Copper-catalyzed aminooxygenation of styrenes with N-fluorobenzenesulfonimide and N-hydroxyphthalimide derivatives

A copper-catalyzed aminooxygenation reaction of styrenes with N-fluorobenzenesulfonimide and N-hydroxyphthalimide derivatives has been developed. The aminooxygenation product could be converted into the corresponding alcohol or free amine through the cleavage of the N–O or C–N bond of the N-hydroxyphthalimide moiety.


Findings
Direct aminooxygenation of alkenes provides a straightforward and powerful approach to construct the 1,2-aminoalcohol skeleton [1], which is ubiquitous in bioactive compounds (such as the drugs bestatin (1) and tamiflu (2), the natural products Al-77-B (3) and hapolosin (4); Figure 1) [2] and has also been widely used as chiral ligands and auxiliaries in asymmetric synthesis [3].Therefore, the development of a new aminooxygenation reaction is still highly attractive [4].Most of the existing aminooxygenation reactions involve an intramolecular cyclization step  to provide various valuable cyclic compounds.Comparatively, methods for an intermolecular three-component aminooxygenation reaction are considerably less established.In 2006, Stahl and co-workers reported a Pd-catalyzed aminooxygenation reaction of alkenes with phthalimide and (diacetoxyiodo)benzene through cis-aminopalladation and S N 2 C-O bond formation [34].In 2013, Zhu and co-workers described an n-Bu 4 NI-catalyzed aminooxygenation of inactive alkenes with benzotriazole and water which underwent a nitrogen-centred radical addition and a nucleophilic oxygen attack [35].Very recently, Studer and co-workers presented an aminooxygenation of alkenes with N-fluorobenzenesulfonimide (NFSI) and sodium 2,2,6,6-tetramethylpiperidine-1-olate (TEMPONa) via nitrogen-centred radical addition to the alkene followed by trapping of 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) [36].
Based on these experimental results and our previous investigations [42][43][44][45][46]48], a plausible mechanism for the coppercatalyzed three-component aminooxygenation of styrenes with NFSI an NHPI is shown in Scheme 2. Initially, the oxidation of Cu(I) with NFSI provided F-Cu(III)-N complex I, which could transform into a copper(II)-stabilized benzenesulfonimide radical II through a redox isomerization equilibrium.Next, the intermolecular radical addition of II to styrene 1g took place, producing benzylic radical III and Cu(II)-F species IV.The combination of the intermediates III and IV gave the Cu(III) species V having a C-Cu bond, which reacted with 2a to generate Cu(III)-O species VI, along with the loss of HF.Finally, the reductive elimination of VI afforded aminooxygenation product 3g.
Finally, we tried to investigate the synthetic value of our new aminooxygenation method.Then, the selective reduction of 3g was conducted (Scheme 3).The cleavage of the N-O bond in 3g readily occurred with Mo(CO) 6 /Et 3 N at 80 °C to give alcohol 4 [36] in 67% yield.Treatment of 3g with NH 2 NH 2 ·H 2 O under mild conditions (25 °C) in CHCl 3 /MeOH gave free amine 5 in 70% yield.
In summary, we have developed a novel copper-catalyzed three-component aminooxygenation reaction of styrenes with NFSI and NHPI derivatives.Furthermore, the aminooxygenation product could be easily converted into the corresponding

Table 1 :
The optimization of reaction conditions a .