Ac omplementing Pd-and Rh-catalyzed dynamic kinetic resolution (DKR) of racemic allenes leading to Nallylated pyrazoles is described. Suchc ompounds are of enormous interest in medicinal chemistry as certified drugs and potential drug candidates.T he new methods feature high chemo-, regio-and enantioselectivities aside from displaying abroad substrate scope and functional group compatibility.A mechanistic rational accounting for allene racemization and trans-alkene selectivity is discussed.
The rhodium-catalyzed asymmetric N-selective coupling of pyrazole derivatives with internal and terminal alkynes features an utmost chemo-, regio-, and enantioselective access to enantiopure allylic pyrazoles, readily available for incorporation in small-molecule pharmaceuticals. This methodology is distinguished by a broad substrate scope, resulting in a remarkable compatability with a variety of different functional groups. It furthermore exhibits an intriguing case of regio-, position-, and enantioselectivity in just one step, underscoring the sole synthesis of just one out of up to six possible products in a highly flexible approach to allylated pyrazoles by emanating from various internal and terminal alkynes.
A rare case of a parallel kinetic resolution of racemic 1,3‐disubstituted allenes by means of a rhodium‐catalyzed addition to 1,3‐diketones furnishing enantiopure allylic 1,3‐diketones is described. Mechanistic experiments demonstrate that the different allene enantiomers react in parallel to either the diastereomeric E‐ or Z‐allylic 1,3‐diketones with the same absolute configuration of the newly formed stereogenic center. A broad substrate scope demonstrates the synthetic utility of this new method.
Arare case of aparallel kinetic resolution of racemic 1,3-disubstituted allenes by means of ar hodium-catalyzed addition to 1,3-diketones furnishing enantiopure allylic 1,3diketones is described. Mechanistic experiments demonstrate that the different allene enantiomers react in parallel to either the diastereomeric E-or Z-allylic 1,3-diketones with the same absolute configuration of the newly formed stereogenic center. Ab road substrate scope demonstrates the synthetic utility of this new method.
ZuschriftenThis work was supported by the Deutsche Forschungsgemeinschaft (DFG) and the Fonds der Chemischen Industrie. JanK lauser (University of Freiburg) is acknowledged for technical assistance.W et hank Dr.M anfred Keller for extensive NMR experimentations and Joshua Emmerich for challenging HPLC separations.
Conflict of interestTheauthors declare no conflict of interest.
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