Asymmetric Synthesis of Stereogenic Phosphorus P(V) Centers Using Chiral Nucleophilic Catalysis

Organophosphates have been widely used in agrochemistry, as reagents for organic synthesis, and in biochemistry. Phosphate mimics possessing four unique substituents, and thereby a chirality center, are useful in transition metal catalysis and as nucleotide therapeutics. The catalytic, stereocontrolled synthesis of phosphorus-stereogenic centers is challenging and traditionally depends on a resolution or use of stochiometric auxiliaries. Herein, enantioenriched phosphorus centers have been synthesized using chiral nucleophilic catalysis. Racemic H-phosphinate species were coupled with nucleophilic alcohols under halogenating conditions. Chiral phosphonate products were synthesized in acceptable yields (33–95%) and modest enantioselectivity (up to 62% ee) was observed after identification of an appropriate chiral catalyst and optimization of the solvent, base, and temperature. Nucleophilic catalysis has a tremendous potential to produce enantioenriched phosphate mimics that could be used as prodrugs or chemical biology probes.

Nucleophilic catalysis of p-substituted aniline derivatives in acylhydrazone formation and exchange

Hydrazone bond formation is a versatile reaction employed in several research fields. It is one of the most popular reversible reactions in dynamic combinatorial chemistry. Under physiological conditions, hydrazone exchange...

N-acylation of amides through internal nucleophilic catalysis

An efficient method for N-acylation of amides is described using a pyridine ring as the internal nucleophilic catalyst to give imides in moderate to excellent yields. The methodology provides a facile, air insensitive, and environmentally friendly route to form diversified imide scaffolds, which exist widely in natural products and biologically active materials.

Synthesis of 2,4-Disubstituted Imidazoles via Nucleophilic Catalysis

A convergent, microwave-assisted protocol for the synthesis of disubstituted NH-imidazoles via nucleophilic catalysis is described. The substituted imidazoles are accessed via the intramolecular addition of a variety of amidoxime substrates to activated alkynes followed by a thermally induced rearrangement of the in situ generated O-vinylamid­oxime species. The unprotected imidazoles contain an aryl group at the 2-position as well as an ester moiety at the 4-position.

Interplay of nucleophilic catalysis with proton transfer in the nitrile reductase QueF from Escherichia coli

Proton relay through an active-site network of hydrogen bonds promotes enzymatic nitrile reduction to amine via a covalent thioimidate enzyme intermediate.

Asymmetric synthesis of multifunctional aryl allyl ethers by nucleophilic catalysis

Asymmetric allylic substitution of Morita–Baylis–Hillman (MBH) carbonates with less-nucleophilic phenols mediated by nucleophilic amine catalysis was successfully developed.