Novel Method for Deracemization: Transformation of Racemic syn-1,3-Polyols to Enantiomerically Pure anti-1,3-Polyols by Enantiodifferentiating Inversion of Stereogenic Centers

1995 ◽  
Vol 117 (49) ◽  
pp. 12346-12347 ◽  
Author(s):  
Toshiro Harada ◽  
Takuya Shintani ◽  
Akira Oku
Keyword(s):  
Enantiomerically Pure ◽  
Stereogenic Centers ◽  
Novel Method

Novel Method for the Preparation of Enantiomerically Pure Propargylic Substituted Compounds

2005 ◽  
Vol 24 (17) ◽  
pp. 4106-4109 ◽  
Author(s):  
Yoshiaki Nishibayashi ◽  
Hiroaki Imajima ◽  
Gen Onodera ◽  
Sakae Uemura
Keyword(s):  
Enantiomerically Pure ◽  
Novel Method

Enantioselective Organocatalytic Construction of Carbocycles: The Nicolaou Synthesis of Biyouyanagin A

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Methyl Ether ◽  
Conjugate Addition ◽  
Unsaturated Aldehyde ◽  
Enantiomerically Pure ◽  
Intramolecular Alkylation ◽  
Stereogenic Centers ◽  
Chinese Academy Of Sciences ◽  
Academy Of Sciences ◽  
Polycyclic System ◽  
Selective Addition

One of the more powerful routes to enantiomerically-pure carbocycles is the desymmetrization of a prochiral ring. Karl Anker Jørgensen of Aarhus University has found (J. Am. Chem. Soc. 2007, 129, 441) that many cyclic β-ketoesters, including the vinylogous carbonate 1, can be homologated with 2 to the corresponding alkyne 3, in high ee. Sanzhong Luo of the Chinese Academy of Sciences, Beijing, and Jin-Pei Cheng, of the Chinese Academy of Sciences and Nankai University, have shown (J. Org. Chem. 2007, 72, 9350) that the catalyst 6 mediated the selective addition of 4-substituted cyclohexanones such as 4 to the nitroalkene 5, establishing three new stereogenic centers. Organocatalysts, alone or complexed with activating metals, have also been used to effect enantioselective ring construction. E. J. Corey of Harvard University has established (J. Am. Chem. Soc. 2007, 129, 12686) that the proline-derived complex 10 will mediate the 2 + 2 addition of a cyclic enol ether with an acrylate to give the cyclobutane 11. Further elaboration led to the cyclohexenone 12. Armando Córdova of Stockholm University has described (Tetrahedron Lett. 2007, 48, 5835) a novel route to cyclopentanones such as 16, via tandem conjugate addition/intramolecular alkylation. Professor Jørgensen has reported (Angew. Chem. Int. Ed . 2007, 46 , 9202) the double addition of 18 to the unsaturated aldehyde 17 to give 20. Earlier last year, Yujiro Hayashi of the Tokyo University of Science had shown (Angew. Chem. Int. Ed. 2007, 46, 4922) that the double addition of the inexpensive 21 to 5 could, depending on conditions, be directed selectively to 22, 23, or 24. As illustrated by the conversion of 8 to 13, organocatalysis can be used to effect the enantioselective construction of polycarbocyclic products. The initial ring prepared in enantiomerically-pure form by organocatalysis can also set the chirality of a polycyclic system. Professor Corey has reported (J. Am. Chem. Soc. 2007, 129, 10346) that Itsuno-Corey reduction of the prochiral diketone 25 led to the ketone 27. Cyclization followed by oxidation and reduction then delivered estrone methyl ether 28.

