Dr. Christopher Cioffi Monday 3/20/2017 9:00AM – 9:50AM

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Presentation transcript:

Dr. Christopher Cioffi Monday 3/20/2017 9:00AM – 9:50AM Organic Chemistry II Dr. Christopher Cioffi Monday 3/20/2017 9:00AM – 9:50AM

Dienes and Conjugation

Dienes and Conjugation

Dienes and Conjugation

Dienes and Conjugation Which systems are conjugated? Which ones are not conjugated?

Which systems are conjugated? Which ones are not conjugated?

The Diels-Alder Reaction

The Diels-Alder Reaction

The Diels-Alder Reaction: Highlights Pericyclic reaction A concerted (one-step) reaction that proceeds via a cyclic transition state [4+2] Cycloaddition reaction between a conjugated diene and a dienophile Forms six-membered ring systems (cyclohexene products) Generates molecular complexity efficiently Accommodates several functional groups, generates a new double-bond, and controls stereochemistry and regiochemistry: can establish up to four stereogenic centers Important reaction in the synthetic chemist’s toolbox

The Diels-Alder Reaction: Use in Total Synthesis cortisone prostaglandin reserpine taxol 1. J. Am. Chem. Soc. 1952, 74, 4223-4251. 2. J. Am. Chem. Soc. 1969, 91, 5675-5677. 3. J. Am. Chem. Soc. 1987, 109, 6124-6134. 4. Nature 1994, 367, 630-634.

The Diels-Alder Reaction: Highlights Active Pharmaceutical Ingredients (APIs) Agrochemicals Flavors and fragrances Funel, J. A.; Abele, S.; Industrial applications of the Diels-Alder reaction. Angew. Chem. Int. Ed. Engl. 2013, 52, 3822-3863.

The Diels-Alder Reaction: A [4+2] Cycloaddition

The Diels-Alder Reaction: A [4+2] Cycloaddition

The Diels-Alder Reaction: [4+2] Cycloaddition The reaction involves 4-p electrons of the diene and 2-p electrons of the dieneophile Converts two p-bonds into two s-bonds Concerted reaction: all bond breaking and bond making happens simultaneously in a single step

The Diels-Alder Reaction: Requirements

The Diels-Alder Reaction: Electronics Requirements Which diene is least reactive? Which diene is most reactive? Why?

The Diels-Alder Reaction: Electronics Requirements Which diene is least reactive? Which diene is most reactive? Why?

Which dieneophile is least reactive? Which dieneophile is most reactive? Why?

Which dieneophile is least reactive? Which dieneophile is most reactive? Why?

Which of the following are expected to be good Diels-Alder dienophiles Which of the following are expected to be good Diels-Alder dienophiles? Why?

Which of the following are expected to be good Diels-Alder dienophiles Which of the following are expected to be good Diels-Alder dienophiles? Why?

Diene Requirement: Conjugation and s-Cis Conformation

Diene Requirement: Conjugation and s-Cis Conformation

How would you rank the reactivity of the following dienes?

How would you rank the reactivity of the following dienes?

The Diels-Alder Reaction: Mechanism

The Diels-Alder Reaction: Mechanism and Syn Stereochemistry

The Diels-Alder Reaction: Mechanism and Syn Stereochemistry

The Diels-Alder Reaction: Mechanism and Syn Stereochemistry

The Diels-Alder Reaction: Mechanism and Syn Stereochemistry

The Diels-Alder Reaction: Mechanism and Syn Stereochemistry

The Diels-Alder Reaction: Mechanism and Syn Stereochemistry

The Diels-Alder Reaction: Mechanism and Syn Stereochemistry

The Diels-Alder Reaction: Mechanism and Syn Stereochemistry

The Diels-Alder Reaction: Mechanism and Syn Stereochemistry Racemic mixtures of enantiomers

Regioselectivity: 1,4- and 1,2-Products

The Diels-Alder Reaction: Pushing and Pulling Electrons via Resonance

The Diels-Alder Reaction: Pushing and Pulling Electrons

The Diels-Alder Reaction: Pushing and Pulling Electrons Can you predict the Diels-Alder Products?

The Diels-Alder Reaction: Pushing and Pulling Electrons Can you predict the Diels-Alder Products?

The Diels-Alder Reaction: The Endo Rule

The Diels-Alder Reaction: The Endo Rule

The Diels-Alder Reaction: The Endo Rule

The Diels-Alder Reaction: The Endo Rule

The Diels-Alder Reaction: Use in Total Synthesis cortisone prostaglandin reserpine taxol 1. J. Am. Chem. Soc. 1952, 74, 4223-4251. 2. J. Am. Chem. Soc. 1969, 91, 5675-5677. 3. J. Am. Chem. Soc. 1987, 109, 6124-6134. 4. Nature 1994, 367, 630-634.