Sequential Reactions with Grubbs Catalyst and AD-mix-α/β Using PDMS Thimbles

Mwangi, Martin T.; Schülz, Michael; Bowden, Ned B.

doi:10.1021/ol8022215

Cited by 27 publications

(18 citation statements)

References 41 publications

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“…12) Seven-membered heterocyclic rings are considered attractive molecules due to the points of structural determination of natural products as well as their interesting pharmacological actions. [3][4][5] In this paper we applied RCM [13][14][15][16][17][18][19][20][21][22][23][24][25][26] for the formation of seven-membered benzo [3,4]azepino [1,2-b]isoquinolinone 5, and the retrosynthetic pathway of benzo [3,4]azepino [1,2-b]isoquinolinone 5 is depicted in Chart 1. The coupling reaction of toluamide 7 with benzonitrile 8 afforded the 3-arylisoquinolinone 6, which could be modified to diene 4 as a key intermediate for the RCM reaction.…”

mentioning

confidence: 99%

Application of Ring-Closing Metathesis for the Synthesis of Benzo[3,4]azepino[1,2-b]isoquinolin-9-ones

Van

Khadka

et al. 2011

CHEMICAL & PHARMACEUTICAL BULLETIN

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NoteIn order to heal cancer, chemotherapeutic treatments have been investigated over the last several decades.1,2) Conformation studies and synthesis of medium-sized heterocyclic compounds, which have been investigated as the scaffolds of many biologically interesting structures, have received more attention.3-5) Recently, we studied the synthesis of 3-arylisoquinoline derivatives such as indeno [1,2-c] 10) as constrained structures through molecular modeling to find plausible antitumor agents. The diversely rigidified 3-arylisoquinoline analogs exhibited promising cytotoxicities and topoisomerase I inhibitory activities.11) We also reported the convenient synthesis of protoberberines using ring-closing metathesis (RCM) as shown in Fig. 1. 12)Seven-membered heterocyclic rings are considered attractive molecules due to the points of structural determination of natural products as well as their interesting pharmacological actions. [3][4][5] In this paper we applied RCM [13][14][15][16][17][18][19][20][21][22][23][24][25][26] for the formation of seven-membered benzo [3,4]azepino[1,2-b]isoquinolinone 5, and the retrosynthetic pathway of benzo [3,4]azepino [1,2-b]isoquinolinone 5 is depicted in Chart 1. The coupling reaction of toluamide 7 with benzonitrile 8 afforded the 3-arylisoquinolinone 6, which could be modified to diene 4 as a key intermediate for the RCM reaction.The synthetic approach of using the RCM reaction to prepare the seven-membered ring was based on the synthesis of 3-arylisoquinolines 4 that contain olefins at the appropriate positions. To synthesize the 3-arylisoquinoline 6a, a coupling reaction between N,N-diethyl-o-toluamide 7a and benzonitrile 8a was performed (Chart 2).10) Generally, the chemical yield of this reaction is low (33 to 49%) due to the unknown side product and it is quite dependent on the substitution pattern of aromatic rings of the starting materials.10) As a part of our continuous research on natural alkaloids synthesis, including biological evaluation of 3-arylisoquinolines, the coupling reaction of o-toluamides with benzonitriles was utilized to provide the desired molecules.27) Significant increases in the topoisomerase I inhibitory activities of these compounds were observed through conversion of flexible 3-aryl rings to rigid forms such as isoindolo[2,1-b]isoquinolinones, benz-[b]oxepines, 12-oxobenzo[c]phenanthridinones and indeno-[1,2-c]isoquinolines, and molecular docking studies were used to explain the potency of these compounds.11) The above coupling reaction has advantages as a synthetic tool for the construction of 3-arylisoquinolines because it is easily adaptable to starting materials with diverse aromatic ring substitutions and it is a one-pot procedure for the construction of all essential carbon atoms in the desired molecules. Cycloaddition reaction between toluamides and benzonitriles was applied to prepare the 3-arylisoquinolines, and their chemical transformation to the dienes 4 was performed. The ring-closing metathesis (RCM) reaction afforded the desir...

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confidence: 99%

Application of Ring-Closing Metathesis for the Synthesis of Benzo[3,4]azepino[1,2-b]isoquinolin-9-ones

Van

Khadka

et al. 2011

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…PDMS was chosen based on our prior work to site-isolate water, Grignard reagents, butyl lithium, PdCl2, and other catalysts and reagents. 70,71,[77][78][79][80] In this prior work, PDMS successfully retained a wide variety of reagents and catalysts based on their low solubility in hydrophobic PDMS.…”

Section: Resultsmentioning

confidence: 99%

“…These membranes were fabricated similar to methods described in prior work. 70,77,78 Sylgard 184 was mixed with a curing agent in a 10:1 ratio and degassed. The PDMS was poured over a flat glass slide while allowing any excess to flow over the side.…”

Section: Methodsmentioning

confidence: 99%

“…Molecules with carboxylic acids, alcohols, amines, aromatic rings, nitro groups, esters, olefins, epoxides, and ketones readily flux through the walls of PDMS thimbles. 70,71,[77][78][79][80][81][82][83][84][85] For instance, when the molecules shown in Molecules that possessed very low flux through the walls of PDMS thimbles included ionic liquids, p-toluenesulfonic acid, and polystyrene. 79,84 Others have shown that ionic liquids have no solubility within PDMS and our results support this.…”

Section: Pdms Thimblesmentioning

confidence: 99%

“…This method was extended to substrates with intermediates that were challenging to isolate. 77 For instance, a metathesis-dihydroxylation cascade reaction was completed on a challenging substrate (Figure 3.16…”

Section: Site-isolation Of the Grubbs' Second Generationmentioning

confidence: 99%

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