Stereoselective synthesis of 2,4,5-trisubstituted piperidines via radical cyclization.

A novel approach to 2,4,5-trisubstituted piperidines is reported, involving the 6-exo cyclization of stabilized radicals onto α,β-unsaturated esters. Only two of the four possible diastereoisomers are observed, with diastereomeric ratios ranging from 3:2 to 40:1 when the radical stabilizing group is vinyl or phenyl. Cyclization of a (triethylsilyl)vinyl-stabilized radical gives the corresponding piperidine radical as a single diastereoisomer that may either be trapped by tributyltin hydride to afford the 2,4,5-trisubstituted piperidine or undergo a second 5-endo cyclization onto the (triethylsilyl)vinyl substituent to produce the 3,5,7-trisubstituted octahydro[2]pyrindene as a single diastereoisomer.

The remarkable cis effect in the ene reactions of nitrosocarbonyl intermediates.

Nitrosocarbonyls are fleeting and highly reactive intermediates that undergo ene reactions in a two-step fashion. The addition steps are rate and product determining and lead to polarized diradicals that readily enter the H-abstraction step yielding the ene products. The addition TSs are reached early, and the stabilizing CH.

Variable Markovnikov orientation and "cis effect" in ene reactions of nitrosocarbonyl intermediates.

Nitrosocarbonyl intermediates, generated at room temperature by the mild oxidation of nitrile oxides, undergo clean ene reactions with trisubstituted olefins. Allylic hydrogens on the more congested side of the alkene are exclusively abstracted (the "cis effect"), thus resembling singlet oxygen behavior. Nitrosocarbonyl benzene follows a Markovnikov orientation and abstracts preferentially the twix hydrogens over the lone ones.

Photochemical generation of nitrosocarbonyl intermediates on solid phase: synthons toward hetero Diels-Alder and Ene adducts through photocleavage.

The synthesis of 1,2,4-oxadiazole-4-oxides on polystyrenic solid phase docked at the position 3 of the heterocyclic ring has been performed through the cycloaddition of stable supported nitrile oxides to amidoximes. The photochemical cycloreversion of these heterocycles afforded the free nitrosocarbonyl intermediates that were trapped by suitable dienes or enes. The method is proposed as a clean and environmental friendly approach to the fleeting nitrosocarbonyl intermediates, which afford valuable adducts for various synthetic applications.