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    Ǧ       ‘˜‡Žƒ‰„”ƒ†   

‡˜‡Ž‘’‡– ƒ† ’’Ž‹ ƒ–‹‘• ‘ˆ ‘Ž›„†‡—Ǧƒ–ƒŽ›œ‡† Š‡‘•‡Ž‡ –‹˜‡‹†‡‡†— –‹‘   ‘˜‡Žƒ‰„”ƒ†

 ̹‘˜‡Žƒ‰„”ƒ†ǡ–‘ Š‘Ž‹˜‡”•‹–›ʹͲͳ͹  ‘˜‡”’‹ –—”‡ǣSearchingfornewMo(CO)6reactions„›ƒ”ƒ¡ŽŽ‡ƒ” ’”‹–ǣͻ͹ͺǦͻͳǦ͹͸ͶͻǦͻͳͳǦͷ ’†ˆǣ ͻ͹ͺǦͻͳǦ͹͸ͶͻǦͻͳʹǦʹ  ”‹–‡†‹™‡†‡„›‹˜‡”•‹–‡–••‡”˜‹ ‡Ǧǡ–‘ Š‘ŽʹͲͳ͹ ‹•–”‹„—–‘”ǣ‡’ƒ”–‡–‘ˆ”‰ƒ‹ Š‡‹•–”›ǡ–‘ Š‘Ž‹˜‡”•‹–›

  

Dz –Š‹›‘—•Š‘—Ž†Œ—•– Š‹ŽŽdz ‘˜‡Žƒ‰„”ƒ†

 

 Abstract

Š‹•–Š‡•‹• ‘˜‡”•–Š‡†‡˜‡Ž‘’‡–‘ˆ ƒ–ƒŽ›–‹ ‡–Š‘†‘Ž‘‰‹‡•ˆ‘” –Š‡ ‹Ž†ƒ† Š‡‘•‡Ž‡ –‹˜‡Š›†”‘•‹Ž›Žƒ–‹‘‘ˆƒ‹†‡•ǤŠ‡ˆ‹”•–’ƒ”– †‡Ǧ • ”‹„‡•–Š‡‹˜‡•–‹‰ƒ–‹‘‘ˆ–Š‡‘ȋȌ͸Ǧ ƒ–ƒŽ›œ‡†”‡†— –‹‘‘ˆ ƒ”„‘šǦ ƒ‹†‡•Ǥ –™ƒ•ˆ‘—†–Šƒ––Š‡”‡†— –‹‘ ‘—Ž†„‡ ‘–”‘ŽŽ‡†„› –—‹‰ –Š‡”‡ƒ –‹‘–‡’‡”ƒ–—”‡ƒ†‡‹–Š‡”ƒ‹‡•‘”ƒŽ†‡Š›†‡• ‘—Ž†„‡‘„Ǧ –ƒ‹‡† •‡Ž‡ –‹˜‡Ž›Ǥ Š‡ •›•–‡ •Š‘™‡† ƒ —’”‡ ‡†‡–‡† Š‡‘•‡Ž‡ Ǧ –‹˜‹–›ƒ†–Š‡ƒ‹†‡”‡†— –‹‘ ‘—Ž†–ƒ‡’Žƒ ‡‹–Š‡’”‡•‡ ‡‘ˆ‘–Š‡” ”‡†— ‹„Ž‡ ˆ— –‹‘ƒŽ ‰”‘—’• •— Šƒ•‡–‘‡•ǡƒŽ†‡Š›†‡•ǡƒ†‹‹‡•Ǥ ‘”‡‘˜‡”ǡ –Š‡ –”ƒ•ˆ‘”ƒ–‹‘ ‘—Ž† „‡ ’‡”ˆ‘”‡† ‘ ƒ ’”‡’ƒ”ƒ–‹˜‡ • ƒŽ‡ƒ†™ƒ•ˆ—”–Š‡”‡’Ž‘›‡†‹–Š‡•›–Š‡•‹•‘ˆ‘‡’‡œ‹Žǡƒ’Šƒ”Ǧ ƒ ‡—–‹ ƒŽ†”—‰—•‡†‹–Š‡–”‡ƒ–‡–‘ˆŽœŠ‡‹‡”Ʋ•†‹•‡ƒ•‡Ǥ Š‡ –Š‹”† Šƒ’–‡” ‘ ‡”• –Š‡ †‡˜‡Ž‘’‡– ‘ˆ –Š‡ ‘ȋȌ͸Ǧ‡†‹ƒ–‡†Š›†”‘•‹Ž›Žƒ–‹‘’”‘–‘ ‘Žˆ‘”–Š‡”‡†— –‹‘‘ˆ ƒ”„‘šǦ ƒ‹†‡• ‘–ƒ‹‹‰ ƒ ‹†‹  ȽǦŠ›†”‘‰‡•Ǥ  –Š‹• ƒ•‡ǡ ‡ƒ‹‡• ™‡”‡ ˆ‘”‡† ƒ† ƒ Š‹‰Š Ž‡˜‡Ž ‘ˆ Š‡‘•‡Ž‡ –‹˜‹–› ™ƒ• ‘„•‡”˜‡†Ǥ ƒ‹‡• ‘–ƒ‹‹‰ •‡•‹–‹˜‡ ˆ— –‹‘ƒŽ ‰”‘—’• •— Š ƒ• ‡–‘‡•ǡ ƒŽ†‡Š›†‡• ƒ† ‹‹‡•™‡”‡‰‡‡”ƒ–‡†ǤŠ‡‡ƒ‹‡•™‡”‡‘–‹•‘Žƒ–‡†„—–—•‡†‹ •—„•‡“—‡– ƒ–ƒŽ›–‹  ”‡†— –‹˜‡ ˆ— –‹‘ƒŽ‹œƒ–‹‘ ‘ˆ ƒ‹†‡•ǡ ™Š‹ Š ‹• †‡• ”‹„‡† ‹ –Š‡ Žƒ•– ’ƒ”– ‘ˆ –Š‡ –Š‡•‹• ȋ Šƒ’–‡”• Ͷ Ȃ ͹ȌǤ Š‡ in situ ˆ‘”‡† ‡ƒ‹‡• ™‡”‡ ”‡ƒ –‡† ™‹–Š ƒ ™‹†‡ ˜ƒ”‹‡–› ‘ˆ ‡Ž‡ –”‘’Š‹Ž‡•ǡ ‰‡‡”ƒ–‹‰ Š‡–‡”‘ › Ž‹  ‘’‘—†• ƒ• –”‹ƒœ‘Ž‹‡•ǡ –”‹ƒœ‘Ž‡•ǡ ͶǡͷǦ†‹Š›†”‘‹•‘šƒœ‘Ž‡• ƒ† ’›”‹‹†‹‡†‹‘‡•Ǥ NǦ•—Žˆ‘›Žˆ‘”ƒ‹†‹‡• ƒ•™‡ŽŽƒ•–Š‹‘ƒ ”›Žƒ‹†‡• ‘—Ž†ƒŽ•‘„‡’”‡’ƒ”‡†™‹–Š–Š‹•ƒ’’”‘ƒ ŠǤ Š‡ ’”‘–‘ ‘Ž• ˆ‘” –Š‡ •›–Š‡•‹• ‘ˆ –”‹ƒœ‘Ž‹‡•ǡ –”‹ƒœ‘Ž‡• ƒ† NǦ•—Žˆ‘›Žˆ‘”ƒ‹†‹‡• ‘—Ž†ƒ††‹–‹‘ƒŽŽ›„‡’‡”ˆ‘”‡†‘ƒ’”‡’ƒ”ƒǦ –‹˜‡• ƒŽ‡ǡ•Š‘™‹‰–Š‡’”ƒ –‹ ƒŽ‹–›‘ˆ–Š‡‡–Š‘†‘Ž‘‰›Ǥ

