An enantioselective total synthesis of the naturally occurring anticancer agent (−)-laulimalide is described. The synthesis is characterized by extensive use of new reaction methodologies based on catalytic asymmetric acyl halide−aldehyde cyclocondensation (AAC) reactions and transformations of the derived enantioenriched β-lactones. The synthesis also incorporates a unique allenylstannane glycal acetate alkylation and chemoselective ring-closing metathesis reaction.