Combined radical and ionic approach for the enantioselective synthesis of ß-functionalized amines from alcohols.

Chiral amines are among the most important organic compounds and have widespread applications. Enantioselective construction of chiral amines is a major aim in organic synthesis. Among synthetic methods, direct functionalization of omnipresent C-H bonds with common organic nitrogen compounds represents one of the most attractive strategies. However, C-H amination strategies are largely limited to constructing a specific type of N-heterocycles or amine derivatives. To maximize the synthetic potential of asymmetric C-H amination, we report here an approach that unites the complementary reactivities of radical and ionic chemistry for streamlined synthesis of functionalized chiral amines. This synthesis merges the development of an enantioselective radical process for 1,5-C(sp 3)-H amination of alkoxysulfonyl azides via Co(II)-based metalloradical catalysis with an enantiospecific ionic process for ring-opening of the resulting five-membered chiral sulfamidates by nucleophiles. Given that alkoxysulfonyl azides are derived from the corresponding alcohols, this approach offers a powerful synthetic tool for enantioselective ß-C-H amination of common alcohols while converting the hydroxy group to other functionalities through formal nucleophilic substitution.

Asymmetric Radical Cyclopropanation of Dehydroaminocarboxylates: Stereoselective Synthesis of Cyclopropyl α-Amino Acids.

A catalytic radical process has been developed for asymmetric cyclopropanation of dehydroaminocarboxylates with in situ-generated α-aryldiazomethanes via Co(II)-based metalloradical catalysis (MRC). Through fine-tuning the environments of D 2-symmetric chiral amidoporphyrin platform as the supporting ligands, the Co(II)-metalloradical system can effectively activate various α-aryldiazomethanes to cyclopropanate different dehydroaminocarboxylates under mild conditions, enabling the stereoselective synthesis of chiral cyclopropyl α-amino acid derivatives. In addition to high yields and excellent enantioselectivities, the Co(II)-catalyzed asymmetric radical cyclopropanation exhibits (Z)-diastereoselectivity, which is the opposite of uncatalyzed thermal reaction. Combined computational and experimental studies support a stepwise radical mechanism for the Co(II)-catalyzed cyclopropanation reaction. The resulting enantioenriched (Z)-α-amino-ß-arylcyclopropanecarboxylates, as showcased for the efficient synthesis of dipeptides, may serve as unique non-proteinogenic amino acid building blocks for the design and preparation of novel peptides with restricted conformations.

Palladium-Catalyzed Direct C(sp2)-H ortho-Arylation of Anilides Using 2-Aminophenylpyrazole as the Directing Group.

Palladium-catalyzed ortho-arylation of anilides was achieved using 2-aminophenyl-1H-pyrazole (2-APP) as a new directing group. Using Pd(OAc)2 as the catalyst and AgO as the promoter, mono- and diarylation of anilides were realized in up to 89% isolated yield. Further manipulation of the arylation product may be accomplished by a 2-step sequence involving an acidic hydrolysis of the methylated amide. More interestingly, in the presence of K2CO3, tandem C-C/C-N cyclization products were obtained for a couple of substrates.