Welwitindolinones. Unusual Alkaloids From Blue-Green Algae. Eric Phillips December 4, R D N Me N H
|
|
|
- Thomasine Melton
- 6 years ago
- Views:
Transcription
1 Welwitindolinones Unusual Alkaloids From Blue-Green Algae C R R D Eric Phillips December 4, 2006
2 verview Background Where is it from and what does it do? Structure Important Characteristics Difficult synthetic properties Synthesis of the skeleton Rawal Synthesis of the Welwitindolinone A Isonitrile racemate by Wood Enantionselective synthesis of Welwitindolinone A Isonitrile by Baran
3 Background A family of welwitindolinones was isolated and characterized in 1994 from blue-green algae. (JACS, 1994, 116, ) They are known to display both antifungal and insecticidal activity. Blue-green algae bloom They are also known to reverse multidrug resistance in chemotherapeutic cancer treatment.
4 Structure C R Welwitindolinone A R D Welwitindolinone congeners 3 quaternary centers 1 neopentyl chlorine atom Spiro-fused cyclobutane, seemingly too strained to exist Welwitindolinone A may be a possible precursor to other welwitindolinones Structures either contain an isocyanate or isothiocyanate
5 C C SC SC C The Welwitindolinone Family
6 Welwitindolinone A Isonitrile
7 Rawal s Rapid Synthesis of the -thylwelwitindolinone Skeleton Br Pd-catalyzed C 2 enolate arylation 2 C C C 3 MacKay, J. A.; Bishop, R. L.; Rawal, V.. rg Lett. 2005, 7, Deng,.; Konopelski, J. P. rg Lett. 2001, 3, 3001 Baudoux, J.; Blake, A. J.; Simpkins,. G. rg. Lett. 2005, 7,
8 Retrosynthetic Analysis P P S C C Curtius R 2 C methylwelwitindolinone C isothiocyanate enolate arylation X LG + R 2 C P P R 2 C P X 6 M 5 4
9 Friedel-Crafts Chemistry/Lewis Acid Promoted Reaction Br Ac, Sn 4 Br Ts, i-pret cat. DMAP Br toluene 95% C % Ts MgBr Br TMS (2.4 equiv.) Ti 4 (2.3 equiv.) Br TF 84% Ts toluene, 76% Ts 10 11
10 thylation and α-esterification Br Ts K Et 99% Br TBA, C 3 I (excess) 2, C % Br C 2 1. LDA, MPA, TF 2. C 3 C()C 96% Br 14
11 Enolate Arylation C 2 Br 14 Ar R'' R' R Pd(Ac) 2 (0.3 equiv.) P t Bu 3 (0.6 equiv.) K t Bu (2 equiv.) toluene, 70 C 74% RE L n Pd 0 A 2 C ArX 15 1 diastereomer R' R" L n Pd R'' R' R PdL n R L n Pd Ar X R' base X R + base R'' For a review see: Culkin, D. A.; artwig, J. F. Acc. Chem. Res. 2003, 36,
12 Curtius Rearrangement 2 C LiI, pyridine 2 C reflux 95% 1. DPPA C 2 2 reflux 2. toluene, 90 C 78% C R Ph P 3 Ph R R R C 10 steps Convergent igh lights the power of the enolate arylation
13 Wood s Synthesis of the Welwitindolinone A Isonitrile Racemate C Wood, J. L.; olubec, A.; Stoltz, B.; Weiss, M.; Dixon, J.; Doan, B.; Shamji, M.; Chen, J.; effron, T. JACS. 1999, 121, Ready, J.; Reisman, S.; irata, M.; Weiss, M.; Tamaka, K.; vaska, T.; Wood, J. Angew. Chem. Int. Ed. 2004, 43, Reisman, S.; Ready, J.; asuoka, A.; Smith, C.; Wood, J. JACS, 2006, 128,
14 Retrosynthetic Analysis C Welwitindolinone A Isonitrile 1 2 C
15 [2 + 2] cycloaddition 6 TF 85%,Et 3 Both regio- and diastereoselective!! 7 T enantioselective! Stepwise mechanism shows formation of allylic carbocation which accounts for regiochemistry. Acetal blocks the top face. Ketene approaches from the bottom to avoide steric interactions.
