In cells, a vast number of membrane lipids are formed by the enzymatic O-acylation of polar head groups with acylating agents such as fatty acyl-CoAs. Although such ester-containing lipids appear to be a requirement for life on earth, it is unclear if similar types of lipids could have spontaneously formed in the absence of enzymatic machinery at the origin of life. There are few examples of enzyme-free esterification of amphiphiles in water and none that can occur in water at physiological pH using biochemically relevant acylating agents. Here we report the unexpected chemoselective O-acylation of 1,2-amino alcohol amphiphiles in water directed by Cu(II) and several other transition metal ions. In buffers containing Cu(II) ions, mixing biological 1,2-amino alcohol amphiphiles such as sphingosylphosphorylcholine with biochemically relevant acylating agents, namely, acyl adenylates and acyl-CoAs, leads to the formation of the O-acylation product with high selectivity. The resulting O-acylated sphingolipids self-assemble into vesicles with markedly different biophysical properties than those formed from their N-acyl counterparts. We also demonstrate that Cu(II) can direct the O-acylation of alternative 1,2-amino alcohols, including prebiotically relevant 1,2-amino alcohol amphiphiles, suggesting that simple mechanisms for aqueous esterification may have been prevalent on earth before the evolution of enzymes.