Streamlining Reaction Discovery and Development Through Kinetic Analysis

Similar documents
Reaction Progress Kinetic Analysis to Probe Catalytic Reactions. Grant Sherborne 2/12/2013

Palladium-Catalyzed Alkylation of sp2 and sp3 C-H Bonds with Methylboroxine and Alkylboronic Acids: Two Distinct C-H Activation Pathways

Catalytic Asymmetric [4+1] Annulation of Sulfur Ylides with Copper Allenylidene Intermediates. Reporter: Jie Wang Checker: Shubo Hu Date: 2016/08/02

There are 15 total pages to this exam. Please be sure your copy has 15 pages before you begin.

Ligand Effects in Nickel Catalysis. Anthony S. Grillo Chem 535 Seminar October 22, 2012

C H activation of aliphatic amines without unnecessary mask M2 Takaya Togo

Mechanistic Studies of Wacker-Type Amidocyclization. and Stereochemical Implications of Proton Transfer

Organic Tutorials 3 rd Year Michaelmas Transition Metals in Organic Synthesis: (General paper level) ! 1! Reading

The Mechanistic Studies of the Wacker Oxidation. Tyler W. Wilson SED Group Meeting

Nickel-Catalyzed Three-Component [3+2+2] Cocyclization of Ethyl Cyclopropylideneacetate and Alkynes

Negishi Coupling of Secondary Alkylzinc Halides with Aryl Bromides and Chlorides

Metal Hydrides, Alkyls, Aryls, and their Reactions

Development of Chiral Phosphine Olefin Ligands and Their Use in Asymmetric Catalysis

Non-Linear Effects in Asymmetric Catalysis: A Useful Tool in Understanding Reaction Mechanisms. Group Meeting Aaron Bailey 12 May 2009

ummary Manipulating Radicals

Additions to Metal-Alkene and -Alkyne Complexes

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

Iridium-Catalyzed Hydrogenation with Chiral P,N Ligands

Joseph Salamoun Current Literature 11/21/15 Wipf Group

Copper-Catalyzed Synthesis of Esters from Ketones. Alkyl Group as a Leaving Group.

Recent Advances in Organic Chemistry

Shi Asymmetric Epoxidation

There are only two important things in chemistry, kinetics and thermodynamics. And, exp(-δg/rt) = k 1 /k -1, so there s really only one thing.

Supporting Information for

CEM 852 Exam-2 April 2, 2016

Name: CHEM 633: Advanced Organic Chemistry: Physical Final Exam. Please answer the following questions clearly and concisely.

Rate Law Summary. Rate Laws vary as a function of time

Scission of Dinitrogen by a Molybdenum(III) Xylidene Complex. CHM 5.33 Fall 2005

CHEM 153 PRACTICE TEST #1 ANSWER KEY

Palladium-catalyzed sp 3 C H activation. Yan Xu Dong Group Meeting Apr. 2, 2014

Direct, Catalytic Hydroaminoalkylation of Unactivated Olefins with N-Alkyl Arylamines

Initials: 1. Chem 633: Advanced Organic Chemistry 2016 Final Exam

Mechanistic Insides into Nickamine-Catalyzed Alkyl-Alkyl Cross-Coupling Reactions

Chapter 14 Chemical Kinetics

Organic Chemistry Laboratory Summer Lecture 6 Transition metal organometallic chemistry and catalysis July

Deactivation Pathways in Transition Metal Catalysis

Reaction Progress Kinetics Analysis of 1,3-Disiloxanediols as Hydrogenbonding

Enzyme Reactions. Lecture 13: Kinetics II Michaelis-Menten Kinetics. Margaret A. Daugherty Fall v = k 1 [A] E + S ES ES* EP E + P

Michaelis-Menten Kinetics. Lecture 13: Kinetics II. Enzyme Reactions. Margaret A. Daugherty. Fall Substrates bind to the enzyme s active site

Transition Metal-Catalyzed Carbon-Carbon Bond Cleavage (C-C Activation) Group Meeting Timothy Chang

Examination Catalysis October

CHEM Exam 1 February 11, 2016 Constants and Equations: R = 8.31 J/mol-K. Beer-Lambert Law: A log bc. Michaelis-Menten Equation: v0 M

Mechanistic Implications in the Morita Baylis Hillman Alkylation: Isolation and Characterization of an Intermediate

