[503-30-0] · C3H6O · Trimethylene Oxide · (MW 58.09)
Alternate Name: oxetane.
Physical Data: bp 50 °C; d 0.893 g cm-3.
Solubility: sol H2O and most common organic solvents.
Form Supplied in: commercially available in 97% purity.
Purification: by distillation.
Trimethylene oxide readily undergoes ring opening with a variety of carbon nucleophiles to give the three-carbon homologated alcohol. Substituted oxetanes undergo analogous reactions. Grignard reagents and alkyllithiums react cleanly, although reduced yields are obtained with secondary Grignard reagents (eq 1).3 Alkyl cuprates,4 alkenyllithium,5 alkenylaluminum,6 alkynyllithium,7 and allyllithium8 reagents have been used to open oxetane. Reaction with ester and amide enolates provides access to 5-hydroxy esters and amides (eq 2)9 and ketone imine salts react with oxetane (eq 3) as well.10 Boron Trifluoride Etherate is frequently used to assist the ring opening. Oxetane reacts with allylsilanes and Titanium(IV) Chloride to give the ring-opened products (eq 4).11
Trimethylene oxide undergoes ring opening with a wide variety of heteroatom nucleophiles. Reaction with Cyanotrimethylsilane gives, after hydrolysis of the isocyanide, 3-aminopropanol (eq 5).12,13 3-Hydroxydimethylsulfonium salts are obtained on reaction with Trifluoromethanesulfonic Acid and Dimethyl Sulfide.14 Phosphonium salts are obtained on reaction with Triphenylphosphine and Trifluoroacetic Acid or triflic acid (eq 6).15 Reaction with phosphine anions gives the 3-hydroxypropylphosphines.16 Trimethylene oxide is readily opened by selenium nucleophiles, such as phenylselenide anion, which gives 3-hydroxypropyl phenyl selenide.17
Reduction with Lithium 4,4´-Di-t-butylbiphenylide (LDDB) gives the 3-lithioalkoxide, which reacts with a wide variety of electrophiles (eq 7).18 A similar opening occurs with the Potassium/18-Crown-6 complex.19
Kevin E. Henegar
The Upjohn Company, Kalamazoo, MI, USA