- Copper-Catalyzed Perfluoroalkylation of Allyl Phosphates with Stable Perfluoroalkylzinc Reagents
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A general and practical method for copper-catalyzed cross-coupling of allyl phosphates with stable perfluoroalkylzinc reagents has been developed. The reaction proceeds under mild reaction conditions with high efficiency, good functional group tolerance, and high regio- A nd stereoselectivities and provides general, straightforward, and useful access to allyl-perfluoroalkyl compounds. Preliminary mechanistic studies reveal that the allyl copper intermediate may be involved in the catalytic cycle.
- Liu, Lihua,Bao, Xifei,Xiao, Hua,Li, Junlan,Ye, Feifan,Wang, Chaoqin,Cai, Qinhua,Fan, Shilu
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- Platinum-catalyzed tandem diboration/asymmetric allylboration: Access to nonracemic functionalized 1,3-diols
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(Matrix presented) A single-pot tandem catalytic diene diboration/carbonyl allylation reaction is described that uses a commercially available chiral diboron reagent. The chirality of the intermediate diboration adduct is transferred to the product in the
- Morgan, Jeremy B.,Morken, James P.
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- BF3·OEt2TMSN3mediated regioselective azidolysis of vinylaziridines
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An easy and general azidolysis of vinylepoxides mediated by BF 3·OEt2and TMSN3recently reported by our group has been extended to vinylaziridines. The reaction affords unsaturated azido derivatives with complete stereosele
- Righi, Giuliana,Bovicelli, Paolo,Marucci, Cristina,Tirotta, Ilaria
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Read Online
- Ligand-controlled cobalt-catalyzed remote hydroboration and alkene isomerization of allylic siloxanes
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The Co-catalyzed remote hydroboration and alkene isomerization of allylic siloxanes were realized by a ligand-controlled strategy. The remote hydroboration with dcype provided borylethers, while xantphos favored the formation of silyl enol ethers.
- Huang, Jiaxin,Li, Jie,Yang, Wen,Zhang, Kezhuo,Zhao, Pei,Zhao, Wanxiang
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p. 302 - 305
(2022/01/03)
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- Synthesis of Enantioenriched 3,4-Disubstituted Chromans through Lewis Base Catalyzed Carbosulfenylation
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A method for the catalytic, enantioselective, carbosulfenylation of alkenes to construct 3,4-disubstituted chromans is described. Alkene activation proceeds through the intermediacy of enantioenriched, configurationally stable thiiranium ions generated from catalytic, Lewis base activation of an electrophilic sulfenylating agent. The transformation affords difficult-to-generate, enantioenriched, 3,4-disubstituted chromans in moderate to high yields and excellent enantioselectivities. A variety of substituents are compatible including electronically diverse functional groups as well as several functional handles such as aryl halides, esters, anilines, and phenols. The resulting thioether moiety is amenable to a number of functional group manipulations and transformations. Notably, the pendant sulfide was successfully cleaved to furnish a free thiol which readily provides access to most sulfur-containing functional groups which are present in natural products and pharmaceuticals.
- Denmark, Scott E.,Laverny, Aragorn,Menard, Travis
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p. 14290 - 14310
(2021/11/12)
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- Multicatalytic approach to one-pot stereoselective synthesis of secondary benzylic alcohols
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One-pot procedures bear the potential to rapidly build up molecular complexity without isolation and purification of consecutive intermediates. Here, we report multicatalytic protocols that convert alkenes, unsaturated aliphatic alcohols, and aryl boronic acids into secondary benzylic alcohols with high stereoselectivities (typically >95:5 er) under sequential catalysis that integrates alkene cross-metathesis, isomerization, and nucleophilic addition. Prochiral allylic alcohols can be converted to any stereoisomer of the product with high stereoselectivity (>98:2 er, >20:1 dr).
- Casnati, Alessandra,Lichosyt, Dawid,Lainer, Bruno,Veth, Lukas,Dydio, Pawe?
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supporting information
p. 3502 - 3506
(2021/05/10)
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- Iridium-Catalyzed Regioselective Hydroalkynylation of Internal Alkenes Directed by an Oxime
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We report here an iridium-catalyzed hydroalkynylation of allylic alcohols protected by an oxime group. Catalytic alkynylation occurs exclusively at the distal position of the alkene. This method generates γ-alkynyl alcohol oximes directly from internal alkenes and terminal alkynes. The oxime group can be readily removed to afford a free alcohol, thus providing an indirect route for the catalytic hydroalkynylation of allylic alcohols.
- Gao, Peng-Chao,Li, Bi-Jie,Wang, Zi-Xuan
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p. 9500 - 9504
(2021/12/14)
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- Catalytic Asymmetric Allylic Substitution with Copper(I) Homoenolates Generated from Cyclopropanols
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By using copper(I) homoenolates as nucleophiles, which are generated through the ring-opening of 1-substituted cyclopropane-1-ols, a catalytic asymmetric allylic substitution with allyl phosphates is achieved in high to excellent yields with high enantioselectivity. Both 1-substituted cyclopropane-1-ols and allylic phosphates enjoy broad substrate scopes. Remarkably, various functional groups, such as ether, ester, tosylate, imide, alcohol, nitro, and carbamate are well tolerated. Moreover, the present method is nicely extended to the asymmetric construction of quaternary carbon centers. Some control experiments argue against a radical-based reaction mechanism and a catalytic cycle based on a two-electron process is proposed. Finally, the synthetic utilities of the product are showcased by means of the transformations of the terminal olefin group and the ketone group.
