Pyrrolidine 1-nitro-1-alkene

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. 

The cation fragment nature exerts negligible impact on selectivity of the Michael reactions that involve enamine intermediates and commonly the stereochemical outcome remains high. Indeed, pyrrolidine derivatives (Figure 22.6) containing pyridinium 87a,b [98], isoquinolinium 88a,b [99], 1,2,3-triazolium 89a,b [100], benzimidazolium 90 [101], and linear 91 [102] or cyclic 92 [103] quaternary ammonium cations in combination with various anions proved efficient catalysts of asymmetric additions of carbonyl compounds to a-nitro alkenes. Desymmetriza-tion of prochiral 4-substituted cyclohexanones can be achieved by analogy [101]. The reaction efficacy was similar under neat conditions in the presence of acidic additives (catalysts 87, 89, 90, 91) or in the IL medium (commonly in [bmim]BF4) (catalysts 88a,b, 92). 

Secondary amines can be added to certain nonactivated alkenes if palladium(II) complexes are used as catalysts The complexation lowers the electron density of the double bond, facilitating nucleophilic attack. Markovnikov orientation is observed and the addition is anti An intramolecular addition to an alkyne unit in the presence of a palladium compound, generated a tetrahydropyridine, and a related addition to an allene is known.Amines add to allenes in the presence of a catalytic amount of CuBr " or palladium compounds.Molybdenum complexes have also been used in the addition of aniline to alkenes. Reduction of nitro compounds in the presence of rhodium catalysts, in the presence of alkenes, CO and H2, leads to an amine unit adding to the alkene moiety. An intramolecular addition of an amine unit to an alkene to form a pyrrolidine was reported using a lanthanide reagent. 

A pyrrolidine-thiourea organocatalyst (69) facilitates Michael addition of cyclohexanone to both aryl and alkyl nitroalkenes with up to 98% de and ee 202 The bifunctional catalyst (69) can doubly hydrogen bond to the nitro group, leaving the chiral heterocycles positioned for cyclohexyl enamine formation over one face of the alkene. 

The 1,3-dipolar cycloaddition reaction of non-stabilized azomethine ylides, derived from A-alkyl-cf-amino acids, with 3-nitro-2-trifluoro(trichloro)methyl-2//-chromenes produced l-benzopyrano[3,4-c]pyrrolidines in good yields." AgOAc-catalysed asymmetric 3 + 2-cycloaddition reactions of azomethine ylides with e-deficient alkenes yielded enr/o-adducts with up to 99% ee. New chiral ferrocenyl P,N-ligands possessing a benzoxazole ring as the Af-donor (35) are effective asymmetric catalysts... 

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