63028-10-4Relevant articles and documents
Three-Component Difunctionalization of Cyclohexenyl Triflates: Direct Access to Versatile Cyclohexenes via Cyclohexynes
Cho, Seoyoung,McLaren, E. J.,Wang, Qiu
supporting information, p. 26332 - 26336 (2021/11/10)
Difunctionalization of strained cyclic alkynes presents a powerful strategy to build richly functionalized cyclic alkenes in an expedient fashion. Herein we disclose an efficient and flexible approach to achieve carbohalogenation, dicarbofunctionalization, aminohalogenation and aminocarbonation of readily available cyclohexenyl triflates. We have demonstrated the novel use of zincate base/nucleophile system for effective formation of key cyclohexyne intermediates and selective addition of various carbon and nitrogen nucleophiles. Importantly, leveraging the resulting organozincates enables the incorporation of a broad range of electrophilic partners to deliver structurally diverse cyclohexene motifs. The importance and utility of this method is also exemplified by the modularity of this approach and the ease in which even highly complex polycyclic scaffolds can be accessed in one step.
DIELS-ALDER CONJUGATION METHODS
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Paragraph 0529-0530, (2021/10/22)
Described herein are protein-payload conjugates and compositions thereof that are useful, for example, for target-specific delivery of therapeutic and/or imaging agent moieties. In certain embodiments, provided are specific and efficient methods for produ
Divergent Synthesis of Bioactive Dithiodiketopiperazine Natural Products Based on a Double C(sp3)?H Activation Strategy
Thesmar, Pierre,Coomar, Seemon,Prescimone, Alessandro,H?ussinger, Daniel,Gillingham, Dennis,Baudoin, Olivier
supporting information, p. 15298 - 15312 (2020/10/21)
This article provides a detailed report of our efforts to synthesize the dithiodiketopiperazine (DTP) natural products (?)-epicoccin G and (?)-rostratin A using a double C(sp3)?H activation strategy. The strategy's viability was first established on a model system lacking the C8/C8’ alcohols. Then, an efficient stereoselective route including an organocatalytic epoxidation was secured to access a key bis-triflate substrate. This bis-triflate served as the functional handles for the key transformation of the synthesis: a double C(sp3)?H activation. The successful double activation opened access to a common intermediate for both natural products in high overall yield and on a multigram scale. After several unsuccessful attempts, this intermediate was efficiently converted to (?)-epicoccin G and to the more challenging (?)-rostratin A via suitable oxidation/reduction and protecting group sequences, and via a final sulfuration that occurred in good yield and high diastereoselectivity. These efforts culminated in the synthesis of (?)-epicoccin G and (?)-rostratin A in high overall yields (19.6 % over 14 steps and 12.7 % over 17 steps, respectively), with the latter being obtained on a 500 mg scale. Toxicity assessments of these natural products and several analogues (including the newly synthesized epicoccin K) in the leukemia cell line K562 confirmed the importance of the disulfide bridge for activity and identified dianhydrorostratin A as a 20x more potent analogue.
Transition-Metal-Free Allylic Borylation of 1,3-Dienes
Maza, Ricardo J.,Davenport, Elliot,Miralles, Núria,Carbó, Jorge J.,Fernández, Elena
supporting information, p. 2251 - 2255 (2019/04/10)
This work explains the reactivity of diboron reagents with 1,3-dienes in a transition-metal-free context. The sole addition of Na2CO3 (30 mol %) to bis(pinacolato)diboron in MeOH allows the 1,4-hydroboration of cyclic and noncyclic 1,3-dienes. The electronic influence on the substrate guarantees the conjugated 1,4-hydroboration versus 1,2-diboration. DFT calculations show that the distribution of charge in the allylic anion intermediate governs the selectivity toward 1,4-hydroboration, while the favored trans configuration in diene reagents determines the preference for the E allyl boronate products.