- Shi, Chang-Yun,Yin, Liang,Zhang, Qi,Zhou, Si-Wei
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supporting information
p. 26351 - 26356
(2021/11/09)
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- Palladium-catalysed regio- And stereoselective arylative substitution of γ,δ-epoxy-α,β-unsaturated esters and amides by sodium tetraaryl borates
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Palladium-catalysed reactions of γ,δ-epoxy-α,β-unsaturated esters and amides with NaBAr4 reagents proceeded regio- and stereoselectively, producing allylic homoallyl alcohols with aryl-substituents in the allylic position for a wide range of substrates. A
- Artok, Levent,Bilgi, Yasemin,Ku?, Melih
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p. 6378 - 6383
(2020/09/07)
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- Copper-Catalyzed Azide–Ynamide Cyclization to Generate α-Imino Copper Carbenes: Divergent and Enantioselective Access to Polycyclic N-Heterocycles
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Here an efficient copper-catalyzed cascade cyclization of azide-ynamides via α-imino copper carbene intermediates is reported, representing the first generation of α-imino copper carbenes from alkynes. This protocol enables the practical and divergent synthesis of an array of polycyclic N-heterocycles in generally good to excellent yields with broad substrate scope and excellent diastereoselectivities. Moreover, an asymmetric azide–ynamide cyclization has been achieved with high enantioselectivities (up to 98:2 e.r.) by employing BOX-Cu complexes as chiral catalysts. Thus, this protocol constitutes the first example of an asymmetric azide–alkyne cyclization. The proposed mechanistic rationale for this cascade cyclization is further supported by theoretical calculations.
- Chen, Yang-Bo,Deng, Chao,Liu, Rai-Shung,Liu, Xin,Luo, Chen,Wang, Ze-Shu,Ye, Long-Wu,Zhai, Tong-Yi,Zhang, Yi-Ping
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p. 17984 - 17990
(2020/08/21)
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- Gold-Catalyzed Asymmetric Thioallylation of Propiolates via Charge-Induced Thio-Claisen Rearrangement
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A gold(I)-catalyzed enantioselective thioallylation of propiolates with allyl sulfides is described. The key mechanistic element is a sulfonium-induced Claisen rearrangement which helps minimize the allyl dissociation and render higher enantioselectivity. This protocol features remarkable scope of the allyl moiety, allowing enantiocontrolled synthesis of all-carbon quaternary centers, and exhibits exceptional functional group compatibility with many Lewis bases and π-bonds. This intermolecular variant of Claisen rearrangement forges both C-S and C-C bonds concomitantly, providing efficient access to interesting optically active organosulfur compounds which can be transformed further through the vinyl sulfide as a functional handle. The rate of the reaction was zeroth order with respect to allyl sulfides, which suggested a reversible inhibition, providing a resting state for the catalyst. The Hammett plot displayed a correlation with σp values, suggesting a turnover-limiting sigmatropic rearrangement where decreased electron-density on sulfur accelerated the rearrangement.
- Kim, Hanbyul,Jang, Jiwon,Shin, Seunghoon
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supporting information
p. 20788 - 20795
(2020/11/27)
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- Highly Enantioselective Synthesis of Functionalized Glutarimide Using Oxidative N-Heterocyclic Carbene Catalysis: A Formal Synthesis of (?)-Paroxetine
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A simple yet highly effective approach toward enantioselective synthesis of trans-3,4-disubstituted glutarimides from readily available starting materials is developed using oxidative N-heterocyclic carbene catalysis. The catalytic reaction involves a formal [3 + 3] annulation between enals and substituted malonamides enabling the production of glutarimide derivatives in a single chemical operation via concomitant formation of C-C and C-N bonds. The reaction offers easy access to a broad range of functionalized glutarimides with excellent enantioselectivity and good yield. Synthetic application of the method is demonstrated via formal synthesis of (?)-paroxetine and other bioactive molecules.
- Porey, Arka,Santra, Surojit,Guin, Joyram
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supporting information
p. 5313 - 5327
(2019/04/16)
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- Multicatalytic Stereoselective Synthesis of Highly Substituted Alkenes by Sequential Isomerization/Cross-Coupling Reactions
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Starting from readily available alkenyl methyl ethers, the stereoselective preparation of highly substituted alkenes by two complementary multicatalytic sequential isomerization/cross-coupling sequences is described. Both elementary steps of these sequences are challenging processes when considered independently. A cationic iridium catalyst was identified for the stereoselective isomerization of allyl methyl ethers and was found to be compatible with a nickel catalyst for the subsequent cross-coupling of the in situ generated methyl vinyl ethers with various Grignard reagents. The method is compatible with sensitive functional groups and a multitude of olefinic substitution patterns to deliver products with high control of the newly generated C=C bond. A highly enantioselective variant of this [Ir/Ni] sequence has been established using a chiral iridium precatalyst. A complementary [Pd/Ni] catalytic sequence has been optimized for alkenyl methyl ethers with a remote C=C bond. The final alkenes were isolated with a lower level of stereocontrol. Upon proper choice of the Grignard reagent, we demonstrated that C(sp2) - C(sp2) and C(sp2) - C(sp3) bonds can be constructed with both systems delivering products that would be difficult to access by conventional methods.
