The Staunton-Weinreb Annulation. SED Group meeting Guanqun Zhang

Similar documents
Requirements for an Effective Chiral Auxiliary Enolate Alkylation

Lecture Notes Chem 51C S. King Chapter 24 Carbonyl Condensation Reactions

ANSWER GUIDE APRIL/MAY 2006 EXAMINATIONS CHEMISTRY 249H

Ynolate Chemistry. Jeff Kallemeyn October 22, 2002

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

James D. White. A very productive professor 64 students graduated from his lab 94 postdocs have worked in his lab. Education Experience

Total Synthesis towards Maoecrystal V

CHEM 330. Final Exam December 5, 2014 ANSWERS. This a closed-notes, closed-book exam. The use of molecular models is allowed

Tips for taking exams in 852

Suggested solutions for Chapter 28

O H HO H. !-D-galactopyranose

Midterm Exam #1 /280 CHEM 6352 Fall 2011

SECTION 12. «POT-POURRI» in Organic Synthesis (2018)

2.222 Practice Problems 2003

Chapter 5 Three and Four-Membered Ring Systems

A Review of Total Synthesis of Spirotryprostatin A and B. Jinglong Chen Supergroup meeting Princeton University June

Reactions at α-position

Organocopper Reagents

Synthesis of Azadirachtin: A Long but Successful Journey

Enols and Enolates. A type of reaction with carbonyl compounds is an α-substitution (an electrophile adds to the α carbon of a carbonyl)

Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (+)-Discodermolide

Alpha Substitution and Condensations of Enols and Enolate Ions. Alpha Substitution

11-Step Enantioselective Synthesis of ( )-Lomaiviticin Aglycon

Three Type Of Carbene Complexes

An Analysis of the Total Syntheses of Aphidicolin

o-palladated cat. [Chem. Comm (1999)] [Org. Lett. 2, 1826 (2000)] [Org. Lett. 2, 2881 (2000)] [JACS 41, 9550 (1999)]

I. Liu Lab. Ka<e Boknevitz 1

Suggested solutions for Chapter 29

Chapter 19. Organic Chemistry. Carbonyl Compounds III. Reactions at the a-carbon. 4 th Edition Paula Yurkanis Bruice

Protecting Groups in Organic Synthesis-1 Ready

Chiral Diol Promoted Boronates Addi3on Reac3ons. Lu Yan Morken Group Boston College

Direct Oxidative Heck Cyclizations: Intramolecular Fujiwara-Moritani Arylations for the Synthesis of Functionalized Benzofurans and Dihydrobenzofurans

Silenes in organic synthesis: a concise synthesis of (±)-epi-picropodophyllin

O OH N. Me OMe N NH HO H Debenzoyltashironin NMe 2. Phalarine. Anne-Marie Dechert

Literature Report 3. Rapid Syntheses of (+)-Limaspermidine and (+)-Kopsihainanine A. Date :

Denmark Group Meeting. & Electrophilic rearrangement of amides

Chap 11. Carbonyl Alpha-Substitution Reactions and Condensation Reactions

A. Review of Acidity and pk a Common way to examine acidity is to use the Bronsted-Lowry acid-base equation:

Heterocyclic Chemistry N S. Chapter 8: Furans

transmetallate displace ox. add. M + (insert) (β-elim.)

CHEMISTRY 252 Exam pts. Section 703 Grand Rapids 27 July 2006

Electrophilic Carbenes

2,3-Sigmatropic Rearrangements in Organic Synthesis

Answer 3 out of the following 6 questions.

A Concise Synthesis of ( )- Aplyviolene Facilitated by a Stragetegic Ter<ary Radical Conjugate Addi<on

Renaud Group Exercise Set

VI. Metal alkyls from oxidative addition / insertion

Chem 263 Nov 19, Cl 2

Synthetic Developments Towards the Preparation of Erythromycin and Erythronolide Derivatives

Total Synthesis of (+/-)-Goniomitine via a Formal Nitrile/Donor-Acceptor Cyclopropane [3 + 2] Cyclization

Syntheses of Leucascandrolide A. Supergroup Meeting August 4 th, 2004 Yu Yuan

C-O C-O C-N A A. (KHMDS) C-N (scheme 1) C-O C-N (1)

Organic Chemistry, Third Edition. Chapter 24 Carbonyl condensations

CHAPTER 19: CARBONYL COMPOUNDS III

Suggested solutions for Chapter 30

Organocopper Chemistry

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

molecules ISSN

ζ ε δ γ β α α β γ δ ε ζ

Organic Electron Donors

Dr. P. Wipf Page 1 of 5 10/7/2009. Cl Ru. Kingsbury, J. S.; Harrity, J. P. A.; Hoveyda, A. H. J. Am. Chem. Soc. 1999, 121, 791.

