Abstract Background Spiroketals and the corresponding aza-spiroketals are the structural features found in a number of bioactive natural products, and in compounds possessing photochromic properties for use in the area of photochemical erasable memory, self-development photography, actinometry, displays, filters, lenses of variable optical density, and photomechanical biomaterials etc. And (1 R ,8a S )-1-hydroxyindolizidine ( 3 ) has been postulated to be a biosynthetic precursor of hydroxylated indolizidines such as (+)-lentiginosine 1 , (-)-2-epilentiginosine 2 and (-)-swainsonine, which are potentially useful antimetastasis drugs for the treatment of cancer. In continuation of a project aimed at the development of enantiomeric malimide-based synthetic methodology, we now report a divergent, concise and highly diastereoselective approach for the asymmetric syntheses of an aza-spiropyran derivative 7 and (1 S ,8a R )-1-hydroxyindolizidine ( ent- 3 ). Results The synthesis of aza-spiropyran 7 started from the Grignard addition of malimide 4 . Treatment of the THP-protected 4-hydroxybutyl magnesium bromide with malimide 4 at -20°C afforded N , O -acetal 5a as an epimeric mixture in a combined yield of 89%. Subjection of the diastereomeric mixture of N , O -acetal 5a to acidic conditions for 0.5 h resulted in the formation of the desired functionalized aza-spiropyran 7 as a single diastereomer in quantitative yield. The stereochemistry of the aza-spiropyran 7 was determined by NOESY experiment. For the synthesis of ent - 3 , aza-spiropyran 7 , or more conveniently, N , O -acetal 5a , was converted to lactam 6a under standard reductive dehydroxylation conditions in 78% or 77% yield. Reduction of lactam 6a with borane-dimethylsulfide provided pyrrolidine 8 in 95% yield. Compound 8 was then converted to 1-hydroxyindolizidine ent - 3 via a four-step procedure, namely, N -debenzylation/ O -mesylation/Boc-cleavage/cyclization, and O -debenzylation. Alternatively, amino alcohol 8 was mesylated and the resultant mesylate 12 was subjected to hydrogenolytic conditions, which gave (1 S ,8a R )-1-hydroxyindolizidine ( ent - 3 ) in 60% overall yield from 8 . Conclusion By the reaction of functionalized Grignard reagent with protected ( S )-malimide, either aza-spiropyran or (1 S ,8a R )-1-hydroxyindolizidine skeleton could be constructed in a concise and selective manner. The results presented herein constitute an important extension of our malimide-based synthetic methodology.