- 2-THIENYL(CYANO)COPPER LITHIUM. A LOWER ORDER, STABLE "CUPRATE IN A BOTTLE" PRECURSOR TO HIGHER ORDER REAGENTS
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The lower order mixed cuprate derived from CuCN and 2-lithiothiophene (i.e.,2-ThCu(CN)Li) is found to have excellent shelf life, thereby providing an easily formed yet itself unreactive precursor to higher order mixed organocuprates.
- Lipshutz, Bruce H.,Koerner, Mike,Parker, David A.
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Read Online
- Bispalladacycle Catalyzed Nucleophilic Enantioselective Allylation of Aldehydes by Allylstannanes
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Enantiopure homoallylic secondary alcohols are very important synthetic building due to the versatility of the hydroxyl and olefin moieties. A key strategy to prepare them is by nucleophilic allylation of aldehydes. A large number of catalyst concepts emerged that allow for high enantioselectivity. Still, in many target-oriented syntheses of complex structures stoichiometric methods are preferred over catalytic ones. The need for high catalyst loadings and long reaction times, plus unsatisfying reproducibility and substrate scopes are reasons for that. In the present study we report the first palladium catalysts capable of controlling asymmetric nucleophilic allylations of aldehydes with allyltributyltin. TONs up to 620 were achieved, which is significantly higher than for any other reported catalyst. The method is also tolerating electronically and sterically unfavorable substrates. We show that a transmetallation occurs, favoring an η1-allyl coordination mode with the bispalladacycles. In contrast, for the corresponding monopalladacycle an unproductive η3 coordination is dominant.
- Frey, Wolfgang,Heberle, Martin,Legendre, Sarah,Peters, René,Wannenmacher, Nick,Weber, Manuel
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- Development of a Practical, Biocatalytic Synthesis of tert-Butyl (R)-3-Hydroxyl-5-hexenoate: A Key Intermediate to the Statin Side Chain
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The HMG-CoA reductase inhibitors, statins, are one of the most effective and bestselling cholesterol-lowering drugs. The use of statins has greatly extended people's lives and improved the quality of their life. Development of a more efficient, stereoselective, and sustainable synthesis of statins is continuingly of utmost importance. In the present study, through screening of ketoreductases (KREDs) and reaction optimization, we have successfully performed a highly stereoselective reduction of ketoester 1a catalyzed by KRED-06 at a pilot-plant scale without the addition of exogenous NADP+, generating 3.21 kg of enantiomerically pure tert-butyl (R)-3-hydroxyl-5-hexenoate ((R)-2a) (96.2% yield, >99.9% enantiomeric excess (ee)). This newly developed biocatalytic process alleviates the cryogenic conditions (-40 °C) employed in our first-generation synthesis of (R)-2a using NaBH4 and (l)-tartaric acid. Coupled with our previously established synthesis of bromocarbonate 3a via a one-pot diastereoselective carboxylation/bromocyclization of (R)-2a, we have developed an innovative, practical synthesis route to statin side chain, possessing great potential to be implemented into industrial production of statins.
- Chen, Fener,Hu, Chen,Huang, Zedu,Liu, Minjie,Yue, Xiaoping
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supporting information
p. 1700 - 1706
(2020/10/26)
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- Bi(cyclopentyl)diol-Derived Boronates in Highly Enantioselective Chiral Phosphoric Acid-Catalyzed Allylation, Propargylation, and Crotylation of Aldehydes
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In this study, we disclose the catalytic addition of bi(cyclopentyl)diol-derived boronates to aldehydes promoted by chiral phosphoric acids, allowing for the formation of enantioenriched homoallylic, propargylic, and crotylic alcohols (up to >99% enantiom
- Yuan, Jinping,Jain, Pankaj,Antilla, Jon C.
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p. 12988 - 13003
(2020/11/23)
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- Stereoselective total synthesis of (?)-galantinic acid and 1-deoxy-5-hydroxysphingolipids via prins cyclization
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The stereoselective total synthesis of (?)-galantinic acid 1 and 1-deoxy-5-hydroxysphingolipids 4 is described via Prins cyclization protocol followed by reductive ring opening sequence of substituted pyrenol derivative 6. The target molecules were synthesized using a common synthetic intermediate epoxide 5. Besides, we also proposed synthetic pathways to achieve other structural analogues using common intermediates.
