- Cobalt-catalyzed hydroazidation of olefins: Convenient access to alkyl azides
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Conversion of olefins to azides was achieved with high Markovnikov selectivity for a broad range of alkenes using 6 mol % Co(BF4)·6H2O and ligand 1, with 3 equiv of TsN3 as nitrogen source and simple silanes (PhSiH3, TMDSO). Copyright
- Waser, Jerome,Nambu, Hisanori,Carreira, Erick M.
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Read Online
- Antibody drug conjugate, intermediate, preparation method, pharmaceutical composition and uses thereof
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Disclosed are an antibody drug conjugate IB, which uses ether linkages for connection, and improves the water solubility, stability and cytotoxicity in vivo and in intro, and an intermediate, a pharmaceutical composition, and uses of the antibody drug conjugate. The antibody drug conjugate has simple synthetic steps and a high yield.
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Paragraph 81; 82; 83; 84
(2019/11/11)
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- Hydroheteroarylation of Unactivated Alkenes Using N-Methoxyheteroarenium Salts
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We report the first reductive coupling of unactivated alkenes with N-methoxy pyridazinium, imidazolium, quinolinium, and isoquinolinium salts under hydrogen atom transfer (HAT) conditions, and an expanded scope for the coupling of alkenes with N-methoxy pyridinium salts. N-Methoxy pyridazinium, imidazolium, quinolinium, and isoquinolinium salts are accessible in 1-2 steps from the commercial arenes or arene N-oxides (25-99%). N-Methoxy imidazolium salts are accessible in three steps from commercial amines (50-85%). In total 36 discrete methoxyheteroarenium salts bearing electron-donating, electron-withdrawing, alkyl, aryl, halogen, and haloalkyl substituents were prepared (several in multigram quantities) and coupled with 38 different alkenes. The transformations proceed under neutral conditions at ambient temperature, provide monoalkylation products exclusively, and form a single alkene addition regioisomer. Preparatively useful and complementary site selectivities in the addition of secondary and tertiary radicals to pyidinium salts are documented: harder secondary radicals favor C-2 addition (2->10:1), while softer tertiary radicals favor bond formation to C-4 (4.7->29:1). A diene possessing a 1,2-disubstituted and 2,2-disubstituted alkene undergoes hydropyridylation at the latter exclusively (61%) suggesting useful site selectivities can be obtained in polyene substrates. The methoxypyridinium salts can also be employed in dehydrogenative arylation, borono-Minisci, and tandem arylation processes. Mechanistic studies support the involvement of a radical process.
- Ma, Xiaoshen,Dang, Hester,Rose, John A.,Rablen, Paul,Herzon, Seth B.
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supporting information
p. 5998 - 6007
(2017/05/04)
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- Enantioselective CuH-catalyzed anti-markovnikov hydroamination of 1,1-disubstituted alkenes
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Enantioselective synthesis of β-chiral amines has been achieved via copper-catalyzed hydroamination of 1,1-disubstituted alkenes with hydroxylamine esters in the presence of a hydrosilane. This mild process affords a range of structurally diverse β-chiral amines, including β-deuterated amines, in excellent yields with high enantioselectivities. Furthermore, catalyst loading as low as 0.4 mol% could be employed to deliver product in undiminished yield and selectivity, demonstrating the practicality of this method for large-scale synthesis.
- Zhu, Shaolin,Buchwald, Stephen L.
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supporting information
p. 15913 - 15916
(2015/02/19)
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- One-pot method for regioselective bromination and sequential carbon-carbon bond-forming reactions of allylic alcohol derivatives
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An efficient one-pot method for the regioselective bromination of allylic alcohol derivatives (two-step reaction sequence) followed by Sonogashira, Negishi, or Suzuki-Miyaura coupling reactions in the same reaction vessel (three-step reaction sequence) ha
- Kutsumura, Noriki,Matsubara, Yusuke,Niwa, Kentaro,Ito, Ai,Saito, Takao
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p. 3337 - 3346
(2013/06/27)
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- Asymmetric hydrogenation routes to deoxypolyketide chirons
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Asymmetric hydrogenations of monoenes and dienes were performed to obtain terminal deoxypolyketide fragments A and the corresponding internal Chirons B and C. The chiral N-heterocyclic carbene catalyst 1 was used throughout. Modest selectivities for hydrogenations of simple monoenes relayed into high selectivities for preparations of the terminal deoxypolyketide fragments in which either two hydrogenations or one and an optically pure starting material were used. Curiously, the face selectivities for hydrogenation of α,β-unsaturated esters were consistently opposite to those that had been observed for styrene and stilbene derivatives in previous work, and to closely related allylic alcohol and ether derivatives in this work. Plausible mechanisms for this differing behavior were deduced by using DFT calculations. It appears that the origin of the unusual stereoselectivity for the ester derivatives is transient metal-coordination of the ester carbonyl whereas there is no evidence that the allylic alcohol or ethers coordinate. The routes developed to α,ω-functionalized internal deoxypolyketide fragments are extremely practical. These begin with the Roche ester being converted into alkene and, in one case, diene derivatives. Catalyst control prevails in the hydrogenations of these substrates, but there is a significant "substrate vector" (a term we used to describe the influence of the substrate on a catalyst-controlled reaction). This is determined by minimization of 1,3-allylic strain and, in some cases, syn pentane interactions. This substrate vector can be constructively paired with the (dominant) catalyst vector by use of the appropriate enantiomer of 1. In the hydrogenation of a diene derivative, two chiral centers could be formed simultaneously with overall 11:1.0 selectivity; this is the first time this has been achieved in any asymmetric synthesis of a deoxypolyketide fragment. Throughout, diastereo-selectivities of the crude material in the syntheses of α,ω-functionalized internal deoxypolyketide fragments were in excess of 11:1.0 and chromatographically purified samples could be isolated in high yields with dr (dr = diastereomeric ratio) values consistently in excess of 40:1.0.