Enantioselektive Katalyse, XVIII Der Einfluß nicht koordinierter Stereozentren auf die enantioselektive Hydrierung/Enantioselective Catalysis, XVIII The Influence of Non-Coordinated Stereocenters on the Enantioselective Hydrogenation

1998 ◽  
Vol 53 (2) ◽  
pp. 211-223 ◽  
Author(s):  
Ulrich Nagel ◽  
Christoph Roller
Keyword(s):  
Michael Addition ◽  
Enantioselective Hydrogenation ◽  
Palladium Complexes ◽  
Enantioselective Catalysis ◽  
Pyrrolidine Ring ◽  
Enantiomerically Pure ◽  
Stereogenic Centers ◽  
Methyl Phenyl ◽  
Phenyl Vinyl

Abstract 3,4-Bis{[2-(methyl-phenyl-oxophosphanyl)-ethyl]phenyl-phosphanyl}pyrrolidines have be­en synthesized by Michael Addition from the corresponding methyl-phenyl-vinyl-phosphane oxides and 3,4-bis(phenylphosphino)pyrrolidines. For purification of the ligands palladium complexes were used and with the enantiomerically pure ligands Rh complexes have been pre­pared. The catalyst has 6 stereogenic centers. In the hydrogenation of Z-α-acetamidocinnamic acid all six stereogenic centers have an influence on the enantioselectivity. The influence is strongest from the C stereocenters of the pyrrolidine ring. Less important are the stereogenic centers on the coordinated P atoms. The influence of the stereocenters on the non-coordinated P = O groups is the least, but it is not negligible. The ee values obtained with the ligands containing P = O groups are much lower than those obtained with ligands which are substituted only with aryl groups. Ketones are hydrogenated with only low ee’s.

Enantioselective synthesis of structurally intricate and complementary polyoxygenated building blocks of Spongistatin 1 (Altohyrtin A)

2009 ◽  
Vol 74 (5) ◽  
pp. 651-769 ◽  
Author(s):  
Alain Braun ◽  
Il Hwan Cho ◽  
Stephane Ciblat ◽  
Dean Clyne ◽  
Pat Forgione ◽  
...  
Keyword(s):  
Suzuki Coupling ◽  
Building Blocks ◽  
Enantioselective Synthesis ◽  
Side Chain ◽  
Spongistatin 1 ◽  
Enantiomerically Pure ◽  
Altohyrtin A ◽  
Stereogenic Centers ◽  
Complex Building ◽  
Synthetic Effort

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.

Alkylated Stereogenic Centers: The Jia Synthesis of (−)-Goniomitine

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Organic Chemistry ◽  
Bimetallic Catalyst ◽  
The Other ◽  
Wild Type Enzyme ◽  
Enantiomerically Pure ◽  
Unsaturated Lactone ◽  
University Of Oxford ◽  
Stereogenic Centers ◽  
The University

John W. Wong of Pfizer and Kurt Faber of the University of Graz used (Adv. Synth. Catal. 2014, 356, 1878) a wild-type enzyme to reduce the nitrile 1 to 2 in high ee. Takafumi Yamagami of Mitsubishi Tanabe Pharma described (Org. Process Res. Dev. 2014, 18, 437) the practical diastereoselective coupling of the racemic acid 3 with the inexpensive pantolactone 4 to give, via the ketene, the ester 5 in high de. Takeshi Ohkuma of Hokkaido University devised (Org. Lett. 2014, 16, 808) a Ru/Li catalyst for the enantioselective addition of in situ generated HCN to an N-acyl pyrrole 6 to give 7 in high ee. Yujiro Hayashi of Tohoku University found (Chem. Lett. 2014, 43, 556) that an aldehyde 8 could be condensed with formalin, leading in high ee to the masked aldehyde 9. Stephen P. Fletcher of the University of Oxford prepared (Org. Lett. 2014, 16, 3288) the lactone 12 in high ee by adding an alkyl zirconocene, prepared from the alkene 11, to the unsaturated lactone 10. In a remarkable display of catalyst control, Masakatsu Shibasaki of the Institute of Microbial Chemistry and Shigeki Matsunaga of the University of Tokyo opened (J. Am. Chem. Soc. 2014, 136, 9190) the racemic aziridine 13 with malonate 14 using a bimetallic catalyst. One enantiomer of the aziridine was converted specifically to the branched product 15 in high ee. The other enantiomer of the aziridine was converted to the regioisomeric opening product. Kimberly S. Peterson of the University of North Carolina at Greensboro used (J. Org. Chem. 2014, 79, 2303) an enantiomerically-pure organophosphate to selec­tively deprotect the bis ester 16, leading to 17. Chunling Fu of Zhejiang University and Shengming Ma of the Shanghai Institute of Organic Chemistry showed (Chem. Commun. 2014, 50, 4445) that an organocatalyst could mediate the brominative oxi­dation of 18 to 19. The ee of the product was easily improved via selective crystalliza­tion of the derived dinitrophenylhydrazone. James P. Morken of Boston College developed (Org. Lett. 2014, 16, 2096) condi­tions for the allylation of an allylic acetate such as 20 with 21, to deliver the coupled product 22 with high maintenance of ee.

