The synthesis of (+)-licochalcone E (1) was accomplished for the first time in 13 steps from aryl bromide (6) with 8% overall yield. Palladium-catalyzed Negishi-Reformatsky coupling reaction of compound 6 with ethyl 2-(tributylstannyl)acetate provided the aryl acetic ester (5), which was converted to aryl acetamide (4) via mixed anhydride formation. Chiral auxiliary-mediated methylation of the (S)-4-benzyl-2-oxazolidinone-derived aryl acetamide (4) provided the key asymmetric benzylic methyl group in compound 1.