Chiral phosphoric acid-catalyzed enantioselective construction of structurally diverse benzothiazolopyrimidines

Abstract

Chiral phosphoric acid catalyzed the formal [4+2]-cycloaddition of 2-benzothiazolimines with enecarbamates to provide benzothiazolopyrimidines with up to 99% yield and >99% ee.

Catalytic Asymmetric Aza‐Diels‐Alder Reaction: Pivotal Milestones and Recent Applications to Synthesis of Nitrogen‐Containing Heterocycles

“…A proper combination of the suitable aza‐DAR category and correct catalyst choice creates amazing opportunities for facile asymmetric construction of various nitrogen heterocycles such as hydrogenated pyridine, diazine, oxazine and oxadiazine derivatives, various tetrahydroquinolines, and numerous annulated polycyclic scaffolds which incorporate these structural motifs. In some cases, theoretical calculations based on density functional theory (DFT) and accurate quantum mechanical methods enable predicting relative energies of alternative transition states and consequently reactivity, regio‐ and stereoselectivity of enantioselective aza DAR (for detailes refer to [127,129,245,253,282,283,310] ).…”

“…Quite recently, Masson et al [283] . found that Brønsted acid catalysis ensuring LUMO lowering activation of the electron deficient diene component is applicable to the IED aza‐DAR of nucleophilic alkenes with 1,3‐diazadienes.…”

Enamides and dienamides in phosphoric acid-catalysed enantioselective cycloadditions for the synthesis of chiral amines

“…Based on the work of Enders et al, we found that 2benzothiazolimines 35 were useful hetero-2-azadienes in the phosphoric acid catalysed asymmetric IED aza-DA reaction with enecarbamates. 36 The more bulky TRIP phosphoric acid catalyst (S)-3d proved to be the most effective, delivering tri-substituted trans-cis benzothiazolopyrimidines 44 with excellent diastereoand enantioselectivity albeit with moderate yields due to catalyst deactivation with the basic isothiourea group of 44. After extensive optimisation studies, we found that the cycloaddition proceeded smoothly at 50 °C when 3 equiv.…”

Diastereo‐ and Enantioselective Mannich/Cyclization Cascade Reaction Access to Chiral Benzothiazolopyrimidine Derivatives

“…Due to the attractive features of the parent units, a multitude of elegant approaches have been developed to the formation of these backbones [3] . Nevertheless, asymmetric catalytic synthesis of the chiral scaffolds has been only limited to few reports [4–7] . Recently, Enders and co‐workers reported an NHC‐catalyzed Mannich/lactamization cascade reaction to build benzothiazolopyrimidines in up to 99 % ee with 20:1 d.r.…”

“…And then, Masson and co‐workers disclosed [4+2] cycloaddition to construct these motifs using chiral phosphoric acid from 2‐benzothiazolimines and enecarbamates (eq. 2) [5] . Later, Song and co‐workers developed mild asymmetric organocatalytic Mannich/cyclization reaction of azlactones to form these heterocycles (eq.…”