First Directed ortho Metalation (DoM) of 1,8-Naphthalene Diamides. Towards Nerve Growth Factor Inhibitors Christopher Jones†, Victor Snieckus†, Greg Ross.

Slides:

Advertisements

Similar presentations

BIOGEOCHEMICAL REACTIONS Used to harness energy for biosynthesis Take advantage of chemical “potential” energy Important consequences for element cycling.

Advertisements

Prepared by : Malak Eshtayah

We are grateful for the generous support from the National Science Foundation (CHE ). Introduction and History Attempted Cyclizations of Diphenyl.

Asymmetric ketone and imine reductions using ruthenium catalysts Jonathan Hopewell, José E. D. Martins and Martin Wills* 1) M. Wills, D. S. Matharu and.

∂. ∂ Efficient Catalytic Syntheses of Organoboronate Esters Ubiquitous building blocks for the fine chemical and pharmaceutical industries NORSC Sustainable.

Organic Chemistry 4 th Edition Paula Yurkanis Bruice Irene Lee Case Western Reserve University Cleveland, OH ©2004, Prentice Hall Chapter 16 Reactions.

A Green Approach to Nitrogen Heterocycles: Application to Biologically Active Compounds Name: Josephine Dimbleby Department: Chemistry Supervisor: Andy.

Hydrogen Bonding within Tyrosinate-Bound Iron Complexes Acknowledgments I would like to thank Kyle Rodriguez and Christian Tooley for advising me through.

Iron-catalyzed Cross Coupling reactions: From Rust to a Rising Star

Target Directed Synthesis via StReCH Chemistry: Pregabalin (LyricaTM)

Introduction Structure of the Carbonyl Group

Catalytic Cross-coupling Reactions with Unactivated Alkyl Electrophiles and Alkyl Nucleophiles Heng Su 04/11/2008 Department of Chemistry Brandeis University.

Cyclic Aminal of TsDPEN: Synthesis and Use as Asymmetric Organocatalysts Rina Soni, Silvia Gosiewska, Guy Clarkson, Martin Wills * Department of Chemistry,

Formation of Methane in Comet Impacts and the Implications for Earth Meredith N. McCarthy December 7, 2004 Based on the paper Formation of Methane in Comet.

Nickel(II) N-Heterocyclic Carbene Complexes

SELECTIVE SYNTHESES AND DERIVATISATION OF A 2 B- TYPE meso-TRIARYLCORROLES E. Dolusic a, H. Radecka b, J. Radecki b and W. Dehaen a a Dept. of Chemistry,

1 Benzene and Aromatic Compounds Buckminsterfullerene—Is it Aromatic? The two most common elemental forms of carbon are diamond and graphite. Their physical.

Palladium Catalyzed C-N Bond Formation Jenny McCahill

Neutralization 1. HAVE YOU SEEN ME? 2 3 Terminology Acids compound that produces H + ions when mixed with water pH 4.

1 Rh-Catalyzed Asymmetric Additions: The Rise of Chiral Dienes Daniela Sustac February 16, 2010 Tamio HayashiErick Carreira.

Isomerization of Xylene Isomers Austin Power Department of Chemistry, University of New Hampshire, Durham, NH 12/5/13 Introduction Early after the discovery.

Lactacystin: An Inhibitor in the Ubiquitin Proteasome Pathway Ami Jun-Yee Chin February 17, 2005.

Palladium Catalyzed Annulation Bei Zhao

Group 2 and Group 12 We will discuss groups 2 an 12 together due to their similar reactivity. Group 12 has completely filled and low-lying d-orbitals,

Norbornene-Mediated Palladium-Catalyzed Synthesis of Fused Aromatic Carbocycles and Heterocycles Dino Alberico Lautens Group University of Toronto Department.

Chapter 21 Carboxylic Acid Derivatives (continued)

Introduction Structure of the Carbonyl Group

化学系 Department of Chemistry Catellani Reaction

Chiral Concave N-Heterocyclic Carbenes 3 rd International Summer School “Supramolecular Systems in Chemistry and Biology“ Tim Reimers Kiel, GER.