- Rahman, Md. Ataur,Haque, Ashanul,Yadav, Jhillu Singh
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- Synthesis, conformation, and biological activities of a des-a-ring analog of 18-deoxy-aplog-1, a simplified analog of debromoaplysiatoxin
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10-Me-Aplog-1 as a simplified analog of tumor-promoting debromoaplysiatoxin and a potent activator of protein kinase C (PKC) is a promising chemotherapeutic agent. In this study, we synthesized a des-A-ring analog (4) of 18-deoxy-aplog-1 as a syntheticall
- Ashida, Yoshiki,Yanagita, Ryo C.,Kawanami, Yasuhiro,Okamura, Mutsumi,Dan, Shingo,Irie, Kazuhiro
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p. 942 - 957
(2019/08/01)
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- AMINOTHIAZINES AND THEIR USE AS BACE1 INHIBITORS
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The present invention provides a compound of Formula I: or a pharmaceutically acceptable salt thereof, and the use of compounds of Formula I for treatment of neurodegenerative diseases and disorders, such as Alzheimer's disease.
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Page/Page column 13
(2018/03/06)
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- Novel compound 6,6-dimethyl tetrahydropyran-2-methanol and preparing method thereof
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The invention discloses a novel compound that is 6,6-dimethyl tetrahydropyran-2-methanol and a preparing method thereof. The method includes preparing benzyloxy ethanol by utilizing a sodium alkoxideprocess; then oxidizing the benzyloxy ethanol into benzyloxy acetaldehyde by utilizing a swern oxidation process; reacting the benzyloxy acetaldehyde and allyltributyltin prepared by utilizing a Grignard reaction to obtain 1-(benzyloxy)-4-penten-2-ol; subjecting the 1-(benzyloxy)-4-penten-2-ol and acetone to cyclization under catalysis of trimethylchlorosilane and potassium iodide to obtain 4-iodo-6,6-dimethyl tetrahydropyran-2-methanol; and subjecting the 4-iodo-6,6-dimethyl tetrahydropyran-2-methanol to hydrogenation to remove iodine to obtain the target product that is the 6,6-dimethyl tetrahydropyran-2-methanol. According to the method, reactions are relatively mild, products can be easily treated and purified, and the method is suitable for batch preparation, and therefore the methodhas important application value.
- -
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Paragraph 0014; 0021-0022; 0027; 0033
(2018/04/03)
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- Divergent reactivity via cobalt catalysis: An epoxide olefination
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Cobalt salts exert an unexpected and profound influence on the reactivity of epoxides with dimethylsulfoxonium methylide. In the presence of a cobalt catalyst, conditions for epoxide to an oxetane ring expansion instead deliver homoallylic alcohol products, corresponding to a two-carbon epoxide homologation/ring-opening tandem process. The observed reactivity change appears to be specifically due to cobalt salts and is broadly applicable to a variety of epoxides, retaining the initial stereochemistry. This transformation also provides operationally simple access to enantiopure homoallylic alcohols from chiral epoxides without use of organometallic reagents. Tandem epoxidation-homologation of aldehydes in a single step is also demonstrated.
- Jamieson, Megan L.,Hume, Paul A.,Furkert, Daniel P.,Brimble, Margaret A.
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p. 468 - 471
(2016/02/18)
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- Stereoselective Synthesis of the C(1)?–?C(28) Fragment of Amphidinol 3
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A stereoselective synthesis of the polyol side chain (C(1)?–?C(28)) of amphidinol 3 has been accomplished following Sharpless epoxidation, Crimmins aldol reaction, Jacobsen kinetic resolution, Sharpless asymmetric dihydroxylation, and our own reaction for
- Yadav, Jhillu S.,Gopalarao, Yerragorla,Chandrakanth, Dandekar,Reddy, Basi V. Subba
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p. 436 - 446
(2016/07/06)
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- C5-C6-OXACYCLIC FUSED IMINOPYRIMIDINONE COMPOUNDS AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE
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In its many embodiments, the present invention provides certain C5-C6-oxacyclic fused iminopyrimidinone compounds, including compounds Formula (I): or a tautomer thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein RN, R1, RA, ring A, m, n, -L1-, ring B, RB, and p are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.
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Page/Page column 46
(2016/06/14)
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- Efficient Synthesis of Dimeric Oxazoles, Piperidines and Tetrahydroisoquinolines from N-Substituted 2-Oxazolones
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A mild and practical method for the construction of heterocycles from N-substituted 2-oxazolones through cascade, BF3·Et2O/H2O-catalyzed reactions involving iminium ion generation and trapping by external or internal olefinic and aryl moieties is described. Mechanistic and computational studies revealed the strong protic acid HBF4as the initiating catalyst for these cascade reactions. Providing access to novel molecular diversity, these processes may facilitate chemical biology studies, drug discovery efforts and natural products synthesis.
