Chiral Superbases with Extended Hydrogen Bond Networks

Area of Science:

• Organic Chemistry
• Computational Chemistry

Background:

• Extended hydrogen bond networks enhance basicity by stabilizing conjugate acids.
• 1,8-bis(dimethylamino)naphthalene is a prototype superbase.

Purpose of the Study:

• To investigate the basicity and enantioselectivity of novel chiral superbases.
• To explore the effect of anilinyl substituents on the properties of 1,8-bis(dimethylamino)naphthalene.

Main Methods:

• Density Functional Theory (DFT) methods, specifically PBE1PBE/6-311+G(d,p), were employed.
• Computational analysis of chiral superbases (9-11) with anilinyl substituents.

Main Results:

• Chiral superbases 9-11 exhibit higher basicity in the gas phase but lower basicity in THF solution compared to the parent superbase 1.
• A significant rotational barrier (approx. 20 kcal mol⁻¹) was observed around the C_aryl-C_aryl bond in chiral superbases 9-11.
• Aminonaphthyl substituents increased this rotational barrier by approximately 10 kcal mol⁻¹.
• Predicted enantiomeric excesses (ee's) for deprotonation of propanal ranged from 58% to 95% using chiral bases 9-11.
• Deprotonation of 4-tert-butylcyclohexanone and cyclohexanoxide by base 9 yielded ee's of 23% and 97%, respectively.

Conclusions:

• The designed chiral superbases demonstrate tunable basicity and potential for enantioselective deprotonation.
• These findings highlight the utility of these chiral superbases as catalysts in asymmetric synthesis.