16 Synthesis Continued 7 8 TF, 78 C 88% 20:1 d.r MgBr 9 rthometallated aniline was uniquely affective. ther grignard reagents led to enolization or decomposition. Grignard reagent approaches from the convex face. Aryl triazenes are excellent protecting groups for aryl amines. Stable to light, air, and basic conditions 2 1., a2 Raney i 2 2., K C 35-90% 50 90%
17 α,β Unsaturated Ketone Raney i 2 ac 3 a MTBE % Ac/ 2 refllux Bu 2 Sn, reflux; BS, C % over 4 steps
18 Selective xidation of Allylic Alcohols Bu 2 Sn Bu 2 Sn Bu 2 Sn Bu 2 Sn Br Bu 2 Sn Bu 2 SnBr 2 Bu 2 Sn Br Soderman, P., Widmalm, G.; Carbohydr. Res ,
19 Application of xindole Synthesis SC 2 C 2 S BF 3 Et, 0 C, 1h S S (C) 2, DMS Et 3, C 2 2 S S 46% 2 Steps cat. DBU 2 C Et 3 S S C SmI 2, Li TF, 78 C 71%, 7:1 d.r. S S 15 16
20 SmI 2 Reductive Coupling SmI 2 SmI 2 R Et SmI 2 SmI 2 R Et R Et Generation of homoenolate R C I 2 Sm R R SmI 2 Et R R Et Umpolung Reactivity!! Kim, Y.K.; Park,.S.; Kwon, D.W. Synth. Commun. 1998, 28,
21 Back to the Synthesis Tf 5 1. TIPSTf DMF, 2,6-lutidine 2. LMDS L-selectride, 78 C then PhTf 2 (78% yield) TIPS 17 Pd 2 (dba) 3 C 3 dppf, DIPEA, C 3 Cn C, 65 C (69% yield) 2 C TIPS MgBr, Ce 3 TF, 40 C to rt (96% yield) TIPS JACS. 2006, 128,
22 Installation of eopentyl Chloride TIPS a Ce C/C 2 2 (78% yield) TIPS 19 1 diastereomer 20 C 3 P P P P P Pinacol P
23 xindole Synthesis TIPS 1. 2 SiF 6, C 65 C 2. 4 B(Ac) 3 Ac, C, rt (82% yield) 1. Martin Sulfurane 2. DM Periodane (74% yield) equiv. DBU, then C 2, Et 3 2. SmI 2, Li, t-bu TF, 78 C (75% yield) 1 diastereomer nuc X C Welwitindolinone A Isonitrile
24 Three-dimensional View 2
25 Alternate Route 1. (Boc) 2, C 2 2 DMAP, DBU 2. 2, pyridine (74% yield) Boc 1. acb 3 Ac 1 diastereomer 2. (77% yield) Boc R Axial attack to afford pseudo-axial hydrogen is critical. 1. SmI 2, TF 2. 3:1 C:TF (71% yield) 2 24
26 Alternative Route C 2, Et 3, 0 C C 2 C R LMDS, TF 78 C (47% yield) C Welwitindolinone A Isonitrile 1 2.5% overall yield over 23 steps
27 Three-Dimensional View C C 25 Deprotonation of α-carbon leads to formation of spirocycle.
28 Conclusion, Part 1 Wood has developed a racemic synthesis of welwitindolinone A isonitrile with a 2.6% yield over 23 steps. Uses a semi-pinacol rearrangement to install the neopentyl chlorine atom. e also has developed a new method for the construction of spirooxindoles.
29 Baran s Enantioselective Total Synthesis of Welwitindolinone A Isonitrile C Baran, P. S.; Richter, R. M. J. Am. Chem. Soc. 2005, 127,
30 Retrosynthetic Analysis C 1 C 2 [] ring contraction C [] 3 4 indole coupling 5
31 The Beginning LMDS (1.2 equiv.) TF, 78 C 30 min Li MgBr 15 C, 15 min (30% yield) (R)-carvone oxide 6 7 PPh 3, CS TF, 18 hr (55% yield) 1. indole (2 equiv.) LMDS (3.1 equiv.) TF, 78 C 2. Cu(II)2-ethylhexanoate (1.5 equiv.), 78 to 23 C 5 15 min 4 (55% yield) single diastereomer
32 Indole Coupling carvone base indole [] The d.r is usually between 5:1 and 25:1. 5 Indole approaches from the top face to avoid the olefin. Baran, P. S.; Richter, J. M. J. Am. Chem. Soc. 2004, 126,
33 Friedel-Crafts Cyclization Montmorillonite K-10 clay µwave irradiation, 120 C 6 min, DCE (40% + 30% recovered) 1. ab 4,, 0 C then py, Ms 2, 69% yield 2. Li 3, DMF, 120 C (58%), then Et, a(g), reflux(66%) C 2, CDMT, MMM DMAP, 23 C, 30 min, 87% 2. Burgess reagent C [] X
34 ( )-fisherindole G C There is minimal orbital overlap between the two hydrogens
35 Friedel-Crafts Cyclization Montmorillonite K-10 clay µwave irradiation, 120 C 6 min, DCE (40% + 30% recovered) acb 3 (10 equiv.) 4 Ac (40 equiv.), TF, 7 days (26% + 46% recovered) Axial attack of the hydride pushes the amine substituent up. Vaillancourt, V.; Albizati, K. F. J. Am. Chem. Soc. 1993, 115,
36 Synthesis of Formyl Amide 2 C 2 (1.3 equiv.) CDMT (1.4 equiv.) DMAP (cat.), MM C 2 2, 23 C, 30 min (87% yield) chloro-4,6-dimethoxy[1,3,5]triazene + MM, C 2 2 R 2 R o epimerization of any stereocenter!!! De Luca, L.; Giacomelli, G.; Porcheddu, A.; Salaris, M. Synlett 2004, 14,
