TiCl₄ Promoted Formal [3 + 3] Cycloaddition of Cyclopropane 1,1-Diesters with Azides: Synthesis of Highly Functionalized Triazinines and Azetidines

Abstract

A TiCl4 promoted formal [3 + 3] cycloaddition of cyclopropane 1,1-diesters with azides has been developed for the synthesis of highly functionalized triazinines. Both stoichiometric and substoichiometric versions of this reaction were accomplished dependent on the choice of solvent. It is noteworthy that the corresponding products could be easily converted to biologically important azetidines by simple thermolysis.

A Stereoselective [3+1] Ring Expansion for the Synthesis of Highly Substituted Methylene Azetidines

“…The [2+ +2] reactions have been well-explored [6] while the corresponding [3+ +1] reactions are less common, although N-atom transfer from an oxaziridine to ad onor-acceptor cyclopropane was recently disclosed, as well as two examples of nucleophilic aziridine opening with sulfoxonium or nitrogen ylides. [7,8] Despite these advances,s tereoselective access to highly substituted, densely functionalized azetidines remains difficult. We hypothesized that an umpolung [3+ +1] approach could address these challenges by engaging strained aziridines with electrophilic one-carbon sources to trigger ar ing-opening, ring-closing cascade to yield the azetidines (Scheme 1C).…”

A Stereoselective [3+1] Ring Expansion for the Synthesis of Highly Substituted Methylene Azetidines

“…[4] Other strategies accomplish ring and stereocenter construction simultaneously by uniting two fragments;however, this often leads to difficulty in establishing the correct regio-and stereochemistry (Scheme 1B). [7,8] Despite these advances,s tereoselective access to highly substituted, densely functionalized azetidines remains difficult. [7,8] Despite these advances,s tereoselective access to highly substituted, densely functionalized azetidines remains difficult.…”

Facile Synthesis of Azetidine Nitrones and Diastereoselective Conversion into Densely Substituted Azetidines

“…[5,6] Examples of strategies involving b-lactam reductions, photo-or formal [2+ +2] cycloadditions,r earrangements,a nd CÀHbond functionalizations have also been reported. [7][8][9][10] A common limitation of these approaches is that they often require functional-group installation prior to azetidine formation. [11,12] We wondered whether simple access to azetidine nitrones could provide an opportunity for the development of simple functionalization strategies to access highly substituted examples of these strained ring systems from ac ommon unsaturated intermediate.…”