Aziridinomitosenes by anionic cyclization: deuterium as a removable blocking group

Area of Science:

• Organic Chemistry
• Synthetic Methodology
• Isotope Effects

Background:

• Intramolecular Michael additions are crucial for constructing complex polycyclic systems.
• Understanding reaction mechanisms, including kinetic isotope effects, aids in optimizing synthetic routes.
• The development of novel synthetic pathways for biologically relevant molecules is an ongoing challenge.

Purpose of the Study:

• To investigate the reaction of organostannanes with methyllithium.
• To explore the mechanistic pathways, including potential kinetic deuterium isotope effects.
• To synthesize novel aziridinomitosene derivatives.

Main Methods:

• Treatment of organostannane precursors (11a and 11b) with methyllithium.
• Utilizing a deuterated analogue (11b) to probe reaction mechanisms via kinetic deuterium isotope effects.
• Quenching reaction mixtures with phenylselenenyl chloride to derivatize products.

Main Results:

• Methyllithium treatment of 11a yielded destannylated product 12 and a minor tetracyclic product.
• Deuterated analogue 11b predominantly formed tetracyclic product 18, indicating a significant kinetic deuterium isotope effect.
• Phenylselenenyl chloride quenched product 17 to form aziridinomitosene 19 in 80% yield, with further conversions demonstrated.

Conclusions:

• The study demonstrates a synthetic route to tetracyclic compounds via intramolecular Michael addition.
• Kinetic deuterium isotope effects provide mechanistic insights, suppressing undesired side reactions.
• The successful synthesis of aziridinomitosene derivatives highlights the utility of this methodology.