A systematic survey of azetidine-ring-opening reagent and N-protecting group (see SI) revealed that the model reaction of 2a with cyclohexane carbonyl chloride was catalyzed by 1a to afford 3a in 99% yield with 97% enantiomeric excess (ee) (Figure ). Squaramide catalyst 1a was then shown to induce high enantioselectivity in the opening of azetidines 2 bearing a wide variety of 3-substituents. Highly enantioenriched ring-opened products 3 were obtained from substrates bearing a variety of aromatic and heteroaromatic substituents (3a-3k), including ones with Lewis basic functional groups such as pyrazoyl and 2-pyridyl (3i and 3k). Azetidines bearing other Csp 2 , Csp and Csp 3 3substituents (3l-3p), as well as a variety of heteroatomcentered substituents (3q-3u) were also identified as excellent substrates. The result obtained with the fluorine-substituted substate (3u) is especially notable (91% ee, 94% yield). Limitations to the scope were observed with azetidines bearing small alkyl substituents (e.g. 3-Me) and vinyl group led to an attenuation in enantioselectivity. Also, ring-opening of 3,3-disubstituted azetidines afforded the desired amide products only with low yields as a racemic mixture. The enantioselectivity imparted by 1a in reactions of 2a was recapitulated across a set of acyl chlorides possessing steric profiles ranging from acetyl to pivaloyl (3v-3w, Figure ). The reaction also proceeded successfully with functionally rich acid chlorides derived from glycine and isonipecotic acid (3x and 3y). N-Phenyl azetidine 2v underwent reaction with allyl and benzyl halides affording tertiary amine products 3z-3ab with 90-91% ee, further illustrating the exceptionally broad scope of reactions promoted successfully by 1a.