Enantioselective intramolecular C–H amination of aliphatic azides by dual ruthenium and phosphine catalysis

Abstract

By combining a chiral-at-metal ruthenium catalyst with catalytic amounts of tris(p-fluorophenyl)phosphine (both 1 mol%), the challenging catalytic enantioselective ring-closing C(sp3)-H amination of unactivated aliphatic azides has been achieved with high enantioselectivities.

Enantioselective Ring-Closing C–H Amination of Urea Derivatives

“…with exclusive metal-centered chirality (only achiral ligands). 24,26,27 We anticipated that this novel class of catalysts would allow us to address the challenge of accessing chiral 2-imidazolidinones by enantioselective C(sp 3 )-H amination from judiciously chosen urea derivatives. We initiated our study with the N-benzoyloxyurea 1aa (see Scheme S1 for substrate preparation) and envisioned that after release of the benzoate leaving group, an intermediate ruthenium nitrenoid would form and engage in an intramolecular C-H amination.…”

“…[4][5][6][7][8] A variety of functional groups serving as nitrene precursors have been developed and the intramolecular version of the reaction renders directing groups obsolete while exerting high control over the regioselectivity. This has been applied to the catalytic asymmetric synthesis of cyclic sulfamidates, [9][10][11] sulfamides, [12][13][14] sulfonamides, [15][16][17][18] carbamates, 19,20 lactams, [21][22][23][24] Boc-protected pyrrolidines, 25,26 and related Boc-protected heterocycles (Figure 1B). 27 However, interestingly, urea derivatives as nitrene precursors leading to chiral cyclic urea, specifically 2-imidazolidinones, are absent from this list.…”

Mechanism and Chemoselectivity of Mn-Catalyzed Intramolecular Nitrene Transfer Reaction: C–H Amination vs. C=C Aziridination

“…Noble metal such as rhodium [20][21][22], silver [23][24][25], ruthenium [26,27], palladium [28,29] and base metal such as iron [30][31][32], cobalt [33,34], copper [35,36] have been shown to accomplish C(sp 3 )-H aminations. Both of them, however, have some drawbacks in either reactivity or chemoselectivity for such catalysis.…”

Imbuing an Old Heterocycle with the Power of Modern Catalysis: An Isoxazolidin-5-one Story

“…Alkyl nitrenes having C-H bond(s) next to the nitrogen are known to be unstable 55) (Chart 11c), and their use in organic synthesis has been underexplored. [56][57][58][59][60][61][62] When suitably substituted isoxazolidin-5-ones were subjected to a catalytic amount of Rh 2 (esp) 2 in HFIP, the expected spirocyclic β-prolines were exclusively formed 63) (Fig. 6).…”