Stereoselective Organic Synthesis

Chapter 19. Carbonyl Compounds III Reaction at the α-carbon

Strategies for Stereocontrolled Synthesis

JOC: 1985 Year in Review

Highlights of Schmidt Reaction in the Last Ten Years

Summary of π Bond Chemistry

Heterocyclic Chemistry

Application of Two Direct C(sp 3 )-H Functionalizations for the Total Synthesis of (+)-Lactacystin

Classics in Tetrahedron Letters

CH 3 TMG, DMF N H 3 CO 2 S. (PPh 3 ) 2 Pd 0

Short Lit

Additions to Metal-Alkene and -Alkyne Complexes

ROC Exam Problem 1

Carbonyl Ylide Cycloadditions

Catellani Reaction (Pd-Catalyzed Sequential Reaction) Todd Luo

Supporting Information

Total Synthesis of Trioxacarcin DC-45-A2

ENOLATES IN ORGANIC SYNTHESIS

Hennoxazole A. Philip Williams Group Meeting December 12, OMe. OMe 1 6 O H

Synthesis and Utility of α Silylamines: A Brief Overview. Literature Presentation 4/6/2K4 Dave Ballweg

Comparative Synthesis of Ingenol. Tyler W. Wilson SED Group Meeting

Reactivity Umpolung-1 Ready

Lecture 24 Two Germans and an Englishman

Reduction. Boron based reagents. NaBH 4 / NiCl 2. Uses: Zn(BH 4 ) 2. Preparation: Good for base sensitive groups Chelation control model.

Olefin-Forming Reactions I

The Vetivane Sesquiterpenes

Lecture 23. The Aldol Condensation. an Aldol! April 12, 2018 O H O H - Chemistry 328N

A Highly Convergent and Biomimetic Total Synthesis of Portentol

Enan$oselec$ve Total Synthesis of Amphidinolide F

Convergent Route to ent-kaurane Diterpenoids: Total Synthesis of Lungshengenin D and 1α6α- Diacetoxy-ent-kaura-9(11),16-dien- 12,15-dione

Problem session (3) Daiki Kuwana. Please fill in the blank and explain reaction mechanisms and stereoselectivities.

OUTLINE 535 LECTURE 4 (2003) Page 31

Protecting Groups. Tactical Considerations

Functionalization of C(sp 3 ) H Bonds Using a Transient Directing Group

Discussion Addendum for: Trifluoromethylation at the -Position of, -Unsaturated Ketones: 4-Phenyl-3-Trifluoromethyl-2-Butanone

OChem2 Course Pack. Practice Problems by Chapter. Practice Exams

Total Synthesis of Celastrol, Celastroid Natural Products

CEM 852 Exam What is the ratio of (S) / (R) alcohol formed during this reaction? (2 pts) baker's yeast. H 2 O, sucrose 25 C

Stereoselective reactions of enolates: auxiliaries

Transcription:

The Staunton-Weinreb Annulation SED Group meeting Guanqun Zhang 2015.04.21

Steven M. Weinreb Brooklyn, Y May 10, 1941 (Age 73) Cornell University, A.B. 1963 University of Rochester, Ph.D. 1967 Advisor: Marshall Gates I Postdoc Fellow Columbia; Gilbert Stork: 1966-1967 MIT: George Buchi: 1967-1970 Fordham University 1970 Associate professor - 1975 Penn State University 1978 Professor of chemistry 1980 Russell and Mildred Marker Professor of atural Products Chemistry 1987 Weinreb, S. M. Acc. Chem. Res. 1985, 18, 16. Weinreb, S. M. Acc. Chem. Res. 2002, 36, 59. Short, P. C&E 2005, 83, 65. Weinreb, S. M. eterocycles 2006, 70, 5.

Early synthetic targets papuamine (1994) pancracine (1997) Me cephalotaxine (1972) olivin ("1984") Me Me 2 streptonigrin (1982) Me 2 Me Me C 2 Me Steve Weinreb 2 C C 2 C 2 methoxatin (1981) Me Me Me Me tri--methylolivin (1984) Me Me tylophorine (1979) Franck, R. eterocycles 2006, 70, 1.

Tri--methylolivin Initial plan: Me Me Me Me Me Me Me Me tri--methylolivin Me C C Me linear synthesis: too many steps Me Cl Convergent synthesis: let s take the naphthalene apart... Me Me Me Me Me Me Me Me TP Me Me Me C 2 atch, R. P.; Shringarpure, J.; Weinreb, S. M. JC 1978, 43, 4172. Todd, J..; Starrett, J. E.; Weinreb, S. M. JACS 1984, 106, 1811.