- Romano, Ciro,Mazet, Clément
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p. 4743 - 4750
(2018/04/10)
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- Stereodivergent Hydroboration of Allenes
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Full details of a stereodivergent hydroboration of allenes are reported. While hydroboration of an allene with 9-BBN provided a thermodynamically stable (E)-allylic alcohol after oxidative work-up, the reaction of an identical allene with HB(Sia)2 (disiamylborane) formed a (Z)-allylic alcohol as the kinetic product. The developed conditions allowed for the synthesis of trisubstituted olefins in a highly stereoselective fashion, which is known to be challenging. The method was also applied to the stereodivergent synthesis of structural motifs such as skipped dienes and allylbenzenes, which are often embedded in biologically active natural products.
- Nagashima, Yoshiyuki,Sasaki, Keiji,Suto, Takahiro,Sato, Takaaki,Chida, Noritaka
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supporting information
p. 1024 - 1028
(2018/03/21)
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- Novel Staphyloxanthin Inhibitors with Improved Potency against Multidrug Resistant Staphylococcus aureus
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Diapophytoene desaturase (CrtN) is a potential novel target for intervening in the biosynthesis of the virulence factor staphyloxanthin. In this study, 38 1,4-benzodioxan-derived CrtN inhibitors were designed and synthesized to overwhelm the defects of leading compound 4a. Derivative 47 displayed superior pigment inhibitory activity, better hERG inhibitory properties and water solubility, and significantly sensitized MRSA strains to immune clearance in vitro. Notably, 47 displayed excellent efficacy against pigmented S. aureus Newman, Mu50 (vancomycin-intermediate MRSA, VISA), and NRS271 (linezolid-resistant MRSA, LRSA) comparable to that of linezolid and vancomycin in vivo.
- Ni, Shuaishuai,Li, Baoli,Chen, Feifei,Wei, Hanwen,Mao, Fei,Liu, Yifu,Xu, Yixiang,Qiu, Xiaoxi,Li, Xiaokang,Liu, Wenwen,Hu, Linghao,Ling, Dazheng,Wang, Manjiong,Zheng, Xinyu,Zhu, Jin,Lan, Lefu,Li, Jian
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p. 233 - 237
(2018/03/21)
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- Discovery of novel piperonyl derivatives as diapophytoene desaturase inhibitors for the treatment of methicillin-, vancomycin- and linezolid-resistant Staphylococcus aureus infections
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Inhibition of S. aureus diapophytoene desaturase (CrtN) could serve as an alternative approach for addressing the tricky antibiotic resistance by blocking the biosynthesis of carotenoid pigment which shields the bacterium from host oxidant killing. In this study, we designed and synthesized 44 derivatives with piperonyl scaffold targeting CrtN and the structure-activity relationships (SARs) were examined extensively to bring out the discovery of 21b with potent efficacy and better hERG safety profile compared to the first class CrtN inhibitor benzocycloalkane derivative 2. Except the excellent pigment inhibitory activity against wild-type S. aureus, 21b also showed excellent pigment inhibition against four pigmented MRSA strains. In addition, H2O2 killing and human whole blood killing assays proved 21b could sensitize S. aureus to be killed under oxidative stress conditions. Notably, the murine study in vivo validated the efficacy of 21b against pigmented S. aureus Newman, vancomycin-intermediate S. aureus Mu50 and linezolid-resistant S. aureus NRS271.
- Wei, Hanwen,Mao, Fei,Ni, Shuaishuai,Chen, Feifei,Li, Baoli,Qiu, Xiaoxia,Hu, Linghao,Wang, Manjiong,Zheng, Xinyu,Zhu, Jin,Lan, Lefu,Li, Jian
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p. 235 - 251
(2018/01/17)
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- Novel Terminal Bipheny-Based Diapophytoene Desaturases (CrtN) Inhibitors as Anti-MRSA/VISR/LRSA Agents with Reduced hERG Activity
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CrtN has been identified as an attractive and druggable target for treating pigmented Staphylococcus aureus infections. More than 100 new compounds were synthesized, which target the overwhelming the defects of the CrtN inhibitor 1. Analogues 23a and 23b demonstrated a significant activity against pigmented S. aureus Newman and 13 MRSA strains (IC50 = 0.02-10.5 nM), along with lower hERG inhibition (IC50 > 30 μM, ~10-fold decrease in comparison with 1). Furthermore, 23a and 23b were confirmed to reduce the staphylococcal load in the kidney and heart in a mouse model with normal treatment deeper than pretreatment ones, comparable even with vancomycin and linezolid. Remarkably, 23a could strongly block the pigment biosynthesis of these nine multidrug-resistant MRSA strains, including excellent activity against LRSA strains and VISA strains in vivo, and all of which demonstrated that 23a has a huge potential against intractable MRSA, VISA, and LRSA issues as a therapeutic drug.
- Li, Baoli,Ni, Shuaishuai,Mao, Fei,Chen, Feifei,Liu, Yifu,Wei, Hanwen,Chen, Wenhua,Zhu, Jin,Lan, Lefu,Li, Jian
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p. 224 - 250
(2018/02/10)
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- Novel Inhibitors of Staphyloxanthin Virulence Factor in Comparison with Linezolid and Vancomycin versus Methicillin-Resistant, Linezolid-Resistant, and Vancomycin-Intermediate Staphylococcus aureus Infections in Vivo
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Our previous work (Wang et al. J. Med. Chem. 2016, 59, 4831-4848) revealed that effective benzocycloalkane-derived staphyloxanthin inhibitors against methicillin-resistant Staphylococcus aureus (S. aureus) infections were accompanied by poor water solubility and high hERG inhibition and dosages (preadministration). In this study, 92 chroman and coumaran derivatives as novel inhibitors have been addressed for overcoming deficiencies above. Derivatives 69 and 105 displayed excellent pigment inhibitory activities and low hERG inhibition, along with improvement of solubility by salt type selection. The broad and significantly potent antibacterial spectra of 69 and 105 were displayed first with normal administration in the livers and hearts in mice against pigmented S. aureus Newman, Mu50 (vancomycin-intermediate S. aureus), and NRS271 (linezolid-resistant S. aureus), compared with linezolid and vancomycin. In summary, both 69 and 105 have the potential to be developed as good antibacterial candidates targeting virulence factors.