Palladium-Catalyzed Asymmetric Benzylic Alkylation Reactions

Palladium Schiff Base Complexes: Potential catalysts for C-C bond reactions

Mild Cobalt-Catalyzed Hydrocyanation of Olefins with Tosyl Cyanide

What is an enzyme? Lecture 12: Enzymes & Kinetics I Introduction to Enzymes and Kinetics. Margaret A. Daugherty Fall General Properties

Palladium-Catalyzed Electrophilic Aromatic C H Fluorination

The Mechanism of Rhenium Catalyzed Olefination of Aldehydes. Nathan Werner Denmark Group Meeting July 22 nd, 2008

Enantioselective 1,1-Arylborylation of. Transfer with Pd Catalysis

You may write your answers in the space provided and/or on additional pages.

CHEM 251 (4 credits): Description

Regioselective Reductive Cross-Coupling Reaction

Asymmetric Copper-Catalyzed Synthesis of α-amino Boronate Esters from N-tert- Butanesulfinyl Aldimines

N-HETEROCYCLIC CARBENES: STRUCTURE AND PROPERTIES

What is an enzyme? Lecture 12: Enzymes & Kinetics I Introduction to Enzymes and Kinetics. Margaret A. Daugherty Fall 2004 KEY FEATURES OF ENZYMES

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

Reactivity within Confined Nano-spaces

Molybdenum-Catalyzed Asymmetric Allylic Alkylation

Electrophilic Carbenes

O H Hydrogen bonding promotes H-atom transfer from C H bonds for C-alkylation of alcohols

Total Synthesis of Verruculogen and Fumitremorgin A Enabled by Ligand-Controlled C H Borylation

Selective Reduction of Carboxylic acids to Aldehydes Catalyzed by B(C 6 F 5 ) 3

Borane-Catalyzed Ring-Opening and Ring-Closing Cascades of Furans Leading to Silicon-Functionalized Synthetic Intermediates

Supplementary Material (ESI) for Chemical Communications This journal is (c) The Royal Society of Chemistry 2008

Chemical Kinetics. Reaction rate and activation energy of the acid hydrolysis of ethyl acetate LEC 05. What you need: What you can learn about

Recent Advances to Improve Chemical Development

Pd(II) Catalyzed C3-selective arylation of pyridine with (hetero)arenes SUPPORTING INFORMATION

Titanacyclopropanes as versatile intermediates for carbon carbon bond formation in reactions with unsaturated compounds*

INTRODUCTORY ORGANIC CHEMISTRY II --- PROBLEM SET #2

O + k 2. H(D) Ar. MeO H(D) rate-determining. step?

Name: UNIT 5 KINETICS NOTES PACEKT #: KINETICS NOTES PART C

Rhodium Catalyzed Hydroacylation

The Role of METAMORPhos Ligands in Transition Metal Complex Formation and Catalysis S. Oldenhof

Aza-Wacker-Type Cyclization. Group Meeting Tuesday, April 19, 2011 William Kuester

May CUME. Department of Chemistry University of Missouri Columbia Saturday, May 10, O Clock Chemistry Reading Room. Dr.

Chemical Reactions and Enzymes. (Pages 49-59)

Kinetic Isotope Effects

Lecture 27. Transition States and Enzyme Catalysis

Highly Efficient, Convergent, and Enantioselective Synthesis of Phthioceranic Acid

Reductive Elimination from High-Valent Palladium. Kazunori Nagao MacMillan Group Meeting

Palladium-Catalyzed Alkylarylation of Acrylamides with

Functionalization of terminal olefins via H migratory insertion /reductive elimination sequence Hydrogenation

Catalytic alkylation of remote C H bonds enabled by proton-coupled electron transfer

CuI CuI eage lic R tal ome rgan gbr ommon

Modified from: Larry Scheffler Lincoln High School IB Chemistry 1-2.1

SUPPORTING INFORMATION

A Tandem Semipinacol Rearrangement/Alkylation of a-epoxy Alcohols: An Efficient and Stereoselective Approach to Multifunctional 1,3-Diols

Denmark s Base Catalyzed Aldol/Allylation

Lewis Base Activation of Lewis Acids: Development of a Lewis Base Catalyzed Selenolactonization

