Hongjian Lu

Cobalt-Catalyzed Asymmetric Cyclopropanation with Diazosulfones: Rigidification and Polarization of Ligand Chiral Environment via Hydrogen Bonding and Cyclization

A new D2-symmetric chiral porphyrin P6 (2,6-DiMeO-ZhuPhyrin) with enhanced chiral rigidity and polarity was designed and synthesized through incorporation of hydrogen bonding and cyclic structure. Its cobalt(II) complex [Co(P6)] is a highly active and selective catalyst for asymmetric cyclopropanation of alkenes with diazosulfones. The [Co(P6)]-based catalytic system is suitable for various aromatic olefins as well as electron-deficient olefins, including alpha,beta-unsaturated esters, ketones, and nitriles, forming the corresponding cyclopropyl sulfones under mild conditions in high yields and high selectivities. In most cases, both excellent diastereo- and enantioselectivities were achieved.

Highly Asymmetric Intramolecular Cyclopropanation of Acceptor-Substituted Diazoacetates by Co(II)-Based Metalloradical Catalysis: Iterative Approach for Development of New-Generation Catalysts

3,5-Di(t)Bu-QingPhyrin, a new D(2)-symmetric chiral porphyrin derived from a chiral cyclopropanecarboxamide containing two contiguous stereocenters, has been developed using an iterative approach based on Co(II)-catalyzed asymmetric cyclopropanation of alkenes. The Co(II) complex of 3,5-Di(t)Bu-QingPhyrin, [Co(P2)], has proved to be a general and effective catalyst for asymmetric intramolecular cyclopropanation of various allylic diazoacetates (especially including those with α-acceptor substituents) in high yields with excellent stereoselectivities. The [Co(P2)]-based intramolecular metalloradical cyclopropanation provides convenient access to densely functionalized 3-oxabicyclo[3.1.0]hexan-2-one derivatives bearing three contiguous quaternary and tertiary chiral centers with high enantiomeric purity.

Cobalt(II)-Catalyzed Intramolecular C−H Amination with Phosphoryl Azides: Formation of 6- and 7-Membered Cyclophosphoramidates

A highly effective Co(II)-based system has been developed for catalytic intramolecular C-H amination with phosphoryl azides without the need of terminal oxidant or other additives, resulting in the high-yielding production of cyclophosphoramidates with nitrogen gas as the byproduct. Additional features of this new catalytic system include the amination of primary C-H bonds and formation of 7-membered-ring structures.

Enantioselective Cyclopropenation of Alkynes with Acceptor/Acceptor-Substituted Diazo Reagents via Co(II)-Based Metalloradical Catalysis

The cobalt(II) complex of a new D(2)-symmetric chiral porphyrin 3,5-diMes-ChenPhyrin, [Co(P2)], has been shown to be a highly effective chiral metalloradical catalyst for enantioselective cyclopropenation of alkynes with acceptor/acceptor-substituted diazo reagents, such as α-cyanodiazoacetamides and α-cyanodiazoacetates. The [Co(P2)]-mediated metalloradical cyclopropenation is suitable to a wide range of terminal aromatic and related conjugated alkynes with varied steric and electronic properties, providing the corresponding trisubstituted cyclopropenes in high yields with excellent enantiocontrol of the all-carbon quaternary stereogenic centers. In addition to mild reaction conditions, the Co(II)-based metalloradical catalysis for cyclopropenation features a high degree of functional group tolerance.

Chemoselective Amination of Propargylic C(sp3)H Bonds by Cobalt(II)‐Based Metalloradical Catalysis

Highly chemoselective intramolecular amination of propargylic C(sp(3))-H bonds has been demonstrated for N-bishomopropargylic sulfamoyl azides through cobalt(II)-based metalloradical catalysis. Supported by D(2h)-symmetric amidoporphyrin ligand 3,5-Di(t)Bu-IbuPhyrin, the cobalt(II)-catalyzed C-H amination proceeds effectively under neutral and nonoxidative conditions without the need of any additives, and generates N2 as the only byproduct. The metalloradical amination is suitable for both secondary and tertiary propargylic C-H substrates with an unusually high degree of functional-group tolerance, thus providing a direct method for high-yielding synthesis of functionalized propargylamine derivatives.