- Ni, Shuaishuai,Wei, Hanwen,Li, Baoli,Chen, Feifei,Liu, Yifu,Chen, Wenhua,Xu, Yixiang,Qiu, Xiaoxia,Li, Xiaokang,Lu, Yanli,Liu, Wenwen,Hu, Linhao,Lin, Dazheng,Wang, Manjiong,Zheng, Xinyu,Mao, Fei,Zhu, Jin,Lan, Lefu,Li, Jian
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p. 8145 - 8159
(2017/10/18)
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- Gold(I)/Chiral N,N′-Dioxide–Nickel(II) Relay Catalysis for Asymmetric Tandem Intermolecular Hydroalkoxylation/Claisen Rearrangement
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A highly efficient asymmetric cascade reaction between alkynyl esters and allylic alcohols has been realized. Key to success was the combination of a hydroalkoxylation reaction catalyzed by a π-acidic gold(I) complex with a Claisen rearrangement catalyzed by a chiral Lewis acidic N,N′-dioxide–nickel(II) complex. A range of acyclic α-allyl β-keto esters were synthesized in high yields (up to 99 %) with good diastereoselectivities (up to 97:3) and excellent enantioselectivities (up to 99 % ee) under mild reaction conditions. These products can be easily transformed into optically active β-hydroxy esters, β-hydroxy acids, or 1,3-diols.
- Li, Jun,Lin, Lili,Hu, Bowen,Zhou, Pengfei,Huang, Tianyu,Liu, Xiaohua,Feng, Xiaoming
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supporting information
p. 885 - 888
(2017/01/13)
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- Gold-Catalyzed [2,3]-Sigmatropic Rearrangement: Reaction of Aryl Allyl Alcohols with Diazo Compounds
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A gold-catalyzed [2,3]-sigmatropic rearrangement reaction has been developed. The intermolecular rearrangement occurs between in situ generated donor-acceptor gold-carbenes and cinnamyl alcohols via tandem oxonium ylide formation. The desired rearranged product has been accomplished selectively over more conventional O-H insertion, cyclopropanation, cycloaddition, and C-H functionalization products under mild, open-air conditions. The scope of the work has been illustrated by synthesizing a new class of substrates that can be used for constructing complex molecular targets.
- Rao, Santhosh,Prabhu, Kandikere Ramaiah
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p. 846 - 849
(2017/02/26)
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- Enantioselective Intermolecular Addition of Aliphatic Amines to Acyclic Dienes with a Pd-PHOX Catalyst
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We report a method for the catalytic, enantioselective intermolecular addition of aliphatic amines to acyclic 1,3-dienes. In most cases, reactions proceed efficiently at or below room temperature in the presence of 5 mol % of a Pd catalyst bearing a PHOX ligand, generating allylic amines in up to 97:3 er. The presence of an electron-deficient phosphine within the ligand not only leads to a more active catalyst but also is critical for achieving high site selectivity in the transformation.
- Adamson, Nathan J.,Hull, Ethan,Malcolmson, Steven J.
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p. 7180 - 7183
(2017/06/05)
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- Discovery of Benzocycloalkane Derivatives Efficiently Blocking Bacterial Virulence for the Treatment of Methicillin-Resistant S. aureus (MRSA) Infections by Targeting Diapophytoene Desaturase (CrtN)
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Antivirulence strategies are now attracting interest for the inherent mechanism of action advantages. In our previous work, diapophytoene desaturase (CrtN) was identified to be an attractive and drugable target for fighting pigmented S. aureus infections. In this research, we developed a series of effective benzocycloalkane-derived CrtN inhibitors with submicromolar IC50. Analogue 8 blocked the pigment biosynthesis of three MRSA strains with a nanomolar IC50 value. Corresponding to its mode of action, 8 did not function as a bactericidal agent. 8 could sensitize S. aureus to immune clearance. In vivo, 8 was proven to be efficacious in an S. aureus Newman sepsis model and abscess formation model. For two typical MRSAs, USA400 MW2 and Mu50, 8 significantly decreased the staphylococcal loads in the liver and kidneys. Moreover, 8 showed minimal antifungal activity compared to that of NTF. In summary, 8 has the potential to be developed as a therapeutic drug, especially against intractable MRSA issues.
- Wang, Youxin,Di, Hongxia,Chen, Feifei,Xu, Yong,Xiao, Qiang,Wang, Xuehai,Wei, Hanwen,Lu, Yanli,Zhang, Lingling,Zhu, Jin,Lan, Lefu,Li, Jian
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p. 4831 - 4848
(2016/06/13)
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- Discovery of Potent Benzofuran-Derived Diapophytoene Desaturase (CrtN) Inhibitors with Enhanced Oral Bioavailability for the Treatment of Methicillin-Resistant Staphylococcus aureus (MRSA) Infections
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Blocking the staphyloxanthin biosynthesis process has emerged as a new promising antivirulence strategy. Previously, we first revealed that CrtN is a druggable target against infections caused by pigmented Staphylococcus aureus (S. aureus) and that naftifine was an effective CrtN inhibitor. Here, we identify a new type of benzofuran-derived CrtN inhibitor with submicromolar IC50 values that is based on the naftifine scaffold. The most potent analog, 5m, inhibits the pigment production of S. aureus Newman and three MRSA strains, with IC50 values of 0.38-5.45 nM, without any impact on the survival of four strains (up to 200 μM). Notably, compound 5m (1 μM) could significantly sensitize four strains to immune clearance and could effectively attenuate the virulence of three strains in vivo. Moreover, 5m was determined to be a weak antifungal reagent (MIC > 16 μg/mL). Combined with good oral bioavailability (F = 42.2%) and excellent safety profiles, these data demonstrate that 5m may be a good candidate for the treatment of MRSA infections.
