Modular Synthesis of Spiroisochromans with Spiro Quaternary Carbon Centers Via TBAT-Promoted Multicomponent Cascade...

Area of Science:

• Organic Chemistry
• Synthetic Chemistry

Background:

• Constructing spiroisochroman frameworks with spiro quaternary carbon centers via multicomponent cascade reactions is synthetically challenging.
• Existing methods often struggle with the synthesis of complex spiro architectures.

Purpose of the Study:

• To develop a facile and efficient one-pot synthetic strategy for spiroisochroman scaffolds.
• To explore the reactivity of oxazolines, aryne precursors, and ketone derivatives in a novel cascade reaction.

Main Methods:

• A tetrabutylammonium triphenyldifluorosilicate-initiated cascade reaction.
• Utilizing oxazolines, aryne precursors, and ketone derivatives.
• Investigating aryne-triggered generation of *ortho*-quinonoid intermediates and subsequent [4 + 2] cycloaddition.

Main Results:

• A facile one-pot synthesis of structurally challenging spiroisochroman scaffolds, including dispiro architectures and spiroisochromanone derivatives.
• Discovery of a substituent-controlled divergent pathway yielding phthalide derivatives.
• Demonstration of broad applicability and operational simplicity.

Conclusions:

• The developed cascade strategy provides a powerful tool for accessing complex spiroisochroman and phthalide derivatives.
• The reaction's operational simplicity, broad scope, and divergent reactivity underscore its synthetic utility.
• This method overcomes significant synthetic challenges in constructing spiro quaternary carbon centers.