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‡ Š¡” ƒ˜Šƒ†Ž‹‰‡ Šƒ†Žƒ” ‘ —–˜‡ Ž‹‰ ƒ˜ •›–‡•‡–‘†‡” ˆÚ” ‡‘•‡Ž‡–‹˜ ƒ‹†”‡†—–‹‘ •ƒ– Š—” †‡••ƒ ƒ ƒ˜¡†ƒ• ˆÚ” ‹Ž† ”‡†—–‹˜ ˆ—–‹‘ƒŽ‹•‡”‹‰Ǥ ‹†‡” ¡” †‡ ‡•– •–ƒ„‹Žƒ ƒ”„‘›ŽˆÚ”‡‹‰ƒ”ƒ˜‹Ž‡–‰Ú”†‡–•˜¤”–ƒ––•‡Ž‡–‹˜–”‡†— ‡”ƒ †‡ ‹ ¡”˜ƒ”‘ƒ˜ƒ†”ƒ‡””‡ƒ–‹˜ƒˆ—–‹‘‡ŽŽƒ‰”—’’‡”Ǥ––‡‘•‡Ž‡–‹˜– ”‡†— ‡”ƒ ƒ‹†‡” ÚŒŽ‹‰‰Ú” ˆÚ” ›ƒ •¡–– ƒ–– –‹ŽŽ˜‡”ƒ ‡‹ƒŽ‹‡”˜‹Ž‡– ƒŽ‡†ƒ–‹ŽŽ›ƒ‘—–ˆ‘”•ƒ†‡ˆÚ”‡‹‰ƒ”•ƒ–‘”–ƒ”‡•›–‡•˜¡‰ƒ”Ǥ ‡ ˆÚ”•–ƒ †‡Ž‡ ƒ˜ ƒ˜Šƒ†Ž‹‰‡ ȋƒ’‹–‡Ž ʹ ‘ Š ͵Ȍ „‡•”‹˜‡” —–˜‡ Ž‹‰‡ƒ˜–˜¤‡‘•‡Ž‡–‹˜ƒ‡–‘†‡”ˆÚ””‡†—–‹‘ƒ˜ƒ‹†‡”–‹ŽŽ ƒŽ†‡Š›†‡”ǡ ƒ‹‡” ‡ŽŽ‡” ‡ƒ‹‡”Ǥ ›•–‡‡ ¡” „ƒ•‡”ƒ†‡ ’¤ ƒ˜¡†ƒ†‡–ƒ˜‡ƒ–ƒŽ›–‹•¡‰†‘ȋȌ͸•‘–‹ŽŽ•ƒƒ•‡†‡ •‹Žƒ ‡šŽ—•‹˜– ”‡ƒ‰‡”ƒ” ‡† ƒ‹†‡” ‹ ¡”˜ƒ”‘ ƒ˜ ƒ†”ƒ ‡” Ž¡––”‡†— ‡”ƒ†‡ ˆ—–‹‘‡ŽŽƒ ‰”—’’‡”Ǥ ˜¡†„ƒ”Š‡–‡ ‘ Š ‡‘•‡Ž‡–‹˜‹–‡–‡ †‡‘•–”‡”ƒ†‡• ‹ ‡ › •›–‡•˜¡‰ ˆÚ” Ž¡‡‡†‡Ž‡– ‘‡’‡œ‹Ž †¡” ‡–‘†‡ ƒ˜¡†‡• ‹ •‹•–ƒ •–‡‰‡– ˆÚ” ƒ–– •‡Ž‡–‹˜–„‹Ž†ƒ ƒ‹‹¡”˜ƒ”‘ƒ˜‡‡””‡ƒ–‹˜‡–‘‰”—’’Ǥ ‡ ƒ†”ƒ †‡Ž‡ ƒ˜ ƒ˜Šƒ†Ž‹‰‡ ȋƒ’‹–‡Ž Ͷ Ȃ ͹Ȍ „‡•”‹˜‡” ƒ˜¡†ƒ†‡–ƒ˜‡‡–‘†ˆÚ”‹Ž†”‡†—–‹˜ˆ—–‹‘ƒŽ‹•‡”‹‰ƒ˜ƒ‹†‡”Ǥ ˜Šƒ†Ž‹‰‡„‡Šƒ†Žƒ”ˆ›”ƒ‘Ž‹ƒ•¡––•‘‹ŽŽ—•–”‡”ƒ”ƒ˜¡†ƒ†‡–ƒ˜ ‡ƒ‹‡” †‡‘”‡”ƒ†‡ ‡† Ž¡––”‡†— ‡”ƒ†‡ ˆ—–‹‘‡ŽŽƒ ‰”—’’‡” ‹ ”‡ƒ–‹‘‡”‡†‡¡‰†‘Ž‹ƒ‡Ž‡–”‘ˆ‹Ž‡”Ǥ¤”–„‹†”ƒ‰Šƒ”Ž‡–––‹ŽŽ‡–– „”‡†ƒ”‡„‹„Ž‹‘–‡ƒ˜ˆÚ”‡‹‰ƒ”•‘‡†ژ”‹‰ƒ‹†ƒ‰„‡ˆ‹–Ž‹‰ƒ‡–‘†‡” ƒ˜ƒ”ƒ› ‡–•˜¤”ƒƒ––ˆ”ƒ•–¡ŽŽƒǤ 

