Total Synthesis of all ( )-Agelastatin Alkaloids
|
|
|
- Russell Davis
- 6 years ago
- Views:
Transcription
1 Total Synthesis of all ( )-Agelastatin Alkaloids Mohammad Movassaghi,* Dustin S. Siegel and Sunkyu an Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States Chem. Sci. 2010, 1 (5), 561 François Brucelle Journal Club Group Meeting March 8, 2012
2 Agelastatin Alkaloids Ø Pyrrole-imidazole family of marine alkaloids: Ø Tetracyclic framework with C4-C8 and C7-12 bond connectivities 2
3 Isolation and Biological Activity Ø ( )-Agelastatin A and B isolated from the Coreal Sea sponge Agelas dendromorpha (Pietra, 1993) Ø ( )-Agelastatin C and D: from Cymbastela sp. native from the Indian cean (Molinski, 1998) Ø ( )-Agelastatin E and F: from the ew Caledonian sponge A. dendromorpha (Al-Mourabit, 2010) Ø ( )-Agelastatin A: Exhibits antitumor activity: inhibits osteopontin-mediated neoplastic transformation and metastasis + slows cancer cell proliferation Selectively inhibits glycogen synthase kinase-3β (a potential target for the treatment of Alzheimer s disease and bipolar disorder) Pietra, F. et al. J. Chem. Soc., Chem. Commun. 1993, 1305 Molinski, T. F. et al. J. at. Prod. 1998, 61, 158 Al-Mourabit, A. et al. J. at. Prod. 2010, 73, 720 3
4 Ø Agelastatins: only isolated pyrrole-imidazole alkaloids with C4-C8 and C7-12 connectivities Derived from linear clathrodin-like precursors: Biosynthetic ypothesis Ø Clathrodin-like precursors derived from histidine and ornithine or proline (Kerr, 1999): Br Br oroidin 2 Br Br vinylogous 2-aminoimidazole 2 2 C 2 ornithine 2 proline 2 C 2 histidine Kerr, R. G. et al. Tetrahedron Lett. 1999, 40,
5 Biosynthetic ypothesis Ø Variation of building blocks by pyrrole bromination: 1 and C3 as nucleophilic sites Ø Reactivity variation of vinylogous 2-aminoimidazoles by tautomeric equilibrium (via proton migration): Vinylogous 2-aminoimidazole intermediate = source of molecular diversity in pyrrole-imidazole alkaloids Al-Mourabit, A.; Potier, P. Eur. J. rg. Chem. 2001, 237 5
6 Ø Common origin for many pyrrole-imidazole alkaloids: Biosynthetic ypothesis Al-Mourabit, A.; Potier, P. Eur. J. rg. Chem. 2001, 237 6
7 Biosynthetic ypothesis Ø Agelastatins: C-ring formation resulting from C8-nucleophilic trapping of a C4-electrophile Early stage biosynthesis of C-ring followed by B-ring formation Stereochemical control by action of enzymes C 30-VIII pre-agelastatins B Al-Mourabit, A.; Potier, P. Eur. J. rg. Chem. 2001, 237 7
8 Previous Syntheses Ø Weinreb (1999): first total synthesis of agelastatin A etero-diels-alder reaction with -sulfinyl dienophile C [2,3]-sigmatropic rearrangement (Mislow- Evans rearrangement) P MPT Ø Agelastatin A obtained in 11 steps from 11 Ø 7% overall yield from cyclopentadiene (14 steps) Weinreb, S. M. et al. J. Am. Chem.Soc. 1999, 121,
9 Previous Syntheses Ø Feldman (2002): first enantioselective total syntheses of ( )-agelastatin A and ( )-agelastatin B C 1,5 C- insertion via alkylidenecarbene 51 Me Stang's reagent Me TolS 2 a ob Tol 2 S ob Ph I Tf Ø ( )-Agelastatin A and B: in 6 steps each from 53 Ø ( )-Agelastatin A: 4% overall yield from 49 (14 steps). ( )-Agelastatin B: 2.4% o. y. from 49 (14 steps) Feldman, K. S. et al. J. Am. Chem. Soc. 2002, 124, 9060 and J. rg. Chem. 2002, 67,
10 Previous Syntheses Ø Du Bois (2009): ( )-4 1) Boc 2 2) ab 4 3) ClS 2 2, DMA 77% (3 steps) C Rh 2 (esp) 2 Intramolecular aziridination of a sulfamate ester and 2 consecutive regioselective ring openings Ø ( )-Agelastatin A obtained in 6 steps from 10 Ø 14% overall yield from ( )-4 (12 steps) Du Bois, J.; Wehn, P. M. Angew. Chem. Int. Ed. 2009, 48,
11 Movassaghi s Approach Ø Reverse polarity in C-ring formation: C4-nucleophilic trapping of a C8-electrophile Ø Introduction of C-ring after B-ring formation Ø Substrate directed stereochemical control (to secure C4-, C5-, and C8-stereocenters) 11
