AbstractHairpin oligodeoxynucleotides incorporating a (2R,3S)‐4‐(methoxyamino)butane‐1,2,3‐triol residue in the middle of the double‐helical stem and opposite to either one of the canonical nucleobases or an abasic 2‐(hydroxymethyl)tetrahydrofuran‐3‐ol spacer were synthesized. Under mildly acidic conditions, aromatic aldehydes reacted reversibly with these oligonucleotides, converting the (2R,3S)‐4‐(methoxyamino)butane‐1,2,3‐triol unit into a 2‐aryl‐N‐methoxy‐1,3‐oxazinane nucleoside analogue. The equilibrium of this reaction was found to be dependent on both the aldehyde and the nucleobase opposite to the modified residue. 9‐Formyl‐9‐deazaadenine, combining a large stacking surface with an array of hydrogen bond donors and acceptors, showed the highest affinity as well as selectivity consistent with the rules of Watson‐Crick base pairing. 5‐Formyluracil or indole‐3‐carbaldehyde, lacking in either stacking or hydrogen bonding ability, were incorporated with a much lower affinity and selectivity.