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Š‹•–Š‡•‹•‹•„ƒ•‡†‘–Š‡ˆ‘ŽŽ‘™‹‰’ƒ’‡”•ǡ™Š‹ Š™‹ŽŽ„‡”‡ˆ‡””‡†–‘„› –Š‡‹” ‘ƒ —‡”ƒŽ• ǦǤ ‡’”‹–• ™‡”‡ ƒ†‡ ™‹–Š –Š‡ ‹† ’‡”‹••‹‘ˆ”‘–Š‡’—„Ž‹•Š‡”•ǤŠ‡ ‘–”‹„—–‹‘„›–Š‡ƒ—–Š‘”–‘‡ƒ Š ’—„Ž‹ ƒ–‹‘‹• Žƒ”‹ˆ‹‡†‹’’‡†‹šǤ

I. Chemoselective Reduction of Tertiary Amides under Thermal Control: Formation of either Aldehydes or Amines ”‡†”‹ ‹‹•ǡȗ Ž‡š‡› ‘Ž‘˜ǡ ‘˜‡ Žƒ‰„”ƒ† ƒ† ƒ•†‘Žˆ••‘ȗ Angewandte Chemie International Editionǡ 2016ǡ 55ǡ Ͷͷ͸ʹǦͶͷ͸͸  II. Transformation of Amides into Highly Functionalized Triazolines ‘˜‡ Žƒ‰„”ƒ†ǡ Ž‡š‡› ‘Ž‘˜ǡ ƒœ ”‹ŽŽ‘ǡ ”‡†”‹ ‹‹•ȗ ƒ† ƒ•†‘Žˆ••‘ȗ ACSCatalysisǡ2017ǡ7ǡͳ͹͹ͳǦͳ͹͹ͷ  III. Mild Reductive Functionalization of Amides into NǦSulfonylformamidines ƒœ ”‹ŽŽ‘ǡ ‘˜‡ Žƒ‰„”ƒ†ǡ ”‡†”‹ ‹‹•ȗ ƒ† ƒ• †‘Žˆ••‘ȗ ChemistryOpenǡ2017ǡ6ǡͶͺͶǦͶͺ͹  IV. An Efficient OneǦpot Procedure for the Direct Preparationof4,5ǦDihydroisoxazolesfromAmides ‘˜‡ Žƒ‰„”ƒ†ǡ ƒ„”‹‡ŽŽƒ ‡”˜‡ˆ‘”•ǡ ”‡†”‹ ‹‹•ȗ ƒ† ƒ•†‘Žˆ••‘ȗ AdvancedSynthesisandCatalysisǡ2017ǡ359ǡͳͻͻͲǦͳͻͻͷ  V. Facile Preparation of Pyrimidinediones and Thioacrylamides by Reductive Functionalization of Amides ƒœ ”‹ŽŽ‘ǡᑽ ‘˜‡ Žƒ‰„”ƒ†ǡᑽ ”‡†”‹‹‹•ȗƒ† ƒ• †‘Žˆ••‘ȗ ChemicalCommunicationsǡ2017ǡ53ǡͻͳͷͻǦͻͳ͸ʹ  ᑽŠ‡•‡ƒ—–Š‘”• ‘–”‹„—–‡†‡“—ƒŽŽ›Ǥ 

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ChemoselectiveReductionofCarboxamides Ž‡š‡› ‘Ž‘˜ǡᑽ ”‡†”‹‹‹•ǡᑽǡȗ ‘˜‡ Žƒ‰„”ƒ†ǡ ƒœ ”‹ŽŽ‘ ƒ† ƒ•†‘Žˆ••‘ȗ ChemicalSocietyReviewsǡ2016ǡ45ǡ͸͸ͺͷǦ͸͸ͻ͹  ThirdǦGeneration Amino Acid FuranosideǦBased Ligands from ૌǦMannose for the Asymmetric Transfer Hydrogenation of Ketones:CatalystswithanExceptionallyWideSubstrateScope °••‹ ƒƒ”‰ƒŽ‡ˆǡ‘˜‡Žƒ‰„”ƒ†ǡ ”‡†”‹‹‹•ǡ ƒ•†‘Žˆ••‘ǡȗ ‘–•‡””ƒ–‹±‰—‡œȗƒ†• ƒ”‹‡•ȗ AdvancedSynthesis&Catalysisǡ2016ǡ358ǡͶͲͲ͸ǦͶͲͳͺ  Bimetallic Catalysis: Asymmetric Transfer Hydrogenation of Sterically Hindered Ketones Catalyzed by Ruthenium and Potassium ‘˜‡Žƒ‰„”ƒ†ǡ‘˜‡‹˜‹Œ¡”˜‹ƒ† ƒ•†‘Žˆ••‘ȗ ChemCatChemǡ2015ǡ7ǡ͵ͶͶͷǦ͵ͶͶͻ  Mo(CO)6 Catalysed Chemoselective Hydrosilylation of Ƚ,ȾǦUnsaturatedAmidesfortheFormationofAllylamines Ž‡š‡› ‘Ž‘˜ǡ ”‡†”‹ ‹‹•ǡȗ ‘˜‡ Žƒ‰„”ƒ†ǡ †ƒ ‡”•Šƒ‰‡ ƒ† ƒ•†‘Žˆ••‘ȗ ChemicalCommunicationsǡ2014ǡ50ǡͳͶͷͲͺǦͳͶͷͳͳ  RutheniumǦCatalyzed TandemǦIsomerization/Asymmetric TransǦ ferHydrogenationofAllylicAlcohols ‘˜‡Žƒ‰„”ƒ†ǡ ‡Ž‡ƒ—†„‡”‰ƒ† ƒ•†‘Žˆ••‘ȗ ChemistryǦAEuropeanJournalǡ2014ǡ20ǡͳ͸ͳͲʹǦͳ͸ͳͲ͸  Automated Annotation and Quantification of Metabolites in 1HNMRDataofBiologicalOrigin ”‹ Žǡ ‘˜‡ Žƒ‰„”ƒ†ǡ Ǥ ƒ‰—• %„‡”‰ǡ ”‹ ƒŠŽ•–”ڏǡ ‰‡Žƒ —•–ƒˆ••‘ƒ† ‘Šƒ‹†„‡”‰ AnalyticalandBioanalyticalChemistryǡ2012ǡ403ǡͶͶ͵ǦͶͷͷ            ᑽŠ‡•‡ƒ—–Š‘”• ‘–”‹„—–‡†‡“—ƒŽŽ›Ǥ 