37 Installation of Isonitrile t-bu, Et 3 TF, 10 min, 0 C C Si 2 /Et 3 C S Et 3 Burgess reagent C Burgess reagent Ph, 23 C, 20 min (47% overall yield) C 2 13
38 Burgess Reagent Et 3 S Burgess reagent R Et 3 S R S R C R S Creedon, S. M.; Crowley,. K.; McCarthy, D. G. J. Chem. Soc., Perkin Trans ,
39 The End.or is it? C 2 (+)-fisherindole 1 They made this But what they need is this C 2 ( )-fisherindole 1
40 Acid Catalyzed Cyclization C t-bu, Et 3 TF, 78 C, 1 min C 95:4:1 TF: 2 :TFA 30 to 0 C, 5 min 2 ( )-fisherindole 1 C (+)-welwitindolinone A :1 C 3-epi-1 28% yield over two steps 0.6% yield over 13 steps
41 Introduction of the Chloride C 2 ( )-fisherindole 1 Convex face is the only available face for a large electrophile such as t-bu.
42 Semi-pinacol Rearrangement C 95:4:1 TF: 2 :TFA 30 to 0 C, 5 min C (+)-welwitindolinone A 1 C 2 C
43 Rationale for Selectivity C TFA C
44 Conclusion, Part 2 Baran has successfully: constructed a very brief (12 steps) synthesis of (+)-welwitindolinone A isonitrile, appied his indole coupling methodology in a high-yielding,selective manner, applied an exceedingly facile oxidative ring contraction, constructed (+)-welwitindolinone A isonitrile without the use of protecting groups and excessive oxidation state manipulations.
45 Comparison Wood Baran Racemic, 23 step synthesis 2.6% yield Uses semi-pinacol rearrangement to install neopentyl chloride and a quaternary center Employs a [2+2] cycloaddition and a unique α-deprotonation to form the other two stereocenters and fused cyclobutane ring Enantioselective, 13 step synthesis starting from a chiral, commercially available material 0.6% yield Installs neopentyl chloride through epoxide opening followed by chlorination. Quaternary centers are installed through a grignard reaction opening of an epoxide and a Prins reaction. Fused cyclobutane installed through a chlorination followed by a semi-pinacol type rearrangement.
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
Recent Total Syntheses! Published in Nature!
Recent Total Syntheses! Published in ature! Eric ewcomb 8/21/2011! 2 S 3 2 2 ature Then and ow! First published ov. 4th, 1869 First issue states two objectives: 'The objective which it is proposed to attain
Additions to Metal-Alkene and -Alkyne Complexes
Additions to tal-alkene and -Alkyne Complexes ecal that alkenes, alkynes and other π-systems can be excellent ligands for transition metals. As a consequence of this binding, the nature of the π-system
Literature Report 3. Rapid Syntheses of (+)-Limaspermidine and (+)-Kopsihainanine A. Date :
Literature Report 3 Rapid Syntheses of (+)-Limaspermidine and (+)-Kopsihainanine A Reporter : Xiao-Yong Zhai Checker : Shubo u Date : 2017-10-30 Pritchett, B. P.; Donckele, E. J.; Stoltz, B. M. Angew.
A Tandem Semipinacol Rearrangement/Alkylation of a-epoxy Alcohols: An Efficient and Stereoselective Approach to Multifunctional 1,3-Diols
A Tandem Semipinacol Rearrangement/Alkylation of a-epoxy Alcohols: An Efficient and Stereoselective Approach to Multifunctional 1,3-Diols B() 2 H H B() 2 H H Hu, X.-D.; Fan, C.-A.; Zhang, F.-M.; Tu, Y.
Keisuke Suzuki. Baran lab Group Meeting 6/11/16. Shigenobu Umemiya. Akira Suzuki. Takanori Suzuki (Hokkaido University)
197.D., Teruaki Mukaiyama, University of Tokyo 193 Assistant Professor, Keio University 197 Lecturer, Keio University 199 Assocate Professor, Keio University 1990 Visiting Professor, ET 1994 ull Professor,
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)
Total synthesis of Spongistatin
Literature Semminar 1. Introduction: Total synthesis of Spongistatin Chen Zhihua (M2) Isolation: Pettit et al. J. rg. Chem. 1993, 58, 1302. Kitagawa et al. Tetrahedron Lett. 1993, 34, 1993. Fusetani et
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.