- Wang, Youxin,Chen, Feifei,Di, Hongxia,Xu, Yong,Xiao, Qiang,Wang, Xuehai,Wei, Hanwen,Lu, Yanli,Zhang, Lingling,Zhu, Jin,Sheng, Chunquan,Lan, Lefu,Li, Jian
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p. 3215 - 3230
(2016/05/19)
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- Dialkylzinc-mediated allylic polyfluoroarylation reaction
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Abstract We present an allylic polyfluoroarylation reaction with broad substrate scope and excellent functional group tolerance, using organozinc reagents under mild conditions. A catalytic amount of triphenylphosphine oxide efficiently promotes iodine-zinc exchange reaction between polyfluoroaryl iodide and dimethylzinc, and the resulting phosphine oxide-activated polyfluoroarylzinc undergoes substitution reaction with allylic halides to afford the corresponding polyfluoroarylated products.
- Kurauchi, Daisuke,Hirano, Keiichi,Kato, Hisano,Saito, Tatsuo,Miyamoto, Kazunori,Uchiyama, Masanobu
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p. 5849 - 5857
(2015/08/03)
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- Synthesis of 1,3-Amino Alcohols, 1,3-Diols, Amines, and Carboxylic Acids from Terminal Alkynes
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The half-sandwich ruthenium complexes 1-3 activate terminal alkynes toward anti-Markovnikov hydration and reductive hydration under mild conditions. These reactions are believed to proceed via addition of water to metal vinylidene intermediates (4). The functionalization of propargylic alcohols by metal vinylidene pathways is challenging owing to decomposition of the starting material and catalytic intermediates. Here we show that catalyst 2 can be employed to convert propargylic alcohols to 1,3-diols in high yield and with retention of stereochemistry at the propargylic position. The method is also amenable to propargylic amine derivatives, thereby establishing a route to enantioenriched 1,3-amino alcohol products. We also report the development of formal anti-Markovnikov reductive amination and oxidative hydration reactions to access linear amines and carboxylic acids, respectively, from terminal alkynes. This chemistry expands the scope of products that can be prepared from terminal alkynes by practical and high-yielding metal-catalyzed methods.
- Zeng, Mingshuo,Herzon, Seth B.
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p. 8604 - 8618
(2015/09/15)
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- Copper-catalyzed vinylsilane allylation
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Soft reaction conditions, particularly important in total synthesis, have dragged many researchers into the field of silylated organic compounds. Hereby, we describe a new copper-catalyzed vinylsilane transformation. Various vinylsilanes were allylated by using a copper(I) salt, and this led to the formation of polysubstituted 1,4-dienes bearing sensitive moieties such as halogens, ketones, and aldehydes. Hereby is described a new copper-catalyzed vinylsilane transformation. Various vinylsilanes were allylated by using copper(I) salts, and this led to the formation of polysubstituted 1,4-dienes bearing sensitive moieties such as halogens, ketones, and aldehydes. TBAT = tetrabutylammonium difluorotriphenylsilicate. Copyright
- Cornelissen, Loic,Vercruysse, Sebastien,Sanhadji, Ayoub,Riant, Olivier
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- Titanium-catalyzed intermolecular hydroaminoalkylation of conjugated dienes
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Ti me kangaroo down: Conjugated dienes undergo intermolecular hydroaminoalkylation in the presence of Ti catalyst [Ind2TiMe 2] (Ind=η5-indenyl). This new reaction offers a highly atom-efficient approach to homoallylic amines from 1,3-butadienes. Copyright
- Preuss, Till,Saak, Wolfgang,Doye, Sven
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p. 3833 - 3837
(2013/04/24)
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- Catalytic enantioselective dibromination of allylic alcohols
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A new dibromination reaction involving the combination of dibromomalonate as the bromonium source and a titanium bromide species as the bromide source has been developed. Enantioselective catalysis has been achieved through apparent ligand acceleration by a tartaric acid-derived diol.
- Hu, Dennis X.,Shibuya, Grant M.,Burns, Noah Z.
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p. 12960 - 12963
(2013/09/24)
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- Simple and efficient 1,3-isomerization of allylic alcohols using a supported monomeric vanadium-oxide catalyst
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Promotion by group high five: Silica-supported monomeric vanadium-oxide promoted the isomerization of various allylic alcohols, including under scaled-up and solvent-free reaction conditions. This catalyst also exhibited high reusability with no drop in activity.
