Titanium-Mediated Addition of Grignard Reagents to Acyl Cyanohydrins: Aminocyclopropane versus 1,4-Diketone Formation

The 1,2-dianion reactivity of the reagent generated from EtMgBr and titanium isopropoxide was illustrated when N-acyl cyanohydrins were used as substrates (>20 examples), giving both aminocyclopropane derivatives and 1,4-dicarbonyl compounds. When the reaction was performed in diethyl ether, 5-hydroxy-1,4-diketones were the main product. Under specific conditions (use of tetrahydrofuran and a bulky carboxylic moiety), the cyclopropane derivatives were obtained in good yields. The observed dichotomy may be explained by a ring-opening of the five-membered titanacycle intermediate followed by a nonselective acyl addition.