Organocopper Reagents
rganocopper eagents General Information!!! why organocopper reagents? - Efficient method of C-C bond formation - Cu less electropositive than Li or Mg, so -Cu bond less polarized - consequences: 1. how
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;
Few Selected Total Synthesis in Group Meeting June 1, Anil Kumar Gupta
Few Selected Total Synthesis in 2007 Group Meeting June 1, 2007 Anil Kumar Gupta Total Synthesis without Protecting Groups Chemoselectivity!! Solution: Protecting group BUT..It adds. Cost Complexity of
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.
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
VINBLASTINE. H MeO 2 C MeO. OAc. CO 2 Me. Me H
VIBLATIE 2 C 1 C 2 Ac a 3: catharanthine C 2 Ac C 2 2: ( )-vindoline xidation 5' 2 C 3' 16' 20' Ac C 2 1: (+)-vinblastine b 4 C 2 TFAA, -50 C Polonovski fragmentation 6' 5' 16' C 2 5 TFA 4' 3' 15' 16'
Facile preparation of α-amino ketones from oxidative ring-opening of aziridines by pyridine N-oxide
Facile preparation of α-amino ketones from oxidative ring-opening of aziridines by pyridine -oxide rg. Biomol. Chem., 2007, 5, 3428 Luo, Z.-B.; Wu, J.-Y.; ou, X.-L.; Dai, L.-X. Ts toluene Ts 80 o C John
Ynolate Chemistry. Jeff Kallemeyn October 22, 2002
Ynolate Chemistry While enolates have numbered among the most important reagents of organic chemistry for more than a century, ynolates have hitherto remained unknown although their chemistry should be
Highlights of Schmidt Reaction in the Last Ten Years
ighlights of Schmidt eaction in the Last Ten Years Dendrobates histrionicus Jack Liu ov. 18, 2003 Introduction Classical Schmidt reaction of aldehydes and carboxylic acids Classical Schmidt reaction of
Spiro Monophosphite and Monophosphoramidite Ligand Kit
Spiro Monophosphite and Monophosphoramidite Ligand Kit metals inorganics organometallics catalysts ligands custom synthesis cgm facilities nanomaterials 15-5162 15-5150 15-5156 15-5163 15-5151 15-5157
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
Application of Two Direct C(sp 3 )-H Functionalizations for the Total Synthesis of (+)-Lactacystin
Application of Two Direct C(sp 3 )- Functionalizations for the Total Synthesis of (+)-Lactacystin two stereoselective C(sp 3 )- functionalisations 2 C S Ac (S)-pyroglutaminol (+)-lactacystin S. Yoshioka,
Short Literature Presentation 10/4/2010 Erika A. Crane
Copper-Catalyzed Enantioselective Synthesis of trans-1- Alkyl-2-substituted Cyclopropanes via Tandem Conjugate Additions-Intramolecular Enolate Trapping artog, T. D.; Rudolph, A.; Macia B.; Minnaard, A.
Scope and Facial Selectivity of the Prins-Pinacol Synthesis of Attached Rings
Scope and Facial Selectivity of the Prins-Pinacol Synthesis of Attached Rings By Larry E. verman and Emile J. Velthuisen Leading Reference J. rg. Chem. 2006, 71, 1581-1587 Presented by Zhenyu Zhong Journal
Overview of Synthesizing Merrilactone A
verview of Synthesizing Merrilactone A = Contents = I. Beginning II. Danishefsky's Route III. irama & Inoue's Route IV. Frontier's Route V. Conclusion 6th / Feb./ 2008 Literature Seminar ~ B4 part ~ Takafumi
Direct Oxidative Heck Cyclizations: Intramolecular Fujiwara-Moritani Arylations for the Synthesis of Functionalized Benzofurans and Dihydrobenzofurans
Direct xidative eck Cyclizations: Intramolecular Fujiwara-Moritani Arylations for the Synthesis of Functionalized Benzofurans and Dihydrobenzofurans by Zhang,.; Ferreira, E. M.; Stoltz, B. M. Angewandte
Total Synthesis of the Chartellines
Total Synthesis of the Chartellines X Y chartelline A, X = Y = chartelline B, X =, Y = chartelline C, X = Y = Mariam Shamszad ovember 1, 2006 Background Chartellines A, B, and C were isolated in the 1980s
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
Total Synthesis of (+)-Suaveolindole
1 Total Synthesis of (+)-Suaveolindole 15 2 C 16 11 Emile J. Velthuisen and Samuel J. Danishefsky J. Am. Chem. Soc. 2007, 9, 10640-10641 Julia Vargas September 15, 2007 2 utline Isolation and Elucidation
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%
The aldol reaction with metal enolates proceeds by a chair-like, pericyclic process: favored. disfavored. favored. disfavored
The aldol reaction with metal enolates proceeds by a chair-like, pericyclic process: Z-enolates: M 2 M 2 syn 2 C 2 favored 2 M 2 anti disfavored E-enolates: M 2 2 C 3 C 3 C 2 favored 2 M M disfavored In
I. B. Seiple, S. Su, I. S. Young, C. A. Lewis, J. Yamaguchi, and P. S. Baran, Angew. Chem. Int. Ed. 2009, 49,
I. B. Seiple, S. Su, I. S. Young, C. A. Lewis, J. Yamaguchi, and P. S. Baran, Angew. Chem. Int. Ed. 09, 49, 95-98. ong Ren @ The Wulff Group 03-05- 2 2 2 Synthesized naturally by Stylotella agminata Cytotoxic
There are 15 total pages to this exam. Please be sure your copy has 15 pages before you begin.
