DIASTEREOSELECTIVE AND REGIOSELECTIVE SINGLET OXYGEN ENE OXYFUNCTIONALIZATION (SCHENCK REACTION) - PHOTOOXYGENATION OF ALLYLIC AMINES AND THEIR ACYL DERIVATIVES

摘要

The photooxygenations of the chiral allylic amine 1a, its ammonium chloride 1b, and the acylated derivatives 1c-f and 1h gave the corresponding regio- and diastereomeric allylic alpha-amino hydroperoxides 2 and 2' through the ene reaction with singlet oxygen. For comparison purposes, also the unfunctionalized chiral alkene 2,4,5,5-tetramethyl-2-hexene (1g) was photooxygenated. While the reactions of the free amine 1a and its ammonium chloride 1b proceeded threo-diastereoselectively, for the acylated allylic amines 1c-f and (Z)-1h, as well as for the chiral alkene 1g, erythro selectivity was observed. The larger the nitrogen-containing moiety, the higher the erythro selectivity; however, for all acylated allylic amines, the stereocontrol was higher than for the alkene 1g. These findings are explained in terms of the formation of diastereomeric perepoxide-like structured exciplexes Ex or bona fide perepoxide D intermediates during the oxyfunctionalization step. With the help of 1,3-allylic strain, the diastereotopic sides of the olefinic plane are differentiated by hindered rotation at the allylic chirality center. The high three selectivities for the functionalized substrates 1a,b are then dictated by attractive interactions between the incipient, negatively charged oxygen atom in the three-Ex and threo-D structures with the amino and ammonium substituents by hydrogen bonding. This makes the relative energy content of the threo structures lower than for the erythro diastereomers. In contrast, the observed erythro selectivities for the acylated allylic amines 1c,f and (Z)-1h and the alkene 1g are best reconciled in terms of the steric repulsion between the terminal oxygen atoms of the three-Ex and threo-D structures and the bulky substituents at the allylic positions. Consequently, the erythro-Ex and erythro-D structures are now energetically favored. In addition, the three-Ex and threo-D structures of the acylated allylic amines are destabilized by the repulsive, electrostatic interactions between the incipient, negatively charged oxygen atoms and the polarized carbonyl functionalities. This manifests itself in the higher erythro selectivity of the acylated allylic amines compared to the alkene 1g, despite the very large tert-butyl group of the latter. Therefore, by the proper choice of the allylic nitrogen functionality, i.e. the free amine versus its acylated derivative, either the three or erythro diastereomer of allylic alpha-amino alcohols can be prepared selectively. [References: 46]