- He, Yun,Agarwal, Piyush K.,Kiran, I. N. Chaithanya,Yu, Ruocheng,Cao, Bei,Zou, Cheng,Zhou, Xinghua,Xu, Huacheng,Xu, Biao,Zhu, Lei,Lan, Yu,Nicolaou
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supporting information
p. 7696 - 7701
(2016/06/09)
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- Highly stereocontrolled synthesis of trans -2,6-disubstituted-5-methyl-3,6-dihydropyrans: Stereoselective synthesis of the bicyclic core of penostatin b
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An efficient, mild, and highly diastereoselective strategy for the synthesis of trans-2,6-disubstituted-5-methyl-3,6-dihydropyran ring systems has been developed starting from δ-hydroxy α-methyl α,β-unsaturated aldehydes and allyltrimethylsilane in the presence of a catalytic amount of ZnBr2 in a highly diastereoselective manner with excellent yield. The versatility of the above method was also demonstrated for the construction of the bicyclic core present in penostatin B in a concise and highly stereoselective manner.
- Reddy, D. Srinivas,Padhi, Birakishore,Mohapatra, Debendra K.
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p. 1365 - 1374
(2015/03/04)
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- Discovery of a series of efficient, centrally efficacious bace1 inhibitors through structure-based drug design
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The identification of centrally efficacious β-secretase (BACE1) inhibitors for the treatment of Alzheimers disease (AD) has historically been thwarted by an inability to maintain alignment of potency, brain availability, and desired absorption, distribution, metabolism, and excretion (ADME) properties. In this paper, we describe a series of truncated, fused thioamidines that are efficiently selective in garnering BACE1 activity without simultaneously inhibiting the closely related cathepsin D or negatively impacting brain penetration and ADME alignment, as exemplified by 36. Upon oral administration, these inhibitors exhibit robust brain availability and are efficacious in lowering central Amyloid β (Aβ) levels in mouse and dog. In addition, chronic treatment in aged PS1/APP mice effects a decrease in the number and size of Aβ-derived plaques. Most importantly, evaluation of 36 in a 2-week exploratory toxicology study revealed no accumulation of autofluorescent material in retinal pigment epithelium or histology findings in the eye, issues observed with earlier BACE1 inhibitors.
- Butler, Christopher R.,Brodney, Michael A.,Beck, Elizabeth M.,Barreiro, Gabriela,Nolan, Charles E.,Pan, Feng,Vajdos, Felix,Parris, Kevin,Varghese, Alison H.,Helal, Christopher J.,Lira, Ricardo,Doran, Shawn D.,Riddell, David R.,Buzon, Leanne M.,Dutra, Jason K.,Martinez-Alsina, Luis A.,Ogilvie, Kevin,Murray, John C.,Young, Joseph M.,Atchison, Kevin,Robshaw, Ashley,Gonzales, Cathleen,Wang, Jinlong,Zhang, Yong,Oneill, Brian T.
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p. 2678 - 2702
(2015/04/14)
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- HEXAHYDROPYRANO[3,4-d][1,3]THIAZIN-2-AMINE COMPOUNDS
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The present invention provides compounds of Formula I, and the tautomers thereof, and the pharmaceutically acceptable salts of the compounds and tautomers, wherein the compounds have the structure wherein the variables R1, R2, R3, R4 and x are as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.
- -
-
Paragraph 0152; 0153
(2014/06/24)
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- CARBOCYCLIC- AND HETEROCYCLIC-SUBSTITUTED HEXAHYDROPYRANO[3,4-d][1,3]THIAZIN-2-AMINE COMPOUNDS
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The present invention provides compounds of formula (I), wherein the variables R1, R2, R5 and b are as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, an
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Page/Page column 37; 38
(2014/07/08)
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- SUBSTITUTED PHENYL HEXAHYDROPYRANO[3,4-d][1,3]THIAZIN-2-AMINE COMPOUNDS
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The present invention is directed to compounds, tautomers and pharmaceutically acceptable salts of the compounds which are disclosed, wherein the compounds have the structure of Formula (I), and the variables R1 and R2 are as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.
- -
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Page/Page column 37; 38
(2014/09/03)
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- Heteroaryl-Substituted Hexahydropyrano[3,4-d][1,3]Thiazin-2-Amine Compounds
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The present invention is directed to compounds, tautomers and pharmaceutically acceptable salts of the compounds which are disclosed, wherein the compounds have the structure of Formula I, and the variables R1 and R2 are as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.
- -
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Paragraph 0163; 0164
(2014/08/19)
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- Practical, highly stereoselective allyl- and crotylsilylation of aldehydes catalyzed by readily available Cinchona alkaloid amide
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We have demonstrated that bidentate Lewis base catalysts can be constructed based on the Cinchona alkaloid structure that promote highly stereoselective reactions of allyl- and crotyltrichlorosilane with aromatic as well as aliphatic aldehydes (90-99% ee, >98% diastereoselectivity). The catalysts are available in a one-pot procedure in >70% yield from cheap starting materials and promote the allylation reactions at ambient temperature. Gram scale reactions with catalyst recovery and reuse showcased the practicality of the catalytic system.