Initials: 1 ame: Chem 633: Advanced rganic Chemistry Midterm 2 Please answer the following questions clearly and concisely. Write your answers in the space provided. Write your initials on each page you
Direct Organocatalytic Enantioselective Mannich Reactions of Ketimines: An Approach to Optically Active Quaternary α-amino Acid Derivatives
Direct rganocatalytic Enantioselective Mannich eactions of Ketimines: An Approach to ptically Active Quaternary α-amino Acid Derivatives Wei Zhang, Steen Saaby, and Karl Anker Jorgensen The Danish ational
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
Total Synthesis of (+)-Sieboldine A J. Am. Chem. Soc. 2010, 132,
Total Synthesis of (+)-Sieboldine A J. Am. Chem. Soc. 2010, 132, 7876 7877. Current Literature Presentation 10JUL2010 Michael Yang Mike Yang @ Wipf Group Page 1 of 15 7/10/2010 Sieboldine A Background
Synthetic Developments Towards the Preparation of Erythromycin and Erythronolide Derivatives
ynthetic Developments Towards the Preparation of Erythromycin and Erythronolide Derivatives Russell C. mith Denmark Group Meeting 8-9-2005 most extensive project in organic synthesis this phenomenon is
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
Huang, C.; Gevorgyan, V. J. Am. Chem. Soc. 2009, 131, Daniel Tzvi Cohen Short Literature Feb. 23, MeO HO OH. COOH ( )-Plicatic Acid OH OH
Asymmetric Total Synthesis of ( )-Plicatic Acid via a Highly Enantioselective and Diastereoselective Nucleophilic Epoxidation of Acyclic Trisubstituted lefins H H H H CH ( )-Plicatic Acid H H Sun, B.F.;
CHEM 330. Final Exam December 8, 2010 ANSWERS. This a closed-notes, closed-book exam. The use of molecular models is allowed
CEM 330 Final Exam December 8, 2010 Your name: ASWERS This a closed-notes, closed-book exam The use of molecular models is allowed This exam contains 10 pages Time: 2h 30 min 1. / 20 2. / 20 3. / 20 4.
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
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.
CEM 852 Final Exam. May 6, 2010
CEM 852 Final Exam May 6, 2010 This exam consists of 7 pages. Please make certain that your exam has all of the necessary pages. Total points possible for this exam are 150. n answering your questions,
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,
Synthesis of Nitriles a. dehydration of 1 amides using POCl 3 : b. SN2 reaction of cyanide ion on halides:
I. Nitriles Nitriles consist of the CN functional group, and are linear with sp hybridization on C and N. Nitriles are non-basic at nitrogen, since the lone pair exists in an sp orbital (50% s character
TMSCl imidazole DMF. Ph Ph OTMS. Michael reaction. Michael reaction Ph R 3. epoxidation O R
eaction using diarylprolinol silyl ether derivatives as catalyst 1) C Et K C 3, ) MgBr, TF TMS hexane, 0 o C TBS p- C 6 4, T C Et 85%, 99% ee Angew. Chem., nt. Ed., 44, 41 (005). rg. Synth., 017, 94, 5.
