An efficient approach to the multigram preparation of 3-azabicyclo[3.1.1]alkanes based on the intramolecular imide formation in the properly functionalized cyclobutane derivative is described. Diastereoselective Strecker reaction of readily accessible 3-oxocyclobutanecarboxylate was used to mount the required functional groups onto the cyclobutane ring with proper stereochemistry. After selective partial hydrolysis of the nitrile group, the key cyclization into the target bicyclic imide proceeded smoothly upon action of a base (t-BuOK). After catalytic debenzylation, 1amino-3-azabicyclo[3.1.1]heptane-2,4-dione, a key building block and intermediate in this study, was obtained on up to 30 g scale. The utility of the proposed protocols was demonstrated by multigram preparation of monoprotected bicyclic diaminesvaluable building blocks for early drug discovery programs. Furthermore, 10 bridged analogs of Thalidomide, a known anticancer drug and an important component of proteolysistargeting chimeras (PROTACs), was prepared on a gram scale.