Tandem 1,5-Hydride Shift/6π Electrocyclization of Ketenimines and Carbodiimides Substituted with Cyclic Acetal and Dithioacetal Functions: Experiments and Computations

• Published in: European Journal of Organic Chemistry 2011-04, Vol.2011 (10), p.1896-1913
• Main Authors: Alajarin, Mateo, Bonillo, Baltasar, Ortin, Maria-Mar, Sanchez-Andrada, Pilar, Vidal, Angel
• Format: Article
• Language: English
• Subjects: Chemistry; Cyc­lization; Density functional calculations; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Hydricity; Hydride shift; Ketenimines; Kinetics and mechanisms; Organic chemistry; Preparations and properties; Reaction mechanisms; Reactivity and mechanisms
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201001372

N‐Aryl ketenimines bearing five‐ and six‐membered cyclic acetal functions – such as 1,3‐dioxolane, 1,3‐dithiolane, 1,3‐dioxane, and 1,3‐dithiane systems – at the ortho position of the N‐aryl substituent transform on mild thermal treatment into quinolines, through a tandem sequence consisting of a [1,5]‐H shift followed by a 6π electrocyclic ring closure. Structurally analogous N‐aryl carbodiimides are converted into quinazolines in comparable tandem processes. Similar sequences can be successfully applied to N‐thienyl and N‐pyrazolyl ketenimines. DFT calculations have established a two‐step mechanism for those conversions, consisting of an initial 1,5‐hydride shift and subsequent 6π electrocyclization, and confirm the beneficial effect of the acetal function, which gives hydride character to the migrating hydrogen atom. The capability to promote the H shift depends on the type of acetal function (acetal better than dithioacetal), its ring size (five‐membered better than six‐membered) and the heterocumulenic fragment (ketenimine better than carbodiimide). Changing the benzene ring connecting the acetal and ketenimine functions for a heterocyclic ring has pronounced consequences for the magnitude of the energy barriers. N‐Aryl‐ and ‐heteroaryl ketenimines and carbodiimides ortho‐substituted with acetal functions undergo thermally induced cyclizations to afford spiro‐fused pyridine andpyrimidine rings, respectively. The key step is a 1,5 hydride shift facilitated by the lone pairs at the acetalic heteroatoms.