- Huang, Yuan,Yang, Licheng,Shao, Panlin,Zhao, Yu
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p. 3275 - 3281
(2013/07/26)
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- Copper(I)-catalyzed borylative exo -cyclization of alkenyl halides containing unactivated double bond
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A borylative exo-cyclization of alkenyl halides has been reported. The reaction includes the regioselective addition of a borylcopper(I) intermediate to unactivated terminal alkenes, followed by the intramolecular substitution of the resulting alkylcopper(I) moiety for the halide leaving groups. Experimental and theoretical investigations of the reaction mechanism have also been described. This reaction provides a new method for the synthesis of alkylboronates containing strained cycloalkyl structures from simple starting materials.
- Kubota, Koji,Yamamoto, Eiji,Ito, Hajime
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supporting information
p. 2635 - 2640
(2013/03/29)
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- COMPOUNDS AND COMPOSITIONS AS C-KIT KINASE INHIBITORS
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The invention provides compounds and pharmaceutical compositions thereof, which are useful as protein kinase inhibitors, as well as methods for using such compounds to treat, ameliorate or prevent a condition associated with abnormal or deregulated kinase activity. In some embodiments, the invention provides methods for using such compounds to treat, ameliorate or prevent diseases or disorders that involve abnormal activation of c-kit or c-kit and PDGFR (PDGFRα, PDGFRβ) kinases.
- -
-
Paragraph 0415; 0416
(2013/03/26)
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- Br?nsted acid-catalyzed asymmetric allylation and propargylation of aldehydes
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A method synthesizing homoallylic or homopropargylic alcohols was developed to react aldehydes with allyl boronates, such as allylboronic acid pinacol ester, or allenylborates in the presence of a catalytic amount of a chiral binaphthyl-derived chiral pho
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Page/Page column 8; 21
(2013/08/28)
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- Hexahydropyrano[3,4-d][1,3]Thiazin-2-Amine Compounds
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Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I, as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.
- -
-
Paragraph 0311
(2013/03/26)
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- Chiral bis(imidazolinyl)phenyl NCN pincer rhodium(III) Catalysts for enantioselective allylation of aldehydes and carbonyl-ene reaction of trifluoropyruvates
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Chiral NCN pincer rhodium(III) complexes with bis(imidazolinyl)phenyl ligands were found to be effective catalysts for the allylation of a variety of electronically and structurally diverse aldehydes with allyltributyltin, giving the corresponding optical
- Wang, Tao,Hao, Xin-Qi,Huang, Juan-Juan,Niu, Jun-Long,Gong, Jun-Fang,Song, Mao-Ping
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p. 8712 - 8721
(2013/09/24)
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- Heterocyclic Substituted Hexahydropyrano[3,4-d][1,3]Thiazin-2-Amine Compounds
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Compounds, tautomers and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I, as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.
- -
-
Paragraph 0130
(2013/11/19)
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- Asymmetric allylboration of aldehydes with pinacol allylboronates catalyzed by 1,1′-spirobiindane-7,7′-diol (SPINOL) based phosphoric acids
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The asymmetric allylboration of aldehydes with pinacolallylboronates catalyzed by 1,1′-spirobiindane-7,7′-diol (SPINOL) based phosphoric acids is described. 6,6′-Bis(2,4,6-triisopropylphenyl)SPINOL-based phosphoric acid was found to be a general, highly e
- Xing, Chun-Hui,Liao, Yuan-Xi,Zhang, Yimei,Sabarova, Darya,Bassous, Monica,Hu, Qiao-Sheng
-
supporting information; experimental part
p. 1115 - 1118
(2012/04/10)
-
- Synthesis of thietane nucleoside with an anomeric hydroxymethyl group
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Thietane nucleoside 5 with an anomeric hydroxymethyl group was synthesized via the Pummerer reaction. The stereochemistry of the sulfoxide and the nature of the protecting group had no significant effect on the yield of the reaction. When a hypervalent iodine reagent was used, sulfide 16 with O-benzoyl protecting groups gave the ring-expanded nucleoside 21. Unfortunately, synthesized compound 6 did not exhibit anti-HSV activity. Copyright
- Nishizono, Naozumi,Akama, Yuji,Agata, Masayuki,Sugo, Michiyasu,Yamaguchi, Yuki,Oda, Kazuaki
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experimental part
p. 358 - 363
(2011/03/19)
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- C2-symmetrical bipyridyldiols as promising enantioselective catalysts in Nozaki-Hiyama allylation
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Several new chiral bipyridyldiol ligands that promote the chromium-catalyzed enantioselective addition of allylic halides to aldehydes in up to 99% ee were synthesized. The chromium-catalyzed allylation of aldehydes using ligands 4 and 4a in the presence
- Huang, Xin-Ren,Pan, Xin-Hong,Lee, Gene-Hsian,Chen, Chinpiao
-
supporting information; experimental part
p. 1949 - 1954
(2011/10/13)
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- Lewis-acid catalyzed formation of dihydropyrans
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A methodology is described for the synthesis of 2,6-disubstituted dihydro[2H]pyrans through a Lewis-acid catalyzed 6-endo-trig cyclization of β-hydroxy-γ,δ-unsaturated alcohols. Employing alkyl-substituted allylic diols and catalytic amounts of a Lewis ac
- Hanessian, Stephen,Focken, Thilo,Oza, Rupal
-
experimental part
p. 9870 - 9884
(2012/02/06)
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- Chiral bronsted acid-catalyzed allylboration of aldehydes
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The catalytic enantioselective allylation of aldehydes is a long-standing problem of considerable interest to the chemical community. We disclose a new high-yielding and highly enantioselective chiral Bronsted acid-catalyzed allylboration of aldehydes. Th
- Jain, Pankaj,Antilla, Jon C.