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„•–”ƒ –ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤ˜‹‹ ‘’—Ž¡”˜‡–‡•ƒ’Ž‹‰ƒƒˆƒ––‹‰’¤˜‡•ƒǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤ˜‹‹‹ ‹•–‘ˆ—„Ž‹ ƒ–‹‘•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤ‹š ‘–‡–•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤš‹ „„”‡˜‹ƒ–‹‘•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤš‹‹‹ ͳǤ –”‘†— –‹‘ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤͳ ͳǤͳ‹†‡•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤͳ ͳǤʹ‡†— –‹‘‘ˆ‹†‡•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤʹ ͳǤʹǤͳ‘Ǧƒ–ƒŽ›–‹ ‡†— –‹‘‘ˆ‹†‡•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤ͵ ͳǤʹǤʹƒ–ƒŽ›–‹  ›†”‘‰‡ƒ–‹‘‘ˆ‹†‡•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤͶ ͳǤʹǤ͵ƒ–ƒŽ›–‹  ›†”‘•‹Ž›Žƒ–‹‘‘ˆ‹†‡•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤͷ ͳǤʹǤͶŠ‡‘•‡Ž‡ –‹˜‡‡†— –‹‘‘ˆ‹†‡•–‘‹‡•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤ͹ ͳǤʹǤͷŠ‡‘•‡Ž‡ –‹˜‡‡†— –‹‘‘ˆ‹†‡•–‘Ž†‡Š›†‡•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤͳͶ ͳǤ͵‡†— –‹˜‡ — –‹‘ƒŽ‹œƒ–‹‘‘ˆ‹†‡•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤͳ͸ ͳǤ͵ǤͳŽ‡ –”‘’Š‹Ž‹  –‹˜ƒ–‹‘‘ˆ‹†‡•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤͳ͹ ͳǤ͵Ǥʹ— Ž‡‘’Š‹Ž‹  –‹˜ƒ–‹‘‘ˆ‹†‡•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤͳͻ ͳǤͶ„Œ‡ –‹˜‡•‘ˆ–Š‡Š‡•‹•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤʹ͵ ʹǤŠ‡‘•‡Ž‡ –‹˜‡‡†— –‹‘‘ˆ‡”–‹ƒ”›‹†‡•—†‡”Š‡”ƒŽ‘–”‘Ž ȋƒ’‡” ȌǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤʹͷ ʹǤͳ‘’‡–‹–‹˜‡–—†›ȂŠ‡‘•‡Ž‡ –‹˜‹–›ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤ͵ͳ ʹǤʹ’’Ž‹ ƒ–‹‘•‘ˆ–Š‡‡†— –‹‘”‘–‘ ‘ŽǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤ͵ͳ ʹǤ͵‘ Ž—•‹‘•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤ͵ʹ

͵Ǥ‘ȋȌ͸Ǧƒ–ƒŽ›œ‡†ƒ‹‡ ‘”ƒ–‹‘ˆ”‘‹†‡•ȋƒ’‡”• ȂȌ ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤ͵͵ ͵Ǥͳ –”‘†— –‹‘ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤ͵͵ ͵Ǥʹ’–‹‹œƒ–‹‘ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤ͵͸ ͵Ǥ͵ ‘’‡ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤ͵͹ ͵ǤͶ‘ Ž—•‹‘•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤͶʹ

š‹  ͶǤ‡†— –‹˜‡ — –‹‘ƒŽ‹œƒ–‹‘‘ˆ‹†‡•‹–‘”‹ƒœ‘Ž‹‡•ƒ†”‹ƒœ‘Ž‡• ȋƒ’‡” ȌǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤͶ͵ ͶǤͳ –”‘†— –‹‘ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤͶ͵ ͶǤʹ‡•—Ž–•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤͶͷ ͶǤ͵‘ Ž—•‹‘•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤͷʹ ͷǤ ‡†— –‹˜‡ — –‹‘ƒŽ‹œƒ–‹‘ ‘ˆ ‹†‡• ‹–‘ NǦ—Žˆ‘›Žˆ‘”ƒ‹†‹‡• ȋƒ’‡” ȌǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤͷ͵ ͷǤͳ –”‘†— –‹‘ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤͷ͵ ͷǤʹ‡•—Ž–•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤͷͶ ͷǤ͵‘ Ž—•‹‘•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤͷͻ ͸Ǥ ‡†— –‹˜‡ — –‹‘ƒŽ‹œƒ–‹‘ ‘ˆ ‹†‡• ‹–‘ ͶǡͷǦ‹Š›†”‘‹•‘šƒœ‘Ž‡• ȋƒ’‡” ȌǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤ͸ͳ ͸Ǥͳ –”‘†— –‹‘ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤ͸ͳ ͸Ǥʹ‡•—Ž–•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤ͸͵ ͸Ǥ͵‘ Ž—•‹‘•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤ͸͸ ͹Ǥ ‡†— –‹˜‡ — –‹‘ƒŽ‹œƒ–‹‘ ‘ˆ ‹†‡• ‹–‘ ›”‹‹†‹‡†‹‘‡• ƒ† Š‹‘ƒ ”›Žƒ‹†‡•ȋƒ’‡”ȌǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤ͸͹ ͹Ǥͳ –”‘†— –‹‘ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤ͸͹ ͹Ǥʹ‡•—Ž–•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤ͸ͺ ͹Ǥ͵‘ Ž—•‹‘•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤ͹Ͷ ‘ Ž—†‹‰‡ƒ”•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤ͹ͷ ’’‡†‹šǣ‘–”‹„—–‹‘‹•–ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤ͹͸ ’’‡†‹šǣ‡’”‹–‡”‹••‹‘•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤ͹͹  ‘™Ž‡†‰‡‡–•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤ͹ͺ ‡ˆ‡”‡ ‡•ǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤǤͺͳ 