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
Intramolecular Ene Reactions Utilizing Oxazolones and Enol Ethers Fisk, J.S. and Tepe, J..J J. Am. Chem. Soc., 2007, 129,
Intramolecular Ene Reactions Utilizing xazolones and Enol Ethers Fisk, J.S. and Tepe, J..J J. Am. Chem. Soc., 2007, 129, 3058-3059 - versus -Arylation of Aminoalcohols: rthogonal Selectivity in Copper-Based
Comparative Synthesis of Ingenol. Tyler W. Wilson SED Group Meeting
Comparative Synthesis of Ingenol Tyler W. Wilson SED Group eting 2.27.07 Ingenol: Biology, Isolation, and istory During WWII a latex was manufactured by precipitating the milky juice of the Euphorbia Ingen
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
Chapter 5 Three and Four-Membered Ring Systems
Chapter 5 Three and Four-mbered ing ystems 5.1 Aziridines Aziridines are good alkylating agents because of their tendency to undergo ring-opening reaction with nucleophiles 例 mitomycin C antibiotic and
Section Practice Exam II Solutions
Paul Bracher Chem 30 Section 7 Section Practice Exam II s Whether problems old r problems new, You d better practice, r you ll fail exam II. -- Anonymous TF Problem 1 a) Rank the following series of electrophiles
Literature Report I. Total Synthesis of (+)-Piperarborenine B. Reporter: Zheng Gu. Date:
Literature Report I Total Synthesis of (+)-Piperarborenine B Reporter: Zheng Gu Checker: Bo Song Date: 2016-12-12 Hu, J. L.; Xie, Z. W.; Tang, Y. J. Am. Chem. Soc. 2016, 138, 13151. Panish, R. A.; Chintala,
Ch.16 Chemistry of Benzene: Electrophilic Aromatic Substitution
Ch.16 Chemistry of Benzene: Electrophilic Aromatic Substitution Electrophilic aromatic substitution: E + E + + Some electrophilic aromatic substitution: X N 2 S 3 R C R alogenation Nitration Sulfonation
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
Radical Reactions. Radical Stability!!! bond dissociation energies X Y X + Y. bond BDE (kcal/mol) bond BDE (kcal/mol) CH 3 CH 3 CH 2 95 O H R 2 C H
adical eactions adical Stability!!! bond dissociation energies X Y X Y bond BDE (kcal/mol) bond BDE (kcal/mol) C 3 104 108 C 3 C 2 98 110 95 2 C 102 (-) 93 (C-) 92 C 3 C 3 36 89 85 C 3 C 3 80 adical eactions
11-Step Enantioselective Synthesis of ( )-Lomaiviticin Aglycon
11-Step Enantioselective Synthesis of ( )-Lomaiviticin Aglycon Seth B. erzon, Liang Lu, Christina M. Woo, and Shivajirao L. Gholap J. Am. Chem. Soc. ASAP DI 10.1021/ja200034b Melissa Sprachman Current
Synthesis of Atisine-type Alkaloids
Literature Report III Synthesis of Atisine-type Alkaloids Reporter : Yang Zhao Checker : Zhou-ao Zhu Date : 2018-7-16 Ma, D. et al. Angew. Chem. Int. Ed. 2018, 57, 6676 Baran, P. S. et al. J. Am. Chem.
Initials: 1. Chem 633: Advanced Organic Chemistry 2011 Final Exam
Initials: 1 ame: Chem 633: Advanced rganic Chemistry 2011 Final Exam Please answer the following questions clearly and concisely. In general, use pictures and less than 10 words in your answers. Write
OC 2 (FS 2013) Lecture 3 Prof. Bode. Redox Neutral Reactions and Rearrangements
C 2 (F 203) Lecture 3 Prof. Bode edox eutral eactions and earrangements Types of edox eutral rganic eactions. eactions with no external reducing or oxidizing agent In this case, one part of the starting
Three Type Of Carbene Complexes
Three Type f arbene omplexes arbene complexes have formal metal-to-carbon double bonds. Several types are known. The reactivity of the carbene and how it contributes to the overall electron counting is
KOT 222 Organic Chemistry II
KOT 222 Organic Chemistry II Course Objectives: 1) To introduce the chemistry of alcohols and ethers. 2) To study the chemistry of functional groups. 3) To learn the chemistry of aromatic compounds and
Organic Chemistry CHM 224
rganic Chemistry CM 224 Final Exam Review Questions This is a compilation example final exam questions. Provide IUPAC names for each of the structures below. 2 ! Propose a structure for the compound that
Suggested solutions for Chapter 40
s for Chapter 40 40 PBLEM 1 Suggest mechanisms for these reactions, explaining the role of palladium in the first step. Ac Et Et BS () 4 2 1. 2. K 2 C 3 evision of enol ethers and bromination, the Wittig
Total Synthesis of Oxazolomycin A
Total Synthesis of xazolomycin A Me xazolomycin A Me Eto, K.; Yoshino, M.; Takahashi K.; Ishihara, J.; atakeyama S. rg. Lett. 2011, 13, 5398 Dimas Paz Wipf group- Current Literature ctober 8, 2011 Dimas
CEM 852 Exam-2 April 2, 2016
CM 852 xam-2 April 2, 2016 This exam consists of 6 pages. Please make certain that your exam has all of the necessary pages. Total points possible for this exam are 100. In answering your questions, please
Synthesis of Amphidinolide X and an Exploration of Key Reactions
PJM 1/12/05 Synthesis of Amphidinolide X and an Exploration of Key eactions Lepage,.; Kattnig, E.; Furstner, A. JACS, 2004, 126, 15970-15971. 7 13 1 6 19 - Produced by marine dinoflagellates, Amphidinium
