A substrate-based methodology that allows the regioselective control of the catalytic aminohydroxylation reaction

Analogous to the Sharpless osmium-catalyzed asymmetric dihydroxylation (AD) reaction, structure I is proposed as the catalytically active species for the asymmetric aminohydroxylation (AA) reaction. Based on this model, the regiochemistry of the reaction can be inferred from the catalyst-substrate complex and is termed either mode A or B (Figure 1). In an effort to control the regiochemical outcome of the AA reaction, steric, electronic, and substrate-catalyst shape complimentarity were investigated. It was determined that each of these interactions has a modest influence on controlling the regiochemistry of the reaction (Table 1), however, the combination of these factors can greatly control the regioselectivity of the reaction (Tables 2 and 3). Thus, olefin 10 showed greater than a 20:1 preference when both steric and substrate catalyst shape complimentarity reinforced each other. Furthermore, with α, β-unsaturated carboxylates, the aggregate effect of steric, electronic, and substrate-catalyst shape complimentarity not only increased regioselectivity, but it also reversed AA regioselectivity. Considering the natural abundance of vicinal amino alcohols/amino acids and the effectiveness of the Sharpless AA reaction, substrate-based regioselective control should further increase the synthetic utility of this important process.