Fluxional Groups Research Articles

Relay PHOS: Ligands with Fluxional Chirality in Asymmetric Palladium-Catalyzed Allylic Alkylation.

A modular route toward the synthesis of P,N ligands containing a fluxional group along the pyrazoline ring core is described. The racemic ligands were accessed in three steps from commercially available fluoroacetophenone in overall yields ranging from 18 to 76%. The enantiopure ligands were obtained using semi-preparative chiral high-performance liquid chromatography and chiral enantioselective phase-transfer catalysis. The effectiveness of the new ligands was assessed in palladium-catalyzed allylic alkylation with diphenylpropenyl acetate and dimethylpropenyl acetate. Under optimized conditions, diphenylpropenyl acetate underwent alkylation with dimethyl malonate in 98% yield and 94% ee. In general, the enantioselectivity for the product correlates with the size of the ligand fluxional group; the larger the fluxional group, the higher the selectivity.

Enantioselective enolate protonations: Evaluation of achiral templates with fluxional brønsted basic substituents in conjugate addition of malononitriles

Enoates derived from α−substituted acrylates containing 3-pyrazolidinone achiral template with Brønsted basic fluxional substituents were evaluated in chiral Lewis acid catalyzed enantioselective protonation reactions. The tandem 1,4-conjuagte addition/enantioselective protonation reaction catalyzed by chiral Lewis acids was found to depend on the fluxional group present on the achiral template. The enantioselectivity of the protonation step is highly dependent on the position of the Brønsted basic atom with respect to the pyrazolidinone nitrogen. A comparison of fluxional substituents without a Brønsted basic site and their impact on selectivity is also reported here. The results we detail here are in sharp contrast to our previous studies on enantioselective conjugate addition of malononitriles. The reaction showed reasonable substrate scope for varying α−substitution. The reactions gave conjugate adducts in good yields and good enantioselectivities up to 83 %.

Fluxionally chiral DMAP catalysts: kinetic resolution of axially chiral biaryl compounds.

Can organocatalysts that incorporate fluxional groups provide enhanced selectivity in asymmetric transformations? To address this issue, we have designed chiral 4-dimethylaminopyridine (DMAP) catalysts with fluxional chirality. These catalysts were found to be efficient in promoting the acylative kinetic resolution of secondary alcohols and axially chiral biaryl compounds with selectivity factors of up to 37 and 51, respectively.

Fluxionally Chiral DMAP Catalysts: Kinetic Resolution of Axially Chiral Biaryl Compounds

AbstractCan organocatalysts that incorporate fluxional groups provide enhanced selectivity in asymmetric transformations? To address this issue, we have designed chiral 4‐dimethylaminopyridine (DMAP) catalysts with fluxional chirality. These catalysts were found to be efficient in promoting the acylative kinetic resolution of secondary alcohols and axially chiral biaryl compounds with selectivity factors of up to 37 and 51, respectively.

The Role of Achiral Pyrazolidinone Templates in Enantioselective Diels−Alder Reactions: Scope, Limitations, and Conformational Insights

We have evaluated the role of achiral pyrazolidinone templates in conjunction with chiral Lewis acids in room temperature, enantioselective Diels-Alder cycloadditions. The role of the fluxional N(1) substituent was examined, with the bulky 1-naphthylmethyl group providing enantioselectivities up to 99% ee, while templates with smaller fluxional groups gave lower selectivities. High selectivities were also observed in reactions of 7d with chiral Lewis acids derived from relatively small chiral ligands, suggesting the pyrazolidinone templates are capable of relaying stereochemical information from the ligand to the reaction center. Lewis acids capable of adapting square planar geometries, such as Cu(OTf)2, Cu(ClO4)2, and Pd(ClO4)2, were found to be particularly effective at providing high selectivities. Additionally, substitution at the C-5 position of the pyrazolidinone templates has been shown to be critical for optimal selectivity. Reactions of the optimal pyrazolidinone appended with a number of common dienophiles and various dienes demonstrate the utility of this achiral template. Furthermore, catalytic loadings could be lowered to 2.5 mol % with essentially no loss in selectivity. Pi-Pi interactions were evaluated as a means to explain the unusually high selectivity observed at room temperature. Finally, non-C2-symmetric ligands were employed as a test to determine if chiral relay was operative.

Chiral Relay in Enantioselective Conjugate Radical Additions Using Pyrazolidinone Templates. How Does Metal Geometry Impact Selectivity?

AbstractFor Abstract see ChemInform Abstract in Full Text.

Enantioselective Diethylzinc Additions to Aldehydes Catalyzed by Chiral Relay Ligands.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Enantioselective diethylzinc additions to aldehydes catalyzed by chiral relay ligands

A new pyrazole ligand system incorporating fluxional chirality was found to catalyze the addition of diethylzinc to aldehydes giving rise to the corresponding secondary alcohol products in excellent yields (74–99%) with moderate to high enantioselectivities (46–93%). The size of the fluxional group on the ligand correlated with the level of enantioselectivity of the product.

Chiral Relay in Enantioselective Conjugate Radical Additions Using ­Pyrazolidinone Templates. How Does Metal Geometry Impact Selectivity?

A novel class of achiral templates containing fluxional groups has been evaluated in conjugate radical additions. Magnesium and copper Lewis acids provide high enantioselectivity (>90% ee) for radical additions. The impact of the metal geometry on enantioselectivity using relay templates has also been assessed.

A New Class of Modular Chiral Ligands with Fluxional Groups.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A new class of modular chiral ligands with fluxional groups.

In ligand design for asymmetric catalysis, the usual norm is to derive the face shielding elements from a chiral source. New ligands in which the face shielding is determined by fluxional groups are introduced. Their design, modular synthesis, and experiments to demonstrate the significance of the fluxional groups are discussed. The advantage is that the fluxional groups, introduced at a later stage, allow for simple tuning of the face shielding group.