Synthetic Strategies toward Substituted Benzenes 16-5 To obtain substitutions in positions incompatible with the directing sense of substituents requires.

Labeling with Genisphere Kit Mary Lee S. Ledbetter College of the Holy Cross.

A Novel Approach to Resin-based Cysteine Alkylation Bin Yang and Richard DiMarchi Department of Chemistry, Indiana University, Bloomington, Indiana,

Aryl halides that have electron-withdrawing substituents can undergo a nucleophilic substitution reaction 9.9 Nucleophilic Aromatic Substitution.

Synthesis of meso-substituted porphyrins

Created by Professor William Tam & Dr. Phillis Chang Ch Chapter 18 Reactions at the  Carbon of Carbonyl Compounds Enols and Enolates.

1 Directed ortho Metalation (DoM) of Naphthalene 1-8-bis-diethylamide: Research Towards Nerve Growth Factor Inhibitors John Stephenson †, Christopher Jones.

February Louis-Philippe Beaulieu Complex-Induced Proximity Effect in Directed Ortho and Remote Metallation Methodologies.

The Work Of Pr Karl A. Scheidt Group Department of Chemistry, Northwestern UniVersity, Evanston.

Light and Palladium Induced Carbonylation Reactions of Alkyl Iodides Mechanism and Development Pusheng Wang Gong Group Meeting April 12 th 2014.

(NHC)Cu 1 (NHC = N-Heterocyclic Carbene) Complexes as Efficient Catalysts for the Reduction of Carbonyl Compounds Nolan, S. P. Organometallics. 2004, 23,

1 First Directed ortho Metalation (DoM) of 1,8-Naphthalene Diamides. Towards Nerve Growth Factor Inhibitors Christopher Jones†, Victor Snieckus†, Greg.

1 Directed ortho Metalation (DoM) of 1,8-Naphthalene diethylamides: Research Towards Nerve Growth Factor Inhibitors. John Stephenson, Christopher Jones†,

Progress towards the Synthesis of 1-Benzoxepin; A Model Oxepin Substrate Ian Smith, Ryan Fitzgerald, Holly Guevara, Arthur Greenberg

Palladium-catalysed reactions involving isocyanides Reporter: Xinzheng Chen Supervisor: Prof. David Zhigang Wang

Bijay Bhattarai Faculty Advisor Debra D. Dolliver Kevin Shaughnessy University of Louisiana System Academic Summit /13/2013 SUZUKI COUPLING OF N-ALKOXYIMIDOYL.

Palladium Catalysis Townsend Group Meeting Dorothy Ackerman August 4, 2015.

A Metathesis Based Approach to the Synthesis of Aromatic Heterocycles Lisa P. Fishlock, Timothy J. Donohoe and Panayiotis A. Procopiou ‡ Chemistry Research.

Reaction Pathways The goal being to synthesize FeL 2 HCl, there are many pathways that can be taken. The figure below represents the various attempts that.

Nitrogen–Carbon Bond Formation from N 2 and CO 2 Promoted by a Hafnocene Dinitrogen Complex Yields a Substituted Hydrazine Wesley H. Bernskoetter, Emil.

© 2006 Thomson Higher Education Chapter 15 Carboxylic Acids and Nitriles.

of novel 1,2,3-triazolyl appended L-ascorbic acid derivatives

1,2 – Disubstituted Aromatics: Directed Ortho Metalation

Oxidation-Reduction & Organometallic

Chap. 1 Solomons: Chapter 12 Alcohols from Carbonyl Compounds: Oxidation-Reduction and Organometallic Compounds.

Results and Discussion

Towards the Synthesis and Characterization of Copper(I)-Arene Compounds Using Phenyl- and Naphthyl-Appended NS2-Macrocyclic Ligands Thora R. Maltais.;

Direct Heteroarylation: A Modern Synthetic Tool for the Synthesis of Liquid Crystalline Organic Semiconductors M. R. Billa, S. P. Kitney, S.M. Kelly The.

