The mechanism of cobalt(II) porphyrin-catalyzed benzylic C-H bond amination of ethylbenzene, toluene, and 1,2,3,4-tetrahydronaphthalene (tetralin) using a series of different organic azides [N(3)C(O)OMe, N(3)SO(2)Ph, N(3)C(O)Ph, and N(3)P(O)(OMe)(2)] as nitrene sources was studied by means of density functional theory (DFT) calculations and electron paramagnetic resonance (EPR) spectroscopy. The DFT computational study revealed a stepwise radical process involving coordination of the azide to the metal center followed by elimination of dinitrogen to produce unusual "nitrene radical" intermediates (por)Co(III)-N(•)Y (4) [Y = -C(O)OMe, -SO(2)Ph, -C(O)Ph, -P(O)(OMe)(2)]. Formation of these nitrene radical ligand complexes is exothermic, predicting that the nitrene radical ligand complexes should be detectable species in the absence of other reacting substrates. In good agreement with the DFT calculations, isotropic solution EPR signals with g values characteristic of ligand-based radicals were detected experimentally from (por)Co complexes in the presence of excess organic azide in benzene. They are best described as nitrene radical anion ligand complexes (por)Co(III)-N(•)Y, which have their unpaired spin density located almost entirely on the nitrogen atom of the nitrene moiety. These key cobalt(III)-nitrene radical intermediates readily abstract a hydrogen atom from a benzylic position of the organic substrate to form the intermediate species 5, which are close-contact pairs of the thus-formed organic radicals R'(•) and the cobalt(III)-amido complexes (por)Co(III)-NHY ({R'(•)···(por)Co(III)-NHY}). These close-contact pairs readily collapse in a virtually barrierless fashion (via transition state TS3) to produce the cobalt(II)-amine complexes (por)Co(II)-NHYR', which dissociate to afford the desired amine products NHYR' (6) with regeneration of the (por)Co catalyst. Alternatively, the close-contact pairs {R'(•)···(por)Co(III)-NHY} 5 may undergo β-hydrogen-atom abstraction from the benzylic radical R'(•) by (por)Co(III)-NHY (via TS4) to form the corresponding olefin and (por)Co(III)-NH(2)Y, which dissociates to give Y-NH(2). This process for the formation of olefin and Y-NH(2) byproducts is also essentially barrierless and should compete with the collapse of 5 via TS3 to form the desired amine product. Alternative processes leading to the formation of side products and the influence of different porphyrin ligands with varying electronic properties on the catalytic activity of the cobalt(II) complexes have also been investigated.

Amino groups exist ubiquitously in natural products and synthetic molecules, and play key roles in a wide range of important applications. Consequently, immense effort has been devoted to the development of efficient and selective processes for the preparation of amines.[1] Among different approaches, the catalytic amination of abundant C À H bonds on the basis of a metal-mediated nitrene-insertion pathway is one of the most general and direct methods for installing nitrogen functionalities.[2] The promise of this approach as a synthetically useful methodology has been demonstrated with a number of intramolecular C À H amination processes through the combined use of Rh II 2 -based catalysts and iminoiodane nitrene sources. [2,3] Notably, Du Bois and coworkers elegantly demonstrated that N-Boc-protected sulfamides could be selectively converted into cyclic sulfamides by [Rh 2 (esp) 2 ] in combination with PhI(OAc) 2 and MgO to provide access to synthetically useful 1,3-diamines (esp = a,a,a',a'-tetramethyl-1,3-benzenedipropionate).[4] The Rh II 2 -based intramolecular amination was shown to be effective for both secondary and tertiary CÀH bonds with stereospecificity and high diastereoselectivity. However, the amination of strong primary CÀH bonds had yet to be demonstrated. [5] Moreover, the catalytic system was unsuitable for simple Nalkyl sulfamides, which were oxidatively degraded by the stoichiometric oxidant, PhI(OAc) 2 . [4] As stable metalloradicals, cobalt(II) complexes of porphyrins, [Co(Por)], have emerged as a new class of catalysts for CÀH amination.[6] The cobalt(II)-based metalloradical amination (MRAm) is different from the commonly studied Rh 2 system, as it can operate effectively with various azide substrates without the need for terminal oxidants and other additives. [7][8][9][10][11] To further validate the utility of C À H amination methodology based on a cobalt(II) catalyst and azides, we envisioned a general strategy for the synthesis of 1,3-diamines from monoamines through the key step of the intramolecular C À H amination of sulfamoyl azides with [Co(Por)] (Scheme 1). We report herein a cobalt(II)-based catalytic system that is highly effective for the intramolecular 1,6-CÀH amination of sulfamoyl azides to furnish six-membered cyclic sulfamides. Not only excellent regioselectivity, but also high diastereoselectivity and stereospecificity were observed with the catalytic system. The cobalt(II)-catalyzed amination is operationally simple, as it proceeds under neutral and nonoxidative conditions without the need for other reagents, and N 2 is the only byproduct. Consequently, the degree of functional-group tolerance is high, and the reaction can be applied to substrates with various substituents, such as oxidizable amide and sulfide groups. An important feature of this catalytic system is the effective amination of strong primary C À H bonds, as well as secondary and tertiary C À H bonds.A wide range of sulfamoyl azides 2 were conveniently prepared from the corresponding amines 1 on the bas...

Highly chemoselective intramolecular amination of propargylic C(sp3)–H bonds has been demonstrated for N-bishomopropargylic sulfamoyl azides via Co(II)-based metalloradical catalysis. Supported by D2h-symmetric amidoporphyrin ligand 3,5-DitBu-IbuPhyrin, the Co(II)-catalyzed C–H amination process can proceed effectively under neutral and nonoxidative conditions without the need of any additives, generating N2 as the only byproduct. The metalloradical amination is suitable to both secondary and tertiary propargylic C–H substrates with an unusually high degree of functional group tolerance, providing a direct method for high-yielding synthesis of functionalized propargylamine derivatives.

The mechanism of cobalt(II) porphyrin-mediated aziridination of styrene with PhSO(2)N(3) was studied by means of DFT calculations. The computations clearly indicate the involvement of a cobalt 'nitrene radical' intermediate in the Co(II)(por)-catalyzed alkene aziridination. The addition of styrene to this species proceeds in a stepwise fashion via radical addition of the 'nitrene radical'C to the C=C double bond of styrene to form a γ-alkyl radical intermediate D. The thus formed tri-radical species D easily collapses in an almost barrierless ring closure reaction (TS3) to form the aziridine, thereby regenerating the cobalt(II) porphyrin catalyst. The radical addition of the 'nitrene radical'C to the olefin (TS2) proceeds with a comparable barrier as its formation (TS1), thus providing a good explanation for the first order kinetics in both substrates and the catalyst observed experimentally. Formation of C is clearly accelerated by stabilization of C and TS1 via hydrogen bonding between the S=O and N-H units. The computed radical-type mechanism agrees well with all available mechanistic and kinetic information. The computed free energy profile readily explains the superior performance of the Co(II)(porAmide) system with H-bond donor functionalities over the non-functionalized Co(TPP).

Hydrogels are important in biological and medical applications, such as drug delivery and tissue engineering. DNA hydrogels have attracted significant attention due to the programmability and biocompatibility of the material. We developed a series of low-cost one-strand DNA hydrogels self-assembled from single-stranded DNA monomers containing multiple palindromic domains. This new hydrogel design is simple and programmable. Thermal stability, mechanical properties, and loading capacity of these one-strand DNA hydrogels can be readily regulated by simply adjusting the DNA domains.