- Mitsudome, Takato,Sueoka, Shoichiro,Ikeda, Satoshi,Mizugaki, Tomoo,Jitsukawa, Koichiro,Kaneda, Kiyotomi
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p. 2879 - 2882
(2013/10/21)
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- Key structural features of cis-cinnamic acid as an allelochemical
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1-O-cis-cinnamoyl-β-d-glucopyranose is one of the most potent allelochemicals isolated from Spiraea thunbergii Sieb. It is suggested that it derives its strong inhibitory activity from cis-cinnamic acid, which is crucial for phytotoxicity. It was synthesized to confirm its structure and bioactivity, and also a series of cis-cinnamic acid analogues were prepared to elucidate the key features of cis-cinnamic acid for lettuce root growth inhibition. The cis-cyclopropyl analogue showed potent inhibitory activity while the saturated and alkyne analogues proved to be inactive, demonstrating the importance of the cis-double bond. Moreover, the aromatic ring could not be replaced with a saturated ring. However, the 1,3-dienylcyclohexene analogue showed strong activity. These results suggest that the geometry of the C-C double bond between the carboxyl group and the aromatic ring is essential for potent inhibitory activity. In addition, using several light sources, the photostability of the cinnamic acid derivatives and the role of the C-C double bond were also investigated.
- Abe, Masato,Nishikawa, Keisuke,Okuda, Katsuhiro,Shindo, Mitsuru,Fukuda, Hiroshi,Nakanishi, Kazunari,Tazawa, Yuta,Taniguchi, Tomoya,Park, So-Young,Hiradate, Syuntaro,Fujii, Yoshiharu
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p. 56 - 67,12
(2012/12/12)
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- Tunable stereoselective alkene synthesis by treatment of activated imines with nonstabilized phosphonium ylides
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A broad range of readily accessible N-sulfonyl imines undergo olefination reaction with nonstabilized phosphonium ylides under mild conditions to afford an array of both Z- and E-isomers of 1,2-disubstituted alkenes, allylic alcohols, and allylic amines in good yields and with greater than 991 stereoselectivity.
- Dong, De-Jun,Li, Yuan,Wang, Jie-Qi,Tian, Shi-Kai
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supporting information; experimental part
p. 2158 - 2160
(2011/03/20)
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- Enantioselective α-and γ-alkylation of α,β- unsaturated aldehydes using dienamine activation
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The enantioselective alkylation of α,β-unsaturated aldehydes with stabilized carbocations as electrophiles via the activation as dienamine intermediates is described. This unique application of dienamine catalysis allows for the first enantioselective γ-a
- Stiller, Julian,Marques-Lopez, Eugenia,Herrera, Raquel P.,Froehlich, Roland,Strohmann, Carsten,Christmann, Mathias
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supporting information; experimental part
p. 70 - 73
(2011/03/22)
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- Spirodiketopiperazine-based CCR5 antagonist: Discovery of an antiretroviral drug candidate
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Following the discovery that hydroxylated derivative 3 (Fig. 1) was one of the oxidative metabolites of the original lead 1, it was found that hydroxylated compound 4 possesses higher in vitro anti-HIV potency than the corresponding non-hydroxylated compo
- Nishizawa, Rena,Nishiyama, Toshihiko,Hisaichi, Katsuya,Minamoto, Chiaki,Matsunaga, Naoki,Takaoka, Yoshikazu,Nakai, Hisao,Jenkinson, Stephen,Kazmierski, Wieslaw M.,Tada, Hideaki,Sagawa, Kenji,Shibayama, Shiro,Fukushima, Daikichi,Maeda, Kenji,Mitsuya, Hiroaki
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p. 1141 - 1145
(2011/04/16)
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- Discovery of 4-[4-({(3R)-1-butyl-3-[(R)-cyclohexyl(hydroxy)methyl]-2,5- dioxo-1,4,9-triazaspiro[5.5]undec-9-yl}methyl)phenoxy]benzoic acid hydrochloride: A highly potent orally available CCR5 selective antagonist
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Based on the original spirodiketopiperazine design framework, further optimization of an orally available CCR5 antagonist was undertaken. Structural hybridization of the hydroxylated analog 4 derived from one of the oxidative metabolites and the new orally available non-hydroxylated benzoic acid analog 5 resulted in another potent orally available CCR5 antagonist 6a as a clinical candidate. Full details of a structure-activity relationship (SAR) study and ADME properties are presented.
- Nishizawa, Rena,Nishiyama, Toshihiko,Hisaichi, Katsuya,Minamoto, Chiaki,Murota, Masayuki,Takaoka, Yoshikazu,Nakai, Hisao,Tada, Hideaki,Sagawa, Kenji,Shibayama, Shiro,Fukushima, Daikichi,Maeda, Kenji,Mitsuya, Hiroaki
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p. 4028 - 4042
(2011/08/21)
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- Iridium-catalyzed asymmetric allylic amination with polar amines: Access to building blocks with lead-like molecular properties
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The combination of an air-stable iridium catalyst and the dipolar aprotic solvent dimethyl sulfoxide (DMSO) allowed, for the first time, the systematic exploitation of highly polar, functionalized amines in asymmetric allylic substitutions: low molecular
- Tosatti, Paolo,Horn, Joachim,Campbell, Amanda J.,House, David,Nelson, Adam,Marsden, Stephen P.
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p. 3153 - 3157
(2011/03/18)
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- Pd-catalyzed enantioselective allyl-allyl cross-coupling
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The Pd-catalyzed cross-coupling of allylic carbonates and allylB(pin) is described. The regioselectivity of this reaction is sensitive to the bite angle of the ligand, with small-bite-angle ligands favoring the branched substitution product. This mode of
- Zhang, Ping,Brozek, Laura A.,Morken, James P.
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supporting information; scheme or table
p. 10686 - 10688
(2010/11/04)
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- Expedient access to branched allylic silanes by copper-catalysed allylic substitution of linear allylic halides
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An unprecedented copper-catalysed allylic transposition enables the regioselective synthesis of branched allylic silanes from linear allylic halides through direct C-Si bond formation.