š‹‹  Abbreviations

„„”‡˜‹ƒ–‹‘•ƒ†ƒ ”‘›•ƒ”‡—•‡†‹ƒ‰”‡‡‡–™‹–Š–Š‡•–ƒ†ƒ”†‘ˆ –Š‡ •—„Œ‡ –Ǥͳ Ž› ‘•–ƒ†ƒ”† ƒ† — ‘˜‡–‹‘ƒŽ ƒ„„”‡˜‹ƒ–‹‘• –Šƒ– ƒ’’‡ƒ”‹–Š‡–Š‡•‹•ƒ”‡Ž‹•–‡†Š‡”‡Ǥ

 ͳǡʹǦ„‹•ȋ†‹‡–Š›Ž•‹Ž›ŽȌ„‡œ‡‡   ʹǡʹ̵Ǧ„‹•ȋ†‹’Š‡›Ž’Š‘•’Š‹‘ȌǦͳǡͳ̵Ǧ„‹ƒ’Š–Š›Ž ‘† ͳǡͷǦ › Ž‘‘ –ƒ†‹‡‡ ‘‡ › Ž‘‘ –‡‡ †„ƒ †‹„‡œ›Ž‹†‡‡ƒ ‡–‘‡ †’’’ ͳǡ͵Ǧ„‹•ȋ†‹’Š‡›Ž’Š‘•’Š‹‘Ȍ’”‘’ƒ‡ ee ‡ƒ–‹‘‡”‹ ‡š ‡•• ʹǦ ›” ʹǦˆŽ—‘”‘’›”‹†‹‡   ƒ–œ• Š‡•–‡”ǡ†‹‡–Š›ŽͳǡͶǦ†‹Š›†”‘Ǧʹǡ͸Ǧ†‹‡–Š›ŽǦ ͵ǡͷǦ’›”‹†‹‡†‹ ƒ”„‘š›Žƒ–‡ ʹǦ ›” ʹǦ‹‘†‘’›”‹†‹‡   Ž‹–Š‹—†‹‹•‘„—–›ŽǦ‹•‘Ǧ’”‘’‘š›ƒŽ—‹—Š›†”‹†‡ ʹǦ‡›” ʹǦ‡–Š‘š›’›”‹†‹‡ ʹǦ‡Ǧ ʹǦ‡–Š›Ž–‡–”ƒŠ›†”‘ˆ—”ƒ ƒ’Š‘• ʹǡʹǯǦ„‹•ȋ†‹’Š‡›Ž’Š‘•’Šƒ›Ž‡–Š›ŽȌǦͳǡͳǯǦ„‹ƒ’Š–Š›Ž ƒ  •‘†‹—„‹•ȋ–”‹‡–Š›Ž•‹Ž›ŽȌƒ‹†‡   ’‘Ž›ȋ‡–Š›ŽŠ›†”‘•‹Ž‘šƒ‡Ȍ  ’›”‹†‹‹—pǦ–‘Ž—‡‡•—Žˆ‘ƒ–‡  ͳǡͳǡ͵ǡ͵Ǧ–‡–”ƒ‡–Š›Ž†‹•‹Ž‘šƒ‡ ”‹’Š‘• „‹•ȋ†‹’Š‡›Ž’Š‘•’Š‹‘‡–Š›ŽȌ’Š‡›Ž’Š‘•’Š‹‡

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1.Introduction

‘†ƒ›ǯ••‘ ‹‡–›‹•‹‡‡†‘ˆ‡™–‡ Š‘Ž‘‰‹‡•ƒ†‡™ Š‡‹ ƒŽ–”ƒ•Ǧ ˆ‘”ƒ–‹‘• ‹ ‘”†‡” –‘ ˆ‘” ƒ •—•–ƒ‹ƒ„Ž‡ ‡˜‹”‘‡–Ǥ Š‡‹•–• ƒ”‘—†–Š‡‰Ž‘„‡‹•‹’—”•—‹–‘ˆƒ‹‰–Š‡™‘”Ž†ƒ‹’”‘˜‡†’Žƒ ‡Ǣ–‘ ’”‘˜‹†‡‡••‡–‹ƒŽ ‘’‘—†••— Šƒ•’Šƒ”ƒ ‡—–‹ ƒŽ•ǡˆ—‡Ž•ǡˆ‘‘†ǡƒ††‹Ǧ –‹˜‡•ƒ†‘–Š‡”‘˜‡Ž ‘’‘—†•Ǥ –‹•‹’‘”–ƒ––‘†‡Ž‹˜‡”–Š‡•‡ Š‡‹Ǧ ƒŽ•—„•–ƒ ‡•‹ƒ‡˜‹”‘‡–ƒŽŽ›„‡‹‰™ƒ›„›ƒ‹‰–Š‡•›–Š‡Ǧ •‹•‘”‡•—•–ƒ‹ƒ„Ž‡Ǥ ‰‡‡”ƒŽǡ–Š‡—•‡‘ˆ ƒ–ƒŽ›•–•‡ƒ„Ž‡•‹Ž†‡””‡Ǧ ƒ –‹‘ ‘†‹–‹‘• ƒ† ƒ †”ƒƒ–‹ ƒŽŽ› ‹’”‘˜‡ –Š‡ ƒ–‘ ‡ ‘‘›‘ˆ –Š‡ –”ƒ•ˆ‘”ƒ–‹‘•Ǥ ‘ †‡ ”‡ƒ•‡ –Š‡ ƒ‘—– ‘ˆ ™ƒ•–‡ǡ –Š‡ —„‡” ‘ˆ ”‡ƒ –‹‘•–‡’•ƒ†’—”‹ˆ‹ ƒ–‹‘••Š‘—Ž†„‡‹‹‹œ‡†ƒ†–Š‡†‡˜‡Ž‘’Ǧ ‡–‘ˆ‡™‘‡Ǧ’‘–”‡ƒ –‹‘•‹•‘ˆŠ‹‰Š‹–‡”‡•–Ǥʹ‡Ǧ’‘–”‡ƒ –‹‘• ƒ ‰‹˜‡ƒ ‡••–‘‘˜‡Ž™ƒ›•‘ˆ ‘•–”— –‹‰ ‘’‘—†•™‹–Š—‹“—‡ ‘Ǧ ’Ž‡š‹–›–Šƒ– ‘—Ž†„‡—ƒ––ƒ‹ƒ„Ž‡–Š”‘—‰Š•–‡’Ǧ™‹•‡”‡ƒ –‹‘•ƒ†‹•‘Ǧ Žƒ–‹‘•Ǥ

