- Palladium-catalyzed anti-markovnikov oxidation of allylic amides to protected β-amino aldehydes
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A general method for the preparation of N-protected β-amino aldehydes from allylic amines or linear allylic alcohols is described. Here the Pd(II)-catalyzed oxidation of N-protected allylic amines with benzoquinone is achieved in tBuOH under ambient conditions with excellent selectivity toward the anti-Markovnikov aldehyde products and full retention of configuration at the allylic carbon. The method shows a wide substrate scope and is tolerant of a range of protecting groups. Furthermore, β-amino aldehydes can be obtained directly from protected allylic alcohols via palladium-catalyzed autotandem reactions, and the application of this method to the synthesis of β-peptide aldehydes is described. From a mechanistic perspective, we demonstrate that tBuOH acts as a nucleophile in the reaction and that the initially formed tert-butyl ether undergoes spontaneous loss of isobutene to yield the aldehyde product. Furthermore, tBuOH can be used stoichiometrically, thereby broadening the solvent scope of the reaction. Primary and secondary alcohols do not undergo elimination, allowing the isolation of acetals, which subsequently can be hydrolyzed to their corresponding aldehyde products.
- Dong, Jia Jia,Harvey, Emma C.,Faans-Mastral, Martn,Browne, Wesley R.,Feringa, Ben L.
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p. 17302 - 17307
(2015/02/05)
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- Aldehyde selective Wacker oxidations of phthalimide protected allylic amines: A new catalytic route to β3-amino acids
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(Chemical Equation Presented) A new method for the synthesis of β3-amino acids is presented. Phthalimide protected allylic amines are oxidized under Wacker conditions selectively to aldehydes using PdCl2 and CuCl or Pd(MeCN)2/s
- Weiner, Barbara,Baeza, Alejandro,Jerphagnon, Thomas,Feringa, Ben L.
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scheme or table
p. 9473 - 9474
(2009/12/06)
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- ALPHA2B AND ALPHA2C AGONISTS
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Described herein are compounds that can be useful as bioactive agents. More specifically, the compounds described herein can be useful as both α2B and α2C adrenergic agonists. Methods of synthesis and administration of the compounds are also disclosed.
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Page/Page column 9
(2009/12/02)
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- Discovery of a novel CCR5 antagonist lead compound through fragment assembly
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CCR5, as the major co-receptor for HIV-1 entry, is an attractive novel target for the pharmaceutical industry in the HIV-1 therapeutic area. In this study, based on the structures of maraviroc and 1,4-bis(4-(7-chloroquinolin-4- yl)piperazin-1-yl)butane-1,4-dione (1), which was identified using structure-based virtual screening in conjunction with a calcium mobilization assay, a series of novel small molecule CCR5 antagonists have been designed and synthesized through fragment assembly. Preliminary SARs were obtained, which are in good agreement with the molecular binding model and should prove helpful for future antagonist design. The novel scaffold presented here might also be useful in the development of maraviroc-derived second generation CCR5 antagonists.
- Liu, Yanqing,Zhou, Enkun,Yu, Kunqian,Zhu, Jin,Zhang, Yu,Xie, Xin,Li, Jian,Jiang, Hualiang
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experimental part
p. 2426 - 2441
(2009/04/11)
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- Highly diastereoselective and enantioselective preparation of homoallylic amines: Application for the synthesis of β-amino acids and γ-lactams
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Reactions of N-silyl- and N-aluminoimines with B- allyldiisopinocampheylborane in the presence of methanol, followed by oxidative workup furnished homoallylic amines in good yields and high ee. A 11B NMR spectroscopy study revealed that the reactions do not proceed, even at room temperature, unless a molar equivalent of water or methanol is added. The first reagent-controlled asymmetric crotylboration and alkoxyallylboration of aldimines furnishing β-methyl or βalkoxy homoallylic amines in very high diastereoselectivity and enantioselectivity are reported herein. Crotylboration and alkoxyallylboration of imines proceed only with the "allyl"-boron "ate" complexes, instead of the "allyl"-dialkylboron reagents used with aldehydes. The addition of methanol is necessary for these reactions as well. Application of this methodology for the conversion of representative nitriles to β-amino acids in two steps has been described. Additionally, a procedure for the preparation of chiral δ-amino alcohols and γ-lactams from nitriles is also reported.
- Ramachandran, P. Veeraraghavan,Burghardt, Thomas E.
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p. 4387 - 4395
(2007/10/03)
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