12 Synthesis of -Me-pre-agelastatin A (19) (+)-22 obtained in one step from D- aspartic acid dimethyl ester (84% yield) C13-Br important: C7- bond in pseudoequatorial position to minimize allylic strain between C13-Br and C6-methylene C7 epimerization prevented Imidazolone formation: addition of transmetallated derivatives of triazone 27 (metal = Li, Mg, Cu, Ce, Zn) to (+)-21 failed Liebeskind-Srogl C-C cross-coupling strategy followed by spontaneous condensative cyclization X-ray structure of (+)-19: C7- methylimidazolone and C8-methoxy group are in a pseudo-diaxial conformation 12
13 Liebeskind-Srogl C-C Cross-Coupling Reaction Ø Liebeskind and Srogl (2000): Pd-catalyzed C-C cross-coupling between thioesters and boronic acids to form ketones under neutral conditions S CCu Cu(I) thiophene-2-carboxylate (CuTC) TFP = tris(2-furyl)phosphane Ø Stoichiometric amount of a copper(i) carboxylate species (like CuTC) needed for thiophilic and borophilic activation (no reaction with copper(i) halide or CuC; works also with copper(i) 3-methylsalicylate of copper(i) diphenylphosphinate) Ø Copper(I) additive scavenges the released thiolate Liebeskind, L. S.; Srogl, J. J. Am. Chem. Soc. 2000, 122, Review: Kappe, C..; Prokopcová,. Angew. Chem. Int. Ed. 2009, 48,
14 Liebeskind-Srogl C-C Cross-Coupling Reaction Ø Unlike Suzuki-Miyaura cross-coupling: no need for a base formation of a ternary complex (sensitive to steric effects): Ø Poor reactivity of boronate esters: no -bonding possible with the copper carboxylate and greater steric demand Ø B-Alkyl 9-BB as coupling partner: need for a base because of the greater steric demand preventing the formation of the ternary complex base-induced activation of the boron reagent Ø Alternative approach: use of organostannanes Cu(I) diphenylphosphinate (CuDPP) better than Cu(I) carboxylates for the work-up (easier removal of nbu 3 SnP()Ph 2 ) Wittenberg, R.; Srogl, J.; Egi, M.; Liebeskind, L. S. rg. Lett. 2003, 5, 3033 Review: Kappe, C..; Prokopcová,. Angew. Chem. Int. Ed. 2009, 48,
15 Synthesis of ( )-Agelastatin A When 19 heated in aq. solution of MeS 3 : ( )-agelastatin A (1) and ( )-4,5-di-epi-agelastatin A obtained in 2:1 ratio Br Me 5 4 ( )-4,5-di-epi-agelastatin A: kinetic product which equilibrates to the thermodynamically favored 1 via tetracyle ( )-30 ( )-4,5-di-epi-agelastatin A ( )-Agelastatin A: 22% overall yield from D- aspartic acid dimethyl ester (8 steps) or 15% o. y. (7 steps) by coupling of thioester 26 with stannylurea 33 ( )-4,5-di-epi-agelastatin A converted to 29 by exposure to Me (then facile separation of 1 and 29) From 19: 1 in 49% yield (1.4 g, 99% ee) and 29 in 22% yield 15
16 Synthesis of ( )-Agelastatin B and C Formation of 3 via intermediate 32: confirmed by quantitative deuterium incorporation at C6 when 3 or 31 treated with MeS 3 in D 2 (1:1 mixture of deuterated 3 and 31 obtained) ( )-Agelastatin B: 18% o. y. from D- aspartic acid dimethyl ester (9 steps) ( )-Agelastatin C: 4% o. y. from D-aspartic acid dimethyl ester (11 steps, first total synthesis) 16
17 Synthesis of ( )-Agelastatin D ovel imidazolone annulation: effective to access pre-agelastatin D (35) Biomimetic cyclisation: 4 obtained in lower yield due to a lower C4- nucleophilicity of 35 (1- instead of 1- Me in 19) ( )-Agelastatin D: 8.4% o. y. from D- aspartic acid dimethyl ester (8 steps, first total synthesis) 17
18 Synthesis of ( )-Agelastatin E and F ( )-Agelastatin E: 21% o. y. from D- aspartic acid dimethyl ester (9 steps, first total synthesis) ( )-Agelastatin F: 7% o. y. from D-aspartic acid dimethyl ester (9 steps, first total synthesis) Ø Semi-synthesis of ( )-agelastatin E (Pietra, 1996): ( )-agelastatin A (isolated from the sponge A. dendromorpha) 1) Ac 2 /Py (3:1), 0 C, o. n. 2) evaporation, Me, rt, 5 h 95% (2 steps) ( )-agelastatin E Pietra, F. et al. elv. Chim. Acta 1996, 79,
19 Key bservations for the Bioinspired C-Ring Synthesis Ø C13-bromopyrrole and imidazolone: key substructures for the C-ring cyclization C13-bromopyrrole beneficial role for the allylic strain restricting C7- bond in a pseudo-equatorial conformation during the cyclization (a) MeS 3, 2, 100 C, 20 min Imidazolone (b) Dowex, 2, 100 C aminoimidazole 43 failed to undergo the cyclization due to the greater propensity of the aminoimidazole substructure to remain protonated and thus less nucleophilic igh probability for biosynthetic introduction of the C13-bromopyrrole and imidazolone substructures prior to C-ring formation 19