Weinreb was inspired by four other people: SPh LDA, TF methyl acrylate -78 o C 68% C 2 Me C LDA (3.3 equiv) MVK (3 equiv) TF, -78 o C 85% auser, 1978 Kraus, 1978 Dodd, J..; Weinreb, S. M. Tetrahedron 1979, 20, 3593. auser, F. M.; Rhee, R. P. JC 1978, 43, 178. Kraus, G. A.; Sugimoto,. TL 1978, 19, 2263.

a (2-3 equiv) Ts Ph Ph 1,2-dimethoxyethane -78 o C 78% Ph Ph van Leusen, 1978 Parker, 1979 Me Et 2 C Me C (1) a, -56 o C (2) K, Et, 2 (3) TFA, TFAA (2:3) (4) C 2 C 2, Ts, C(Et) 3 47% over 4 steps Me Me C Dodd, J..; Weinreb, S. M. Tetrahedron 1979, 20, 3593. Wildeman, J.; Borgen, P. C.; Pluim,.; Rouwette, P..F.M.; van Leusen, A. M. TL 1978, 19, 2213. Parker, K. A.; Kallmerten, J. L. TL 1979, 20, 1197.

Me Me Me Me Me FS 3 LDA, TF -78 o C 35% Me Me Me Me Et (1) LDA, TF, -78 o C Me Me Me (2) 2 C 2 48% over two steps Jim Staunton And this brings us to the Staunton-Weinreb annulation Dodd, J..; Weinreb, S. M. Tetrahedron 1979, 20, 3593. Evans, G. E.; Leeper, F. J.; Murphy, J. A.;Staunton, J. JCS Chem. Comm. 1979, 205 and 406.

Staunton-Weinreb annulation general scheme R 1 R 2 Y LDA TF R 1 Y Me X -78 o C rt R 1 = R 2 = alkyl, Bn, MM, MEM X = usually or Me Y = C 2 or o-toluate is preformed with base o-toluate anion is bright yellow electrophile is added later Michael acceptor can be acyclic or cyclic, esters or ketones It s a stepwise sequence involving Michael addition followed by Dieckmann condensation and subsequent aromatization

Staunton-Weinreb annulation general mechanism Me Me LDA TF R 1 Me Me Me -78 o C rt LDA -78 o C - Me Me Me Me Me Me Me Me Me Me Me Me can be isolated if quenched at 0 o C can be isolated if quenched at -78 o C Evans, G. E.; Leeper, F. J.; Murphy, J. A.;Staunton, J. JCS Chem. Comm. 1979, 205 and 406.

Staunton-Weinreb annulation general mechanism Me Me LDA TF Me Me Me -78 o C rt Me if a leaving substituent is absent, tetralones will be isolated Me Me Me R Me LDA TF -78 o C rt Me R Me if the alpha position is saturated, decarboxylation can be done to aromatize Evans, G. E.; Leeper, F. J.; Murphy, J. A.;Staunton, J. JCS Chem. Comm. 1979, 406. Mahidol, C.; Tarnchopoo, B.; Thebtaranonth, C.; Thebtaranonth, Y. TL 1989, 30, 3861.

The reaction works great with... variety of o-toluates α,β-unsaturated esters/ketones Br Me Bn C 2 Ph Boc C 2 Ph Me Boc C 2 Ph Me 2 Et 2 C Et Boc C 2 Ph C 2 Et Me C 2 Ph Boc C 2 Ph C 2 Et S Me Me Me SPh 8 Me TBS Me TMS Donnor, C. D. Tetrahedron 2013, 69, 3747.

Essentials in the nucleophile Me C 2 Me LDA, TF Me S S 34% -78 o C 67% without Ph 2 S 2 Me Me Me Me LDA, TF C 2 Et S S C 2 Me -78 o C SPh 87% Me Li Me A methyl ether ortho to the ester group is necessary to stabilize the anion auser, F. M.; Rhee, R. P.; Prasanna, S.; Weinreb, S. M.; Dodd, J.. Synthesis 1980, 72, 74.

Aryl Substituent effects R C 2 Me LDA (2 equiv) -65 o C, TF C 2 Me R Me TBS 6 steps from aspartic acid slow warm to rt 30 min R TBS Me C 2 Me 0% Me C 2 Me 46% Me C 2 Me <5% Piv Me Me C 2 Me C 2 Me MEM C 2 Me 0% 0% 0% Me Me Me Me C 2 Me MEM C 2 Me TBS C 2 Me 41% 49% 0% Br Me C 2 Me 20% Me Me C 2 Me "10%" It s a three-way balance between steric interactions, electron density on the toluate and the stabilization offered by chelation Tan,. P..; Donner, C. D. TL 2008, 49, 4160.