Effective Synthesis of Chiral N‐Fluoroaryl Aziridines through Enantioselective Aziridination of Alkenes with Fluoroaryl Azides

Catalytic aziridination of alkenes with nitrene sources via “C2+N1” addition represents a general approach for the direct synthesis of aziridines, the smallest three-membered N-heterocycles.[1] The enantioselective version of this catalytic process allows for efficient access to chiral nonracemic aziridines, which are versatile synthetic intermediates in asymmetric synthesis.[1-2] Several classes of transition metal-based chiral catalysts, such as Mn, Fe, Cu, Rh and Co complexes, have been found effective in catalyzing asymmetric olefin aziridination with different nitrene sources.[1,3] Besides iminoiodanes and haloamines, organic azides have been actively pursued as alternative nitrene sources for metal-catalyzed aziridination as they enjoy several advantages.[3] While sulfonyl and phosphoryl azides have been effectively employed for metal-catalyzed asymmetric aziridination,[4] catalytic processes based on the use of other types of azides, such as aryl azides, have been less developed. In addition to generating environmentally friendly nitrogen gas as the only byproduct, asymmetric catalytic aziridination with readily available aryl azides provides an attractive approach for the synthesis of valuable N-aryl aziridines through direct introduction of N-aryl groups concurrently with the ring formation.[5,6] This would avoid two additional steps of deprotection and N-arylation when other types of nitrene sources are used for preparing N-aryl aziridines.[7] However, few catalytic systems have been shown to be effective for asymmetric olefin aziridination with aryl azides.[4d,6]

Stereoselective radical amination of electron-deficient C(sp3)-H bonds by Co(II)-based metalloradical catalysis: direct synthesis of α-amino acid derivatives via α-C-H amination.

The cobalt(II) complex of 3,5-Di(t)Bu-IbuPhyrin, [Co(P1)], is an effective catalyst for intramolecular amination of electron-deficient C-H bonds, including those adjacent to electron-withdrawing CO(2)R, C(O)NR(2), C(O)R, and CN groups, in excellent yields with high regio- and stereoselectivity. The [Co(P1)]-catalyzed amination system provides a direct method for the synthesis of α-amino acid derivatives from the corresponding carboxylate precursors.

Carbene Radicals in Cobalt(II)–Porphyrin-Catalysed Carbene Carbonylation Reactions; A Catalytic Approach to Ketenes

One-pot radicals: Cobalt(III)-carbene radicals, generated by metallo-radical activation of diazo compounds and N-tosylhydrazone sodium salts with cobalt(II) complexes of porphyrins, readily undergo radical addition to carbon monoxide, allowing the catalytic production of ketenes. These ketenes subsequently react with various amines, alcohols and imines in one-pot tandem transformations to produce differently substituted amides, esters and β-lactams in good isolated yields.

Chemoselective intramolecular allylic C–H aminationversus CC aziridination through Co(II)-based metalloradical catalysis

Excellent chemoselectivity for intramolecular allylic C–H aminationversus CC aziridination was achieved through Co(II)-based metalloradical catalysis. Metalloradical catalyst [Co(P1)], the cobalt(II) complex of D2h-symmetric porphyrin 3,5-DitBu-IbuPhyrin, was shown to be highly effective for selective intramolecular allylic C–H amination of both N-bishomoallylic and N-allylic sulfamoyl azides. The Co(II)-catalyzed intramolecular 1,6-C–H amination of these azides provides a general and efficient method to access the synthetically useful allylic 1,3-diamines under neutral and non-oxidative conditions, without complication from the competitive olefin aziridination. The origin of this remarkable chemoselectivity has direct relevance to the radical mechanism of Co(II)-based metalloradical amination.

Cobalt-Catalyzed Decarboxylative 2-Benzoylation of Oxazoles and Thiazoles with α-Oxocarboxylic Acids

Cobalt-catalyzed decarboxylative cross-coupling of oxazoles and thiazoles with α-oxocarboxylic acids was developed through an sp(2) C-H bond functionalization process. This work represents the first example of cobalt-catalyzed decarboxylative C-H bond functionalization and provides an efficient means of building some important bioactive heteroaryl ketone derivatives.