20 Key Points Ø Total syntheses of all known agelastatin alkaloids Ø Use of a unified strategy inspired by a biosynthetic hypothesis: o confirmation for the proposed biosynthesis but chemical validation for the proposed mode and timing of bond and ring formations Ø Key features of the syntheses: Concise multi-gram scale enantioselective preparation of pre-agelastatin derivatives Use of bromopyrrole substructure to suppress C7-deprotonation Synthesis of imidazolone derivatives by a new annulation strategy Validation of a bioinspired 5-exo-trig cyclisation to form C-ring verall efficiency of the strategy highlighted by a 1.4 g batch enantioselective synthesis of ( )-agelastatin A 20
Bioinspired Total Synthesis of Agelastatin A
Bioinspired Total Synthesis of Agelastatin A Jeremy Chris P. Reyes and Daniel Romo Benjamin R. Eyer Wipf Group-Current Literature August 25, 2012 Angewandte Chemie International Edition. 2012, 51(28),
Asymmetric Catalysis by Lewis Acids and Amines
Asymmetric Catalysis by Lewis Acids and Amines Asymmetric Lewis acid catalysis - Chiral (bisooxazoline) copper (II) complexes - Monodentate Lewis acids: the formyl -bond Amine catalysed reactions Asymmetric
Synthesis of Abyssomicin C. Marie-Caroline Cordonnier Litterature Review 23/01/2009
Synthesis of Abyssomicin C Marie-Caroline Cordonnier Litterature Review 23/01/2009 Isolation Isolated in 2004 from the actinomycete Verrucosispora strain collected from a sediment at a depth of 289m in
CHEM 330. Final Exam December 5, 2014 ANSWERS. This a closed-notes, closed-book exam. The use of molecular models is allowed
CEM 330 Final Exam December 5, 2014 Your name: ASWERS This a closed-notes, closed-book exam The use of molecular models is allowed This exam consists of 12 pages Time: 2h 30 min 1. / 30 2. / 30 3. / 30
Electrophilic Carbenes
Electrophilic Carbenes The reaction of so-called stabilized diazo compounds with late transition metals produces a metal carbene intermediate that is electrophilic. The most common catalysts are Cu(I)
Tips for taking exams in 852
Comprehensive Tactical Methods in rganic Synthesis W. D. Wulff 1) Know the relative reactivity of carbonyl compounds Tips for taking exams in 852 Cl > > ' > > ' N2 eg: 'Mg Et ' 1equiv. 1equiv. ' ' Et 50%
Aldehydes and Ketones : Aldol Reactions
Aldehydes and Ketones : Aldol Reactions The Acidity of the a Hydrogens of Carbonyl Compounds: Enolate Anions Hydrogens on carbons a to carbonyls are unusually acidic The resulting anion is stabilized by
Advanced Organic Chemistry
D. A. Evans, G. Lalic Question of the day: Chemistry 530A TBS Me 2 C Me toluene, 130 C 70% TBS C 2 Me H H Advanced rganic Chemistry Me Lecture 16 Cycloaddition Reactions Diels _ Alder Reaction Photochemical
Nuggets of Knowledge for Chapter 17 Dienes and Aromaticity Chem 2320
Nuggets of Knowledge for Chapter 17 Dienes and Aromaticity Chem 2320 I. Isolated, cumulated, and conjugated dienes A diene is any compound with two or C=C's is a diene. Compounds containing more than two
CuI CuI eage lic R tal ome rgan gbr ommon
Common rganometallic eagents Li Et 2 Li Mg Et 2 Li alkyllithium rignard Mg Mg Li Zn TF ZnCl 2 TF dialkylzinc Zn 2 2 Zn Li CuI TF ganocuprate CuI 2 2 CuI common electrophile pairings ' Cl ' '' ' ' ' ' '
Total synthesis of marine natural products without using protecting groups
Total synthesis of marine natural products without using protecting groups ature (London, United Kingdom), Vol 446, March 2007, p. 404-408 Phil S. Baran, Thomas J. Maimone & Jeremy M. Richter Presented
Tautomerism and Keto Enol Equilibrium
Tautomerism and Keto Enol Equilibrium Enols & enolates are important nucleophiles in organic & biochemistry. Keto-Enol Equilibrium: Tautomerisation can be catalyzed by either acids or bases. Relative stability
VI. Metal alkyls from oxidative addition / insertion
V. Metal alkyls from oxidative addition / insertion A. Carbonylation - C insertion very facile, metal acyls easily cleaved, all substrates which undergo oxidative addition can in principle be carbonylated.
