Isothiourea‐Mediated Asymmetric O‐ to C‐Carboxyl Transfer of Oxazolyl Carbonates: Structure–Selectivity Profiles and Mechanistic Studies

Abstract

The structural motif within a series of tetrahydropyrimidine-based isothioureas necessary for generating high asymmetric induction in the asymmetric Steglich rearrangement of oxazolyl carbonates is fully explored, with crossover and dynamic (19)F NMR experiments used to develop a mechanistic understanding of this transformation.

Diastereoselective Ugi reaction of chiral 1,3-aminoalcohols derived from an organocatalytic Mannich reaction

“…Using caesium carbonate, carbamoyl sulfones were converted into the corresponding N -Boc-protected imines 2 that were immediately submitted to List's organocatalytic Mannich reaction [29–30]. The resulting aldehydes 3 were not isolated (also in view of their known stereochemical lability) but directly reduced to alcohols 4 [32–33]. Purification was carried out through chromatography and, in some cases, by additional crystallization, affording these key intermediates in high ee and de ( syn relative configuration, see Supporting Information File 1).…”

Enantioselective Catalysis by Chiral Isothioureas

“…With HyperBTM ( 9 ), Smith designed an analogue to Birman's HBTM ( 7 ) in which the isopropyl group plays the role of a conformational lock . The pseudo‐equatorial conformation of this group forces the phenyl substituent to adopt a pseudo‐axial conformation even in the non‐acylated form . The Steglich rearrangement was then also extended to furanyl carbonates with moderate enantioselectivities (up to 83 % ee )…”

Single-Handed Helical Poly(quinoxaline-2,3-diyl)s Bearing Achiral 4-Aminopyrid-3-yl Pendants as Highly Enantioselective, Reusable Chiral Nucleophilic Organocatalysts in the Steglich Reaction

“…Incorporation of pyridyl pendants is highly attractive, because they serve not only as a ligand in transition-metal catalysts but also as chiral bases or nucleophilic organocatalysts. , In this paper, we report the synthesis of a series of PQXs bearing 4-aminopyrid-3-yl pendants and their use in asymmetric Steglich rearrangement. − We found high catalytic activity of one of the derivatives, which allows us to attain high enantioselectivity with remarkably low catalyst loading and to reuse the catalyst at least 11 times without any drop of selectivity or catalytic activity.…”

“…The obtained ( P )-( R )-PQX derivatives were used in asymmetric Steglich rearrangement, , in which oxazolyl carbonates isomerize to C -carboxyazlactones forming a quaternary stereocenter (Table ). In the presence of ( P )-( R )- PQXdmap ( C1 ) (0.5 mol % pyridyl pendants), rearrangement of oxazolyl carbonate 4Aa proceeded at 0 °C.…”