The Castle Synthesis of (-)-Acutumine

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Sigmatropic Rearrangement ◽  
Allylic Alcohol ◽  
Cope Rearrangement ◽  
Enantiomerically Pure ◽  
Quaternary Centers ◽  
Brigham Young University ◽  
Weinreb Amide ◽  
Facial Selectivity ◽  
Stereogenic Centers ◽  
Diastereoselective Reduction

The complex tetracyclic alkaloid (-)-acutumine 3, isolated from the Asian vine Menispermum dauricum, shows selective T-cell toxicity. The two adjacent cyclic all-carbon quaternary centers of 3 offered a particular challenge. Steven L. Castle of Brigham Young University solved (J. Am. Chem. Soc. 2009, 131, 6674) this problem by effecting net enantioselective conjugate allylation of the enantiomerically pure substrate 1 to give 2 with high diastereocontrol. The starting coupling partners ( Organic Lett . 2006, 8, 3757; Organic Lett. 2007, 9, 4033) for the synthesis were the Weinreb amide 4, prepared over several steps from 2,3- dimethoxyphenol, and the diastereomerically- and enantiomerically-pure cyclopentenyl iodide 5, prepared by singlet oxygenation of cyclopentadiene followed by enzymatic hydrolysis. Transmetalation of 5 by the Knochel protocol, addition of the resulting organometallic to 4 and enantioselective (and therefore diastereoselective) reduction of the resulting ketone delivered the alcohol 6. Methods for installing cyclic halogenated stereogenic centers are not well developed. Exposure of the allylic alcohol to mesyl chloride gave the chloride 7 with inversion of absolute configuration. Remarkably, this chlorinated center was carried through the rest of the synthesis without being disturbed. A central step in the synthesis of 3 was the spirocyclization of 7 to 8. Initially, iodine atom abstraction generated the aryl radical. The diastereoselectivity of the radical addition to the cyclopentene was set by the adjacent silyloxy group. The α-keto radical so generated reacted with the Et3Al to give a species that was oxidized by the oxaziridine to the α-keto alcohol, again with remarkable diastereocontrol. Conjugate addition to the cyclohexenone 1 failed, so an alternative strategy was developed, diastereoselective 1,2-allylation of the ketone followed by oxy-Cope rearrangement. The stereogenic centers of 1 are remote from the cyclohexenone carbonyl, so could not be used to control the facial selectivity of the addition. Fortunately, the stoichiometric enantiomerically-pure Nakamura reagent delivered the allyl group preferentially to one face of the ketone 1, to give 9. The subsequent sigmatropic rearrangement to establish the very congested second quaternary center of 2 then proceeded with remarkable facility, at 0°C for one hour.

Synthesis of Chiral N-Nitro-oxazolidin-2-ones and O-(β-Nitraminoalkyl) Carbamates in Liquefied 1,1,1,2-Tetrafluoroethane Medium

Synthesis ◽  
2020 ◽  
Vol 52 (22) ◽  
pp. 3485-3491
Author(s):  
Sergei G. Zlotin ◽  
Svetlana S. Arabadzhi ◽  
Mikhail N. Zharkov ◽  
Ilya V. Kuchurov
Keyword(s):  
Amino Acid ◽  
Nitro Compounds ◽  
Hek293 Cells ◽  
Human Embryonic Kidney ◽  
Enantiomerically Pure ◽  
Dinitrogen Pentoxide ◽  
Convenient Synthesis ◽  
Stereogenic Centers

AbstractA convenient synthesis of chiral N-nitro-oxazolidin-2-ones by nitration of α-amino acid derived 1,3-oxazolidin-2-ones containing one or two stereogenic centers with dinitrogen pentoxide in liquefied 1,1,1,2-tetrafluoroethane medium has been developed. The obtained N-nitroheterocycles were converted into enantiomerically pure O-(β-nitraminoalkyl) carbamates by treatment with ammonia or amines in the same solvent. The synthesized N-nitro compounds are slightly toxic in vitro to Human Embryonic Kidney 293 (HEK293) cells.