Skipping the preformed enolate (1) E (2) LDA, MPA Me 2 E = C 2 Ph -95-50 o C 76% Bn TBS Bn TBS Br C 2 Ph (1) E (2) n-buli -100-70 o C 81% Me 2 Bn TBS Br C 2 Ph Me (1) E (2) n-buli -100-0 o C 75% Me Me 2 Bn TBS Charest, M. G.; Lerner, C. D.; Brubaker, J. D.; Siegel, D. R.; Myers, A. G. Science 2005, 308, 395.

Two additional enolate generation methods...sn Me C 2 Et (1) LDA, TF, -78 o C Me C 2 Et (1) n-buli, -78 o C Me (2) Bu 3 SnCl SnBu 3 (2) E, -78 25 o C (75%) 60% 75% Me TMS 71% Me TMS 51% 74% 83% Me TMS 62% Me SPh 47% ill, B.; Rodrigo, R. L 2005, 7, 5223.

Two additional enolate generation methods...si C 2 Me TMS C 2 Me R CsF, MPA 60 o C, 3 h C 2 Me R C 2 Me R C 2 Me C 2 Me C 2 Me C 2 Me C 2 Me C 2 Me 17% 14% 41% C 2 Me C 2 Me C 2 Me C 2 Me C 2 Me C 2 Me 21% C 2 Me 43% C 2 Me 15% C C 2 Me 2 Me C 2 Me Me 2 C C 2 Me C 2 Me 33% 28% C 2 Me C 2 Me C 2 Me 0% C 2 Me Me 2 C C 2 Me Ph C 2 Me C 2 Me Ph 0% 0% C 2 Me 70% C 2 Me C 2 Me Ph C 2 Me 26% 41% Aono, M.; Terao, Y.; Achiwa, K. Chem. Lett. 1985, 339.

Two additional enolate generation methods...si C 2 Me TMS Me 2 C C 2 Bn one step C 2 Bn C 2 Me C 2 Me TMS Me 2 C C 2 Bn CsF, MPA 60 o C C 2 Me C 2 Bn C 2 Me (1) 2, Pd/C (2) 150 o C C 2 Me 60% ame, Me, TF C 2 Me C 2 Me 96% over two steps quant. Xiang, J.-.; ambi, P.; hlstein, E..; Elliott, J. D. Bioorg. Med. Chem. 1998, 6, 695.

Characteristics of electrophiles Acyclic Michael acceptor are hit/miss and generally don t work well Me C 2 Me Me Me R Me LDA, TF -78 o C Me Me R Me R = Me 50% R = Me 0% R 1 Me C 2 Me R 2 Me (1) LDA, TF, -78 0 o C (2) Cl, Me, reflux R 1 Me R 2 R 1 = R 2 = 41% R 1 =, R 2 = Me 40% R 1 = Me, R 2 = 52% R 1 = R 2 = Me 51% Yields aren t so great Dodd, J..; Garigipati, R. S.; Weinreb, S. M. JC 1982, 47, 4045. Tarnchopoo, B.; Thebtaranonth, C.; Thebtaranonth, Y. Synthesis 1986, 785.

A cyclic Michael acceptor Me 2 C C 2 Me 2 eq. Me C 2 Me LDA (2 equiv) TF, -78 o C Me Me Me C 2 Me C 2 Me Me (1) a (aq.), Me, dioxane (2) (Me) 3 C, Ts, Me LDA, -78 o C 74% rt Me Me (3) DDQ, Ph (4) BCl 3, DCM 57% over 4 steps C 2 Me 500 o C, 0.01 torr Me Me 92% Me Me C 2 Me (1) a, Et, TF (2) Me 2 S 4, K 2 C 3 48% over two steps Me 2 C C 2 Me Me C 2 Me LDA, -78 o C rt 80% Me C 2 Me C 2 Me DDQ, dioxane reflux 60% Me C 2 Me C 2 Me Mahidol, C.; Tarnchopoo, B.; Thebtaranonth, C.; Thebtaranonth, Y. TL 1989, 30, 3861.

