Metalated Nitriles: Stereodivergent Cation-Controlled Cyclizations1.

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Stereoselective Synthesis

Background:

• Cyclization reactions are fundamental in synthesizing complex cyclic molecules.
• Controlling stereochemistry in cyclizations remains a key challenge in organic synthesis.

Purpose of the Study:

• To develop a stereodivergent cyclization strategy for gamma-hydroxy cyclohexanecarbonitriles.
• To investigate the role of the cation in controlling the stereochemical outcome of cyclization.

Main Methods:

• Deprotonation of gamma-hydroxy cyclohexanecarbonitriles using different alkylmetal bases (e.g., i-PrMgBr, BuLi).
• Analysis of cyclization products using stereochemical and mechanistic studies.

Main Results:

• Using i-PrMgBr leads to C-magnesiated nitriles that undergo stereoelectronic control, yielding cis-fused products.
• Using BuLi results in sterically controlled electrophilic attack, producing trans-fused products.
• Demonstrated versatility in synthesizing cis- and trans-hydrindanes, decalins, and bicyclo[5.4.0]undecanes.

Conclusions:

• The choice of cation in alkylmetal bases is a simple yet powerful tool for controlling stereochemistry in these cyclizations.
• The study reveals crucial geometric requirements for intramolecular S(N)2 and S(N)2' displacements.