The invention discloses a synthesis method of substituted isoindoline, which comprises the following steps: reacting Boc-protected isoindolinone with a Grignard reagent or a metal lithium reagent to obtain an intermediate of ketone or hemiacetal, and reducing ketone or hemiacetal to obtain an intermediate of alcohol, finally, conducting hydroxyl activation to form an easily-leaving group, furtherconducting ring closing under the mild condition, so as to obtain substituted isoindoline. The method is simple and convenient to operate, and can realize rapid preparation in laboratories.