Cycloadditions to 1-azetines and 1-azetin-4-ones

Luheshi, A-BN

Abstract

1-Azetines (1) have until recently been unknown. Prepared for the first time in 1967, they since have met with little interest. The azetine system is a thermolabile one, as to be expected from a strained four-membered ring incorporating a C=N bond.
1,3-Dipolar cycloadditions and [4+2] cycloadditions to the C=N bond of 1-azetines would yield bi-cyclic systems of related structure to the beta-lactam nucleus of beta-lactam antibitics.
Thus, three 1-azetine systems (2-4) were prepared by alkylation of their precursor azetidinones and thioazetidinones.
The ability of these systems to enter into cycloaddition reactions with a variety of 1,3-dipoles and dienes was investigated.
Nitrile oxides (5) and nitrile ylides (7) were found to add smoothly to the 1-azetine systems to yield the bicyclic adducts (6) and (8) respectively.
Nitrile imines (9) also add to 1-azetines in a similar fashion to yield the bi-cyclic adduct (10). In some cases, however, these adducts were found to undergo a rearrangement reaction to the bi-cyclic triazoles (11).
Attempted [4+2] cycloadditions using electron rich and electron deficient dienes to 1-azetines were unsuccesful.
In an extension of this work, addition of 1,3-dipoles to l-azetin-4-one (12) was also attempted, in a bid to establish a new route to the highly sought after beta-lactam antibiotics. Unfortunately, azetinone (12) was found to be unreactive towards both nitrile oxides and imines.
This lack of reactivity of azetinone (12) is believed to be due to steric hinderance by the geminal ¿-butyl groups. Hence, several attempts were made to synthesise an azetinone species free of these constraints were made. This work remains incomplete, and is expected to attract further research.
Finally, some work was done to investigate the effectiveness of aryl iminophosphoranes (13) as precursors to a variety of heterocyclic systems, including 1,3-benzoxazoles, 1,4- benzoxazines, and benzodiazepines.

Citation

Luheshi, A. Cycloadditions to 1-azetines and 1-azetin-4-ones. (Thesis). University of Salford

• Thesis Type: Thesis
• Deposit Date: Sep 8, 2021
• Publicly Available Date: Sep 8, 2021
• Publisher URL: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.327973
• Related Public URLs: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.327973
• Award Date: Nov 1, 1988