Strategies for Catalytic Asymmetric Electrophilic a Halogenation of Carbonyl Compounds
Strategies for Catalytic Asymmetric Electrophilic a alogenation of Carbonyl Compounds 1 2 Y Catalyst [X + ] 1 X! 2 Y intermann, L. ; Togni, A. Angew. Chem. Int. Ed. 2000, 39, 4359 4362 amashima, Y.; Sodeoka,
sp 3 C-H insertion by α-oxo Gold Carbene B4 Kei Ito
1 sp 3 C-H insertion by α-oxo Gold Carbene B4 Kei Ito 2016. 1. 30 1. Introduction 2 About Carbene 3 Brief history of carbene (~2000) Carbene Neutral compounds featuring a divalent carbon atom with only
Lecture Notes Chem 51C S. King Chapter 24 Carbonyl Condensation Reactions
Lecture Notes Chem 51C S. King Chapter 24 Carbonyl Condensation Reactions I. Reaction of Enols & Enolates with ther Carbonyls Enols and enolates are electron rich nucleophiles that react with a number
Total Synthesis of the Sesquiterpenoid Periconianone A Based on a Postulated Biogenesis
Total Synthesis of the Sesquiterpenoid Periconianone A Based on a Postulated Biogenesis C 3 C3 Liffert, R., Linden, A., Gademann, K. J. Am. Chem. Soc. 2017, 139, 16096 Presented by: Brendyn Smith CEM 852
Rhodium Catalyzed Alkyl C-H Insertion Reactions
Rhodium Catalyzed Alkyl C-H Insertion Reactions Rh Rh Jeff Kallemeyn 5/17/05 1. Cyclopropanation The Versatile and Reactive Rhodium Carbene R + Et Rh 2 (Ac) 4 R C 2 Et N 2 2. [2,3] sigmatropic rearrangement
Amphoteric Molecules < Chemistry of Andrei K. Yudin > Hyung Min Chi 17 JUNE 2014
Amphoteric Molecules < Chemistry of Andrei K. Yudin > Hyung Min Chi 17 JUNE 2014 1 Amphoteric molecules Amphoteric? Greek word amphoteros (both of two) Amphoterism in acid/base chemistry Amino acids (thermodynatic
Synthetic Efforts Toward Palau'amine
ynthetic Efforts Toward Palau'amine Doug Behenna, Ryan McFadden Eric Ashley, Jenn tockdill Akihiko Iwashita August 9, 2004 2 2 2 Isolation of Palau'amine and Congeners R 2 R 1 R 1 R 2 2 2 2 2 2 2 R 1 =
H 3 C. biotin dependent O O. C O + Pi 2 + ADP 3 + H H 2 C C SCoA malonyl-scoa
1 EXAM F SCIETIFIC CULTUE CEMISTY BLEM 1: BISYTESIS F FATTY ACIDS The biosynthesis of fatty acids proceeds by lengthening of a hydrocarbon chain by condensation of two-carbon units derived from acetyl-coenzyme
Total Synthesis and Absolute Stereochemical Assignment of ( )-Communesin F
Total Synthesis and Absolute Stereochemical Assignment of ( )-Communesin F Zhiwei Zuo, Weiqing Xie, Dawei Ma* Shanghai Institute of rganic Chemistry, Shanghai, China J. Am. Chem. Soc. 2010, 132, 13226-13228.
Domino Reactions in Total Synthesis! Reporter: Tianhe Yang! Supervisors: Prof. Yang! Prof. Chen! Prof. Tang!
1! Domino Reactions in Total Synthesis! Reporter: Tianhe Yang! Supervisors: Prof. Yang! Prof. Chen! Prof. Tang! 2! utline! 1. Brief Introduction! 2. ucleophilic Dominoes! 3. Electrophilc Dominoes! 4. Radical
2.222 Practice Problems 2003
2.222 Practice Problems 2003 Set #1 1. Provide the missing starting compound(s), reagent/solvent, or product to correctly complete each of the following. Most people in the class have not done this type
Enols and Enolates. A type of reaction with carbonyl compounds is an α-substitution (an electrophile adds to the α carbon of a carbonyl)
Enols and Enolates A type of reaction with carbonyl compounds is an α-substitution (an electrophile adds to the α carbon of a carbonyl) E+ E In the preceding chapters, we primarily studied nucleophiles
Stereoselective reactions of the carbonyl group
1 Stereoselective reactions of the carbonyl group We have seen many examples of substrate control in nucleophilic addition to the carbonyl group (Felkin-Ahn & chelation control) If molecule does not contain
Only five of the molecules below may be prepared as the sole product of allylic halogenation of the respective alkene. Circle those five.
Chem 232 D. J. Wardrop wardropd@uic.edu Problem Set 6 Answers Question 1. nly five of the molecules below may be prepared as the sole product of allylic halogenation of the respective alkene. Circle those
Total Synthesis of (+)-Cytosporolide A via a Biomimetic
Literature report Total Synthesis of (+)-Cytosporolide A via a Biomimetic etero-diels Alder Reaction Reporter: Zhang-Pei Chen Checker: Shu-Bo u Date: 29/12/2015 Takao, K. et al. Takao, K. et al. J. Am.
Chem 253 Problem Set 7 Due: Friday, December 3, 2004
Chem 253 roblem Set 7 ue: Friday, ecember 3, 2004 Name TF. Starting with the provided starting material, provide a concise synthesis of. You may use any other reagents for your synthesis. It can be assumed
1. Radical Substitution on Alkanes. 2. Radical Substitution with Alkenes. 3. Electrophilic Addition
1. Radical Substitution on Alkanes Only Cl and Br are useful at the laboratory level. Alkane reactivity: tertiary > secondary > primary > methyl Numbers below products give their relative yield. Relative
CHAPTER 19: CARBONYL COMPOUNDS III
CHAPTER 19: CARBONYL COMPOUNDS III A hydrogen bonded to a carbon adjacent to a carbonyl carbon is sufficiently acidic to be removed by a strong base. The carbon adjacent to a carbonyl carbon is called
1/4/2011. Chapter 18 Aldehydes and Ketones Reaction at the -carbon of carbonyl compounds
Chapter 18 Aldehydes and Ketones Reaction at the -carbon of carbonyl compounds The Acidity of the Hydrogens of Carbonyl Compounds: Enolate Anions Hydrogens on carbons to carbonyls are unusually acidic
I. Introduction. Peng Zhao. Liu lab