CH 3 TMG, DMF N H 3 CO 2 S. (PPh 3 ) 2 Pd 0
1. (a) rovide a reasonable mechanism for the following transformation. I S 2 C 3 C 3 ( 3 ) 2 2, CuI C 3 TMG, DMF 3 C 2 S TMG = Me 2 Me 2 ICu ( 3 ) 2 0 I S 2 C 3 S 2 C 3 Cu I 3 3 3 C 2 S I 3 3 3 C 2 S 3
Suggested solutions for Chapter 32
s for Chapter 32 32 PBLEM 1 Explain how the stereo- and regio- chemistry of these reactions are controlled. Why is the epoxidation only moderately diastereoselective, and why does the amine attack where
A Review of Total Synthesis of Spirotryprostatin A and B. Jinglong Chen Supergroup meeting Princeton University June
A Review of Total Synthesis of Spirotryprostatin A and B Jinglong Chen Supergroup meeting Princeton University June 28 2006 ovel Mammalian Cell Cycle Inhibitors, Spirotryprostatins A and B Me Spirotryprostatin
Amines. Amines are organic compounds containing a nitrogen functionality. primary secondary tertiary quaternary
Amines Amines are organic compounds containing a nitrogen functionality Depending upon the number of alkyl, or aryl, groups attached to nitrogen determines its classification, or order 2 primary secondary
Syntheses of Leucascandrolide A. Supergroup Meeting August 4 th, 2004 Yu Yuan
Syntheses of Leucascandrolide A Supergroup Meeting August 4 th, 2004 Yu Yuan Leucascandrolide A Me Me Me Dambrosio, M.; Guerriero, A.; Debitus, C.; Pietra, F. elvetica Chimica Acta 1996, 79, 51-60 Me 1
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
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,
Nucleophilic Heterocyclic Carbene Catalysis. Nathan Werner Denmark Group Meeting September 22 th, 2009
Nucleophilic Heterocyclic Carbene Catalysis Nathan Werner Denmark Group Meeting September 22 th, 2009 Thiamine Thiamine Vitamin B 1 The first water-soluble vitamin described Is naturally synthesized by
Mechanism Problem. 1. NaH allyl bromide, THF N H
Mechanism Problem 1. a allyl bromide, TF 2. 9-BB (1.2 equiv), TF, rt; ame (1.2 equiv); t-buli (2.4 equiv), TMEDA (2.4 equiv) 30 to rt; allyl bromide; 30% 2 2, aq. a, 0 C (58% yield) Mechanism Problem 9-BB
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
CHEM 330. Final Exam December 11, This a closed-notes, closed-book exam. The use of molecular models is allowed. This exam contains 12 pages
CEM 330 Final Exam December 11, 2007 Your name: 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 2. / 20 3. / 30 4. / 40
Enantioselective Synthesis of Pactamycin, a Complex Antitumor Antibiotic
Journal Club (3) Tomoya akamura Enantioselective Synthesis of Pactamycin, a Complex Antitumor Antibiotic Justin T. Malinowski, Robert J. Sharpe, Jeffrey S. Johnson Science 03, 30, 80 8.. Introduction -.
Total Synthesis of (+/-)-Goniomitine via a Formal Nitrile/Donor-Acceptor Cyclopropane [3 + 2] Cyclization
![Total Synthesis of (+/-)-Goniomitine via a Formal Nitrile/Donor-Acceptor Cyclopropane [3 + 2] Cyclization](/thumbs/82/85235286.jpg "Total Synthesis of (+/-)-Goniomitine via a Formal Nitrile/Donor-Acceptor Cyclopropane [3 + 2] Cyclization")
Total Synthesis of (+/-)-Goniomitine via a Formal itrile/donor-acceptor Cyclopropane [3 + 2] Cyclization (-)-Goniomitine Christian L. Morales and Brian Pagenkopf* rganic Letters, ASAP Current Literature
UNIVERSITY OF MANITOBA DEPARTMENT OF CHEMISTRY
PAGE 1 of 7 UNIVERSITY F MANITBA DEPARTMENT F CEMISTRY 2.339 STRUCTURAL TRANSFRMATINS IN RGANIC CEMISTRY FINAL EAMINATIN Dr. Phil ultin Thursday December 14, 2000. NAME: ANSWERS STUDENT NUMBER: 1) (15
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
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
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,
Total Syntheses of Nominine
Total Syntheses of ominine i Literature t Group eting Lizzie Bryan ctober 17, 2007 Aconite Alkaloids Atidane V eatchane Cycloveatchane Aconitane etisan Muratake,. M.; atsume, M.; akai,. Tetrahedron, 2006,
Midterm Exam #1 /280 CHEM 6352 Fall 2011
Midterm Exam #1 /280 CEM 6352 Fall 2011 ( %) Name Sept 30 th, 2011 18:00-21:00 You may NT use any references or aids to complete the following with the exception of a chemical model set and the scrap paper
Introduction to Synthesis: Design (CHE686) Spring 2015 Exam #1 3/6/15
Introduction to ynthesis: Design (CE686) pring 2015 Exam #1 3/6/15 AME: KEY ome Pointers: 1. ELAX!! 2. ead the instructions for each question carefully. Be sure you understand what is required. If you
CHEM 203. Final Exam December 18, 2013 ANSWERS. This a closed-notes, closed-book exam. You may use your set of molecular models
CEM 203 Your name: Final Exam December 18, 2013 ANSWERS This a closed-notes, closed-book exam You may use your set of molecular models This test consists of 10 pages Time: 2h 30 min 1. / 20 2. / 20 3.