CHEM 109A Organic Chemistry

The aldol reaction with metal enolates proceeds by a chair-like, pericyclic process: favored. disfavored. favored. disfavored

TWO ENZYME CATALYSIS OVERVIEW OBJECTIVES INTRODUCTION

2. Which of the following are nucleophiles and which are electrophiles?

Final Exam /415 ( CHEM 6352 Fall %) Name

Biology Slide 1 of 34

sp 3 C-H Alkylation with Olefins Yan Xu Dec. 3, 2014

COLLISION THEORY AND REACTION RATES

Name Student number. UNIVERSITY OF GUELPH CHEM 4540 ENZYMOLOGY Winter 2002 Quiz #1: February 14, 2002, 11:30 13:00 Instructor: Prof R.

Journal Club Presentation by Remond Moningka 04/17/2006

Transcription:

Streamlining Reaction Discovery and Development Through Kinetic Analysis R 3 Si X Ni(0) Ligand R 3 Si X [Substrate] 0 0 Time J. Am. Chem. Soc. 2011, 133, 5728 Professor Ryan D. Baxter

utline: Direct Comparison of Initial Rates vs. Reaction Progression "Ynal" R 3 Si X Ni(0) Ligand R 3 Si X CF 3 H C 2 K R Pd(II)-cat. Ligand CF 3 C 2 K R 0.12 0.09 D[Ynal] Initial Rates, Dt verlay» Relative Rates [Ynal] (mol/l) 0.06 0.03 [Substrate] 0.00 0 1000 2000 3000 4000 5000 Time (seconds) Time (minutes) - rder in [ynal], [silane], [Ni] - 30 experiments - rder in [substrate], [olefin], [Pd] - Catalyst stability, product inhibition, relative binding constants - 12 experiments

Nickel Catalyzed Reductive Couplings (Montgomery Group, 2010)

Distinguishing Between Mechanistic Possibilities - Crossover experiment probes cleavage of Si H/D bond - Silane scrambling seems to be ligand-dependent - Mechanism for silane? (1) L n Ni(0) Ni Et 3 Si-H Et 3 Si H (2) Et 3 Si-H Ni(0) L n Ni H SiEt 3

In Situ Monitoring of Aldehyde/Alkyne Couplings "Ynal" + Et 3 Si-H 10% Ni(CD) 2 20% PCy 3 Et 3 Si THF (0.1 M) -25 o C 1.0 equiv 2.0 equiv 86% H Et 3 Si X X = D, 90% X = H, 10% Pr 3 Si X X = D, 11% X = H, 89% ~10% crossover with PCy 3

In Situ Monitoring of Aldehyde/Alkyne Couplings "Ynal" + Et 3 Si-H 10% Ni(CD) 2 20% PCy 3 Et 3 Si THF (0.1 M) -25 o C 1.0 equiv 2.0 equiv 86% H Et 3 Si X X = D, 90% X = H, 10% Pr 3 Si X X = D, 11% X = H, 89% ~10% crossover with PCy 3

Rate Dependence on Catalyst Concentration "Ynal" + Et 3 Si-H X% Ni(CD) 2 2X% PCy 3 Et 3 Si THF (0.1 M) -25 o C H 1.0 equiv 2.0 equiv 12 0.12 [Ynal]/ time (M/s) * 10-5 8 4 [Ynal](mol/L) 0.08 0.04 10 mol% Ni(CD)2 15 mol% Ni(CD)2 20 mol% Ni(CD)2 25 mol% Ni(CD)2 0 0.00 0.01 0.02 0.03 0.00 0 1000 2000 3000 4000 [Ni(CD) 2 ] (mol/l) Time (seconds)

Rate Dependence on Substrate Concentration "Ynal" + Et 3 Si-H 10% Ni(CD) 2 20% PCy 3 Et 3 Si THF (0.1 M) -25 o C H 0.5 1.0 equiv 2.0 equiv 12 D [Ynal]/ D time (M/s) * 10-5 8 4 0 0.00 0.04 0.08 0.12 0.16 [Ynal] (mol/l) 0.12 0.08 0.04 0.00-1000 0 1000 2000 [Ynal] (mol/l) Time (seconds)