Arrays of Stereogenic Centers: The Shin/Chandrasekhar Synthesis of (+)-Lactacystin

2017 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Major Product ◽  
South Florida ◽  
Allylic Alcohol ◽  
Israel Institute ◽  
University Of Illinois ◽  
Enantiomerically Pure ◽  
Boston College ◽  
Stereogenic Centers ◽  
Institute Of Technology ◽  
The University

Kami L. Hull of the University of Illinois established (J. Am. Chem. Soc. 2014, 136, 11256) conditions for the diastereoselective hydroamination of 1 with 2 to give 3. Jon C. Antilla of the University of South Florida employed (Org. Lett. 2014, 16, 5548) an enantiomerically-pure Li phosphate to direct the opening of the prochiral epoxide 4 to 5. Jordi Bujons and Pere Clapés of IQAC-CSIC engineered (Chem. Eur. J. 2014, 20, 12572) an enzyme that mediated the enantioselective addition of glycolaldehyde 7 to an aldehyde 6, leading to 8. Takahiro Nishimura of Kyoto University set (J. Am. Chem. Soc. 2014, 136, 9284) the two stereogenic centers of 11 by adding 10 to the diene 9. Amir H. Hoveyda of Boston College added (J. Am. Chem. Soc. 2014, 136, 11304) the propargylic anion derived from 13 to the aldehyde 12 to give, after oxida­tion, the diol 14. Yujiro Hayashi of Tohoku University constructed (Adv. Synth. Catal. 2014, 356, 3106) 17 by the combination of 15 with 16. Yitzhak Apeloig and Ilan Marek of Technion-Israel Institute of Technology prepared (J. Org. Chem. 2014, 79, 12122) the bromo diol 20 by rearranging the adduct between the alkyne 19 and the acyl silane 18. James P. Morken, also of Boston College, effected (J. Am. Chem. Soc. 2014, 136, 17918) enantioselective coupling of 22 with the bis-borane 21. The prod­uct allyl borane added to benzaldehyde to give the alcohol 23. Sentaro Okamoto of Kanagawa University reduced (Org. Lett. 2014, 16, 6278) the aryl oxetane 24 to an intermediate that coupled with allyl bromide to give the alco­hol 25. In the presence of catalytic CuCN, the alternative diastereomer was the major product. Erick M. Carreira of ETH Zürich used (Angew. Chem. Int. Ed. 2014, 53, 13898) a combination of an Ir catalyst and an organocatalyst to couple the aldehyde 27 with the allylic alcohol 26. The four possible combinations of enantiomerically pure catalysts worked equally well, enabling the preparation of each of the four enan­tiomerically pure diastereomers of 28.

C-O Ring Natural Products: (-)-Serotobenine (Fukuyama-Kan), (-)-Aureonitol (Cox), Salmochelin SX (Gagné), Botcinin F (Shiina), (-)-Saliniketal B (Paterson), Haterumalide NA (Borhan)

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Indole Alkaloid ◽  
Chiral Auxiliary ◽  
Michigan State University ◽  
State University ◽  
Ene Reaction ◽  
Enantiomerically Pure ◽  
Cambridge University ◽  
Stereogenic Centers ◽  
Ready Access ◽  
The University