1.1Amides

ƒ”„‘šƒ‹†‡• ‹• ƒ ‹’‘”–ƒ– Žƒ•• ‘ˆ ‘’‘—†• –Šƒ– ƒ”‡ ‘‘ ‘–‹ˆ•‹’Šƒ”ƒ ‡—–‹ ƒŽ•ǡ’‘Ž›‡”•ƒ†ƒ‰”‘ Š‡‹ ƒŽ•Ǥ͵ǡͶǡͷ Š‡ ƒ‹†‡ ˆ— –‹‘ƒŽ‹–›‹•ƒŽ•‘‘™ƒ•–Š‡’‡’–‹†‡„‘†ƒ† ‘•–‹–—–‡•–Š‡Ž‹Ǧ ƒ‰‡„‡–™‡‡ƒ‹‘ƒ ‹†•–Šƒ–ƒ‡•—’–Š‡„ƒ „‘‡‘ˆƒŽŽ’”‘–‡‹•ƒ† ‡œ›‡•‹ƒ–—”‡Ǥ Šƒ”ƒ –‡”‹•–‹ ’”‘’‡”–›‘ˆƒ‹†‡•‹•–Š‡‹Š‡”‡– •–ƒ„‹Ž‹–› –Šƒ– ƒ”‹•‡• ˆ”‘ –Š‡ ”‡•‘ƒ ‡ •–ƒ„‹Ž‹œƒ–‹‘ ‘ˆ –Š‡ Ȃ „‘†ǡ ™Š‹ Š‹•‘ˆ’ƒ”–‹ƒŽ†‘—„Ž‡„‘† Šƒ”ƒ –‡”ȋ ‹‰—”‡ͳȌǤ͸ǡ͹Š‡†‡Ž‘ ƒŽ‹œƒǦ –‹‘‘ˆ–Š‡‡Ž‡ –”‘•‹†— ‡•ƒ’Žƒƒ”‹–›‘ˆ–Š‡ƒ‹†‡„‘†ƒ††‡ ”‡ƒ•Ǧ ‡•–Š‡‡Ž‡ –”‘’Š‹Ž‹ ‹–›‘ˆ–Š‡ ƒ”„‘›Ž ƒ”„‘ǡƒ‹‰‹–Ž‡•••—• ‡’–‹„Ž‡ ˆ‘”— Ž‡‘’Š‹Ž‹ ƒ––ƒ Ǥ 

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 Figure1.a)Theresonancestabilizationbythenitrogenlonepair,theoriginof thestability.b)Theorbitaloverlapthatcontributestotheplanarconformation oftheamides.c)Orderofstabilityfordifferentcarbonylcompounds.

Š‡•–ƒ„‹Ž‹–›‘ˆ–Š‡ƒ‹†‡‹ ‘„‹ƒ–‹‘™‹–Š–Š‡’‘‘”‡Ž‡ –”‘’Š‹Ž‹ ‹–› ƒ‡• –Š‹• ‘‹‡–› –Š‡ Ž‡ƒ•– ”‡ƒ –‹˜‡ ƒ‘‰ –Š‡ ƒ”„‘›Ž ‘’‘—†•Ǥ —‡–‘Ž‘™‡””‡ƒ –‹˜‹–›ǡŠƒ”•Š”‡ƒ‰‡–•ƒ”‡‰‡‡”ƒŽŽ›”‡“—‹”‡†ˆ‘”–Š‡‹” –”ƒ•ˆ‘”ƒ–‹‘ǡ ”‡•—Ž–‹‰ ‹ Ž‡•• ‡š’Ž‘”ƒ–‹‘ ‘ˆ –Š‡‹” —•‡ ƒ• •›–Š‡–‹  ‹–‡”‡†‹ƒ–‡•Ǥͺ‘‘˜‡” ‘‡–Š‡’‘‘””‡ƒ –‹˜‹–›‹–‹•’‘••‹„Ž‡–‘ˆ‘” ‡ •–‡”‹ „—Ž‘–‘–Š‡NǦ•—„•–‹–—‡–•ǡ”‡•—Ž–‹‰‹ƒ‘Ǧ’Žƒƒ”•–”— –—”‡ ‘ˆ–Š‡ƒ‹†‡ǡƒ‹‰‹–Ž‡•••–ƒ„‹Ž‹œ‡†Ǥ͵Ž‘›†Ǧ ‘‡•ƒ†‘‘‡”Ǧ‹Ž„—” —•‡†–Š‹•ƒ’’”‘ƒ Š–‘†‡˜‡Ž‘’ƒ‹Ž†ƒ‹†‡•—„•–‹–—–‹‘’”‘ ‡†—”‡‘ ‘ˆ‘”ƒ–‹‘ƒŽŽ›–™‹•–‡†ƒ‹†‡•ȋ Š‡‡ͳȌǤͻ

 Scheme1.SubstitutionreactionofnonǦplanaramidewithmethanol.

1.2ReductionofAmides

—‡–‘–Š‡•–ƒ„‹Ž‹–›‘ˆƒ‹†‡•–Š‹•ˆ— –‹‘ƒŽ‹–›‹•–Š‡‘•–†‹ˆˆ‹ —Ž––‘ ”‡†— ‡ƒ‘‰–Š‡ ƒ”„‘›Ž‰”‘—’•ǤŠ‡”‡†— –‹‘‰‹˜‡•ƒ ‡••–‘ƒ˜ƒ”‹Ǧ ‡–› ‘ˆ ˜ƒŽ—ƒ„Ž‡ ‘’‘—†•ǡ •— Š ƒ• ƒ‹‡•ǡͳͲ ƒŽ ‘Š‘Ž•ǡͳͳ ƒŽ†‡Š›†‡•ǡͳʹ †‡ƒ ›Žƒ–‡†ƒ‹‡•ͳ͵ƒ†‡ƒ‹‡•ͳͶȋ Š‡‡ʹȌǤ‹†‡”‡†— –‹‘•ƒ”‡ ‘•– ‘‘Ž›’‡”ˆ‘”‡†„›–Š‡—•‡‘ˆŠ›†”‹†‡”‡ƒ‰‡–•ǡŠ›†”‘‰‡ƒǦ –‹‘‘”Š›†”‘•‹Ž›Žƒ–‹‘Ǥ

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 Scheme2.Differentproductsformedinthereductionofamidesthrough(a)C–O and(b)C–Nbondcleavage.c)Amidereductionintoenamine.

