Enantioselective Copper-Catalyzed Hydroamination of Vinylarenes with Anthranils

Abstract

Copper hydride-catalyzed asymmetric hydroamination of olefins with anthranils has been realized in high efficiency and high enantioselectivity, affording enantioenriched secondary arylamines tethered to a benzylic alcohol. The bifunctionality of the product has been employed in diverse derivatization reactions.

Copper-Catalyzed Asymmetric Hydroamination: A Unified Strategy for the Synthesis of Chiral β-Amino Acid and Its Derivatives

“…Moreover, without any racemization, the chiral center in 5a was observed under harsh conditions [e.g., in the presence of NaOH or trifluoroacetic acid (TFA)], indicating that these types of chiral compounds might have the capacity to transfer into more complicated chiral compounds while maintaining the enantioselectivity. According to previous reports, [40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56]62,63 a mechanism involving a regio-and enantioselective insertion of CuH into C-C double bond in a Michael acceptor to form benzylcopper intermediate, followed by an amination process with hydroxylamine 4 to provide expected chiral β-amino carbonyls, might be possible. Other mechanisms cannot be excluded, and further studies need to be carried out to illuminate the origin of this unusual regio-and enantionselectivity.…”

“…Transition-metal-catalyzed asymmetric hydroamination of unsaturated hydrocarbons is a straightforward and powerful approach for rapid assembly of a variety of biologically active chiral amines. [36][37][38][39] In this context, asymmetric hydroamination of various alkenes and alkynes [40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] with in situ generated CuH catalysts [56][57][58][59][60][61] has attracted much attention since the pioneering reports by Buchwald 62 and Hirano, and Miura in 2013. 63 Besides, an array of electronically matched CuH-catalyzed asymmetric transformations of Michael acceptors, namely undergoing the 1,4-hydrocupration process, have also been disclosed in past decades (Scheme 1b).…”

Iron‐Catalyzed Electrophilic Amination of Sodium Sulfinates with Anthranils

“…First, 2 a reacts with FeCl 2 to give intermediate A , which coordinates with anthranils 1 a to produce intermediate B [17a] . This intermediate undergoes oxidative insertion to the N−O bond of anthranil to afford iron nitrene species C [17b–g] . Finally, 1,1‐migratory insertion of C occurs to give D , [17h] which undergoes hydrolysis to deliver the desired product 3 aa .…”

Anthranils: versatile building blocks in the construction of C–N bonds and N-heterocycles

“…In 2018, the group of Li developed an elegant asymmetric hydroamination of olefins with the use of anthranils as electrophilic aminating reagents (Scheme 5). 10 In this transformation, CuOAc and PhSiH 3 were used to generate the highly reactive CuH species and (S,S)-Ph-BPE proved to be the best ligand. This protocol provided an efficient and highly enantioselective method to construct chiral secondary arylamines tethered to a benzylic alcohol 14.…”