Asymmetric Total Synthesis of Mycoleptodiscin A Shupeng Zhou, Hao Chen, Yijie Luo, Wenhao Zhang and Ang Li Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai
Pericyclic reactions
Pericyclic reactions In pericyclic reactions the breaking and making of bonds occur simultaneously by the way of a single cyclic transition state (concerted reaction). There are no intermediates formed
Copper-Catalyzed Diastereoselective Arylation of Tryptophan Derivatives: Total Synthesis of (+)-
Literature Report Copper-Catalyzed Diastereoselective Arylation of Tryptophan Derivatives: Total Synthesis of (+)- aseseazines A and B Reporter: Mu-Wang Chen Checker: Zhang-Pei Chen Date: 2013-05-28 Reisman,
Asymmetric Lewis Base Strategies for Heterocycle Synthesis
Asymmetric Lewis Base trategies for eterocycle ynthesis Dr Andrew mith EatCEM, chool of Chemistry, University of t Andrews 1st cottish-japanese ymposium of rganic Chemistry, University of Glasgow Friday
CHEM 330. Final Exam December 11, 2007 A N S W E R S. This a closed-notes, closed-book exam. The use of molecular models is allowed
CEM 330 Final Exam December 11, 2007 Your name: A S W E R S This a closed-notes, closed-book exam The use of molecular models is allowed This exam contains 12 pages Time: 2h 30 min 1. / 20 / 20 3. / 30
Suggested solutions for Chapter 41
s for Chapter 41 41 PBLEM 1 Explain how this synthesis of amino acids, starting with natural proline, works. Explain the stereoselectivity of each step after the first. C 2 C 2 3 CF 3 C 2 2 Pd 2 C 2 +
Chapter 19. Organic Chemistry. Carbonyl Compounds III. Reactions at the a-carbon. 4 th Edition Paula Yurkanis Bruice
Organic Chemistry 4 th Edition Paula Yurkanis Bruice Chapter 19 Carbonyl Compounds III Reactions at the a-carbon Disampaikan oleh: Dr. Sri Handayani 2013 Irene Lee Case Western Reserve University Cleveland,
Molybdenum-Catalyzed Asymmetric Allylic Alkylation
Molybdenum-Catalyzed Asymmetric Allylic Alkylation X MoL n u u * Tommy Bui 9/14/04 Asymmetric Allylic Alkylation from a Synthetic Viewpoint X X M u u * and/or u form a C-C bond with the creation of a new
Mechanistic Studies in Copper Catalysis
chanistic Studies in Copper Catalysis Jen Alleva May 1st 2013 Timeline of Achievements in Copper Chemistry General istorical verview first cross-couplings 1869 Ullmann Goldberg Glaser 1903 Glaser, C. Ann.
[3,3]-sigmatropic Processes. [2,3]-sigmatropic Processes. Ene Reactions. Generalized Sigmatropic Processes X,Y=C, N, O, S X,Y=C, N, O, S
![[3,3]-sigmatropic Processes. [2,3]-sigmatropic Processes. Ene Reactions. Generalized Sigmatropic Processes X,Y=C, N, O, S X,Y=C, N, O, S](/thumbs/94/119475672.jpg "[3,3]-sigmatropic Processes. [2,3]-sigmatropic Processes. Ene Reactions. Generalized Sigmatropic Processes X,Y=C, N, O, S X,Y=C, N, O, S")
Generalized igmatropic Processes [3,3]-sigmatropic Processes 1 3,=C,,, 1 3 3,=C,,, 3 [2,3]-sigmatropic Processes 1 3,=C,,, 1 3 Ene eactions 1 3 1 3 Cope earrangement [3,3]- igmatropic earrangements Transition
Mechanistic Insides into Nickamine-Catalyzed Alkyl-Alkyl Cross-Coupling Reactions
Mechanistic Insides into Nickamine-Catalyzed Alkyl-Alkyl Cross-Coupling Reactions Abstract Within the last decades the transition metal-catalyzed cross-coupling of non-activated alkyl halides has significantly
Chapter 9. Nucleophilic Substitution and ß-Elimination
Chapter 9 Nucleophilic Substitution and ß-Elimination Nucleophilic Substitution Nucleophile: From the Greek meaning nucleus loving. A molecule or ion that donates a pair of electrons to another atom or
Aldol Reactions pka of a-h ~ 20
Enolate Anions Chapter 17 Hydrogen on a carbons a to a carbonyl is unusually acidic The resulting anion is stabilized by resonance to the carbonyl Aldehydes and Ketones II Aldol Reactions pka of a-h ~
Problem session (3) Daiki Kuwana. Please fill in the blank and explain reaction mechanisms and stereoselectivities.
Problem session (3) Daiki Kuwana Please fill in the blank and explain reaction mechanisms and stereoselectivities. 1. 1-1 1. (Ac) 2 (10 mol%), DPEphos (20 mol%) Et 3, toluene, 90 C 2. s 4 (14 mol%), M;
Zr-Catalyzed Carbometallation
-Catalyzed Carbometallation C C C C ML n C C ML n ML n C C C C ML n ML n C C ML n Wipf Group esearch Topic Seminar Juan Arredondo November 13, 2004 Juan Arredondo @ Wipf Group 1 11/14/2004 Carbometallation
Metalloporphyrin. ~as efficient Lewis acid catalysts with a unique reaction-field~ and. ~Synthetic study toward complex metalloporphyrins~
Metalloporphyrin ~as efficient Lewis acid catalysts with a unique reaction-field~ and ~Synthetic study toward complex metalloporphyrins~ Literature Seminar Kenta Saito (D1) 1 Topics Chapter 1 ~as efficient
Suggested solutions for Chapter 30
s for Chapter 30 30 PRBLEM 1 uggest a mechanism for this synthesis of a tricyclic aromatic heterocycle. 2 Cl base A simple exercise in the synthesis of a pyridine fused to a pyrrole (or an indole with
Renaud Group Exercise Set
Renaud Group Exercise Set Prepared by ick Tappin 08/07/16 Spectroscopy 1. Deduce the structures for compounds A, B, and C C 6 10 3 A IR: 1745 and 1720 cm -1 13 C-MR: δ 208, 172, 51, 37, 32, and 27 ab 4
Catalytic Asymmetric Total Syntheses of Quinine and Quinidine
Catalytic Asymmetric Total Syntheses of Quinine and Quinidine 8 7 9 2 1 3 4 6 5 7 9 8 2 1 3 4 6 5 Quinine Zhensheng Ding Quinidine January 22 2004 Chinese ew Year Day 1. Jacobsen, E.,. J. Am. Chem. Soc.
