Spiroaminals – Crystal Structure and Computational Investigation of Conformational Preferences and Tautomerization Reactions. Issue 25 (21st July 2014)

• Record Type: Journal Article
• Authors: Loerbroks, Claudia; Böker, Birte; Cordes, Jens; Barrett, Anthony G. M.; Thiel, Walter
• Is Part Of: European journal of organic chemistry. Issue 25(2014)
• Page Start: 5476
• Page End: 5486
• Publication Date: 2014-07-21
• Subjects: Spiro compounds -- Spiroaminals -- Nitrogen heterocycles -- Tautomerism -- Computational chemistry -- Conformation analysis; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201402576
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: We report the first X‐ray structure of a spiroaminal hydrochloride. The chiral spiroaminal crystallizes as a racemic hydrochloride in the monoclinic space group P 21 / n and adopts the thermodynamically most stable conformation. Density functional calculations on several spiroaminals were used to establish correlations between trends in conformational energies, steric repulsions, and anomeric effects and to reveal the mechanism of the ring‐opening tautomerization reaction. In the unsubstituted and backbone‐substituted spiroaminals, the aminal tautomer is thermodynamically preferred. N ‐Substituted spiroaminals favor the amine/imine form for steric reasons, except for those with bridging N, N′ groups. The tautomerization from the aminal to the amine/imine is endergonic and kinetically hindered in the neutral species but quite facile after protonation. Anomeric effects lower the barriers but are less important than steric factors for relative energies. Abstract : A joint experimental and computational study reveals the driving forces in the equilibria of spiroaminals. Although thermodynamic and electronic factors such as the anomeric effect lower the energy of the spiroaminal form, steric repulsion in combination with kinetic barriers favor the amine/imine structure. DFT calculations elucidate the mechanism of tautomerization.