Twofold C−H Activation‐Based Enantio‐ and Diastereoselective C−H Arylation Using Diarylacetylenes as Rare Arylating Reagents

Abstract

C-H bond activation has been established as an attractive strategy to access axially chiral biaryls, and the most straightforward method is direct C-H arylation of arenes. However, the arylating source has been limited to several classes of reactive and bulky reagents. Reported herein is rhodium-catalyzed 1:2 coupling of diarylphosphinic amides and diarylacetylenes for enantio-and diastereoselective construction of biaryls with both central and axial chirality. This twofold C-H activation reaction stays contrast to the previously explored Miura-Satoh type 1:2 coupling of arenes and alkynes in terms of chemoselectivity and proceeded under mild conditions with the alkyne acting as a rare arylating reagent. Both C-H activation events are stereo-determining and are under catalyst control, with the 2 nd C-H activation being diastereo-determining in a remote fashion. Analysis of the stereochemistries of the major and side products suggests moderated enantioselectivity of the initial C-H activation-desymmetrization process. However, the minor stereoisomeric (R) intermediate is consumed more readily in undesired protonolysis, eventually resulting in high enantio-and diastereoselectivity of the major product. File list (2) download file view on ChemRxiv manuscript.pdf (656.75 KiB) download file view on ChemRxiv SI.pdf (4.50 MiB)

Iridium-Catalyzed Enantioselective C–H Borylation of Diarylphosphinates

“…Apart from using chiral auxiliaries and resolution techniques, catalytic asymmetric methods, such as C–H activation, phenolic OH functionalization, alkyne diversification, allyl alkylation reaction, phosphonoalkylation/arylation/amination, ring-closing metathesis, halogenative cyclization, hydroarylation, and hydrophosphination, have emerged as viable tools in the past years. In particular, transition-metal-catalyzed asymmetric C–H activation has received considerable interest .…”

Twofold C−H Activation‐Based Enantio‐ and Diastereoselective C−H Arylation Using Diarylacetylenes as Rare Arylating Reagents

“…Theabsolute configuration of 3 has been determined by X-ray crystallography (CCDC 2006608). [19] Table 1: Initial optimizationo fthe directing group. [a] [a] Reaction conditions: 1 (0.05 mmol), 2a (0.15 mmol), (R)-Rh1 (4 mol %), AgOTf(16 mol %), AgOAc (0.15 mmol), CyCO 2 H(0.1 mmol), DCM (1 mL), 24 h, 50 8 8C.…”

“…Ther eaction seemed sensitive to steric effect;introduction of an ortho Me group inhibited the reaction. Other N,N-dialkylphosphinamides reacted with slightly lower enantioselectivity (18)(19)(20)(21). Similarly,t ertiary alkyl amine-derived phosphinamides also reacted with attenuated enantioselectivity (22 and 23).…”

Synthesis of Atropisomers by Transition-Metal-Catalyzed Asymmetric C–H Functionalization Reactions

“…In a further development, Li et al applied de novo construction of aromatic rings to achieve the coupling of phosphinamides 99 with two diarylacetylenes for the synthesis of axially chiral biaryls 100 bearing a P-stereogenic center under mild conditions and with high diastereo- and enantio­selectivities (up to >19:1 dr and 96% ee, Scheme ). The reaction first proceeds by C–H activation, likely via carboxylate-assisted CMD and insertion of the first equivalent of diphenylacetylene to give intermediate I , which undergoes cis – trans isomerization to afford Rh­(III) vinyl intermediate J . A stable rhodacyclic intermediate K is generated after the second ortho C–H activation, and insertion of a second equivalent of diphenylacetylene followed by reductive elimination leads to the formation of product 100 .…”