Rh(III)-Catalyzed Atroposelective C–H Iodination of 1-Aryl Isoquinolines

Abstract

The rhodium-catalyzed enantioselective C–H iodination of 1-aryl isoquinolines under mild conditions is disclosed. Direct C–H iodination of 1-aryl isoquinolines with N-iodosuccinimide (NIS) catalyzed by chiral CpRh(III) complexes afforded a series of axially chiral biaryl iodides in excellent yields and enantioselectivity (up to 99% yield and 97% ee). Furthermore, the atroposelective C–H bromination and chlorination reactions were also compatible. Notably, the axially chiral biaryl iodides could be easily transformed to QUINAP-type and N,N-type chiral ligands.

Construction of unsymmetrical heterobiaryls via the Cp*Rh(iii)-catalysed C–H/C–H coupling of heteroarenes

“…As this process is feasible under the reaction conditions, further oxidation of Rh( iv ) to Rh( v ) is not considered. 17 In complex 2 I IV , the spin density is mainly located on Rh, which confirms that Rh is oxidized during the oxidation reaction (Fig. S5, ESI†).…”

“…On the basis of literature reports 17,18 and mechanistic results, a tentative mechanism is postulated (Scheme 1). First, QNO undergoes C–H activation in the presence of OPiv − ion to generate a five-membered rhodacycle [ I ].…”

“…In the presence of 2a , <5% deuteration at the C8-position of 1a showed that the benzoxazolylation process is faster than the protodemetallation of a rhodacycle intermediate (Scheme S6, ESI†). 14 Kinetic isotope effect studies showed that the C–H activation step may be the rate-determining step (RDS) (Schemes S8 and S9, ESI†).…”

“…DFT calculations were performed to explore the reaction mechanism involving the Cp*Rh-catalyzed directed C–H heteroarylation, 15 as well as the role of additives in the developed reaction conditions. 16 The current oxidative coupling reaction 17 involves the C–H activation of 1 and 2 , reductive elimination, and reoxidation of the Cp*Rh catalyst by the Ag-oxidant. Hence, there are many probable paths by which the reaction can proceed (Fig.…”

“…The Ag-complexes are known to oxidise Cp*Rh( iii ) and Cp*Ir( iii ) complexes and help in reductive elimination. 17 Hence, the probable oxidation of species H is explored before reductive elimination. Reductive elimination from Rh( iv ) ( 2 H IV ) is kinetically accessible with a 12.4 kcal mol −1 barrier and is exergonic by 15.6 kcal mol −1 .…”