Academic literature on the topic 'Ortho- metalation'

Stephen G. DiMagno of the University of Nebraska developed (Chem. Eur. J. 2015, 21, 6394) a protocol for the clean monoiodination of 1 to 2. The bromomethylation (or chloromethylation, with HCl) of a benzene derivative is straightforward with formal­dehyde and HBr. Naofumi Tsukada of Shizuoka University designed (Organometallics 2015, 34, 1191) a Cu catalyst that mediated the coupling of an alkyne with the benzyl bromide so produced, effecting net propargylation of 3 with 4 to give 5. Triazenes such as 7, versatile intermediates for organic synthesis, are usually prepared by diazotization of the corresponding aniline. Kay Severin of the Ecole Polytechnique Fédérale de Lausanne established (Angew. Chem. Int. Ed. 2015, 54, 302) an alternative route from the aryl Grignard reagent 6. Ping Lu and Yanguang Wang of Zhejiang University showed (Chem. Commun. 2015, 51, 2840) that dimethylformamide could serve as the carbon source for the conversion of 8 to the nitrile 9. Junha Jeon of the University of Texas at Arlington effected (J. Org. Chem. 2015, 80, 4661; Chem. Commun. 2015, 51, 3778) the reductive ortho silylation of 10 to give 11. Vladimir Gevorgyan of the University of Illinois at Chicago found (Angew. Chem. Int. Ed. 2015, 54, 2255) that the phenol derivative 12 could be ortho carboxylated, leading to 13. Lutz Ackermann of the Georg-August-Universität Göttingen, starting (Chem. Eur. J. 2015, 21, 8812) with the designed amide 14, effected ortho metala­tion followed by coupling, to give the methylated product 15. Tetsuya Satoh and Masahiro Miura of Osaka University used (Org. Lett. 2015, 17, 704) the dithiane of 16 to direct ortho metalation. Coupling with acrylate followed by reductive desulfu­rization led to the ester 17. Jin-Quan Yu of Scripps/La Jolla designed (Angew. Chem. Int. Ed. 2015, 54, 888) the phenylacetamide 18 to direct selective meta metalation, leading to the unsat­urated aldehyde 19. In an extension of the Catellani protocol, Guangbin Dong of the University of Texas prepared (J. Am. Chem. Soc. 2015, 137, 5887) the biphenyl 21 by net meta metalation of the benzylamine 20. Several methods for the de novo assembly of benzene derivatives have recently been put forward. Rajeev S. Menon of the Indian Institute of Chemical Technology condensed (Org. Lett. 2015, 17, 1449) the unsaturated aldehyde 22 with the sulfonyl ester 23 to give 24.

The hexacyclic indole diterpenoid paspalinine 3, produced by the ergot Claviceps paspali, induces tremors in domestic animals that graze on pasture grass infected by that fungus. Shigefumi Kuwahara of Tohoku University envisioned (Angew. Chem. Int. Ed. 2012, 51, 12833) assembly of the tetracyclic nucleus of 3 by the oxidative cyclization of 1 to 2. The challenge, then, was the assembly of the angularly substituted trans–anti-trans-6-6-5 alicyclic nucleus of 1. The synthesis began with the Wieland-Miescher ketone 4, which is available commercially in enantiomerically pure form. Exposure to ethylene glycol under acidic conditions converted 4 to the known monoketal 5. The alkylation with 6 followed by selective hydrolysis gave 7 as an inconsequential mixture of diastereomers. Exposure to base effected both equilibration to the more stable equatorial diastereomer and cyclization to give the enone 8. There was still the problem of the introduction of the axial angular methyl group. This was solved by selective reduction of 8 to the endo alcohol. Hydroxyl-directed Simmons-Smith cyclopropanation followed by oxidation gave 9. The enolate resulting from the dissolving metal reduction of 9 was trapped with Comins reagent to generate the enol triflate 10. Acetanilide 11 was converted to the stannane 12 by ortho metalation following the literature protocol. Pd-mediated coupling of 12 with 10 proceeded efficiently to give 1. Oxidation with stoichiometric Pd trifluoroacetate then induced Type 5 indole formation (Tetrahedron 2011, 67, 7195). Hydrolysis and conjugation completed the synthesis of 2. To introduce the sidechain, the enone was converted to the allyl enol carbonate. Pd-mediated rearrangement converted that to the α-allyl enone, which participated in Ru-catalyzed metathesis with 14 to give 15. Asymmetric dihydroxylation proceeded with only modest diastereoselectivity, but only the desired diastereomer cyclized onto the ketone to give 16. The ketone 16 was an intermediate in Smith’s earlier synthesis. Professor Kuwahara devised an alternate end game, selenylation followed by oxidation and sigmatropic rearrangement, to install the axial OH and complete the synthesis of paspalinine 3.