1.2.1NonǦCatalyticReductionofAmides

Š‡‹– ‘‡•–‘Š›†”‹†‡”‡ƒ‰‡–•ǡŽ‹–Š‹—ƒŽ—‹—Š›†”‹†‡ȋ Ȍ‹• ‘™ –‘ ”‡†— ‡ ƒ ™‹†‡ ”ƒ‰‡ ‘ˆ ˆ— –‹‘ƒŽ ‰”‘—’•ǡ ‹ Ž—†‹‰ ƒ‹†‡• ‹–‘ƒ‹‡•Ǥͳͷǡͳ͸Š‹•”‡ƒ‰‡–‹• ‘‡ –‡†™‹–ŠŠƒœƒ”†•ƒ†”‡ƒ –•˜‹‘Ǧ Ž‡–Ž› ™‹–Š „‘–Š ‘‹•–—”‡ ƒ† ƒ‹”Ǥͳ͹ —”–Š‡”‘”‡ǡ –Š‡ ˆ‘”‡† „›’”‘†Ǧ — –• ƒ„‡†‹ˆˆ‹ —Ž––‘•‡’ƒ”ƒ–‡ˆ”‘–Š‡†‡•‹”‡†’”‘†— –Ǥ‡•’‹–‡–Š‡ †”ƒ™„ƒ • ƒ••‘ ‹ƒ–‡† ™‹–Š  ǡ ‹– ‹• •–‹ŽŽ ˆ”‡“—‡–Ž› —•‡† ™‹–Š‹ ƒ ƒǦ †‡‹ƒƒ•™‡ŽŽƒ•‹‹†—•–”›Ǥͳͺ‹Ž†‡””‡†— ‹‰ƒ‰‡–‹••‘†‹—„‘”‘Ǧ Š›†”‹†‡ ȋƒ ͶȌǡ™Š‹ Š‡‡†•–‘„‡ˆ—”–Š‡”ƒ –‹˜ƒ–‡†„›ƒƒ††‹–‹˜‡ǡ •— Šƒ•ƒ ‡–‹ ƒ ‹†ǡͳͻ–”ƒ•‹–‹‘‡–ƒŽ•ʹͲǡʹͳ‘”‡™‹•ƒ ‹†•ʹͲǡʹʹ–‘”‡†— ‡ ƒ‹†‡•Ǥ ‰‡‡”ƒŽǡŠ›†”‹†‡”‡ƒ‰‡–•ƒ”‡‘– Š‡‘•‡Ž‡ –‹˜‡ƒ†ƒ™‹†‡ ”ƒ‰‡‘ˆˆ— –‹‘ƒŽ‰”‘—’•ƒ”‡‘––‘Ž‡”ƒ–‡†Ǥ  ‡˜‡”–Š‡Ž‡••ǡ–Š‡”‡ƒ”‡‡šƒ’Ž‡•‘ˆ‹Ž†”‡†— ‹‰ƒ‰‡–•ǡ•— Šƒ• „‘”ƒ‡•ȋ ͵ǡ‡– ǤȌǡ™Š‡”‡‡•–‡”ƒ†‹–”‘‘‹‡–‹‡•ƒ”‡–‘Ž‡”ƒ–‡†‹–Š‡ ”‡†— –‹‘‘ˆƒ‹†‡•‹–‘ƒ‹‡•Ǥʹ͵ǡʹͶˆ‘”–—ƒ–‡Ž›ǡ–Š‹•”‡ƒ‰‡–‹•‰ƒ•‡Ǧ ‘—•ƒ–”‘‘–‡’‡”ƒ–—”‡ǡƒ‹‰‹–†‹ˆˆ‹ —Ž––‘Šƒ†Ž‡ƒ†‹•–Š‡”‡ˆ‘”‡ ‘‡” ‹ƒŽŽ› ƒ˜ƒ‹Žƒ„Ž‡ ƒ• –Š‡ –‡–”ƒŠ›†”‘ˆ—”ƒ ȋ Ȍ ƒ† †‹‡–Š›ŽǦ •—Žˆ‹†‡ ƒ††— –• ȋ ͵ȉ ƒ† ͵ȉ‡ʹȌǤ  ƒ††‹–‹‘ǡ ‡–Š‘†• Šƒ˜‡ „‡‡†‡˜‡Ž‘’‡†–‘‰‡‡”ƒ–‡†‹ˆˆ‡”‡–„‘”ƒ‡Ǧ–›’‡”‡ƒ‰‡–•insituˆ”‘ †‹ˆˆ‡”‡–„‘”ƒ‡”‡ƒ‰‡–•‡’Ž‘›‹‰‡–ƒŽ„‘”‘Š›†”‹†‡•‹ ‘„‹ƒǦ –‹‘™‹–Š‹‘†‹‡ǡ–”‹‡–Š›Ž•‹Ž›Ž ŠŽ‘”‹†‡ǡƒŽ›Ž•‡Ž‡‹†‡•‘”‡–Šƒ‡•—ŽǦ ʹͷ ˆ‘‹ ƒ ‹†Ǥ ”‹ˆŽ‹ ƒŠ›†”‹†‡ȋˆʹȌŠƒ•„‡‡—•‡†ˆ‘”‹Ž†ƒ‹†‡ƒ –‹Ǧ ˜ƒ–‹‘ ƒ† ‡ƒ„Ž‡† Š‡‘•‡Ž‡ –‹˜‡ ”‡†— –‹‘ǡ ™Š‹ Š ‹• ˆ—”–Š‡” †‹•Ǧ —••‡†‹•‡ –‹‘ͳǤʹǤͶ Š‡•‡Ž‡ –‹˜‡”‡†— –‹‘‘ˆƒ‹†‡•‹–‘ƒŽ†‡Š›†‡• ƒ„‡ƒ Š‹‡˜‡† „›‡’Ž‘›‹‰ƒŽ›ŽǦ‘”ƒŽ‘š›Ǧ•—„•–‹–—–‡†ƒŽ—‹—Š›†”‹†‡”‡ƒ‰‡–•Ǥ ‹‹•‘„—–›Ž ƒŽ—‹— Š›†”‹†‡ ȋ Ǧ Ȍǡʹ͸ Ž‹–Š‹— †‹‹•‘„—–›ŽǦ‹•‘Ǧ

