Synthesis of α‐Aminophosphines by Copper‐Catalyzed Regioselective Hydroamination of Vinylphosphines

Abstract

A copper-catalyzed net hydroamination of vinylphosphine boranes with hydrosilanes and O-benzoylhydroxylamines has been developed. The reaction proceeds regioselectively to form the corresponding α-aminophosphine boranes of potent interest in medicinal and pharmaceutical chemistry. This copper catalysis is based on an umpolung, electrophilic amination strategy and provides a new electrophilic amination approach to α-aminophosphine derivatives. Additionally, although still preliminary, asymmetric synthesis has also been achieved by judicious choice of a chiral bisphosphine-ligated copper complex.

Regio‐ and Enantioselective Formal Hydroamination of Enamines for the Synthesis of 1,2‐Diamines

“…In 2013, the groups of Hirano, Miura, and Buchwald independently developed an efficient copper(I) hydride protocol for the regio‐ and enantioselective formal hydroamination of olefins. Since then, this approach has been well demonstrated for a variety of substrates, and has established its broad generality and applicability . We speculated that this approach could be extended to the regio‐ and enantioselective formal hydroamination of enamines, thus allowing ready access to 1,2‐diamines, and herein report our results (Scheme c).…”

Cobalt-Catalyzed Hydroamination of Alkenes with 5-Substituted Tetrazoles: Facile Access to 2,5-Disubstituted Tetrazoles and Asymmetric Intermolecular Hydroaminations

“…In particular, the asymmetric intermolecular hydroamination of nonactivated olefins still remains one of the unsolved challenges in modern synthetic organic chemistry, 19) with reported reactions resulting in low enantioselectivity 20) or requiring activated olefin substrates, such as styrenes, 20-28) allenes, 5) dienes, 29,30) allylamines, [31][32][33] etc. [6][7][8][9][10][11][34][35][36][37][38][39][40][41][42] We chose 1a, 1g, and 1l as test substrates for the asymmetric reaction. Although the asymmetric induction on 1a did not improve beyond 20% enantiomeric excess (ee) with any of the tested catalysts, 1g with (S,S)-Co5 and 1l with (S,S)-Co6 gave (−)-3g and (+)-3l with a moderate enantioselectivity 46% ee and 39% ee, respectively (entries 4 and 5).…”

Earth-Abundant 3d Transition Metal Catalysts for Hydroalkoxylation and Hydroamination of Unactivated Alkenes

“…It is indeed efficient for the regio-and enantiocontrolled hydroamination of vinylsilanes [148], 1,1-disubstitued alkenes [149], symmetric [150] or unsymmetrical (E)-1,2dialkylsubstituted alkenes [151] (including the feedstock olefin, (E)-2-butene [146]), alkenyl 1,8-diaminonaphthyl boronates [152], vinylphosphine boranes [153], 1-trifluoromethylalkenes [154], enamines [155], N-protected γ-substituted allylic amines [156], unprotected allylic alcohols [157] delivering a range of structurally diverse β-chiral, αand β-functionalized tertiary amines in moderate-to-high enantiopurity as privileged building blocks (Figure 25). Although minimal alteration of the initial reaction conditions using the DTBM-SEGPHOS ligand (L 3 ) as privileged ancillary ligand is usually required, structural optimization of the amine transfer agent, hydrosilane, ligand and substrate or use of additional monodentate phosphine ligand (PPh 3 , P(p-tolyl )3 ), proton source (tBuOH) or specific external bases (Li-OtBu, CsOAc) was needed in some cases to broaden the scope to new compound families and/or overall improve the process efficiency.…”

“…Although minimal alteration of the initial reaction conditions using the DTBM-SEGPHOS ligand (L 3 ) as privileged ancillary ligand is usually required, structural optimization of the amine transfer agent, hydrosilane, ligand and substrate or use of additional monodentate phosphine ligand (PPh 3 , P(p-tolyl )3 ), proton source (tBuOH) or specific external bases (Li-OtBu, CsOAc) was needed in some cases to broaden the scope to new compound families and/or overall improve the process efficiency. For instance, the use of an electron-enriched amine transfer agent (such as p-NMe 2 C 6 H 4 CO 2 NR 1 R 2 ) instead of the original BzONR 1 R 2 was crucial for the productive enantioselective transformation of the challenging unactivated internal alkenes [146], vinylphosphine boranes [149], enamines [151], allylic amines and alcohols [152,153]. This electronic effect may result in a better ability to restore the competent active Cu(I)-H in the rate-determing transmetation step for the catalytic cycle and a dismished non-productive deterioration of the electrophilic amine by the catalyst.…”