Titanium isopropoxide-mediated cis -selective synthesis of 3,4-substituted butyrolactones from CO 2

We report a Ti(OiPr) -mediated multicomponent reaction, which produces 3,4-substituted -δ-lactones from alkyl magnesium chloride, benzaldehyde and CO . The key intermediate, titanacyclopropane, is formed from Ti(OiPr) and a Grignard reagent, which enables 1,2-dinucleophilic reactivity that is used to insert carbon dioxide and an aldehyde. An alternative reaction route is also described where a primary alkene is used to create the titanacyclopropane. A computational analysis of the elementary steps shows that the carbon dioxide and the aldehyde insertion proceeds through an inner-sphere mechanism. A variety of -butyrolactones can be synthesized with up to 7 : 1 diastereoselectivity and 77% yield.