Titanium isopropoxide-mediated cis-selective synthesis of 3,4-substituted butyrolactones from CO2

Aleksi Sahari; Cuong Dat Do; Jere K Mannisto; Emanuele Antico; Angelo Amaratunga; Kathrin H Hopmann; Timo Repo

doi:10.1039/d2cc00446a

Titanium isopropoxide-mediated cis-selective synthesis of 3,4-substituted butyrolactones from CO₂

Chem Commun (Camb). 2022 Mar 1;58(18):3027-3030. doi: 10.1039/d2cc00446a.

Authors

Aleksi Sahari¹, Cuong Dat Do², Jere K Mannisto¹, Emanuele Antico¹, Angelo Amaratunga¹, Kathrin H Hopmann³, Timo Repo¹

Affiliations

¹ Department of Chemistry, University of Helsinki, FI-00014 University of Helsinki, Finland. timo.repo@helsinki.fi.
² Hylleraas Center for Quantum Molecular Sciences, Department of Chemistry, UiT The Arctic University of Norway, 9037 Tromsø, Norway.
³ Department of Chemistry, UiT The Arctic University of Norway, 9037 Tromsø, Norway. kathrin.hopmann@uit.no.

PMID: 35156667
DOI: 10.1039/d2cc00446a

Abstract

We report a Ti(OiPr)₄-mediated multicomponent reaction, which produces 3,4-substituted cis-δ-lactones from alkyl magnesium chloride, benzaldehyde and CO₂. The key intermediate, titanacyclopropane, is formed in situ from Ti(OiPr)₄ 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 cis-butyrolactones can be synthesized with up to 7 : 1 diastereoselectivity and 77% yield.