Tohru Fukuyama of the University of Tokyo and Toshiyuki Kan of the University of Shizuoka devised ( J. Am. Chem. Soc. 2008, 130, 16854) the chiral auxiliary-directed Rh-mediated cyclization of 1, setting the two stereogenic centers of 2 with high stereocontrol. The ester 2 was carried on to the indole alkaloid (-)-Serotobenine 3. In the course of a synthesis of (-)-Aureonitol 6, Liam R. Cox of the University of Birmingham developed (J. Org. Chem. 2008, 73, 7616) the diastereoselective intramolecular addition of an allyl silane 4 to give the tetrahydrofuran 5. In analogy to what is known about the intramolecular ene reaction, the diastereocontrol observed for this cyclization may depend on the allyl silane being Z. Michel R. Gagné of the University of North Carolina found (J. Am. Chem. Soc. 2008, 130, 12177) that the Ni-catalyzed coupling of organozinc halides could be extended to glycosyl halides such as 7. This opened ready access to C -alkyl and C -aryl glycosides, including Salmochelin SX 10. Isamu Shiina of the Tokyo University of Science established (Organic Lett. 2008, 10, 3153) that the acid-mediated cyclization of the Sharpless-derived epoxide 10 proceeded with clean inversion, to give 11. The highly-substituted tetrahydropyran core 11 was then elaborated to the antifungal Botcinin F 12. Ian Paterson of Cambridge University optimized (Organic Lett. 2008, 10, 3295) the Pd-catalyzed spirocyclization of the ene diol 13, leading to 14, the enantiomerically-pure bicyclic core of (-)-Saliniketal B 15. Haterumalide NA 18 presented the particular challenge of assembling the geometrically-defined chloroalkene, in addition to closing the macrolide ring. Babak Borhan of Michigan State University addressed (J. Am. Chem. Soc. 2008, 130, 12228) both of these challenges together, electing to employ a chlorovinylidene chromium carbenoid, as developed by Falck and Mioskowski, to effect the macrocyclization of 16 to 17.

Stereocontrolled Construction of Arrays of Stereogenic Centers

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Aldol Condensation ◽  
Simple Procedure ◽  
Unsaturated Ester ◽  
Magnesium Bromide ◽  
National Chemical Laboratory ◽  
Chemical Laboratory ◽  
Enantiomerically Pure ◽  
Stereogenic Centers ◽  
Diastereoselective Addition ◽  
The University

Complex natural products and even some complex pharmaceuticals contain arrays of stereogenic centers. Sometimes, the desired array is readily available from a natural product, but usually, such arrays of multiple stereogenic centers must be assembled. Armando Córdova of Stockholm University has reported (Angew. Chem. Int. Ed. 2007, 46, 778) a simple procedure for the organocatalyst-mediated addition of the nitrene equivalent 2 to an α, β-unsaturated aldehyde to give the protected aziridine 4 in high ee. Organocatalysis was also used (Organic Lett. 2007, 9, 1001) by Arumugam Sudalai of the National Chemical Laboratory, Pune, to effect coupling of the aldehyde 5 with dibenzylazodicarboxylate 6 to give, following the List procedure, the intermediate aldehyde 7. Osmylation of the derived unsaturated ester 8 proceeded with high diastereocontrol, to give 9. Products 4 and 9 have adjacent stereogenic centers. Hisashi Yamamoto of the University of Chicago has introduced (J. Am. Chem. Soc. 2007, 129, 2762) the linchpin reagent acetaldehyde “super”silyl enol ether 11. Diastereoselective addition of 11 to the enantiomerically-pure aldehyde 10, with concomitant silyl transfer, followed by the addition of allyl magnesium bromide delivered the protected triol 12 in high de and ee. Arrays that combine alkylated and oxygenated or aminated centers are also important. Akio Kamimura of Yamaguchi University took (J. Org. Chem. 2007, 72, 3569) a Baylis- Hillman like approach, adding thiophenoxide to t -butyl acrylate in the presence of an enantiomerically-pure aldehyde N-sulfinimine such as 13 to give the adduct 14 with high diastereocontrol. Keiji Maruoka of Kyoto University has designed (Angew. Chem. Int. Ed. 2007, 46, 1738) the chiral amine 17, that catalyzed the condensation of an aldehyde with ethyl glyoxylate 16 with high enantiocontrol. In a very thoughtful approach, Liu-Zhu Gong of the University of Science and Technology of China in Hefei extended (Chem. Commun. 2007, 736) the now-classic aldol condensation of cyclohexanone to 4-substituted cyclohexanones such as 19. The product 21 could be carried in many directions, including to the Bayer-Villiger product 22. Arrays of alkylated and polyalkylated centers have been among the most challenging to prepare.

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