A Chiral Rhodium Carboxamidate Catalyst for Enantioselective C−H Amination

Abstract

Catalytic intramolecular C-H amination has advanced as a general technology for chemical synthesis. 1 The utility of the heterocyclic products fashioned from such processes validates efforts to identify chiral transition-metal complexes capable of effecting asymmetric insertion (Figure 1). On a more fundamental level, the challenges associated with the design of a catalytic system able to support a reactive oxidant that can discriminate between two hydrogen atoms on a prochiral methylene center are significant. Nonetheless, success of this type has been realized in enantioselective C-H insertion reactions of diazoalkane derivatives and in select instances involving intra-and intermolecular C-Hamination. 2-5 This report describes the development and performance of Rh 2 (S-nap) 4 , a valerolactam-derived dirhodium complex that affords some of the highest levels of asymmetric control to date in cyclization reactions of sulfamate esters. The strong preference of this catalyst for promoting allylic C-H bond insertion is also highlighted.Our earliest efforts to identify chiral catalysts for asymmetric C-H amination focused primarily on dirhodium tetracarboxylate complexes derived from α-amino acids. In all cases examined, cyclized sulfamate products were formed with conspicuously poor enantiomeric induction (0-20% ee). Studies to evaluate % ee as a function of product conversion clearly established that the enantiomeric ratio was decreasing over the reaction time course. Such results are indicative of a change in catalyst structure owing to the lability of the bridging carboxylate groups. Our interest thus turned toward alternative classes of ligands including carboxamide-based designs. In principle, the strongly donating carboxamidate groups increase the capacity of the dirhodium centers for backbonding to the π-acidic nitrene ligand, thus affording a more stable and potentially more discriminating oxidant. 6,7 Unfortunately, simple dirhodium tetracarboxamidate complexes such as Rh 2 (cap) 4 1 are ineffective catalysts for C -H amination because of their propensity to undergo facile one-electron oxidation when combined with PhI(OAc) 2 or related hypervalent iodine reagents (Figure 2). 8 The resulting mixed-valent Rh 2+ /Rh 3+ dimer appears to be catalytically inactive for C-H amination. Accordingly, in order for a dirhodium carboxamide to promote nitrene-mediated insertion, we concluded that its oxidation potential would have to be increased significantly relative to that of Rh 2 (cap) 4 .The basis for the design of Rh 2 (S-nap) 4 4 was Rh 2 (PTPI) 4 2, a complex originally developed by Hashimoto for asymmetric alkene cyclopropanation (Figure 2). 9 The measured Rh 2+ / Rh 2+ →Rh 2+ /Rh 3+ redox potential for Rh 2 (PTPI) 4 is 120 mV vs SCE, marking the rather significant influence of the proximal phthalimide group on the donating strength of the carboxamidate ligand. 10 We reasoned that replacement of the phthalimide moiety with a 2°s ulfonamide would allow for intramolecular hydrogen bonding between the N-H and the E...

Complementary Strategies for Directed C(sp3)−H Functionalization: A Comparison of Transition‐Metal‐Catalyzed Activation, Hydrogen Atom Transfer, and Carbene/Nitrene Transfer

“…This is exemplified by reports from the groups of Che, [198] Davis, [199] and Du Bois. [200] Ah ighly enantioselective asymmetric intramolecular nitrene transfer to unactivated C(sp 3 ) À Hb onds remains to be developed. Similar to transition-metal catalysis,b ut in contrast to radical reactions,the cyclic transition state for intramolecular carbene/nitrene transfer provides an opportunity for ap reexisting stereogenic center to communicate effectively with aforming one.T hus,ahigh level of diastereomeric control is sometimes observed.…”

Palladium(II)‐katalysierte C‐H‐Aktivierung/C‐C‐Kreuzkupplung: Vielseitigkeit und Anwendbarkeit

“…[90] Kürzlich wurde auch über eine enantioselektive Nitreninsertion als vielversprechende asymmetrische C-H-Aminierungsmethode berichtet. [91] Trotz aller Erfolge bei der Entwicklung der Pd-katalysierten asymmetrischen Katalyse erbrachten die Studien zur enantioselektiven Funktionalisierung von C-H-Bindungen über eine Pd-Insertion bislang kaum positive Ergebnisse. [92][93][94][95] Es scheint, dass vor allem zwei Probleme die Weiterent- -katalysierten C-H-Aktivierung/C-C-Kupplung erzielen konnten, nahmen wir uns vor, enantioselektive Varianten dieser Reaktionen zu entwickeln (Schema 57).…”

Alkane Catalytic Functionalization by Carbene or Nitrene Insertion Reactions

“…In the rhodium case, some authors have proposed the concerted pathway, although not all the experimental evidences are in complete accord with this. For instance, work by Müller [103,126] proposed the one step mechanism on the basis of several experiments (also supported by Du Bois' studies) [127,128] whereas Dauban has shown some doubts due to the collection of contradictory data: [129] Hammett analyses supported the concerted pathway but KIE studies did not. DFT studies have shown that singlet and triplet states for Rh 2 -II, II -NR are very close in energy [130], and therefore small changes in the catalytic system could influence the reaction pathway.…”