Scheme 3. Substrate scope of the Mannich reaction of 5 to α-amido sulfone 3. Reactions were performed with 5 (0.1 mmol), 3 (0.12 mmol), KF (0.3 mmol), and (R)-1b (10 mol%) in o-xylene (1.5 mL) at 25 °C. The yield was determined after chromatographic purification, and the ee value was determined by HPLC analysis using a chiral stationary phase. Diastereomeric ratio was determined by 1H NMR.
To demonstrate the scalability of the process and the application potential of the resulting chiral Mannich adducts, several useful transformations were devised (Schemes 4 and 5). A gram-scale reaction between ketone 2a and α-amido sulfone 3a furnished Mannich product 4a without compromising the excellent yield and stereoselectivity. The deprotection of the …show more content…
Initially, complex I is formed by the complexation of KF with catalyst, which then cordinates with α-amidosulfone. Subsequently, the elimination of the sulfinate group from α-amidosulfone affords an imine activated through hydrogen bonding as dictated in complex II. The subsequent coordination of potassium enolate (generated in situ from cyclic ketones with KF) to the catalyst (complex III) was followed by its addition to the imine to provide the enantio- and diastereo-enriched adducts (up to 99% ee and up to >20:1 d.r. (anti:syn)). As shown in complex III, in a confined space, catalytic sites activate both the reacting partners (imine and enolate) simultaneously and keep them in enforced proximity, thus enhancing the reactivity and efficiently transferring the stereochemical information. Gratifyingly, all the proposed intermediates were observed by electrospray ionization high-resolution mass spectroscopy (ESI-HRMS) (positive-ion mode). The signals at m/z 1228.8168, 1433.9260, 1451.9171, and 1636.9672 correspond to [I – F-], [II – PhSO2-], and [III + H+], …show more content…
(anti:syn). The cation-binding catalysis in a densely confined chiral space in situ formed by the incorporation of potassium salt is the key to this successful catalysis. Like enzymes, in a confined space, catalytic sites activate both reacting partners (imine and enolate) simultaneously and keep them in a close proximity, thus enhancing the reactivity and efficiently transferring the stereochemical information. The extension of this strategy to the synthesis of quaternary carbon in an acyclic system and further application of our cooperative cation binding catalysis concept for the discovery of new challenging organic transformations is currently underway in our
To demonstrate the scalability of the process and the application potential of the resulting chiral Mannich adducts, several useful transformations were devised (Schemes 4 and 5). A gram-scale reaction between ketone 2a and α-amido sulfone 3a furnished Mannich product 4a without compromising the excellent yield and stereoselectivity. The deprotection of the …show more content…
Initially, complex I is formed by the complexation of KF with catalyst, which then cordinates with α-amidosulfone. Subsequently, the elimination of the sulfinate group from α-amidosulfone affords an imine activated through hydrogen bonding as dictated in complex II. The subsequent coordination of potassium enolate (generated in situ from cyclic ketones with KF) to the catalyst (complex III) was followed by its addition to the imine to provide the enantio- and diastereo-enriched adducts (up to 99% ee and up to >20:1 d.r. (anti:syn)). As shown in complex III, in a confined space, catalytic sites activate both the reacting partners (imine and enolate) simultaneously and keep them in enforced proximity, thus enhancing the reactivity and efficiently transferring the stereochemical information. Gratifyingly, all the proposed intermediates were observed by electrospray ionization high-resolution mass spectroscopy (ESI-HRMS) (positive-ion mode). The signals at m/z 1228.8168, 1433.9260, 1451.9171, and 1636.9672 correspond to [I – F-], [II – PhSO2-], and [III + H+], …show more content…
(anti:syn). The cation-binding catalysis in a densely confined chiral space in situ formed by the incorporation of potassium salt is the key to this successful catalysis. Like enzymes, in a confined space, catalytic sites activate both reacting partners (imine and enolate) simultaneously and keep them in a close proximity, thus enhancing the reactivity and efficiently transferring the stereochemical information. The extension of this strategy to the synthesis of quaternary carbon in an acyclic system and further application of our cooperative cation binding catalysis concept for the discovery of new challenging organic transformations is currently underway in our