Chiral Supramolecular U-Shaped Catalysts Induce the Multiselective Diels-Alder Reaction of Propargyl Aldehyde
Hatano, Manabu,Sakamoto, Tatsuhiro,Mizuno, Tomokazu,Goto, Yuta,Ishihara, Kazuaki
supporting information, p. 16253 - 16263 (2018/11/27)
The Diels-Alder reaction, which is a traditional [4 + 2] cycloaddition with two carbon-carbon bond formations, is one of the most powerful tools to synthesize versatile and unique six-membered rings. We show that chiral supramolecular U-shaped boron Lewis acid catalysts promote the unprecedented multiselective Diels-Alder reaction of propargyl aldehyde with cyclic dienes. Independent from the substrate control, enantio-, endo/exo-, π-facial-, regio-, site-, and substrate-selectivities could be controlled by the present U-shaped catalysts. The obtained reaction products could access the concise synthesis of chiral diene ligands and a key intermediate of (+)-sarkomycin. The results presented here might partially contribute to the development of artificial enzyme-like supramolecular catalysts for multiselective reactions, which will be able to target organic compounds that have thus far eluded synthesis.
Synthesis of Polycyclic Nitrogen Heterocycles via Cascade Pd-Catalyzed Alkene Carboamination/Diels-Alder Reactions
White, Derick R.,Wolfe, John P.
supporting information, p. 2378 - 2381 (2015/06/02)
Cascade Pd-catalyzed alkene carboamination/Diels-Alder reactions between bromodienes and amines bearing two pendant alkenes are described. These transformations generate 4 bonds, 3 rings, and 3-5 stereocenters to afford polycyclic nitrogen heterocycles wi
Jacobsen protocols for large-scale epoxidation of cyclic dienyl sulfones: Application to the (+)-pretazettine core
Ebrahimian, G. Reza,Du Jourdin, Xavier Mollat,Fuchs, Philip L.
scheme or table, p. 2630 - 2633 (2012/07/17)
A Jacobsen epoxidation protocol using H2O2 as oxidant was designed for the large-scale preparation of various epoxy vinyl sulfones. A number of cocatalysts were screened, and pH control led to increased reaction rate, higher turnover
Asymmetric 1,4-dihydroxylation of 1,3-dienes by catalytic enantioselective diboration
Burks, Heather E.,Kliman, Laura T.,Morken, James P.
supporting information; scheme or table, p. 9134 - 9135 (2009/12/05)
(Chemical Equation Presented) Asymmetric 1,4-dihydroxylations of 1,3-dienes, and other transformations, are initiated by the Pt-catalyzed enantioselective addition of bis(pinacolato)diboron (B2(pin) 2) to conjugated dienes. The studies reported in this communication suggest that both cyclic and acyclic substrates will participate in this reaction; however, dienes which are unable to adopt the S-cis conformation are unreactive. For most substrates, 1,4-addition is the predominant pathway. In addition to oxidation to the derived 2-buten-1,4-diol, stereoselective carbonyl allylation with the intermediate bis(boronate) ester is also described.
Intermolecular nitroso Diels-Alder cycloaddition of α-acetoxynitroso derivatives in aqueous medium
Calvet, Geraldine,Guillot, Regis,Blanchard, Nicolas,Kouklovsky, Cyrille
, p. 4395 - 4401 (2007/10/03)
The Diels-Alder cycloadditions of the α-acetoxynitroso dienophile 1 in water are reported. The rapid and high yielding synthesis of structurally diverse 3,6-dihydro-1,2-oxazines complements the straightforward elaboration of aminoalcohols obtained from th
Palladium(II)-Catalyzed Intramolecular 1,4-Oxyacyloxylation of Conjugated Dienes. A Stereocontrolled Route to Fused Six-Membered Lactones and Pyrans
Verboom, Renzo C.,Persson, B. Anders,Baeckvall, Jan-E.
, p. 3102 - 3111 (2007/10/03)
Stereocontrolled palladium(II)-catalyzed intramolecular 1,4-oxidations of dienyl acids and alcohols proceed under mild conditions to give fused δ-lactones and pyrans, respectively, in good yields. The stereo- and regioselectivity was affected by the presence of LiCl and solvent composition (HOAc/acetone). The products obtained were used for further functionalizations using copper(I)-mediated reactions. Stoichiometric reactions of preformed dibutylcyanocuprates with pyrans containing an allylic acetate gave cis- and trans-fused ring systems with high γ-selectivity and in high yields.
