218900-28-8Relevant articles and documents
Palladium-Catalyzed C(sp3)-H Arylation of N-Boc Benzylalkylamines via a Deprotonative Cross-Coupling Process
Hussain, Nusrah,Kim, Byeong-Seon,Walsh, Patrick J.
supporting information, p. 11010 - 11013 (2015/11/10)
Diarylmethylamines are key intermediates and products in the pharmaceutical industry. Herein we disclose a novel method toward the synthesis of these important compounds via C-H functionalization. Presented is a reversible deprotonation of N-Boc benzylalkylamines at the benzylic C-H with in situ arylation by a NiXantPhos-based palladium catalyst (50-93 % yield, 29 examples). The method is also successful with N-Boc-tetrahydroisoquinolines. The advantages of this method are it avoids strong bases, low temperatures, and the need to transmetallate to main group metals for the coupling. Skipping steps! Diarylmethylamines are key intermediates and products in the pharmaceutical industry. A novel method toward the synthesis of these important compounds via C-H functionalization is reported. A reversible deprotonation of N-Boc benzylalkylamines at the benzylic C-H is coupled with in situ arylation with a (NiXantPhos)Pd-based catalyst (50-93 % yield, 29 examples). The advantages of this method are that it avoids strong bases, low temperatures, and the need to transmetallate to main group metals for the coupling.
One-pot reductive coupling of N-acylcarbamates with activated alkenes: Application to the asymmetric synthesis of pyrrolo[1,2-a]azepin-5-one ring system and (-)-xenovenine
Liu, Xue-Kui,Zheng, Xiao,Ruan, Yuan-Ping,Ma, Jie,Huang, Pei-Qiang
scheme or table, p. 1275 - 1284 (2012/03/07)
The one-pot reductive coupling of N-acylcarbamates with activated alkenes is described. The method is based on partial reduction of N-acylcarbamates with DIBAL-H, followed by N-acyliminium ion formation and SmI2-mediated radical coupling with activated alkenes. Both acyclic and cyclic N-acylcarbamates can be used as stable substrates, and a range of activated alkenes serve as effective radical receptors. The reductive coupling of l-N-acylcarbamates 12/13 gave 2,5-disubstituted pyrrolidine derivatives in high trans-diastereoselectivities. The reductive coupling with penta-2,4-dienoate proceeded exclusively in a 1,6-addition fashion, producing a single non-conjugated E-isomer. On the basis of this method, a three-step construction of pyrrolo[1,2-a]azepin-5-one 16, the skeleton of many stemona alkaloids and lehmizidine alkaloids, and a seven-step synthesis of (-)-xenovenine (pyrrolizidine cis-223H, ent-6), the unnatural enantiomer of the frog/ant venom alkaloid possessing potent inhibitory activity towards nAChR channel, were achieved starting from l-12. The Royal Society of Chemistry 2012.
Reactivity and Enantioselectivity in the Reactions of Scalemic Stereogenic α-(N-Carbamoyl)alkylcuprates
Dieter, R. Karl,Oba, Gabriel,Chandupatla, Kishan R.,Topping, Chris M.,Lu, Kai,Watson, Rhett T.
, p. 3076 - 3086 (2007/10/03)
Stereogenic 2-(N-carbamoyl)pyrrolidinylcuprates prepared from scalemic (i.e., enantioenriched) N-Boc-2-lithiopyrrolidine and THF soluble CuCN·2LiCl react with vinyl iodides, vinyl triflates, β-iodo-α,β-enoates, propargyl mesylates, and allyl bromide to afford the substitution products with excellent enantioselectivity. Excellent enantiomeric ratios are obtained in the conjugate addition reactions with methyl vinyl ketone while low enantiomeric ratios can be achieved with acrylate esters using HMPA/TMSCl activation. Enantiomeric ratios vary with substrate substitution patterns and the observed enantioselectivities appear to be more a function of cuprate-electrophile reactivities than of the reaction type (e.g., substitution, conjugate addition). Low enantiomeric ratios are obtained with the α-(N-carbamoyl)benzylcuprates. The lithium-copper transmetalation and cuprate vinylation reactions proceed with retention of configuration.