There are several possible arrangements for a molecule which contains two double bonds (diene): 1. Isolated: (two or more single bonds between them)
1 Chapter 15: Conjugation and Reactions of Dienes I. Introduction to Conjugation There are several possible arrangements for a molecule which contains two double bonds (diene): 1. Isolated: (two or more
When H and OH add to the alkyne, an enol is formed, which rearranges to form a carbonyl (C=O) group:
Next Up: Addition of, : The next two reactions are the Markovnikov and non-markovnikov additions of and to an alkyne But you will not see alcohols form in this reaction! When and add to the alkyne, an
Intramolecular Huisgen-Type Cyclization of Platinum-Bound Pyrylium Ions with Alkenes and Subsequent Insertion into a Benzylic C-H Bond
Intramolecular uisgen-type Cyclization of Platinum-Bound Pyrylium Ions with Alkenes and Subsequent Insertion into a Benzylic C- Bond Chang o h,* Ji o Lee, Su Jin Lee, Jae Il Kim, and Chang Seop ong Department
Nine-Step Enantioselective Total Synthesis of (+)-Minfiensine
ine-step nantioselective Total Synthesis of (+)-Minfiensine Jones, S. B.; Simmons, B.; MacMillan, D. W. C.* J. Am. Chem. Soc. 2009, ASAP. DI: 10.1021/ja906472m Kara George Wipf Group - Current Literature
A. Review of Acidity and pk a Common way to examine acidity is to use the Bronsted-Lowry acid-base equation:
1 Chapter 22: Reactions of Enols and Enolates I. Alpha Substitution verview: A. Review of Acidity and pk a Common way to examine acidity is to use the Bronsted-Lowry acid-base equation: Recall that the
ChemWiki BioWiki GeoWiki StatWiki PhysWiki MathWiki SolarWiki
Ashley Robison My Preferences Site Tools Popular pages MindTouch User Guide FAQ Sign Out If you like us, please share us on social media. The latest UCD Hyperlibrary newsletter is now complete, check it
Total Synthesis of ( )-Himandrine
Total Synthesis of ( )-imandrine M. Movassaghi,* M. Tjandra and J. Qi J. Am. hem. Soc. 2009, 131, 9648-9650 Bz Adam T. oye urrent Literature ctober 3, 2009 Adam oye @ Wipf Group Page 1 of 22 10/3/2009
A Stereoselective Synthesis of (+)-Gonyautoxin 3
A Stereoselective Synthesis of (+)-Gonyautoxin 3 Mulcahy, J. V.; Du Bois, J. J. Am. Chem. Soc. 2008, 130, 12630-12631 Total Synthesis of (+)-Lithospermic Acid by Asymmetric Intramolecular Alkylation via
Organocopper Chemistry
rganocopper Chemistry ave a great historical importance, but still remain highly useful reactions. If not the first organometallic reactions developed they are among the first. Most often used in conjugate
II. Special Topics IIA. Enolate Chemistry & the Aldol Reaction
P. Wipf - Chem 2320 1 3/20/2006 II. Special Topics IIA. Enolate Chemistry & the Aldol Reaction Boger Notes: p. 147-206 (Chapter VIII) Carey/Sundberg: B p. 57-95 (Chapter B 2.1) Problem of the Day: Wang,
O + k 2. H(D) Ar. MeO H(D) rate-determining. step?
ame: CEM 633: Advanced rganic Chem: ysical Problem Set 6 (Due Thurs, 12/8/16) Please do not look up references until after you turn in the problem set unless otherwise noted. For the following problems,
Catellani Reaction (Pd-Catalyzed Sequential Reaction) Todd Luo
Catellani Reaction (Pd-Catalyzed Sequential Reaction) Todd Luo 2014.1.6 1 Content Introduction Progress of Catellani Reaction o-alkylation and Applications o-arylation and Applications Conclusion and Outlook
Total Syntheses of Manzamine A.
Total yntheses of Manzamine. R E Winkler, 1998 hv D B R akagawa, 2000 [4+2] B R Me P 2 Me B TBDP Pandit, 1991 [4+2] E manzamine Martin, 1999 [4+2] R Me 2 B R R Ramil Baiazitov. ED group meeting. February
Module No and Title. PAPER No: 5 ; TITLE : Organic Chemistry-II MODULE No: 25 ; TITLE: S E 1 reactions
Subject Chemistry Paper No and Title Module No and Title Module Tag 5; Organic Chemistry-II 25; S E 1 reactions CHE_P5_M25 TABLE OF CONTENTS 1. Learning Outcomes 2. Introduction 3. S E 1 reactions 3.1
Organic Chemistry. Second Edition. Chapter 19 Aromatic Substitution Reactions. David Klein. Klein, Organic Chemistry 2e
Organic Chemistry Second Edition David Klein Chapter 19 Aromatic Substitution Reactions Copyright 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e 19.1 Introduction to Electrophilic
CHEM 251 (4 credits): Description
CHEM 251 (4 credits): Intermediate Reactions of Nucleophiles and Electrophiles (Reactivity 2) Description: An understanding of chemical reactivity, initiated in Reactivity 1, is further developed based
Copper-Catalyzed Synthesis of Esters from Ketones. Alkyl Group as a Leaving Group.