Rate Dependence on Silane Concentration "Ynal" + Et 3 Si-H 10% Ni(CD) 2 20% PCy 3 Et 3 Si THF (0.1 M) -25 o C H 1.0 equiv 1.0 4.0 equiv [Ynal]/ time (M/s) * 10-5 12 8 4 [Ynal] (M) 0.12 0.08 0.04 0.1 M Et3SiH 0.2 M Et3SiH 0.3 M Et3SiH 0.4 M Et3SiH 0 0.0 0.1 0.2 0.3 0.4 0.5 0.00 0 1000 2000 3000 [Et 3 SiH] (mol/l) Time (seconds)

Role of Silane in Reductive Coupling H (1.0 equiv) + Et 3 Si-H Et 3 Si-D 10% - Ni(CD) 2 Et 3 Si 20% - PCy 3 THF (0.1M, 45 o C) H/D (3.0 equiv each) H/D = 50:50 KIE = 1.00 No observable kinetic isotope effect FIRST-RDER FIRST-RDER L n Ni(0) Ni rate-determining Et 3 Si-H fast ZER-RDER 100 mol% Ni/PCy 3 added But what about crossover?!

A Tale of Two Catalytic Cycles products without crossover H products with crossover Et 3 Si H L n Ni II Ni(0)L n Ni H L n Ni(0)L n L n Ni II H SiEt 3 + Pr 3 Si H L n Ni II Et 3 Si-H L n Ni II L Ni Ni L SiEt 3 Ni L H Ni Pr 3 Si-H Et 3 Si-H J. Am. Chem. Soc. 2014, 136, 17495

Summary of Nickel-Catalyzed Reductive Coupling "Ynal" + Et 3 Si-H 10% Ni(CD) 2 20% PCy 3 Et 3 Si THF (0.1 M) -25 o C 1.0 equiv 2.0 equiv 86% H Et 3 Si X X = D, 90% X = H, 10% Pr 3 Si X X = D, 11% X = H, 89% ~10% crossover with PCy 3 [Ynal] (mol/l) 0.12 0.09 0.06 0.03 D[Ynal] Initial Rates, Dt - rder in [ynal], [silane], [Ni] - 30 experiments - 1/2 of a.d 0.00 0 1000 2000 3000 4000 5000 Time (seconds)

Traditional Kinetic Analysis: Initial Rates catalyst A + B C - A large excess of B ensures a small change in concentration during the first portion of the reaction (~10%) - The majority of the acquired data is not factored into rate 0.12 [Ynal] (mol/l) [A] 0.09 0.06 0.03 Initial Rates, D[A] Dt D[A]/Dt * 10-5 0.00 0 1000 2000 3000 4000 5000 Time Time (seconds) [A] (mol/l)

Traditional Kinetic Analysis: Initial Rates catalyst A + B C - A large excess of B ensures a small change in concentration during the first portion of the reaction (~10%) - The majority of the acquired data is not factored into rate 0.12 [Ynal] (mol/l) [A] 0.09 0.06 0.03 Initial Rates, D[A] Dt D[A]/Dt * 10-5 0.00 0 1000 2000 3000 4000 5000 Time Time (seconds) [A] (mol/l)

Traditional Kinetic Analysis: Initial Rates catalyst A + B C - A large excess of B ensures a small change in concentration during the first portion of the reaction (~10%) - The majority of the acquired data is not factored into rate 0.12 [Ynal] (mol/l) [A] 0.09 0.06 0.03 Initial Rates, D[A] Dt straight into the garbage! D[A]/Dt * 10-5 0.00 0 1000 2000 3000 4000 5000 Time Time (seconds) [A] (mol/l)

Traditional Kinetic Analysis: Initial Rates catalyst A + B C - A large excess of B ensures a small change in concentration during the first portion of the reaction (~10%) - The majority of the acquired data is not factored into rate 0.12 [Ynal] (mol/l) [A] 0.09 0.06 0.03 Initial Rates, D[A] Dt D[A]/Dt * 10-5 note [A] 0 for a subsequent reaction 0.00 0 1000 2000 3000 4000 5000 Time Time (seconds) [A] (mol/l)

