Palladium/Norbornene‐Catalyzed Indenone Synthesis from Simple Aryl Iodides: Concise Syntheses of Pauciflorol F and Acredinone A

Liu, Feipeng; Dong, Zhe; Wang, Jian-Chun; Dong, Guangbin

doi:10.1002/anie.201813699

Cited by 75 publications

(50 citation statements)

References 84 publications

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“…Mechanism of tethered substrate. We began our mechanistic incursions with the mechanism of Aucatalyzed cyclization of tethered acetal 2-alkynylaldehyde (1a) to form 2-(4-methoxyphenyl)spiro[indene-1,2'- [1,3]dioxolane] (2a) ( Figure 2). The reaction overall composes of five important steps; Au insertion, 1,5-shift, cyclization, 1,2-shift and elimination.…”

Section: Resultsmentioning

confidence: 99%

“…Indenones represent common motifs of carbocycles with a prime of importance in many structurally complex bioactive compounds or natural products. 1 Several synthetic methods of indenone have been shown to give moderate selectivities and yields using gold catalysis, 2,3 iodine-mediated strategy, 4 and organolithium reagents. 5 Therefore, advancing a catalytically efficient approach has motivated and attracted many synthetic groups by which a metal-catalyzed cyclization was a premier rout being targeted.…”

Section: Introductionmentioning

confidence: 99%

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Revealing Mechanism and Origin of Reactivity of Au(I)-Catalyzed Functionalized Indenone Formation of Cyclic and Acyclic Acetals of Alkynylaldehydes

Hussein

Ali²

2020

Preprint

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<p><a>Density functional theory exploited with the (SMD)-B3LYP-D3/def2-TZVP//B3LYP/6-31G(d),LANL2DZ level of theory is presented to offer mechanistic insights and explications of experimentally intriguing observations in the Au(I)-catalyzed cyclization of cyclic and acyclic acetals of alkynylaldehydes that lead to indenone formation. The reactivity of catalytic cycles with and without methoxy migration is computationally defined when alkyne terminus is phenylated in addition to the unreactive cycle when alkyne terminus is not phenylated. The reaction mechanism of indenone formation proceeds first with coordination of Au(I) to alkyne to initiate the reaction with 1,5-H shift as a rate-determining step and the fastest 1,5-H shift is achieved when one phenyl ring carries electron-donating group and the other one is substituted with electron-withdrawing group. The absence of tethered acetal unit considerably outpaces any 1,5-H shift and instead activates 1,5-methoxy migration, giving methoxy-migrated indenone, with the step of 1,2-OMe shift is a rate-limiting step during reaction pathway. Following 1,5-H shift the cyclization and 1,2-H shift are kinetically and thermodynamically feasible, which are followed by elimination to persist the iterative cycle, but the reactivity of both steps is highly affected by the existence of phenyl group on alkyne terminus. The unreactivity of alkyne terminus being not beared a phenyl ring is due to that the cyclization is thermodynamically disfavorable, subsequently deactivating the 1,2-H shift kinetically and thermodynamically. </a></p>

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Revealing Mechanism and Origin of Reactivity of Au(I)-Catalyzed Functionalized Indenone Formation of Cyclic and Acyclic Acetals of Alkynylaldehydes

Hussein

Ali²

2020

Preprint

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“…Among them, we mainly discussed about reactions triggered by six kinds of pathways: (1) acid as the directing group; (2) decarboxylation; (3) deprotonation; (4) nucleophilic methylenes; (5) nucleophilic acids; (6) electrophilic acids. Especially, nucleophilic methylenes, Friedel‐Crafts reaction, nucleophilic acids and electrophilic acids have been used in total synthesis of (−)‐pauciflorol F, moxaverine, (−)‐6‐O‐desmethylantofine and (+)‐6‐O‐desmethylantofine, derivate of salvianolic acid B, communesin F and perophoramidine, (+)‐O‐methylthalibrine, sparstolonin B, lennoxamine, chilenine, fumaridine, 8‐Oxypseudoplamatine, 2‐O‐methyloxyfagaronine, (S)‐equol, xiamenmycin A and (±)‐glabridin . However, challenges still existed: (1) C−N and C−X (X=F, Cl, Br, I) bond may be constructed simultaneously during one procedure by the aid of decarboxylation and formation of radicals; (2) Decarboxylative cross coupling or tandem applications with boron reagent, diazonium salt, 1,3‐dicarbonyls were anticipated; (3) The ketones from reactions of arylacetic acids with aryl acids may function as useful intermediates in tandem reactions and show their significances in construction of diverse heterocycles.…”

