Selective Intramolecular CH Amination through the Metalloradical Activation of Azides: Synthesis of 1,3‐Diamines under Neutral and Nonoxidative Conditions

Abstract

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...

Dirhodium(II) Carboxylate Catalyzed Formation of 1,2,3‐Trisubstituted Indoles from Styryl Azides

“…Zuschriften of other established nitrogen-atom-transfer catalysts, including copper, [13] iron, [14] ruthenium, [15] cobalt, [16] or iridium [17] complexes did not result in improved reaction outcomes (entries 9-13). Changing the reaction media to ethereal, chlorinated, or other aromatic solvents also did not increase the yield of the migration reaction.…”

Product‐Derived Bimetallic Palladium Complex Catalyzes Direct Carbonylation of Sulfonylazides

“…[18] Together with the above investigation of the interaction of sulfonylurea and Pd(OAc) 2 ,one reasonable explanation was that the presence of different sulfonylurea products would affect the rate of TsNCO formation. Then we further studied relative rates of the reactions of 2awith only Pd(OAc) 2 Figure 1b.This data is important evidence that the sulfonylureas from primary amines are superior to the acetate ligand in terms of coordination to palladium, that this product-bridged palladium species,w hich has higher reactivity,i st he real active catalyst in sulfonylazide carbonylation with primary amines.…”

“…Pd(OAc) 2 ,the best catalyst in our reaction, is also acommon palladium species used in bimetallic Pd II /hypervalent Pd catalytic cycles. [16] Control experiments were carried out to compare the activity of different anions (Table 3).…”

“…To investigate the interaction of sulfonylurea and Pd-(OAc) 2 Further NMR studies [17] also suggested that the acetate of Pd(OAc) 2 [a] Reaction was carried out with 1.0 equiv of 1a,a nd 1.2 equiv of 2a.…”

“…Further investigation of the reaction conditions [12] revealed that this reaction gives comparable yields in MeCN,THF,and PhMe,w hereas high-polarity solvents such as DMF afforded poor yields.C omparison experiments showed that Pd(OAc) 2 is the best catalyst. Furthermore,t his carbonylation carried out directly from TsCl (4a)i nao ne-pot fashion also succeeded.…”