Synthesis of 1,3-Aminoalcohols and Spirocyclic Azetidines via Tandem Hydroxymethylation and Aminomethylation Reaction of β-Keto Phosphonates with -Nosyl--(2-bromoethyl)hydroxylamine.

An unprecedented tandem α-hydroxymethylation and α-aminomethylation reaction of aromatic cyclic β-keto phosphonates with -nosyl--(2-bromoethyl)hydroxylamine in the presence of DBU base has been developed, affording a range of 1,3-aminoalcohols in good yields. The resultant products could be flexibly transformed into the spirocyclic and bispirocyclic azetidines via one step of Mitsunobu reaction. Mechanistic study revealed that hydroxylamine in situ generated the formaldehyde and nosylamide, which in turn triggered the sequential Horner-Wadsworth-Emmons, Michael, and aldol reactions.