Section: Resultsmentioning

confidence: 99%

Arylacetic Acids in Organic Synthesis

et al. 2019

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Arylacetic acids are widely used in organic reactions and their recent advances are summarized in six categories according to their triggered pathways: (1) the acid as directing group in ortho-or meta-CÀ H activation; (2) decarboxylation; (3) deprotonation; (4) nucleophilic methylenes; (5) nucleophilic acids; (6) electrophilic acids. Reactions with alkenes, alkynes, aldehydes, amines, water, Grignard reagents, silanes and so forth are discussed. We hope this Minireview will promote future research in this area. Recently, the Zeng group [3g] reported a weakly coordinationassisted alkynylation of arylacetic acids with iridium catalysis under air atmosphere (Eq. 2-2). It was supported the sixmembered ring cycloiridiated 2.5 acted as the key intermediate. The alkynylation of indole, thiophene, pyrrole, and benzo[b] thiophene afforded better yields than phenylacetic acids. The acid moiety could also participated in the intramolecular ortho-CÀ H activation, which was developed by the Shi group to obtain lactonization 2.6 (Eq. 2-3) (Scheme 2). Meta-CÀ H ArylationThe study of Yu group [3e] in 2017 revealed a successful control of meta selectivity 3.1 of arylation from aryl iodides (Eq. 3-1). The use of mono-protected 3-amino-2-hydroxypyridine (as ligand) and 2-carbomethoxynorbornene (NBE-CO 2 Me) were crucial. In the absence of NBE-CO 2 Me, only ortho-arylated product was obtained. This method was still efficient in a gramsale (Scheme 3). Decarboxylation Decarboxylative CouplingAs shown in Scheme 4, the decarboxylation could generate benzyl radicals 4.1. Then, direct couplings of 4.1 with diverse [ + ] These authors contributed equally. Scheme 1. Six categories based on triggered mechanism. 2 3 4 5 6 7 8 . Passerini Three-Component ReactionThe Passerini reaction was the oldest multicomponent reaction (MCR) [37d] in which isocyanides, carboxylic acids and aldehydes were used. It was powerful for the rapid construction of complex molecules. The tactic to expand the scope of Passerini reaction was to use surrogates of the carbonyl partners. As described in Scheme 51, syn-chlorooximes, [37b] diazoketones, [37c] alcohols, [37d,e] azirines [37f] and isatins [37g] could be employed instead of aryl or alkyl aldehydes [37a] (Scheme 51). Besides, in 2018, Zhang and co-workers [37] have firstly reported asymmetric phosphoric acid-catalyzed four-component Ugi reaction, which Scheme 45. BTM-catalyzed cycloaddition. Scheme 46. HBTM-catalyzed cycloaddition. Scheme 47. TFA-catalyzed reaction. Scheme 48. Friedel-Crafts triggered tandem reactions. Scheme 49. C-acylation of 1,3-diones. Scheme 50. C-acylation of 1,3-indandiones.

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“…Pd/NBE cooperative catalysis 14–16 , originally discovered by Catellani 17 , has emerged as a useful tool for preparing multi-substituted arenes 18–33 . Compared to the conventional arene functionalization, this approach enables simultaneous functionalization of arene vicinal positions regioselectively using simple aryl halides as substrates (Fig.…”

Section: Introductionmentioning

confidence: 99%

Sulfenamide-enabled ortho thiolation of aryl iodides via palladium/norbornene cooperative catalysis

Zhou

Yoon

et al. 2019

Nat Commun

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Poly-substituted aromatic sulfur compounds are widely found in pharmaceuticals, agrochemicals and organic materials. However, the position that a sulfur moiety can be introduced to is largely restricted to a pre-functionalized site; otherwise, use of electronically biased substrates or auxiliary groups that direct catalysis is required. Here we report a general ortho thiolation of common aryl and heteroaryl iodides via palladium-norbornene cooperative catalysis. Using this approach, an aryl or alky sulfur moiety can be site-selectively introduced at the arene ortho position without using sterically or electronically biased substrates. The arene ipso functionalization is simultaneously achieved through Heck, Suzuki or Sonogashira termination. The reaction is enabled by a unique class of electrophiles in palladium-norbornene cooperative catalysis, which are sulfenamides derived from seven-membered lactams. The broad substrates scope and high chemoselectivity could make this method attractive for synthesis of complex sulfur-containing aromatic compounds.

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Palladium/Norbornene‐Catalyzed Indenone Synthesis from Simple Aryl Iodides: Concise Syntheses of Pauciflorol F and Acredinone A

Cited by 75 publications

References 84 publications

Revealing Mechanism and Origin of Reactivity of Au(I)-Catalyzed Functionalized Indenone Formation of Cyclic and Acyclic Acetals of Alkynylaldehydes

Revealing Mechanism and Origin of Reactivity of Au(I)-Catalyzed Functionalized Indenone Formation of Cyclic and Acyclic Acetals of Alkynylaldehydes

Arylacetic Acids in Organic Synthesis

Sulfenamide-enabled ortho thiolation of aryl iodides via palladium/norbornene cooperative catalysis

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