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
Towards Maoecrystal V: A Comparison of Recent Strategies
Towards Maoecrystal V: A Comparison of Recent Strategies Reactant/Reagent Current Literature: November 14, 2009 lissa Sprachman lissa Sprachman @ Wipf Group Page 1 of 14 12/28/2009 Maoecrystal V: Structural
CHEM 203. Final Exam December 18, This a closed-notes, closed-book exam. You may use your set of molecular models
CEM 203 Final Exam December 18, 2013 Your name: This a closed-notes, closed-book exam You may use your set of molecular models This test consists of 10 pages Time: 2h 30 min 1. / 20 2. / 20 3. / 30 4.
Total Synthesis of Cyclosporine: Access to N-Methylated Peptides via Isonitrile Coupling Reactions
Total Synthesis of Cyclosporine: Access to -thylated Peptides via Isonitrile Coupling Reactions Xiangyang Wu, Jennifer L. Stockdill, Ping Wang, Samuel J. Danishefsky* J. Am. Chem. Soc. 2010,132, 4098-4100
Requirements for an Effective Chiral Auxiliary Enolate Alkylation
Requirements for an Effective Chiral Auxiliary Enolate Alkylation 1. Xc must be low cost, and available in both enentiomeric forms 2. The cleavage of Xc from the substrate must occur under mild enough
Decarboxylation of allylic β-ketoesters
M.C. White, Chem 253 π-allyl chemistry -224- Week of ovember 8, 2004 Decarboxylation of allylic β-ketoesters Indicate the mechanism of the following transformation: d 2 dba 3 2.5 mol% h 3 10-20 mol% TF,
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
Enantioselective Total Synthesis of (-)-Acetylaranotin, a Dihydrooxepine Epidithiodiketopiperazine
Enantioselective Total Synthesis of (-)-Acetylaranotin, a Dihydrooxepine Epidithiodiketopiperazine Julian A. Codelli, Angela L. A. Puchlopek, and Sarah E. Reisman* JACS. ASAP. ct. 24, 2011 DI: 10.1021/ja209354e
Negishi Coupling of Secondary Alkylzinc Halides with Aryl Bromides and Chlorides
Negishi Coupling of Secondary Alkylzinc alides with Aryl Bromides and Chlorides X X = Br, Cl 2 1 ZnBr 1, 2 = Alkyl Cat. Pd(OAc) 2 Ligand TF/Toluene rt or 60 o C 1 2 J. Am. Chem. Soc. 2009, ASAP Article
Prof. Ang Li. Literature Seminar Kosuke Minagawa (D2)
Prof. Ang Li Literature Seminar 2017. 10. 28 Kosuke Minagawa (D2) 1 2 3 aspidodasycarpine 1) 2 C sespenine 3) atural Products Synthesized by Ang Li group clostrubin 6) drimentine A 7) i-bu rubriflordilactone
Asymmetric Nucleophilic Catalysis
Asymmetric ucleophilic Catalysis Chiral catalyst X 2 Chiral catalyst X = alkyl, X 1 2 1 Vedejs, E.; Daugulis,. J. Am. Chem. Soc. 2003, 125, 4166-4173 Shaw, S. A.; Aleman,.; Vedejs, E. J. Am. Chem. Soc.
Carbonyl Ylide Cycloadditions
Carbonyl Ylide Cycloadditions cond. icholas Anderson Denmark Group eting 07/13/10 Carbonyl Ylides Uncharged 1,3-Dipole Conjugated π-system ighly reactive on-isolable Generate in-situ Carbonyl Ylide Stability
Given that conditions for pyrazine formation have been established in prior
Chapter 2 Efforts in ur Laboratory 17 Chapter 2 Efforts in ur Laboratory 2.1 RETRSYNTETIC ANALYSIS Given that conditions for pyrazine formation have been established in prior synthetic reports by Shair