Traditional Kinetic Analysis: Initial Rates catalyst A + B C - A large excess of B ensures a small change in concentration during the first portion of the reaction (~10%) - The majority of the acquired data is not factored into rate 0.12 [Ynal] (mol/l) [A] 0.09 0.06 0.03 Initial Rates, D[A] Dt D[A] Dt D[A] Dt D[A] Dt D[A] Dt D[A]/Dt * 10-5 note [A] 0 for a subsequent reaction 0.00 0 1000 2000 3000 4000 5000 Time Time (seconds) [A] (mol/l)

Reaction Progress Kinetic Analysis (RPKA) catalyst A + B C - Reagents A and B are present in synthetic concentrations - As A reacts with B, the concentration difference between them should remain unchanged - EXCESS: [A] 0 - [B] 0 [Ynal] (mol/l) [A] 0.12 0.09 0.06 0.03 [A] 0 = 0.10 M, [B] 0 = 0.15 M excess = 0.05 M Conversion [A] (mol/l) [B] (mol/l) excess 0.00 0.10 0.15 0.05 0.25 0.075 0.125 0.05 0.50 0.05 0.10 0.05 0.75 0.025 0.075 0.05 0.00 0 1000 2000 3000 4000 5000 Time Time (seconds) now we can compare data from experiments where both A and B are changing synthetic conditions!

Reaction Progress Kinetic Analysis (RPKA)

C-H Activation of Arylacetic Acids ~ 30-fold rate increase with amino acid ligands

C-H Activation of Arylacetic Acids IR NMR ReactIR TM 45M fitted with a dicomp ATR probe - absorbance data converted directly to concentration - NMR calibration confirmed IR measurement of reaction progression with Dave Sale,.D.

C-H Activation of Arylacetic Acids: Same Excess

C-H Activation of Arylacetic Acids: Same Excess - The values of [1] and [2] will coincide when reaction a) is at 50% conversion and reaction b) is at 0% conversion - Look for graphical overlay

C-H Activation of Arylacetic Acids: Same Excess - The values of [1] and [2] will coincide when reaction a) is at 50% conversion and reaction b) is at 0% conversion - Look for graphical overlay

C-H Activation of Arylacetic Acids: Same Excess, Product Added - The values of [1] and [2] will coincide when reaction a) is at 50% conversion and reaction b) is at 0% conversion - Look for graphical overlay

C-H Activation of Arylacetic Acids: Same Excess, Product Added - The values of [1] and [2] will coincide when reaction a) is at 50% conversion and reaction b) is at 0% conversion - Look for graphical overlay

C-H Activation of Arylacetic Acids: Different Excess

C-H Activation of Arylacetic Acids: Different Excess

C-H Activation of Arylacetic Acids: Different Excess

C-H Activation of Arylacetic Acids: Different Excess

C-H Activation of Arylacetic Acids: Different Excess

C-H Activation of Arylacetic Acids: Different Excess

Piecing Together the Mechanistic Puzzle: Driving Forces

Piecing Together the Mechanistic Puzzle: Driving Forces

Piecing Together the Mechanistic Puzzle: ff Cycle Catalyst Binding CF 3 2b Ac K Pd C 2 n-hex HN PG R' K eq,2b Negative rder in 2 CF 3 Ac K H PG N Pd R' K eq,3b Negative rder in Product CF 3 K R Pd Ac 3b C 2 n-hex HN PG R' R = arylacetic acid product binding is stronger that substrate binding!

Piecing Together the Mechanistic Puzzle: Role of the Ligand

Piecing Together the Mechanistic Puzzle: Role of the Ligand favored for C-H activation

Summary of C-H Activation of Arylacetic Acids

Summary: Initial Rates vs. Reaction Progression "Ynal" R 3 Si X Ni(0) Ligand R 3 Si X CF 3 H C 2 K R Pd(II)-cat. Ligand CF 3 C 2 K R 0.12 0.09 D[Ynal] Initial Rates, Dt verlay» Relative Rates [Ynal] (mol/l) 0.06 0.03 [Substrate] 0.00 0 1000 2000 3000 4000 5000 Time (seconds) Time (minutes) - rder in [ynal], [silane], [Ni] - 30 experiments - rder in [substrate], [olefin], [Pd] - Catalyst stability, product inhibition, relative binding constants - 12 experiments

Acknowledgements Nickel Chemistry M. Taylor Haynes,. D. Professor John Montgomery* Palladium Chemistry David Sale,. D. Keary M. Engle,. D. Professor Jin-Quan Yu Professor Donna G. Blackmond*

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