Copper-Catalyzed Synthesis of Esters from Ketones. Alkyl Group as a Leaving Group. akatani, Y.; Koizumi, Y.; Yamasaki, R.; Saito, S. rg. Lett. 2008, 10, 2067-2070. An Annulation Reaction for the Synthesis
Reactions at α-position
Reactions at α-position In preceding chapters on carbonyl chemistry, a common reaction mechanism observed was a nucleophile reacting at the electrophilic carbonyl carbon site NUC NUC Another reaction that
Recent Advances in the Chemistry of Alleneamides. Denmark Group Meeting Nate Duncan-Gould
Recent Advances in the hemistry of Alleneamides Denmark Group eting ate Duncan-Gould 9-25-07 allene The Structure allenamine ummulenes!!! X X X!!! X X ummulene omparison of M s FM at PM3 level M LUM alculated
Dehydrohalogenation of Alkyl Halides E2 and E1 Reactions in Detail
Dehydrohalogenation of Alkyl Halides E2 and E1 Reactions in Detail b-elimination Reactions Overview dehydration of alcohols: X = H; Y = OH dehydrohalogenation of alkyl halides: X = H; Y = Br, etc. X C
Enantioselective Protonations
Enantioselective Protonations Marc Timo Gieseler 25.02.2013 15.03.2013 Group Seminar AK Kalesse 1 verview Introduction Enantioselective Protonation of Cyclic Substrates Enantioselective Protonation of
The synthesis of molecules containing quaternary stereogenic centers via the intramolecular asymmetric Heck reaction. Eric Gillis 4/19/07
The synthesis of molecules containing quaternary stereogenic centers via the intramolecular asymmetric Heck reaction Eric Gillis 4/19/07 Quaternary stereocenters in complex small molecules Retrosynthetic
Learning Guide for Chapter 17 - Dienes
Learning Guide for Chapter 17 - Dienes I. Isolated, conjugated, and cumulated dienes II. Reactions involving allylic cations or radicals III. Diels-Alder Reactions IV. Aromaticity I. Isolated, Conjugated,
Organocatalytic stereoselective [8+2] and [6+4] cycloadditions
![Organocatalytic stereoselective [8+2] and [6+4] cycloadditions](/thumbs/85/92727022.jpg "Organocatalytic stereoselective [8+2] and [6+4] cycloadditions")
rganocatalytic stereoselective [8+2] and [6+4] cycloadditions Joel Walker Current Literature March 4 th, 2017 Mose, R.; Preegel, G.; Larsen, J.; Jakobsen, S.; Iversen, E..; Jørgensen, K. A. Nature Chem.
Stereoselective Organic Synthesis
Stereoselective rganic Synthesis Prabhat Arya Professor and Leader, Chemical Biology Program Dean, Academic Affairs, Institute of Life Sciences (An Associate Institute of University of yderabad Supported
Chapter 15: Conjugated Systems, Orbital Symmetry, and UV Spectroscopy
Chapter 15: Conjugated Systems, Orbital Symmetry, and UV Spectroscopy Conjugated unsaturated systems have a p orbital on a carbon adjacent to a double bond The p orbital can come from another double (e.g.
I. Introduction. II. Retrosynthetic Analysis. Andrew Baggett. Liu lab
Total Synthesis of Limonin Shuji Yamashita,* Akito Naruko, Yuki Nakazawa, Le Zhao, Yujiro Hayashi, Masahiro Hirama Tohoku University, Department of Chemistry, Aramaki-aza aoba, Aoba-ku, Sendai 980-8578
Chap 11. Carbonyl Alpha-Substitution Reactions and Condensation Reactions
Chap 11. Carbonyl Alpha-Substitution eactions and Condensation eactions Four fundamental reactions of carbonyl compounds 1) Nucleophilic addition (aldehydes and ketones) ) Nucleophilic acyl substitution
Organic Chemistry I (Chem340), Spring Final Exam
rganic Chemistry I (Chem340), pring 2005 Final Exam This is a closed-book exam. No aid is to be given to or received from another person. Model set and calculator may be used, but cannot be shared. Please
Page 1 of 9. Sessional Examination (November 2017) Max Marks: 20 Date: Time: One Hour. Model Answers
Page 1 of 9 Sessional Examination (November 2017) Class: B. Pharm-II yr (III sem) Subject: Pharma Org. Chem-II Max Marks: 20 Date: 14.11.2017 Time: One Hour Model Answers Q. 1. Solve the following (ANY
Direct, Catalytic Hydroaminoalkylation of Unactivated Olefins with N-Alkyl Arylamines
Current Literature - May 12, 2007 Direct, Catalytic ydroaminoalkylation of Unactivated lefins with -Alkyl ylamines ' '' Ta[ 2 ] 5 (4-8 mol%), 160-165 o C 24-67h 66-95% ' '' S. B. erzon and J. F. artwig,
Lecture Notes Chem 51C S. King. Chapter 20 Introduction to Carbonyl Chemistry; Organometallic Reagents; Oxidation & Reduction
Lecture Notes Chem 51C S. King Chapter 20 Introduction to Carbonyl Chemistry; rganometallic Reagents; xidation & Reduction I. The Reactivity of Carbonyl Compounds The carbonyl group is an extremely important