- Vyas, Devendra J.,Oestreich, Martin
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supporting information; experimental part
p. 568 - 570
(2010/05/01)
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- Enantioselective synthesis of allylboronates bearing a tertiary or quaternary B-substituted stereogenic carbon by NHC-Cu-catalyzed substitution reactions
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Allylic substitutions that afford α-substituted allylboronates bearing B-substituted tertiary or quaternary carbon stereogenic centers are presented. C-B bond-forming reactions, catalyzed by chiral bidentate Cu-NHC complexes, are performed in the presence of commercially available bis(pinacolato)diboron. Transformations proceed in high yield (up to >98%) and site selectivity (>98% SN2′), and in up to >99:1 enantiomer ratio. Trans- or cis-disubstituted alkenes can be used; alkyl- (linear as well as branched) and aryl-trisubstituted allylic carbonates serve as effective substrates. Allylboronates that bear a quaternary carbon center are air-stable and can be easily purified by silica gel chromatography; in contrast, secondary allylboronates cannot be purified in the same manner and are significantly less stable. Oxidation of the enantiomerically enriched products furnishes secondary or tertiary allylic alcohols, valuable small molecules that cannot be easily obtained in high enantiomeric purity by alternative synthesis or kinetic resolution approaches.
- Guzman-Martinez, Aikomari,Hoveyda, Amir H.
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supporting information; scheme or table
p. 10634 - 10637
(2010/11/05)
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- Iridium-catalyzed regio- and enantioselective N-allylation of indoles
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Iridium is blind to C: Highly regio- and enantioselective, iridium-catalyzed N-allylations of indoles, which complement the more common reactivity of indoles as carbon nucleophiles, have been developed (see scheme). These reactions form highly enantioenri
- Stanley, Levi M.,Hartwig, John F.
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supporting information; body text
p. 7841 - 7844
(2010/04/02)
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- TETRAHYDROINDOLE DERIVATIVES FOR TREATMENT OF ALZHEIMER'S DISEASE
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Tetrahydroindole derivatives of formula (I): are disclosed. These compounds modulate the activity of gamma-secretase and hence find use in treatment or prevention of Alzheimer's disease.
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Page/Page column 25
(2010/11/27)
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- Screening of ligands in the asymmetric metallocenethiolatocopper(I)-catalyzed allylic substitution with Grignard reagents
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Screening of metallocenethiolate ligands for copper(I)-catalyzed substitution of allylic acetates with Grignard reagents has been carried out. The previously used ligand, lithium (R,Sp)-2-(1-dimethylaminoethyl)ferrocenylthiolate (4a), possessing both central and planar chirality, was the starting point for the screening. It was found that the diastereomeric ligand lithium (R,Rp)-2-(1-dimethylaminoethyl)ferrocenylthiolate (4b) exhibiting reversed planar chirality gave increased enantioselectivity in the allylic substitution, at least when cinnamyl acetate was used as a substrate. The ruthenocene-based ligand lithium (R,Sp)-2-(1-dimethylaminoethyl)ruthenocenylthiolate (4c) gave an enhanced reaction rate, but lower chiral induction. The use of disulfide bis[(R,Sp)-2-(1-dimethylaminoethyl)ferrocenyl]disulfide (7a) as a ligand precursor worked well but resulted in lower enantioselectivity.
- Cotton, Hanna K.,Norinder, Jakob,B?ckvall, Jan-E.
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p. 5632 - 5640
(2007/10/03)
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- Asymmetric synthesis of cyclic β-hydroxyallylsilanes via sequential allyltitanation-ring closing metathesis
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Highly enantioenriched cyclic β-hydroxyallylsilanes have been prepared via enantioselective allylation of unsaturated aldehydes using a chiral allyltitanium reagent, followed by a ring-closing metathesis. Functionalized rings of various sizes have been sy
- Adam, Jean-Michel,De Fays, Laurence,Laguerre, Michel,Ghosez, Léon
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p. 7325 - 7344
(2007/10/03)
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- Kinetic resolution of acyclic secondary allylic silyl ethers catalyzed by chiral ketones
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Kinetic resolution of acyclic secondary allylic silyl ethers by chiral dioxiranes generated in situ from chiral ketones (R)-1 and (R)-2 and Oxone was investigated. An efficient and catalytic method has been developed for kinetic resolution of those substrates with a CCl3, tert-butyl, or CF3 group at the α-position. In particular, high selectivities (S up to 100) were observed for kinetic resolutions of racemic α-trichloromethyl allylic silyl ethers 7 and 9-15 catalyzed by ketones (R)-2. Both the recovered substrates and the resulting epoxides were obtained in high enantiomeric excess. On the basis of steric and electrostatic interactions between the chiral dioxiranes and the racemic substrates, a model was proposed to rationalize the enantioselectivities and diastereoselectivities in the chiral ketone-catalyzed kinetic resolution process.
- Yang,Jiao,Yip,Lai,Wong
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p. 4619 - 4624
(2007/10/03)
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- Catalytic asymmetric cyclopropanation of allylic alcohols with titanium-TADDOLate: Scope of the cyclopropanation reaction
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A substoichiometric amount of titanium-TADDOLate complex was effective at catalyzing the cyclopropanation reaction of allylic alcohols in the presence 1 equiv of bis(iodomethyl) zinc. After initial optimization of the catalyst structure, excellent yields and enantiomeric ratios were obtained for 3-aryl- or 3-heteroaryl-substituted allylic alcohols (up to 97:3). Alkyl-substituted allylic alcohols gave modest yields and enantiomeric ratios (up to 87:13) but these compare favorably with those observed with other substoichiometric chiral ligands. The full synthetic scope of the reaction is presented in this paper.
