A unique organocatalytic kinetic resolution (KR) of nitroallylic acetates has been developed. A variety of racemic nitroallylic acetates (1a-n) were resolved with chiral enamines formed in situ from the reaction of aldehydes and ketones with organocatalyst 2b (2.5 mol-%) and 14c (20 mol-%), respectively, through an interesting S N2′ reaction. The densely functionalized products 3-5 were obtained with high to excellent levels of stereoselectivities (up to >99:1 dr and >99%) in good to high chemical yields. The unreactive starting substrates 1a-n were recovered with good to high optical purity (up to 98%). The scope and generality of the kinetic resolution was expanded to include a wide range of nitroallylic acetates with various aldehydes and ketones as the donor sources. The absolute stereochemistry of the functionalized products and the unreacted substrate were determined. Synthetic application was demonstrated when (S)-citronellal was treated with rac-1a in the presence of 2b to give 12 as a single diastereomer, which was further cyclized to give a tetrasubstituted cyclohexane derivative 13 with excellent stereoselectivity. Transition-state models were proposed to account for the stereochemical bias in the KR process.
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