Organic Chemistry, Third Edition. Chapter 24 Carbonyl condensations
rganic Chemistry, Third Edition Chapter 24 Carbonyl condensations 1 Review: enolates LDA, -78 C TF kinetic RX R = Me, 1 alkyl R Na TF, RT RX R = Me, 1 alkyl thermodynamic R enolates = nucleophiles React
Nilson, M. G.; Funk, R. L. Org. Lett. 2010, ASAP. Chad Hopkins Wipf Group Literature Presentation
TtlS Total Synthesis of ( ) akadomarin kd A ilson, M. G.; Funk, R. L. rg. Lett. 2010, ASAP. Chad opkins Wipf Group Literature Presentation 10 23 10 Chad opkins @ Wipf Group Page 1 of 11 12/5/2010 Isolation
Lecture Notes Chem 51B S. King I. Conjugation
Lecture Notes Chem 51B S. King Chapter 16 Conjugation, Resonance, and Dienes I. Conjugation Conjugation occurs whenever p-orbitals can overlap on three or more adjacent atoms. Conjugated systems are more
Chapter 22 Enols and Enolates
Chapter Enols and Enolates Acidity of the α hydrogen o The position next door to a carbonyl is called the α position o When an α proton is abstracted, the resulting carbanion is resonancestabilized. This
Scalable Total Syntheses of N-Linked Tryptamine Dimers by Direct Indole-Aniline Coupling: Psychotrimine and Kapakahines B and F
Scalable Total Syntheses of -Linked Tryptamine Dimers by Direct ndole-aniline Coupling: Psychotrimine and Kapakahines B and F tryptamine X electrophilic nitrogen source 2 methodology development innovative
Chapter 19. Carbonyl Compounds III Reaction at the α-carbon
Chapter 19. Carbonyl Compounds III Reaction at the α-carbon There is a basic hydrogen (α hydrogen) on α carbon, which can be removed by a strong base. 19.1 The Acidity of α-hydrogens A hydrogen bonded
CHAPTER The calculations are shown for each molecule using values from Table 1.5 in Chapter 1. K eq = B A = B 1-B
Chapter CPTER. The calculations are shown for each molecule using values from Table.5 in Chapter. 2 C N 2 C 2 N 2 C C-C N 2 C C 2 C C C (a) = CR2 + C = 2. + 0.2 = 2. kcal mol - If + = = NR + G C + G CR2
Shi Asymmetric Epoxidation
Shi Asymmetric Epoxidation Chiral dioxirane strategy: R 3 + 1 xone, ph 10.5, K 2 C 3, H 2, C R 3 formed in situ catalyst (10-20 mol%) is prepared from D-fructose, and its enantiomer from L-sorbose oxone,
Answer 3 out of the following 6 questions.
Answer 3 out of the following 6 questions. . J. Chem. Theory Comput. 205,, 4054 4063. (DI: 0.02/acs.jctc.5b00359) A. What is DLP-CCSD(T)? What does DLP stand for? Why is DLP-CCSD(T) faster than CCSD(T)?
JOC Year-in-Review, 1984
Baran Lab Group eting JC Year-in-eview, 198 Y oshihiro Ishihara Statistics for J. rg. Chem. 198, Volume 9, Issues 1-26: 1313 Papers 1 erbert C. Brown 8 Albert Padwa 8 Leo A. Paquette 7 Dale L. Boger 7
Hyperlearning MCAT Instructor Qualifying Exam Organic Chemistry
Hyperlearning MCAT Instructor Qualifying Exam Organic Chemistry 30 Questions (5 pages); Time limit = 45 minutes Use of books or notes is not permitted. 1. When analyzed with a polarimeter, which of the
"-Amino Acids: Function and Synthesis
"-Amino Acids: Function and Synthesis # Conformations of "-Peptides # Biological Significance # Asymmetric Synthesis Sean Brown MacMillan Group eting ovember 14, 2001 Lead eferences: Cheng,. P.; Gellman,
Chiral Brønsted Acid Catalysis
Chiral Brønsted Acid Catalysis Aryl Aryl Aryl Aryl S CF 3 2 P Fe CF 3 CF 3 2 Jack Liu ov. 16, 2004 CF 3 Introduction Chiral Brønsted acid catalysis in nature: enzymes and peptides Chiral Brønsted acid
Total Syntheses of Minfiensine
Total Syntheses of Minfiensine Douany, A. B.; umphreys, P. G.; verman, L. E.*; Wrobelski, A. D., J. Am. Chem. Soc. 2008, ASAP. D: 10.1021/ja800163v Shen, L.; Zhang, M.; Wu, Y.; Qin, Y.*, Angew. Chem. nt.
{ReBr(CO) 3 (THF)} 2 (2.5 mol%) 4-Å molecular sieves toluene, 115 o C, 24 h
VII Abstracts 2018 p1 10.2 Product Class 2: Benzo[c]furan and Its Derivatives. Kwiecień This chapter is a revision of the earlier cience of ynthesis contribution describing methods for the synthesis of
Organic Cumulative Exam October 13, 2016
rganic Cumulative Exam ctober 3, 206 Answer only three of the five questions. o more than three question answers will be graded and any work not to be considered must be clearly marked as such. Clearly
Name: CHEM 633: Advanced Organic Chem: Physical Problem Set 5 Due 11/10/17
ame: CEM 633: Advanced rganic Chem: ysical Problem Set 5 Due 11/10/17 Please do not look up references until after you turn in the problem set unless otherwise noted. For the following problems, please