Alkenes pyrrolidine nitrones

Tandem pericyclic reactions are a powerful strategy for construction of complex, polycyclic compounds. In recent years tandem [4 + 2]/[3 + 2] chemistry of nitro-alkenes and nitronates has been developed by Denmark et al. as a general approach to functionalized pyrrolidine-containing structures [118]. Within the subclass of inter [4 -I- 2]/intra [3 + 2] cycloadditions, they have documented the fused mode (/3-tether, Eq. 77), spiro mode (a-tether, Eq. 78), and bridged mode (a-tether, Eq. 79 or /3-tether, Eq. 80) constructions. These are highly stereoselective processes in the presence of Lewis acid such as SnCU and are amenable to asymmetric modification by use of chiral vinyl ethers. Finally, the nitroso acetals are readily transformed, by hydroge-nolysis, into polycyclic, a-hydroxypyrrolidinones, 4-aminocyclohexanones, and cyclo-pentylamines. 

An efficient and straightforward synthesis of isomers of DMDP 36 (2,5-dihy-droxymethyl-3,4-dihydroxypyrrolidine), a known naturally occurring glycosidase inhibitor, has been recently reported. o-Xylose is converted into nitrone 37 in a few steps. Vinylation of 37 gives hydroxyamine 38 which is reduced into the corresponding pyrrolidine with zinc. N-Protection, alkene ozonolysis, and reduction with NaBH4 lead to compound 39. Final deprotection gives 2,5-dideoxy-2,5-imino-L-mannitol (e f-36) (Scheme 14) [92]. 

The cycloadducts have been transformed into pyrrolidines by reductive ring contraction. However, cycloadducts bearing a suitable alkene functionality in the side chain usually undergo [3+2] cycloaddition upon warming to room temperature. Inter- and intramolecular combinations of hetero Diels-AIder reactions with 1,3-dipoIar cycloadditions of the resulting nitrone have been intensively studied, developed and have been recently reviewed by Denmark et al. ... 

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