Palladium-Catalyzed Cs₂CO₃-Promoted Arylation of Unactivated C(sp³)–H Bonds by (Diacetoxyiodo)arenes: Shifting the Reactivity of (Diacetoxyiodo)arenes from Acetoxylation to Arylation

Abstract

PdCl2(CH3CN)2-catalyzed arylation of unactivated C(sp(3))-H bonds using (diacetoxyiodo)arenes as arylation reagents is reported. The reactivity of (diacetoxyiodo)arenes as arylation reagents is enabled in the presence of Cs2CO3 under the reaction conditions. This arylation method is highly efficient and occurs without the use of silver salt. The reaction tolerates a broad substrate scope that was not demonstrated by other silver salt-free C(sp(3))-H bond arylation conditions. The synthetic utility of the method is further illustrated in the synthesis of the psychotropic drug phenibut. A detailed mechanism study has been conducted to understand the reaction pathway.

A Guide to Directing Group Removal: 8‐Aminoquinoline

“…Due to the stability of the amide bond, it is extremely challenging to achieve chemoselectivity in the presence of more reactive functional groups, as demonstrated by global deprotection of all acid‐sensitive groups in 49 (Scheme 7). [50] As expected, N ‐Phth ( 51 ) [29] and N ‐Boc ( 52 ) [51] protecting groups are hydrolyzed during AQ‐removal. While benzyl protecting groups are generally inert under the conditions used for acid/base hydrolysis of AQ‐amides ( 54 ), this is not always the case, as can be seen in the base‐mediated AQ‐cleavage of 55 , during which the equatorial O‐Bn group also underwent deprotection [52] …”

Synthesis of Alkyl-Substituted Pyridines by Directed Pd(II)-Catalyzed C–H Activation of Alkanoic Amides

“…Substrates 1c and 1f-1h were prepared through general procedure B. 1c 5 , 1g 6 and 1h 1 were reported and the characterization data obtained are consistent with those reported in the literatures. 2-iodoisonicotinic acid methyl ester 9 and 2-acetamido-5-iodopyridine 10 were produced through known procedures.…”

A comprehensive overview of directing groups applied in metal-catalysed C–H functionalisation chemistry

“…Qin reported on Pd( ii )-catalysed arylation of unactivated aliphatic amides using (diacetoxyiodo)arenes as arylation reagents via a Ag salt-free process, a real asset compared to other approaches ( Scheme 77A ). 461 Note that in this transformation the presence of Cs 2 CO 3 was crucial. The selective mono-functionalisation of secondary C(sp 3 )–H bonds was achieved, albeit in case of a primary C(sp 3 )–H, a mixture of mono- and di-functionalised products was obtained.…”