- Charette,Molinaro,Brochu
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p. 12168 - 12175
(2007/10/03)
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- Kinetics and mechanism of the ( - )-Sparteine-mediated deprotonation of (E)-N-Boc-N-(p-methoxyphenyl)-3-cyclohexylallylamine
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The ( - )-sparteine-mediated asymmetric lithiation-substitution of (E)-N-Boc-N-(p-methoxyphenyl)3-cyclohexylallylamine ((E)-5) to afford γ-substituted enantiomerically enriched products 6 is reported. The solution structure for the lithiated intermediate
- Pippel,Weisenburger,Faibish,Beak
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p. 4919 - 4927
(2007/10/03)
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- Iridium complex-catalyzed allylic amination of allylic esters
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Iridium complex-catalyzed allylic amination of allylic carbonates was studied. The solvent strongly affected the catalytic activity. The use of a polar solvent such as EtOH is essential for obtaining the products in high yield. The reaction of (E)-3-substituted-2-propenyl carbonate and 1-substituted-2-propenyl carbonate with pyrrolidine in the presence of a catalytic amount of [Ir(COD)Cl]2 and P(OPh)3 (P/Ir=2) gave a branch amine with up to 99% selectivity. Both secondary and primary amines could be used for this reaction. When a primary amine was used, selective monoallylation occurred. No diallylation product was obtained. The reaction of 1,1-disubstituted-2-propenyl acetate with amines exclusively gave an α,α-disubstituted allylic amine. This reaction provides an alternative route to the addition of an organometallic reagent to ketimines for the preparation of such amines. The reaction of (Z)-3-substituted-2-propenyl carbonate with amines gave (Z)-linear amines with up to 100% selectivity. In all cases, no (E)-linear amine was obtained. The selectivities described here have not been achieved in similar palladium complex-catalyzed reactions.
- Takeuchi,Ue,Tanabe,Yamashita,Shiga
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p. 9525 - 9534
(2007/10/03)
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- The hydroboration of propargyl bromide. Simple one-pot three-component routes to (Z)-1-bromoalk-1-en-4-ols and to anti-homoallylic alcohols
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The hydroboration of propargyl bromide with dialkylboranes takes place regioselectively to give 3-bromoprop-1-en-1-yl dialkylboranes 13 which, upon quaternization with bromide ion, undergo a series of transformations into a number of allylic boron species. By a suitable choice of the experimental conditions it is possible to trap the reaction intermediates with aldehydes and to steer the process toward either the synthesis of (Z)-1-bromoalk-1-en-4-ols 6 or anti-homoallylic alcohols 8. Two one-pot three-component processes were developed based on a sequence of four reactions; preparation of dialkylborane and hydroboration of propargyl bromide are the first steps. Then, quaternization with TEBABr may be carried out either in the presence of the aldehyde when (Z)-1-bromoalk-1-en-4-ols 6 are requested, or in the absence of the aldehyde in order to allow the formation of γ-substituted allyl borane 18 which, successively, adds to the aldehyde affording antihomoallylic alcohols 8.
- Lombardo,Morganti,Trombini
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p. 8767 - 8773
(2007/10/03)
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- Application of 1,2:5,6-di-O-cyclohexylidene-D-mannitol as the chiral director in Matteson's asymmetric homologation
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1,2:5,6-Di-O-cyclohexylidene-D-mannitol is the good chiral director in Matteson's asymmetric homologation as indicated by the high enantiomeric excesses (ee's) of the secondary alcohols produced by treatment of the homologation products with alkyllithium
- Li, Guisheng,Kabalka, George W.
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- Synthesis and anti-HIV activity of novel N-1 side chain-modified analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT)
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A series of 33 N-1 side chain-modified analogs of 1-[(2- hydroxyethoxy)methyl]-6-(phenylthio)thymine (1, HEPT) were synthesized and evaluated for their anti-HIV-1 activity. In particular, the influence of substitution of the terminal hydroxy group of the acyclic structure of HEPT and the structural rigidity of this side chain were investigated. Halo (7, 8), azido (9), and amino (10-15) derivatives were synthesized from HEPT via the p-tosylate derivative 6. Acylation of the primary amine 15 afforded the amido analogs 16-20. The diaryl derivatives 26-29 were prepared by reaction of HEPT, or of the 6-(2-pyridylthio) analog 23, with diaryl disulfides in the presence of tri-n-butylphosphine. Compounds 39-41, in which the N-1 side chain is rigidified by incorporation of an E-configured double bond, were obtained by palladium(0)-catalyzed coupling of several different 6- (arylthio)uracil derivatives (37, 38) with allyl acetates 33. Compounds 13, 40a,c,d,f, and 41, incorporating an aromatic ring at the end of the acyclic side chain, were found to be more potent than the known diphenyl-substituted HEPT analog BPT (2), two of them, 40c,d, being 10-fold more active.
- Pontikis, Renée,Benhida, Rachid,Aubertin, Anne-Marie,Grierson, David S.,Monneret, Claude
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p. 1845 - 1854
(2007/10/03)
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- Prostaglandin derivatives
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A prostaglandin derivative represented by formula STR1 wherein R1 represents a hydrogen atom or a C1 -C6 alkyl group, and R2 represents a cyclohexyl group or a cyclopentylmethyl group. This compound has physiolo
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