of nitroalkenes were provided. Illustrations of how these charts can be used for retrosynthetic analysis (e.g.. Scheme 16.54) were also provided. For the most complex modes, such as double intramolecular cycloadditions, a similar chart would be too complex and of limited utility because of the myriad of theoretically possible tether lengths and placements. Moreover, only a handful of variants have been realized in practice. 

The examples of the tandem cycloadditions of nitroalkenes reviewed here demonstrate a well-developed strategy that can and has been applied for syntheses of many natural... 

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