Facile Synthesis of Alkylidene Phthalides by Rhodium‐Catalyzed Domino C−H Acylation/Annulation of Benzamides with Aliphatic Carboxylic Acids

Abstract

The Rh-catalyzed ortho-C(sp 2 )À H functionalization of 8-aminoquinoline-derived benzamides with aliphatic acyl fluorides generated in situ from the corresponding acids has been developed. This reaction initiated with 8-aminoquinoline-directed ortho-C(sp 2 )À H acylation, which was accompanied by subsequent intramolecular nucleophilic acyl substitution of amide group to produce alkylidene phthalides This approach exhibits high stereo-selectivity for Z-isomer products, and tolerates a variety of functional groups as well as aliphatic carboxylic acids with diverse structural scaffolds.The directing-group-assisted transition metal-catalyzed CÀ H bond functionalization reactions have been explored extensively over the last decades and therefore evolved into a powerful synthetic tool to rapidly forge new carbon-carbon and carbon-heteroatom bonds. [1] In this context, 8-aminoqunoline has been identified as a versatile bidentate auxiliary directing group to streamline syntheses of bioactive compounds via CÀ H bonds functionalization (Scheme 1a). [2] Among these approaches, the downstream conversion or removal of 8-aminoquinoline normally requires extra synthetic steps and harsh conditions, which are incompatible with certain subtle functionalities thus posing an obstacle to their synthetic applications. [3] To circumvent the manipulation of undesired directing groups, an ideal process is that directing-group-assisted CÀ H functionalization perform in tandem with subsequent transformations of directing groups, as demonstrated by Scheme 1b. [4] The methods established in this domain generally require the utilization of specific amides as directing groups, such as activated tertiary amides [4e-i] and secondary amides, [4j-t] which probably because their weakened amide CÀ N bonds due to steric distortion. [5] In spite of these significant progresses, the protocols that involve 8-aminoquinoline-based amide-directed CÀ H bond functionalization and subsequent conversion of 8aminoquinoline in a tandem manner remain rare. In this regard, only a handful of pioneering researches have been recently reported by Hirano and Miura, [6] Chatani, [7] Cheng [8] and Zhang, [9] which employed 8-aminoquinoline-based amide directing groups to promote CÀ H bond functionalization while forming additional CÀ O or CÀ C bonds in a one-pot cascade fashion (Scheme 1c). In these transformations, the 8-aminoquinoline released through carbon-nitrogen bond cleavage could be [a]

Preparation of 3‐Alkylidenephthalides: Recent Advances

“…More recently, Su and Shang developed a rhodium‐catalyzed protocol for cascade C−H acylation/intramolecular nucleophilic acyl substitution of benzamides with a large range of available carboxylic acids using 8‐aminoquinoline as directing group (Scheme 33). [40] Aliphatic acyl fluorides were generated in situ from the corresponding acids using fluoro‐dipyrrolidinocarbenium‐hexafluorophosphate (BTFFH) as fluorinating reagent.…”