lecture 04 slides

8/7/2019 Lecture 04 Slides

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Lecture 4 (9/10/10)

Analysis of Organic Compounds

Purification and Isolation

Mass Spectrometry

Electromagnetic Radiation

X-Ray Diffraction

Spectroscopy

Infrared

Nuclear Magnetic Resonance

Chemical Shifts

Associated readings: Clayden pp. 50-54, 55-62, 65-67



Total Synthesis of Lactacystin

OTMS

5 steps1 column

57% overall yield

SiMe Me

O

NH

O

PhNC CO2Et

NHPMB

(S,S )-[(salen)Al]2O10 mol%

t -BuOH, 2.0 equivcyclohexane ( 0.1 M), rt, 84 h

N

O

CO2Me

CNSi

PMB

Me Me

99:1 ratio of enantiomers90:10 ratio of diastereomers

N

O

CO2Me

CNSi

PMB

Me Me

Me

LHMDS (1.5 equiv),THF, –78 °C;

MeI (4.0 equiv)NaBH4

MeOH, 0 °C N

O

CNSi

PMB

Me Me

Me

OH

58% (3 steps)

N

O

CNSi

PMBMe

Me MeMe

OH

1. Dess–Martin reagent,pyridine, CH2Cl2, rt

2.

THF, –78 oC

MeBrMg

73% (2 steps), > 95:5 dr

N

O

Si

PMB

Me

Me

Me

O

Me

CHO

Red-Al, toluene –78 to 0 °C;

1M tartaric acid0 °C

N

O

Si

PMB

Me

Me

Me

O

Me

CO2H

N

O

HO2CHO

PMBMe

OHMe

NaClO2, NaH2PO4

2-methyl-2-butenet -BuOH, H2O, rt

H2O2, KF,

KHCO3, DMF, rt

1. H2, Pd/C,

MeOH, AcOH, 8 h

2. Tf2O, CH2Cl2,

DMAP, pyr, 0 oC;

N

O

PMBMe

TfOO

O

Me

Me

NaNO2

DMF, rt N

O

PMBMe

HOO

O

Me

Me

1. CAN, CH3CN

H2O, 0o

C

2. N -acetyl-L-cysteine

EtNMe2, CH2Cl2, rt

lactacystin

NH

O

OHMe

MeMe

HO

OH

S

CO2H

AcHN

well-establishedchemistry

18 total steps6% overall yield

49% (3 steps),single diastereomer

75% (3 steps)

68% (2 steps)

EP Balskus, EN Jacobsen JACS 2006, 128 , 6810



HPLC Trace of a Mixture of Pesticides



Mass Spectrometer Schematic



Mass Spectrum of n -Hexane



Electromagnetic Radiation



“Unambiguous” Characterization of a Key Intermediate in a Total Synthesis

NH

O

HO

Me

HO

O

SHO2C

AcHN

Lactacystin

N

O

NC

Si

Me

Me

Me

HO

Me

OMe

(8 steps into the synthesis)

EP Balskus, EN Jacobsen JACS 2006, 128 , 6810



Potassium Channel --Streptomyces lividans



Infrared (IR) Vibrational Modes



Frequency (cm -1 )

m 1 + m 2

ν = 12πc m 1m 2

f



O

H Phenylacetaldehye(phenylethanal)



Nuclear Spins Nuclear Spins in a Magnetic Field



NH

O

HO

Me

Me

Me

HO

O

SHO2C

NH

Lactacystin

Me

O

N

Pyridine(solvent)

13 C NMR Spectrum of Synthetic Lactacystin



Lecture 5 (9/13/10)

Structure and Bonding RevisitedVSEPR Theory

Molecular Orbital Theory

Electronegativity

Non-Polar and Polar Covalent Bonding

Hybridization

Antibonding Orbitals

Associated Readings: Clayden Ch. 4 (pp. 87-110)



Lecture 6 (9/15/10)

Organic Reaction MechanismsHow to Break/Make Bonds

Homolytic Mechanisms

Heterolytic Mechanisms

The Arrow-Pushing Convention

Nucleophiles and Electrophiles

MO Analysis of Reactivity

Associated Readings for Lectures 6 and 7:Clayden Ch. 5 (pp. 113-133)



Lecture 7 (9/17/10)

Organic Reaction Mechanisms (cont.)Frontier Molecular Orbital (FMO) Theory

Thermodynamics

Energy Diagrams

Kinetics

Rate Laws

Transition State Theory

Reactive Intermediates

Associated Readings for Lectures 6 and 7:Clayden Ch. 5 (pp. 113-133)

lecture 04 slides

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