- Zhou, Jianguang,Ogle, James W.,Fan, Yubo,Banphavichit, Yorawit,Zhu, Ye,Burgess, Kevin
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p. 7162 - 7170
(2008/03/12)
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- α,ω-functionalized 2,4-dimethylpentane dyads and 2,4,6-trimethylheptane triads through asymmetric hydrogenation
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A match made in heaven: All the possible stereoisomers of α,ω-functionalized 2,4-dimethylpentane dyad and 2,4,6-tri- methylheptane triad chirons (see picture; A and B, respectively; FG = functional group, PG = protecting group) can be reached by using a c
- Zhou, Jianguang,Burgess, Kevin
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p. 1129 - 1131
(2008/03/14)
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- Hydrazines and azides via the metal-catalyzed hydrohydrazination and hydroazidation of olefins
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The discovery, study, and implementation of the Co- and Mn-catalyzed hydrohydrazination and hydroazidation reactions of olefins are reported. These reactions are equivalent to direct hydroaminations of C-C double bonds with protected hydrazines or hydrazoic acid but are based on a different concept in which the H and the N atoms come from two different reagents, a silane and an oxidizing nitrogen source (azodicarboxylate or sulfonyl azide). The hydrohydrazination reaction using di-tert-butyl azodicarboxylate is characterized by its ease of use, large functional group tolerance, and broad scope, including mono-, di-, tri-, and tetrasubstituted olefins. Key to the development of the hydroazidation reaction was the use of sulfonyl azides as nitrogen sources and the activating effect of tert-butyl hydroperoxide. The reaction was found to be efficient for the functionalization of mono-, di-, and trisubstituted olefins, and only a few functional groups are not tolerated. The alkyl azides obtained are versatile intermediates and can be transformed to the free amines or triazoles without isolation of the azides. Preliminary mechanistic investigations suggest a rate-limiting hydrocobaltation of the alkene, followed by an amination reaction. Radical intermediates cannot be ruled out and may be involved.
- Waser, Jerome,Gaspar, Boris,Nambu, Hisanori,Carreira, Erick M.
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p. 11693 - 11712
(2007/10/03)
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- Direct preparation of allylstannanes from allyl alcohols: Convenient synthesis of β-substituted allylstannanes and of stereodefined γ-substituted allylstannanes
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Primary allyl alcohols are converted into allyltributylstannanes in a one-pot operation. It entails (i) deprotonation with BuLi, (ii) sulfonylation with mesyl chloride, and (iii) nucleophilic substitution by LiSnBu3. Conversions are quantitative with isolated yields ranging from 70% to 100%. If the starting allyl alcohol contains a stereogenic double bond its configuration is retained.
- Weigand, Stefan,Brueckner, Reinhard
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p. 475 - 482
(2007/10/03)
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- 6-amido-1-methyl-2-(substituted-thio)carbapenems
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New antibacterial 6-amido-1-methyl-2-(substituted-thio)-carbapenems and process for their synthesis involving new azetidinone intermediates.
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- STUDIES ON FORSKOLIN RING C FORMING REACTIONS
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Labdane derivative 27 has been prepared from (E,E)-farnesol (4).Selenium- and mercury-mediated cyclization of 24 leads to compounds with the opposite configuration at C-8 as found in forskolin.
- Jordine, Guido,Bick, Stefan,Moeller, Uwe,Welzel, Peter,Daucher, Birgit,Maas, Gerhard
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p. 139 - 160
(2007/10/02)
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