-
supporting information; experimental part
p. 11884 - 11886
(2010/11/17)
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- NOVEL FUSED AMINODIHYDROTHIAZINE DERIVATIVE
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A compound represented by the general formula: wherein Ring A is a C6-14 aryl group or the like, L is —NRLCO— or the like (wherein RL is a hydrogen atom or the like), Ring B is a C6-14 aryl group or the like, X is a C1-3 alkylene group or the like, Y is a C1-3 alkylene group or the like, Z is an oxygen atom or the like, R1 and R2 are each independently a hydrogen atom or the like, and R3, R4, R5 and R6 are independently a hydrogen atom, a halogen atom or the like, or a pharmaceutically acceptable salt thereof, or a solvate thereof, has an Aβ production inhibitory effect or a BACE1 inhibitory effect and is useful as a therapeutic agent for a neurodegenerative disease caused by Aβ and typified by Alzheimer-type dementia.
- -
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Page/Page column 49; 50
(2010/04/30)
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- The stereoselective total synthesis of (6S)-5,6-dihydro-6-[(2R)-2-hydroxy- 6-phenylhexyl]-2H-pyran-2-one via Prins cyclization
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The stereoselective total synthesis of an antiproliferative and antifungal a-pyrone natural product (6S)-5,6-dihydro-6-[(2R)-2-hydroxy-6-phenylhexyl]-2H- pyran-2-one is described. The key steps involved are the Prins cyclization, Mitsunobu reaction, and r
- Yadav, Jhillu Singh,Chandrakanth, Dandekar,Rao, Yerragorla Gopala,Ravindar, Kontham,Subba Reddy, Basi V.
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scheme or table
p. 1432 - 1438
(2010/09/12)
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- Short diastereoselective synthesis of the C1-C13 (AB Spiroacetal) and C17-C28 fragments (CD spiroacetal) of spongistatin 1 and 2 through double chain-elongation reactions
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A unique and practical synthetic sequence for rapid access to polyketides and to further the spiroacetals derived from them, which utilizes a bidirectional Hosomi-Sakurai allylation approach around key allylsilanes in the synthesis of the AB and CD ring s
- Flowers, Christopher L.,Vogel, Pierre
-
scheme or table
p. 14074 - 14082
(2011/02/23)
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- Spongipyran synthetic studies. Total synthesis of (+)-spongistatin 2
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Evolution of a convergent synthetic strategy to access (+)-spongistatin 2 (2), a potent cytotoxic marine macrolide, is described. Highlights of the synthesis include: development of a multicomponent dithiane-mediated linchpin union tactic, devised and implemented specifically for construction of the spongistatin AB and CD spiro ring systems; application of a CaII ion controlled acid promoted equilibration to set the thermodynamically less stable axial-equatorial stereogenicity in the CD spiroketal; use of sulfone addition/Julia methylenation sequences to unite the AB and CD fragments and introduce the C(44)-C(51) side chain; and fragment union and final elaboration to (+)-spongistatin 2 (2) exploiting Wittig olefination to unite the advanced ABCD and EF fragments, followed by regioselective Yamaguchi macrolactonization and global deprotection. Correction of the CD spiro ring stereogenicity was subsequently achieved via acid equilibration in the presence of CaII ion to furnish (+)-spongistatin 2 (2). The synthesis proceeded with a longest linear sequence of 41 steps.
