Herein, we disclose the first metal-free synthesis of primary aromatic amines from arylboronic acids, a reaction that has eluded synthetic chemists for decades. This remarkable transformation affords ...structurally diverse primary arylamines in good chemical yields, including a variety of halogenated primary anilines that often cannot be prepared via transition-metal-catalyzed amination. The reaction is operationally simple, requires only a slight excess of aminating agent, proceeds under neutral or basic conditions, and, importantly, can be scaled up to provide multigram quantities of primary anilines. Density functional calculations reveal that the most likely mechanism involves a facile 1,2-aryl migration and that the presence of an ortho nitro group in the aminating agent plays a critical role in lowering the free energy barrier of the 1,2-aryl migration step.
A hydroxylamine-derived electrophilic aminating reagent produces a transient and bulky aminium radical intermediate upon in situ activation by either TMSOTf or TFA and a subsequent electron transfer ...from an iron(II) catalyst. Density functional theory calculations were used to examine the regioselectivity of arene C–H amination reactions on diversely substituted arenes. The calculations suggest a simple charge-controlled regioselectivity model that enables prediction of the major C(sp2)–H amination product.
The importance of axial chirality in enantioselective synthesis has been widely recognized for decades. The practical access to certain structures such as biaryl amino phenols known as NOBINs in ...enantiopure form, however, still remains a challenge. In drug delivery, the incorporation of axially chiral molecules in systematic screening has also received a great deal of interest in recent years, which calls for innovation and practical synthesis of structurally different axially chiral entities. Herein we present an operationally simple catalytic N-alkylation of sulfonamides using commercially available chiral amine catalysts to deliver two important classes of axially chiral compounds: structurally diverse NOBIN analogs as well as axially chiral N-aryl sulfonamides in excellent enantiopurity. Structurally related chiral sulfonamide has shown great potential in drug molecules but enantioselective synthesis of them has never been accomplished before. The practical catalytic procedures of our methods also bode well for their wide application in enantioselective synthesis.
Streamlining amine synthesis Kuerti, Laszlo
Science (American Association for the Advancement of Science),
05/2015, Letnik:
348, Številka:
6237
Journal Article
Recenzirano
Bulky amine groups that help make many drugs more bioavailable can be added readily to organic compounds
Also see Research Article by
Gui
et al.
Amines, a collective name for compounds that contain ...one or more nitrogen atoms, and their derivatives make up the overwhelming majority of drug molecules and agrochemicals, as well as many compounds that are produced by plants and living organisms (i.e., natural products) (
1
,
2
). Not surprisingly, organic chemists spend a considerable amount of time with the synthesis and late-stage functionalization of amines. On page 886 of this issue, Gui
et al.
(
3
) report a highly innovative iron-catalyzed cross-coupling of olefins with nitroarenes, both of which are readily available and inexpensive, to afford bulky secondary arylamines that are either very difficult to obtain or inaccessible with existing methods.
O-Unprotected keto- and aldoximes are readily C-allylated with allyl diisopropyl boronate in the presence of arylboronic acid catalysts to yield highly substituted N-α-secondary and tertiary ...homoallylic hydroxylamines. The method was used in the total synthesis of the trace alkaloid N-Me-Euphococcine.
A new molecular rearrangement, the aza-Quasi-Favorskii rearrangement, has been developed for the construction of highly substituted aziridines. Electron-deficient O-sulfonyl oximes react readily with ...α,α-disubstituted acetophenone-derived enolates to furnish highly substituted aziridines via this unprecedented domino process. In-depth computational studies reveal an asynchronous yet concerted nitrenoid-type rearrangement pathway.
Methods for generating solvated electronsfree electrons in solutionhave focused primarily on alkali metal ionization or high-energy electrons or photons. Here we report the generation of solvated ...electrons by exciting the plasmon resonance of Al nanocrystals suspended in solution with visible light. Two chemical reactions were performed: a radical-addition reaction with the spin-trap 2-methyl-2-nitrosopropane, and a model cyclization reaction with the radical clock 6-bromohex-1-ene. A quantum efficiency of at least ∼1.1% for plasmon absorbed photon to solvated electron generation can be inferred from the measured radical clock reaction concentration. This study demonstrates a simple way to generate solvated electrons for driving reductive organic chemical reactions in a quantifiable and controlled manner.
The biosynthetic origins of the structurally related racemic isoxazolidine Papaveraceae alkaloids Setigerumine I, Dactylicapnosinine and Dactylicapnosine have remained elusive since their original ...isolation over two decades ago. Herein we report the first biosynthetic hypothesis for their formation and, inspired by it, the first synthesis of (±)‐Setigerumine I with accompanying computational rationale. Based on the results, these isoxazolidine alkaloids arise from racemizing oxidative rearrangements of prominent isoquinoline alkaloids Noscapine and Hydrastine. The key steps featured in this synthesis are a room temperature Cope elimination and a domino oxidation/inverse‐electron demand 1,3‐dipolar cycloaddition of an axially chiral, yet configurationally unstable, intermediate. The work opens this previously inaccessible family of natural products for biological studies.
The first synthesis of (±)‐Setigerumine I, an isoxazolidine Papaveraceae alkaloid, is realized through a biomimetic strategy. The synthesis sheds light to the possible biosynthetic origins of these elusive natural product family members.
A method for the synthesis of highly substituted cyclopropanes via a quasi-Favorskii rearrangement is described. The method includes the combination two chemical transformations starting from ...α,α-dichlorocyclobutanones prepared via the 2 + 2 Staudinger ketene cycloaddition between either terminal- or cis-olefins and dichloroketene. First, α,α-dichlorocyclobutanones are reacted with organocerium reagents to afford the corresponding tertiary alcohols in good to excellent yields through a nucleophilic addition reaction that provided exclusively anti-products. Second, upon irreversible deprotonation, the tertiary α,α-dichlorocyclobutanols underwent a ring-contraction reaction (i.e., quasi-Favorskii rearrangement) to form structurally diverse cyclopropanes in moderate to good yields. The syn-stereoselectivity during the quasi-Favorskii rearrangement was evaluated using DFT analysis.
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