Chiral Bidentate Boryl Ligand Enabled Iridium-Catalyzed Asymmetric C(sp²)–H Borylation of Diarylmethylamines

Abstract

Optically active organoboronic acids and their derivatives are an important family of target compounds in organic chemistry, catalysis, and medicinal chemistry. Yet there are rare asymmetric catalytic examples reported for the synthesis of these compounds via atom and step economic ways. Herein, we report a chelate-directed iridium-catalyzed asymmetric C(sp 2 )−H borylation of aromatic C−H bonds directed by free amine groups. The success of these transformations relies on a novel family of chiral bidentate boryl ligands (L). They can be synthesized straightforwardly in three steps starting from readily available (S,S)-1,2diphenyl-1,2-ethanediamie ((S,S)-DPEN). The Ir-catalyzed C(sp 2 )−H borylation comprises two parts. The first part is desymmetrization of prochiral diarylmethylamines. In the presence of L3/Ir, a vast array of corresponding borylated products were obtained with high regioselectivity and good to excellent enantioselectivities (26 examples, up to 96% ee). The second part, kinetic resolution of racemic diarylmethylamines, was also conducted. Good selectivity values (up to 68%, 11 examples) were obtained when L8 was used. We also demonstrated the synthetic utility of the current method on gram-scale reaction for several transformations.

Synthesis of A Pincer‐IrVComplex with A Base‐Free Alumanyl Ligand and Its Application toward the Dehydrogenation of Alkanes

“…Since transition-metal complexes having X-type boronbased multidentate ligands have found applications in catalysis, [28] one can expect that the present complex 5 could also be applied as acatalyst. Thethermal stability of the alumanylpincer Ir complex 5 enabled the catalytic activity of 5 in the transfer dehydrogenation of cyclooctane (COA) [29] to also be explored (Scheme 3).…”

Enantioselective remote C–H activation directed by a chiral cation

“…Only very recently did Yu and co-workers 20 achieve enantioselective desymmetrization through direct arylation at the arene meta position (Figure 1, C) (33), taking advantage of an ingenious relay strategy via the ortho position, although relatively high loadings of the chiral norbornene mediator (CTM, 20-50 mol%) were required. C-H borylation reactions have the useful attribute that the new C-B bond can undergo numerous diverse transformations (34,35), but so far enantiocontrol in arene borylation has been realized 25 only in two recent reports, from Shi, Hartwig and co-workers (30) and Xu, Ke and co-workers (31). In both cases the chiral information is covalently incorporated into the ligand scaffold in the conventional manner and a directing group guides borylation to the ortho position.…”

Iridium‐Catalyzed Enantioselective Unbiased Methylene C(sp3)–H Borylation of Acyclic Amides

“…In stark contrast, when CBL2 bearing 2,6‐Ph 2 C 6 H 3 at the C5 position of pyridinyl group was used, product 2 was obtained in 44 % yield with 71 % ee after oxidation (Table 1, entry 2). To explain the difference in reactivity between CBL1 and CBL2 , two putative models A and B are proposed as shown in Figure 1 [17c–e] . In model A , due to the lack of steric hindrance in the pyridine ring, two vacant sites of Ir center could be occupied by two substrate molecules, which leads to catalyst deactivation.…”