Catalytic C−H Amination for the Preparation of Substituted 1,2-Diamines

Abstract

Vicinal diamines appear frequently as structural units in biological and medicinal molecules of interest and as auxiliary groups or ligands for catalytic processes. 1 The rich and varied applications for 1,2-diamines belie the rather modest number of general methods for the efficient preparation of such compounds. 2 Accordingly, we have attempted to capitalize on the power of sulfamate ester C-H amination to address this problem (Figure 1).

Asymmetric Synthesis of Diamine Derivatives via Sequential Palladium and Rhodium Catalysis

“…1 Recently, one of our labs has disclosed a method that takes advantage of Rh-catalyzed C–H insertion to synthesize differentially substituted 1,2-diamines from hydroxylamine-derived sulfamate esters. 2 With an interest in facilitating access to optically active, polyfunctionalized diamines, we envisioned a sequential process featuring asymmetric synthesis of N -allyl hydroxylamine- O -sulfamates and catalytic intramolecular aziridination (Figure 1). Palladium-catalyzed allylic amination was viewed as a particularly attractive means for preparing allylic hydroxylamine-derived sulfamate esters in enantioenriched form.…”

“…2 In the first example, reduction of the heterocycle and the azido group in 4 unveiled the singly protected triamino ester 5 . The availability of this material in optically active form in just four steps starting from the racemic allylic carbonate underscores the effectiveness of these combined methods.…”

2.9 C—N Bond Formation by C—H Functionalization via Metal-Catalyzed Nitrene Insertion

“…Incorporation of a 4-methoxybenzenesulfonyl (Mbs) protecting group allows for insertion into tertiary and benzylic C-H bonds (entries 1-3). [16] However, the Mbs-protected products are susceptible to base-mediated fragmentation, making purification and derivatization difficult. N-(2,2,2-Trichloroethoxycarbonyl) (Troc) protection extends the scope of this reaction to secondary C-H bonds (entries 4-6).…”

“…Reductive opening of the [1,2,3,6]-oxathiadiazinane 2,2-dioxide heterocycles reveals 1,2-diamines. [16] 260 C-H Activation 2.9 Metal-Catalyzed Nitrene Insertion…”

“…Unauthorized distribution is strictly prohibited. [1,2,3,6]-Oxathiadiazinane 2,2-Dioxides 22; General Procedure: [16] Solid MgO (14 mg, 0.35 mmol, 2.3 equiv), Rh(II) catalyst (2 mg, 3.00 ìmol, 0.02 equiv), and PhI(OAc) 2 (53 mg, 0.17 mmol, 1.1 equiv) were added sequentially to a soln of substrate 21 (0.15 mmol) in benzene (1.5 mL) (CAUTION: carcinogen). The green suspension was stirred at 25 8C for 4 h, diluted with CH 2 Cl 2 (1-2 mL), and filtered through a small pad of Celite.…”