- Smith III, Amos B.,Lin, Qiyan,Doughty, Victoria A.,Zhuang, Linghang,McBriar, Mark D.,Kerns, Jeffrey K.,Boldi, Armen M.,Murase, Noriaki,Moser, William H.,Brook, Christopher S.,Bennett, Clay S.,Nakayama, Kiyoshi,Sobukawa, Masao,Lee Trout, Robert E.
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scheme or table
p. 6470 - 6488
(2011/02/25)
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- Total synthesis of bongkrekic acid via sequential suzuki-miyaura coupling reactions
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An efficient total synthesis of (+)-bongkrekic acid, a potent apoptosis inhibitor, has been accomplished by employing a convergent strategy based on the Suzuki-Miyaura coupling of three fully functionalized segments. Georg Thieme Verlag Stuttgart.
- Kanematsu, Makoto,Shindo, Mitsuru,Yoshida, Masahiro,Shishido, Kozo
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experimental part
p. 2893 - 2904
(2010/03/03)
-
- A concise enantioselective synthesis of (+)-lentiginosine
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A high yielding enantioselective synthesis of the indolizidine alkaloid, (+)-lentiginosine, has been described based on asymmetric aza-Cope rearrangement and the l-proline catalyzed α-aminooxylation of aldehydes. The strategy also makes use of ring-closin
- Shaikh, Tanveer Mahamadali,Sudalai, Arumugam
-
experimental part
p. 2287 - 2292
(2010/03/24)
-
- Enantioselective synthesis of structurally intricate and complementary polyoxygenated building blocks of spongistatin 1 (altohyrtin a)
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Enantioselective approaches to the construction of four complex building blocks of the structurally intricate marine macrolide known as spongistatin 1 are presented. The first phase of the synthetic effort relies on a practical approach to a desymmetrized, enantiomerically pure spiroketal ring system incorporating rings A and B. Concurrently, the C17-C28 subunit, which houses one-fifth of the stereogenic centers of the target in the form of rings C and D, was assembled via a composite of stereocontrolled aldol condensations. Once arrival at the entire C1-C28 sector had been realized, routes were devised to provide two additional highly functionalized sectors consisting of C29-C44 and C38-C51. A series of subsequent transformations including cyclization of the E ring and hydroboration to afford the B-alkyl intermediate for the key Suzuki coupling to append the side chain took advantage of efficient stereocontrol. Ultimately, complete assembly and functionalization of the western EF sector of spongistatin was thwarted by an inoperative Suzuki coupling step intended to join the side chain to the C29-C44 sector, and later because of complications due to protecting groups, which precluded the complete elaboration of the late stage C29-C51 intermediate.
- Braun, Alain,Cho, Ii Hwan,Ciblat, Stephane,Clyne, Dean,Forgione, Pat,Hart, Amy C.,Huang, Guoxiang,Kim, Jungchul,Modolo, Isabelle,Paquette, Leo A.,Peng, Xiaowen,Pichlmair, Stefan,Stewart, Catherine A.,Wang, Jizhou,Zuev, Dmitry
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experimental part
p. 651 - 769
(2010/02/27)
-
- Enantioselective iridium-catalyzed carbonyl allylation from the alcohol or aldehyde oxidation level via transfer hydrogenative coupling of allyl acetate: Departure from chirally modified allyl metal reagents in carbonyl addition
-
Under the conditions of transfer hydrogenation employing an iridium catalyst generated in situ from [Ir(COd)Cl]2, chiral phosphine ligand (R)-BINAP or (R)-Cl,MeO-BIPHEP, and m-nitrobenzoic acid, allyl acetate couples to allylic alcohols 1a-c, aliphatic alcohols 1d-1, and benzylic alcohols 1m-u to furnish products of carbonyl allylation 3a-u with exceptional levels of asymmetric induction. The very same set of optically enriched carbonyl allylation products 3a-u are accessible from enals 2a-c, aliphatic aldehydes 2d-1, and aryl aldehydes 2m-u, using iridium catalysts ligated by (-)-TMBTP or (R)-Cl,MeO-BIPHEP under identical conditions, but employing isopropanol as a hydrogen donor. A catalytically active cyclometallated complex V, which arises upon ortho-C-H insertion of iridium onto m-nitrobenzoic acid, was characterized by single-crystal X-ray diffraction. The results of isotopic labeling are consistent with intervention of symmetric iridium π-allyl intermediates or rapid interconversion of σ-allyl haptomers through the agency of a symmetric π-allyl. Competition experiments demonstrate rapid and reversible hydrogenation-dehydrogenation of the carbonyl partner in advance of C-C coupling. However, the coupling products, which are homoallylic alcohols, experience very little erosion of optical purity by way of redox equilibration under the coupling conditions, although isopropanol, a secondary alcohol, may serve as terminal reductant. A plausible catalytic mechanism accounting for these observations is proposed, along with a stereochemical model that accounts for the observed sense of absolute stereoinduction. This protocol for asymmetric carbonyl allylation transcends the barriers imposed by oxidation level and the use of preformed allyl metal reagents.