Applications of this annulation in natural product synthesis C Me 2 Me semiviriditoxin Me (R)-atrochrysone FtsZ inhibitor; broad spectrum antibiotic activity against gram-positive pathogens A family of anthranoids, which has displayed antibacterial, anti-malarial, and insect antifeedant activities neojusticidin B Interesting skeleton for organic synthesis

Synthesis of semiviriditoxin 2 C 2 (1) a 2, 2 S 4, KBr, 2, 0 o C, 4 h (91%) (2) B 3 -Me 2 S, TF, -30 o C to rt, 18 h (97%) C 2 (3) K 2 C 3, DCM, 72 h (96%) (4) TBSCl, imidazole, DCM, 4 h (98%) TBS methyl propiolate n-buli, BF 3 -Et 2 TF, -78 o C, 30 min (72%) C 2 Me TBS LDA, TF, -60 o C, 30 min (36%) Me Me Me Me TBS ame, Me, 16 h (80%) Me Me TBS (1) TF, 10% Cl, 16 h (2) PhI(Ac) 2, TEMP, DCM, 20 h (3) acl 2, tbu, 2, a 2 P 4, 3 h (4) Me, conc'd 2 S 4, 16 h (5) BCl 3, DCM, 6 h 44% over 5 steps Me C 2 Me Donner, C. D.; Tan,. P.. Tetrahedron 2009, 65, 4007.

Synthesis of atrochrysone pig liver esterase TBDMS-Tf, lutidine TBDMS Me 2 C C 2 Me p 8, 92 % Me 2 C C 2 DCM, 0 o C to rt 86% Me 2 C C 2 TBDMS Me TBDMS (1) K 2 C 3, Me (2) Tf 2, DMAP, DCM Me 40-80% over two steps TBDMS C 2 TBDMS Tebbe reagent, TF -78 o C, 30 min, then rt, 1 h 61-85% Me Me Me (1) LDA, TF, -78 o C (25%) (2) F, MeC (78%) Me Muller, M.; Lamottke, K.; Low, E.; Magor-Veenstra, E.; Steglich, W. JCS Perkin Trans 1 2000, 2483.

Synthesis of neojusticidin B C 2 Et (1) LDA, TF, -78 o C (2) p-cymene, 10% Pd/C, reflux C 2 Et not attempted Kobayashi, K.; Maeda, K.; Uneda, T.; Morikawa,.; Konishi,. JCS Perkin Trans 1 1997, 443.

The molecule in hand... TMSE 2 C 2 equiv LiMDS, TF, -78 o C C 2 Me TMSE 2 C Ts Cl -Cl C 2 Me TMSE 2 C TMSE 2 C C 2 Me Ts C 2 Me TMSE 2 C Ts C 2 Me alstilobanine A C 2 Me Feng, Y.; Majireck, M. M.; Weinreb, S. M. ACIE 2012, 51, 12846.

Staunton-Weinreb Annulation Discovered Independently by Staunton and Weinreb in 1979 for synthesizing linear polycycles Me Me Me Me Me Me Me Me Me C 2 Et Tandam Michael addition, Dieckmann condensation followed by optional aromatization ortho-toluates Me Me Me Me Me Me C 2 Et Me Me Generally requires an ether group ortho to ester for anion stabiliztion Me Me C 2 Et Br...unless the Anion is generated in situ by lithium-halogen exchange cyclic esters and ketones are generally better electrophiles Me 2 C C 2 Me Me C 2 Ph still acyclic

What happened to auser, Kraus, van Leusen, and Parker?

Supposingly, this should be the beginning of this part of history Me LDA Me (1) Ac 2, py C 2, TF (2) a, 2-78 o C C 2 (3) Ac 2, Cl 4 90% 68% over 3 steps Me ethyl bromoacetate Zn, Ph refulx Me (1) K, Me 2 S 4 (2) 2 Et Me Me 73% Frank auser then on and on for longer polycyclic chains auser, F. M.; Rhee, R. JACS 1977, 99, 4533.

(Stabilized) phthalide nucleophiles SPh LDA, TF methyl acrylate -78 o C 68% C 2 Me C 2 (1) PhS, Ph, reflux (2) mcpba, DCM 87% over two steps S 2 Ph LDA, TF methyl acrylate -78 o C 86% C 2 Me Frank auser ne oxidation state higher than the Staunton-Weinreb version C 2 Me S 2 Ph auser, F. M.; Rhee, R. JC 1978, 43, 178.

Synthesis of neojusticidin B C 2 Et LDA, TF, -78 o C not attempted LDA, TF, -78 o C I 2, CCl 3 C 2 2, 0 o C Me 50% over two steps Kobayashi, K.; Maeda, K.; Uneda, T.; Morikawa,.; Konishi,. JCS Perkin Trans 1 1997, 443.

2024 © sciencedocbox.com Privacy Policy | Terms of Service | Feedback