Catalytic Amine Synthesis

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Catalytic Amine Synthesisfrente a distintas bases de Lewis

University of British Columbia

Othoniel Reyes CamachoProfessor: Laurel Schafer

using metal of low cost and low toxicity

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1 Introduction

Amines: Valuable and important class of compounds used in pharmaceutical ,agricultural and industrial areas

Hydroamination

Direct addition of an amine across a carbon-carbon multiple bond

Ricci, A., Modern Amination Methods . Wiley VCH, Weinheim, 2000

Anti-Markovnikov Markovnikov

Most efficient route:amines, imines , enamines

No byproduct – 100% atom economy

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2 Alkynes Hydroamination

General Aspects:

Frauke Pohlki and Sven Doye, The catalytic hydroamination of alkynes.Chem. Soc. Rev. , 2003

Enamine Imine

• Hydroamination of alkynes are “less” difficult than alkenesone

• Hydroamination of alkynes can be seen as an advantagebecause it offers high synthetic flexibility

• Thermodynamically favourable

• Entropically disfavourable

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3 Alkynes Hydroamination Cycle

Doye, S., et al., Angew. Chem. Int. Ed. Engl. 1999, 3389

Amine Activation - deprotonation

[2+2] Cycloadition

RNH 2 Coordination

Proton transfer

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4 Summer Work Diagram

*Internalalkynes: 5% or10% LC , 110 ° C

*

*Internalalkynes: 5% or10% LC , 110 ° C

Not explored with internal alkynes

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5 Alternative Reduction Methods

• The requirements for practical asymmetric synthesis include highstereoselectivity , high rate and productivity, atom economy , costefficiency, operational simplicity, environmental friendliness, andlow-energy consumption.

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6 Hydroamination with a LC Standar Solution and NaBH 4

Reduction

*Internal alkynes: 10%LC , 110 ° C

Alkyne Amine Yield Alkyne Amine Yield

65% 39.11%

77% 90%

112%(Wet)

67.47%

5.72% 6.09%

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7 Hydroamination with a LC Standar Solution and NaBH 4

Reduction

*Internalalkynes: 5% or10% LC , 110 ° C

Alkyne Amine Yield

52%

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8 Hydroamination with a LC StandarSolution and H 2, Pd/C Reduction

*Internalalkynes: 5% or10% LC , 110 ° C

Alkyne Amine Yield

85.28%

80.28%

44.90%

• Atom Economy (atom efficiency)

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9 Results

1H RMR Espectrum

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10 Results

GC-MS Espectrocopy

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11Hydroamination with a LC Standar Solution and Reduction by

Transfer Hydrogenation

Alkyne Amine Yield

Pending

Pending

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12 Results: Transfer Hydrogenation with RuCl2(PPh 3)3

GC-MS Espectrocopy

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13 Acknowledgments

National Autonomous University of Mexico

Faculty of Chemistry UNAM

Institut of Chemistry UNAM

University of British Columbia

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14 Sponsor

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15 Alkynes Hydroamination Cycle (Extended)

Berns F Straub and Rober G Bergman The mechanism of Hydroamination Angw Chem Int Ed 2001

Amine Activation - deprotonation

[2+2] Cycloadition

RNH 2 Coordination

Proton transfer