Electrophilic Amination of Ketone Enolates

Variation of 2-alkyl substituent exerted an effect upon diastereoselectivity. The best diastereoselection was obtained when incorporating a 2-ethyl substituent for acyl dithiane oxides (Table 3.6). The diastereoselectivity and the sense of induced stereochemistry can be rationalized on the basis of a simple chelation control model. 

Both enantiomers of the 2-ethyl- 1,3-dithiane-l -oxide starting material may be prepared selectively in up to optical purity. The aminated products are of interest as potential synthons for chiral synthesis of both enantiomers of a-amino acids. 

Deprotonation of the imine 86 (R1 = H, R2 = Bn, entry 1) with LDA (1 equiv.) at -35 °C afforded an azaenolate which was diastereoselectively attacked at -78 °C by the electrophilic reagent DBAD (1.5 equiv.). After 3 min the reaction was quenched with a 10 % aqueous NH4C1 solution. After classical work-up and flash chromatography, the aminated product 87 was obtained in 66% yield as a 7 3 mixture of diastereomers 87a 87b (method A). The major diastereomer was characterized by NMR spectroscopy (DMSO-d6,100 °C). Due to an imine-enamine tautomer-ism, 86 could be aminated without previous deprotonation 86 reacted with DBAD (1.4 equiv.) in THF at 0 °C for 1 h. After evaporation of the solvent and flash chromatography, 87a and 87b were isolated in 72 % yield with a diastereomeric ratio of 75 25 (method B). 

Analogous reactions were performed with DTBAD (entries 2, 3, 4, and 5). The absolute configuration of the created stereogenic center at the 2 position turned to be 

P-Aminotetralins 88 were obtained after reduction of the imine functionality, reductive removal of the chiral auxiliary and deprotection and hydrogenolysis of the hydrazino group. The ee of the p-aminotetralins were determined by HPLC analysis after derivatisation of the amines with (R)-phenylethylisocyanate. 

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The diastereoselective electrophilic amination of ketone enolates in 2-substituted 2-acyl-1,3-dithiane 1-oxides 19 with di-/m-butyl azodicarboxylate (DBAD) was reported recently21. The un/i-isomcr, anti-19, led to the major isomer anti-20, while. vyn-19 gave predominantly. 9171-20. 

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