- Kim, In Su,Ngai, Ming-Yu,Krische, Michael J.
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supporting information; experimental part
p. 14891 - 14899
(2009/02/08)
-
- Prins and RCM protocols for the synthesis of the pheromones of the giant white butterfly Idea leuconoe
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The total syntheses of (6R)-6-[(2R)-2-hydroxyhexyl]tetrahydro-2H-2-pyranone and 7-hydroxy-5-dodecanolide are described utilizing a Prins reaction and ring closing metathesis reaction sequence.
- Sabitha, Gowravaram,Fatima, Narjis,Reddy, E. Venkata,Yadav
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scheme or table
p. 6087 - 6089
(2009/04/04)
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- Catalytic enantioselective allyl- and crotylboration of aldehydes using chiral diol·SnCl4 complexes. Optimization, substrate scope and mechanistic investigations
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We report a novel class of C2-symmetric chiral diols derived from the hydrobenzoin skeleton. The combination of these diols with SnCl 4 under Yamamoto's concept of Lewis acid assisted Bronsted acidity (LBA catalysis) leads to high levels of asymmetric induction in the allylboration of aldehydes by commercially available allylboronic acid pinacol ester 1a. The corresponding homoallylic alcohol products of synthetically useful aliphatic aldehydes are obtained in excellent yields with up to 98:2 er. This combined acid manifold is also efficient in catalyzing the diastereo- and enantioselective crotylboration of aldehydes, thus providing the propionate units in >95:5 dr and up to 98:2 er. The X-ray crystal structure of the optimal diol·SnCl4 complex, Vivol (4m)·SnCl 4, unambiguously shows the Bronsted acidic character of this LBA catalyst and its highly dissymmetrical environment. Further controls have ruled out a possible boron transesterification mechanism with the chiral diol and point to LBA catalyst-derived activation of the pinacol allylic boronates 1. Due to slow dissociation of the diol·SnCl4 complex, a small excess of diol is required in order to suppress a competing racemic cycle catalyzed by free SnCl4.
- Rauniyar, Vivek,Zhai, Huimin,Hall, Dennis G.
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supporting information; scheme or table
p. 8481 - 8490
(2009/02/02)
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- Solid-phase synthesis of [5.5]-spiroketals
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An efficient and reliable multi-step synthesis of 251 natural product-like [5.5]-spiroketals on solid supports has been developed. As central key step, a double intramolecular hetero-Michael (DIHMA) reaction to alkynones was applied. The sequence allows for introduction of numerous substituents on the scaffold and for variation of stereochemistry. [5.5]-Spiroketals bearing an additional ketone were obtained in high overall yields. Further diversification was achieved by reduction of the ketone and reductive amination using polymer-supported borohydride, Grignard reaction and conversion to oxime derivatives in the solution phase.
- Sommer, Stefan,Kuehn, Marc,Waldmann, Herbert
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supporting information; experimental part
p. 1736 - 1750
(2009/08/14)
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- Stereoselective synthesis of anti-1,3-diol units via Prins cyclisation: application to the synthesis of (-)-sedamine
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The scope of the Prins cyclisation, the higher stereoselective synthesis of multisubstituted tetrahydropyrans from aldehydes and homoallylic alcohols, is expanded. A new approach for the stereoselective synthesis of polyketide precursors containing anti-1
- Yadav,Reddy, M. Sridhar,Rao, P. Purushothama,Prasad
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p. 4397 - 4401
(2007/10/03)
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- Catalytic enantioselective Nozaki-Hiyama allylation reaction with tethered bis(8-quinolinolato) (TBOx) chromium complex
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The utility of the new class of chiral ligand, tethered bis(8-quinolinol) (TBOxH), is further explored. Its chromium complex, TBOxCr(III)Cl, effectively catalyzes the Nozaki-Hiyama allylation reactions of various aldehydes at room temperature with high yield (up to 95%) and high enantioselectivity (up to 99% ee). The scope of the present method is shown to be wide, and this method represents an efficient access to chiral homoallylic alcohols. Copyright
- Xia, Guoyao,Yamamoto, Hisashi
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p. 2554 - 2555
(2007/10/03)
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- Total synthesis of (R)-(+)-goniothalamin and (R)-(+)-goniothalamin oxide: first application of the sulfoxide-modified Julia olefination in total synthesis
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A short and efficient synthesis of (R)-(+)-goniothalamin 1 and (R)-(+)-goniothalamin oxide 2 is described. During this approach, the sulfoxide-modified Julia olefination was used as a key step to connect aldehyde 5 to sulfoxide 6. The desired styryl-containing adduct is obtained in good yield and with excellent E/Z selectivity.