Development of New Arsenic Based Amidation Catalysts

Ayk BEDUOĞLU and Altuğ Mert SEVİM

Transition Metal Catalyzed Amide Bond Formation

Novel Nitroxyl Radical Synthesis

Recent Progress of Selective Monohydrolysis of Symmetric Diesters

Chemoselective and Regioselective Oxidative

Éric Godin Literature Meeting October 12th 2016

Introduction Structure of the Carbonyl Group

from Water Katherine Dombroski, Dejun Dong, Hannah Coco

Efficient Synthesis of Heterocycles with the Aid of Electrophilic

The First Conventional Synthesis of 1-methyl-4-silatranone and

Thomas Schaub, Marc Backes, and Udo Radius*

Synthesis of Hydrogels for the Protection of Phosphorene

Presentation transcript:

First Directed ortho Metalation (DoM) of 1,8-Naphthalene Diamides. Towards Nerve Growth Factor Inhibitors Christopher Jones†, Victor Snieckus†, Greg Ross ‡ † Department of Chemistry, Queen’s University, Kingston, ON, CANADA K7L 3N6 ‡ Department of Physiology, Queen’s University, Kingston, ON, CANADA K7L 3N6

Nerve Growth Factor (NGF) Involved in the neuronal development in the Central Nervous System and Peripheral Nervous System. Nerve Growth Factor is implicated in Alzheimer’s, epilepsy, stroke and pain. Production is stimulated in patients suffering from Arthritis pain. Inhibition of NGF causes reduction in pain levels. Ross, G. et al. J. Amer. Chem. Soc, , 1997

Previously Identified NGF Inhibitors Target Molecules Ross, G. et al. J. Amer. Chem. Soc, , 1997

Directed ortho Metalation (DoM) Reactions in Organic Synthesis E+E+ Hartung, C, Snieckus, V. Modern Arene Chemistry, Wiley-VCH, Weinheim. 2002, 330

Advantages of Directed ortho Metalation Recent Work 1. Kalinin,A.; Snieckus, V. et al. J Org Chem, 2003, 68, Chauder, B.; Snieckus, V. et al. Org Lett, 2002, 4, 815

Previous Work Involving 2,7-Disubstituted 1,8-Naphthalene Systems Wuest, J et al Organometallics, 1996,15, 1296

Double DoM of Naphthalene1,8-bis-Diethylamide 1 99 TL 6671

Bromo Ipsodesilaytion of Naphthalene- 1,8-dicarboxylic acid bis-diethylamide Colvin, E.W. Silicon in Organic Synthesis. Butterworth: London, 1988 General Ipso-substitution Reaction Synthesize unconventional substitution patterns. Alternative short route with improved yield. Regioselective,clean reaction with mild conditions. 78%

Mono or Di Deprotonation of Naphthalene bis-Diethylamide.What pathway does the deprotonation follow?? Mono or Di Deprotonation of Naphthalene bis-Diethylamide. What pathway does the deprotonation follow?? Determined by CD 3 OD Quench Experiments

Mono vs Bis Incorporation of Deuterium Monitored by EI + MS over Time [M + -NEt 2 ] Peak at 254 [M + -NEt 2 ] Peak (254) diappears after addition of SecBuLi and quench with CD 3 OD Time does not increase or decrease the 256 peak Equivalents of base = 4.4 Time 010 Min 20 Min30 Min 1 Hr 6 Hr [M +2 -NEt 2 ] Peak at 256

What Role Does the Equivalents of Base Have on formation of Mono or Bis? Starting Material 1.1 Eqv 2.2 Eqv 3.3 Eqv 4.4 Eqv Equilibrium can be seen for 1.1 equivalents [M + -NEt 2 ] Peak at 254

VT NMR Study Naphthalene-1,8-bis-Diethylamide Coalescence of AB System at 368°K AB System for CH 2 of Amides (CH 3 decoubled) Alkyl = Me, CH 2 Me, CH 2 Et, CH 2 Pr i, CHME 2, CH 2 Ph R =Me, COOH, COOMe, H

Suzuki - Miyaura Cross Coupling of 2,7 – diHalo Naphthalene 1,8-Bis-Diethylamide