Chiral Brønsted Acid Catalyzed Enantioselective Dehydrative Nazarov-Type Electrocyclization of Aryl and 2-Thienyl Vinyl Alcohols

Abstract

An efficient chiral Brønsted acid-catalyzed enantioselective dehydrative Nazarov-type electrocyclization (DNE) of electron-rich aryl- and 2-thienyl-β-amino-2-en-1-ols is described. The 4π conrotatory electrocyclization reaction affords access to a wide variety of the corresponding 1 H-indenes and 4 H-cyclopenta[ b]thiophenes in excellent yields of up to 99% and enantiomeric excess (ee) values of up to 99%. Experimental and computational studies based on a proposed intimate contact ion-pair species that is further assisted by hydrogen bonding between the amino group of the substrate cation and chiral catalyst anion provide insight into the observed product enantioselectivities.

A Computational Study of Model Parent Systems and Reported Aza‐(Iso)Nazarov/Aza‐(Iso)Piancatelli Electrocyclic Reactions

“…2‐Carbonylamino‐Nazarov cyclizations using amide derivatives of Vc , catalyzed by Lewis acids, have been described by Ochiatto et al, and these substrates were shown to react similarly to the 2‐alkoxy analogues having the same substitution pattern . Dehydrative Nazarov‐like electrocyclizations of aryl‐ and 2‐thienyl‐vinyl alcohols represented by Vc to afford the corresponding 1 H ‐indenes and 4 H ‐cyclopenta[ b ]thiophenes have been recently described . This reaction was promoted by a chiral enantiopure Brønsted acid catalyst and provided reaction products in high yields and enantiomeric excess.…”

“…This reaction was promoted by a chiral enantiopure Brønsted acid catalyst and provided reaction products in high yields and enantiomeric excess. Computations at the M06‐CPCM/6‐31+G(d,p)//M06‐CPCM/6‐31G(d) level indicated the relevance of intimate contact ion‐pair formation further assisted by hydrogen bonding between the amino group of the aminopentadienyl intermediate and the anion of the chiral catalyst …”

Kinetic Resolution of Tertiary 2‐Alkoxycarboxamido‐Substituted Allylic Alcohols by Chiral Phosphoric Acid Catalyzed Intramolecular Transesterification

“…Our group and Kartika and co‐workers independently reported the asymmetric synthesis of β‐indolyl cyclopentenamides from α‐hydroxy cyclopentenamides by chiral phosphoric acid catalysis (Figure a). On the other hand, Chan and co‐workers reported a dehydrative Nazarov‐type electrocyclization of α‐hydroxy enamides that provides access to chiral 1 H ‐indene derivatives under chiral Brønsted acid catalysis (Figure b). In these examples, chiral‐anion‐paired 2‐amidoallyl cations ( INT A ) were proposed as the key intermediates, in which the chiral center from the starting material is eliminated.…”

Chiral Brønsted Acid and Gold Catalyzed Enantioselective Synthesis of 1,8‐Dihydroindeno[2,1‐b]pyrroles

“…To our knowledge, this approach to chiral induction in functional group transformations involving the substrate class has so far remained unexplored. With this in mind, we were drawn to the potential reactivity of electron‐rich aryl and 2‐thienyl vinyl β ‐amino alcohols (Scheme b) ,. We had previously reported the substrate class to undergo chiral Brønsted acid‐catalyzed asymmetric DNE to give the corresponding 1 H ‐indene and 4 H ‐cyclopenta[ b ]thiophene derivatives.…”