Enantioselective Synthesis of Axially Chiral Sulfone-Containing Styrenes Based on Ion-Exchange Strategy.

A novel ion exchange strategy has been developed to enable the asymmetric construction of axially chiral sulfone-containing styrenes. This approach provides a practical synthesis pathway for various axially chiral sulfone-containing styrenes with good yields, exceptional enantioselectivities, and nearly complete E/Z selectivities. Additionally, the reaction mechanism is elucidated in detail through density functional theory (DFT) calculations.

Cooperative Cu/azodiformate system-catalyzed allylic C-H amination of unactivated internal alkenes directed by aminoquinoline.

Aliphatic allylic amines are common in natural products and pharmaceuticals. The oxidative intermolecular amination of C(sp3)-H bonds represents one of the most straightforward strategies to construct these motifs. However, the utilization of widely internal alkenes with amines in this transformation remains a synthetic challenge due to the inefficient coordination of metals to internal alkenes and excessive coordination with aliphatic and aromatic amines, resulting in decreasing the reactivity of the catalyst. Here, we present a regioselective Cu-catalyzed oxidative allylic C(sp3)-H amination of internal olefins with azodiformates to these problems. A removable bidentate directing group is used to control the regiochemistry and stabilize the π-allyl-metal intermediate. Noteworthy is the dual role of azodiformates as both a nitrogen source and an electrophilic oxidant for the allylic C-H activation. This protocol features simple conditions, remarkable scope and functional group tolerance as evidenced by >40 examples and exhibits high regioselectivity and excellent E/Z selectivity.

An Axially Chiral Styrene-Phosphine Ligand for Pd-Catalyzed Asymmetric N-Alkylation of Indoles.

An efficient palladium-catalyzed enantioselective direct N-alkylation of indoles using a novel type of axially chiral styrene-phosphine ligand SJTU-PHOS-1 was developed. This reaction demonstrated good functional group compatibility and a wide range scope of substrates in mild conditions. Moreover, the DFT calculations expounded the coordination mode of the metal catalyst and the axially chiral styrene-phosphine ligand in the enantioselectivity control.

Organocatalytic Direct Asymmetric Indolization from Anilines by Enantioselective [3 + 2] Annulation.

We report the efficient syntheses of chiral tetrahydroindole pyrazolinones by the asymmetric [3 + 2] cascade cyclizations (indolizations) of simple aniline derivatives with pyrazolinone ketimines as 2C synthons. The chiral phosphoric-acid-catalyzed system uses a concerted π-π interaction/dual H-bond control strategy to catalytically direct the asymmetric aniline, which undergoes a highly chemo-, regio-, and enantioselective [3 + 2] cascade annulation, furnishing a series of optically active tetra-hydroindole pyrazolinones with two contiguous chiral aza-quaternary carbon centers in excellent yields with excellent enantioselectivities. This method features a relatively broad substrate scope for amines and 2-naphthylamines and highlights the emerging value of direct chiral indolizations from simple amine sources in organic synthesis.

Co-Catalyzed Direct Regio- and Enantioselective Intermolecular γ-Amination of N-Acylpyrazoles.

A cobalt-catalyzed regio- and enantioselective γ-amination of ß,γ-unsaturated N-acylpyrazoles that delivers the corresponding γ-amination products in good regio- and enantioselectivity has been established. Moreover, the nitrogen-containing compounds could be easily synthesized. DFT calculations have been provided to explain regio- and enantioselectivity for this γ-amination. The chiral γ-amination products were readily converted into the chiral γ-amino acid derivatives.

Highly Chemo-, Site-, and Enantioseletive para C-H Aminoalkylation of N-Monosubstituted Aniline Derivatives Affording 3-Amino-2-oxindoles.

In general, enantioselective C-H functionalization of N-monosubstituted anilines is a highly challenging task owing to the competitive chemoselective N-H bond insertion reactions. In this paper, we reported a direct highly chemo-, site-, and enantioselective para C-H aminoalkylation of N-monosubstituted aniline derivatives with isatin-derived ketimines in the presence of chiral phosphoric acids (CPAs) and offered a practical strategy for para asymmetric C-H functionalization of anilines containing N-H bonds.

Highly atroposelective synthesis of nonbiaryl naphthalene-1,2-diamine N-C atropisomers through direct enantioselective C-H amination.

Nonbiaryl N-C atropisomer is an important structural scaffold, which is present in natural products, medicines and chiral ligands. However the direct enantioselective C-H amination to access optically pure N-C atropisomer is still difficult and rare. Here we report a π-π interaction and dual H-bond concerted control strategy to develop the chiral phosphoric acids (CPAs) catalyzed direct intermolecular enantioselective C-H amination of N-aryl-2-naphthylamines with azodicarboxylates as amino sources for the construction of atroposelective naphthalene-1,2-diamines. This type of N-C atropisomers is stabilized by intramolecular hydrogen bond and the method features a broad range of substrates, high yields and ee values, providing a strategy to chirality transfer via the modification of N-C atropisomers.

Rhodium(III)-Catalyzed Redox-Neutral Cascade [3 + 2] Annulation of N-Phenoxyacetamides with Propiolates via C-H Functionalization/Isomerization/Lactonization.

A Rh(III)-catalyzed cascade [3 + 2] annulation of N-phenoxyacetamides with propiolates under mild conditions using the internal oxidative O-N bond as the directing group has been achieved. This catalytic system provides a regio- and stereoselective access to benzofuran-2(3 H)-ones bearing exocyclic enamino motifs with exclusive Z configuration selectivity, acceptable to good yields and good functional group compatibility. Mechanistic investigations by experimental and density functional theory studies suggest that a consecutive process of C-H functionalization/isomerization/lactonization is likely to be involved in the reaction.

Experimental and computational studies on H2O-promoted, Rh-catalyzed transient-ligand-free ortho-C(sp2)-H amidation of benzaldehydes with dioxazolones.

An efficient and convenient ligand-free, rhodium-catalyzed ortho-C(sp2)-H amidation of benzaldehydes with dioxazolones using H2O as the key promoter is described. Using this protocol, a wide range of benzaldehyde substrates were selectively amidated in good to excellent yields with broad functional group compatibility. KIE experiments revealed that the C-H bond activation was likely the rate-limiting step. In addition, computational studies indicated that the catalyst precursor interacted with water and dioxazolones to generate the active catalytic species. Notably, the practicality and efficacy of this method were illustrated by a late-stage amidation of an estrone-derived molecule and further transformations of the amidated product.

Metal-Controlled, Regioselective, Direct Intermolecular α- or γ-Amination with Azodicarboxylates.

A metal-controlled, regioselective intermolecular amination of unsaturated N-acylpyrazoles with azodicarboxylates is described. Under zinc catalysis, the N-acylpyrazole substrates undergo amination at the α-position of the N-acylpyrazole moiety. Conversely, with silver as the catalyst, the reaction gave γ-amination products. Both catalytic protocols provided alternative, convenient, and simple strategies for efficiently and regioselectively accessing structurally unique C-N-bond containing compounds. The synthetic utility of this method was illustrated by a gram-scale experiment and subsequent efficient synthesis of the γ-amino acid analogue.