- Pospí?il, Ji?í,Markó, István E.
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p. 5933 - 5937
(2007/10/03)
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- Stereoselective syntheses of (-)-tetrahydrolipstatin via Prins cyclisations
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Stereoselective syntheses of (-)-tetrahydrolipstatin have been achieved via two divergent approaches through Prins cyclisations as the key steps. PCC mediated oxidative cleavage, Frater alkylation, Keck allylation, Sharpless asymmetric epoxidation and allylic cleavage were the other key steps employed.
- Yadav,Reddy, M. Sridhar,Prasad
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p. 4995 - 4998
(2007/10/03)
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- Natural product-guided synthesis of a spiroacetal collection reveals modulators of tubulin cytoskeleton integrity
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The spiro[5.5]ketal moiety forms the underlying structural skeleton of numerous biologically active natural products. Since simplified but characteristic spiroketals derived from the parent natural products retain biological activity, the spiro[5.5]ketal
- Barun, Okram,Kumar, Kamal,Sommer, Stefan,Langerak, Anette,Mayer, Thomas U.,Mueller, Oliver,Waldmann, Herbert
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p. 4773 - 4788
(2007/10/03)
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- Convergent highly stereoselective preparation of the C12-C24 fragment of macrolactin A
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The convergent synthesis of the C12-C24 fragment (lower part) of macrolactin A is described. The adapted strategy allowed building up the lower moiety by the assembly of three key intermediates via organometallic addition. One hydroxylic stereogenic cente
- Bonini, Carlo,Chiummiento, Lucia,Pullez, Maddalena,Solladie, Guy,Colobert, Francoise
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p. 5015 - 5022
(2007/10/03)
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- Ruthenium-catalyzed olefin metathesis double-bond isomerization sequence
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A novel ruthenium-catalyzed tandem ring-closing metathesis (RCM) double-bond isomerization reaction is described in this paper. The utility of this method for the efficient syntheses of five-, six-, and seven-membered cyclic enol ethers is demonstrated. It relies on the conversion of a metathesis-active ruthenium carbene species to an isomerization-active ruthenium-hydride species in situ. This conversion is achieved by using various additives. Scope and limitations of the different protocols are discussed, and some mechanistic considerations based on 31P and 1H NMR spectroscopic studies are presented.
- Schmidt, Bernd
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p. 7672 - 7687
(2007/10/03)
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- Scope and limitations of the scandium-catalyzed enantioselective addition of chiral allylboronates to aldehydes
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Scandium triflate catalyzes the addition of camphor-derived allyl-, methallyl-, and crotylboronates to aldehydes to provide homoallylic alcohols with excellent diastereo- and enantioselectivity. Aromatic, aliphatic, and propargylic aldehydes can be used successfully in this system. Additional advantages of the camphor-diol allylboronates are their ease of synthesis, their availability in both enantiomeric forms, and their stability towards silica gel chromatography. The usefulness of this methodology is further demonstrated by the gram-scale synthesis of various homoallylic alcohols of high enantiomeric excess and by the concise synthesis of the pheromone (4S)-2-methyloctan-4-ol. 1 Introduction 2 Results and Discussion 2.1 Optimization 2.2 Substrate Scope 2.3 Synthetic Applications 2.4 Mechanistic Considerations 3 Conclusion.
- Gravel, Michel,Lachance, Hugo,Lu, Xiaosong,Hall, Dennis G.
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p. 1290 - 1302
(2007/10/03)
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- Scandium-catalyzed allylboration of aldehydes as a practical method for highly diastereo- and enantioselective construction of homoallylic alcohols
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A general approach for the allylation of aldehydes using stable, air-tolerant camphor-based chiral allylboronates under Sc(OTf)3 catalysis is described. This practical methodology provides both syn and anti propionate units and other homoallylic alcohols with very high levels of diastereo- and enantioselectivity for several substrates, including functionalized aliphatic aldehydes useful toward the elaboration of complex natural products. Copyright
- Lachance, Hugo,Lu, Xiaosong,Gravel, Michel,Hall, Dennis G.
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p. 10160 - 10161
(2007/10/03)
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- Acid-promoted prins cyclizations of enol ethers to form tetrahydropyrans
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(Matrix presented) Trifluoroacetic acid efficiently catalyzes Prins cyclizations of enol ethers 8 to provide tetrahydropyrans 9 and 10. These tetrahydropyrans are isolated with combined yields of 42-85% and stereoselectivities at C4 ranging fro
- Hart, David J.,Bennett, Chad E.
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p. 1499 - 1502
(2007/10/03)
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