BIMP‐Catalyzed 1,3‐Prototropic Shift for the Highly Enantioselective Synthesis of Conjugated Cyclohexenones

Abstract

A bifunctional iminophosphorane (BIMP)‐catalysed enantioselective synthesis of α,β‐unsaturated cyclohexenones through a facially selective 1,3‐prototropic shift of β,γ‐unsaturated prochiral isomers, under mild reaction conditions and in short reaction times, on a range of structurally diverse substrates, is reported. α,β‐Unsaturated cyclohexenone products primed for downstream derivatisation were obtained in high yields (up to 99 %) and consistently high enantioselectivity (up to 99 % ee). Computational studies into the reaction mechanism and origins of enantioselectivity, including multivariate linear regression of TS energy, were carried out and the obtained data were found to be in good agreement with experimental findings.

Auto Tandem Catalysis: Asymmetric Vinylogous Cycloaddition/Kinetic Resolution Sequence for the Enantioselective Synthesis of Spiro‐Dihydropyranone from Benzylidene Meldrum's Acid

“…The inside mechanism of the first cycle is based on our previous body of work [8] . Based on a study by Dixon and co‐workers, [16d] basic catalyst deprotonates the weakly acidic α‐position of ( S )‐ 3 a to form the intermediate ( S )‐ I . A regioselective reprotonation of the extended enolate ( S )‐ I would then occur preferentially at the γ‐position to afford the product ( S )‐ 4 a .…”

A bifunctional iminophosphorane squaramide catalyzed enantioselective synthesis of hydroquinazolinesviaintramolecular aza-Michael reaction to α,β-unsaturated esters

“…Due to the conformational freedom and the existence of two potential activation modes of the BIMP catalyst, we computed and compared all the possible TSs for the enantio-determining Michael reaction step involving substrate 1ae (see the ESI † for additional details). 32 The most energetically preferred transition structures that lead to either ( R )- or ( S )-product are shown in Scheme 4 . The TS–ModeA–LA1–RA1–R that forms the ( R )-product was found to be favoured by 1.2 kcal mol −1 , which agrees with the experimentally confirmed absolute stereochemical configuration by single crystal X-ray diffraction studies.…”

Extended Enolates: Versatile Intermediates for Asymmetric C‐H Functionalization via Noncovalent Catalysis

“…Very recently, Paton and Dixon reported a bifunctional iminophosphorane C18 ‐catalyzed enantioselective synthesis of α,β‐unsaturated cyclohexanones 113 through a facially selective 1,3‐prototropic shift of β,γ‐unsaturated prochiral isomers 112 (Scheme 30 ). [77] The key and enantioselectivity‐determining step in this downstream derivatization process is the reprotonation at Cγ of a thiourea‐stabilized dienolate intermediate in which the catalyst basic site acts as a proton shuttle.…”