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’”‘’‘š› ƒŽ—‹— Š›†”‹†‡ ȋ Ȍǡʹ͹†‹Ǧƒ†–”‹‡–Š‘š›ƒŽ—‹— Š›†”‹†‡•ʹͺ ƒƒŽ•‘„‡—•‡†ˆ‘”–Š‡•‡Ž‡ –‹˜‡”‡†— –‹‘‘ˆ–‡”–‹ƒ”›ƒ‹†‡• ‹–‘ƒŽ†‡Š›†‡•Ǥ ‘–Š‡”‡–Š‘†–‘ˆ‘”ƒŽ†‡Š›†‡•ˆ”‘ƒ‹†‡•‹•„›”‡†— ‹‰ NǦ‡–Š‘š›ǦNǦ‡–Š›Žƒ‹†‡•ȋ‡‹”‡„ƒ‹†‡•Ȍǡ™Š‹ Š„‡•‹†‡•ˆ‘”‹‰ ƒ •–ƒ„Ž‡ ˆ‹˜‡Ǧ‡„‡”‡† ‹–‡”‡†‹ƒ–‡ Šƒ• ƒ „‡––‡” Ž‡ƒ˜‹‰ ‰”‘—’ǤŠ‡ –‡–”ƒŠ‡†”ƒŽ‹–‡”‡†‹ƒ–‡ ‘ŽŽƒ’•‡•‹–‘–Š‡ƒŽ†‡Š›†‡•’‡ ‹‡•ˆ‹”•–—’‘ ™‘”Ǧ—’ǤʹͻŠ‹•™ƒ•†‡‘•–”ƒ–‡†„›–Š‡ƒ‹•Š‡ˆ•›‰”‘—’™Š‡”‡ƒ ‡‹”‡„ ƒ‹†‡ ™ƒ• ”‡†— ‡† –‘ –Š‡ ‘””‡•’‘†‹‰ ƒŽ†‡Š›†‡• —•‹‰ ͵Ͳ  Ǧ Ǥ ‘”‡‘˜‡”ǡ–Š‡—•‡‘ˆ Š™ƒ”–œ”‡ƒ‰‡–ȋ”’ʹ ŽȌƒ†ˆʹ ƒŽŽ‘™•ˆ‘”ƒ –‹˜ƒ–‹‘‘ˆƒ‹†‡•ƒ†Šƒ•„‡‡—•‡†–‘ Š‡‘•‡Ž‡ –‹˜‡Ž› ‘˜‡”–ƒ‹†‡•‹–‘ƒŽ†‡Š›†‡•ǡƒ†‹•ˆ—”–Š‡”†‹• —••‡†‹•‡ –‹‘ͳǤʹǤͷǤ

1.2.2CatalyticHydrogenationofAmides

ƒ–ƒŽ›–‹  Š›†”‘‰‡ƒ–‹‘ ‘ˆ ƒ‹†‡• ‡’Ž‘›‹‰ Š›†”‘‰‡ ‰ƒ• ƒ• –Š‡”‡Ǧ †— –ƒ–‹•‹–Š‡‘”›„‘–Šƒƒ–‘‡ ‘‘‹ ƒŽƒ•™‡ŽŽƒ•‡˜‹”‘‡–ƒŽǦ Ž› ˆ”‹‡†Ž› ’”‘ ‡•• ƒ† ‹†‡ƒŽŽ› ‘Ž› ™ƒ–‡” ‹• ˆ‘”‡† ƒ• „›’”‘†— –Ǥ͵ͳǡ͵ʹ ˆ‘”–—ƒ–‡Ž›ǡŠ›†”‘‰‡ƒ–‹‘‘ˆƒ‹†‡•”‡“—‹”‡•Šƒ”•Š”‡ƒ –‹‘ ‘†‹Ǧ –‹‘•ǡ‹‰‡‡”ƒŽȋŠ‹‰Š–‡’‡”ƒ–—”‡ǡŠ‹‰Š’”‡••—”‡ǡŽ‘‰”‡ƒ –‹‘–‹‡•Ȍǡ ƒ†–Š‡’”‘–‘ ‘Ž•‘ˆ–‡•—ˆˆ‡”ˆ”‘Ž‘™ˆ— –‹‘ƒŽ‰”‘—’–‘Ž‡”ƒ ‡Ǥ͵͵  –Š‡ ƒ•‡ ‘ˆ ƒ‹†‡ ”‡†— –‹‘ǡ Ȃ „‘† Ž‡ƒ˜ƒ‰‡ ƒ ‘ —”ǡ ‰‹˜‹‰ –Š‡ †‡ƒ ›Žƒ–‡†ƒ‹‡ƒ••‹†‡’”‘†— –ȋ Š‡‡ʹȌǤ͵Ͷ‡‡šƒ’Ž‡‘ˆƒ Š‡‘•‡Ž‡ –‹˜‡ƒ‹†‡Š›†”‘‰‡ƒ–‹‘‹•–Š‡”—–Š‡‹—Ǧ ƒ–ƒŽ›œ‡†”‡†— Ǧ –‹‘‘ˆƒ‹†‡•†‡˜‡Ž‘’‡†„›—ƒetal.ȋ Š‡‡͵ȌǤ͵ͷ ‡”‡ǡƒ ‘„‹ƒǦ –‹‘‘ˆ–™‘ ƒ–ƒŽ›•–•™ƒ•—•‡†Ǣƒ‡™‹•ƒ ‹†–‘ƒ –‹˜ƒ–‡–Š‡ •‡ ‘†ƒ”› ƒ‹†‡•ƒ†ƒ”—–Š‡‹— ‘’Ž‡šˆ‘”–Š‡Š›†”‘‰‡ƒ–‹‘‘ˆ–Š‡•‡ƒ –‹Ǧ ˜ƒ–‡† ƒ††— –•Ǥ ‹˜‡ †‹ˆˆ‡”‡– ƒ‹‡• ‘–ƒ‹‹‰ ‡•–‡” ˆ— –‹‘ƒŽ‹–‹‡• ™‡”‡‘„–ƒ‹‡†‹Š‹‰Š–‘‡š ‡ŽŽ‡–›‹‡Ž†•—•‹‰–Š‹•’”‘–‘ ‘ŽǤ

 Scheme 3. Chemoselective hydrogenation of a secondary amide containing an estermoiety.

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1.2.3CatalyticHydrosilylationofAmides

›†”‘•‹Ž›Žƒ–‹‘‹•ƒ™‡ŽŽǦ‡•–ƒ„Ž‹•Š‡†”‡†— –‹‘‡–Š‘†‘Ž‘‰›™Š‡”‡–Š‡ ‹Ȃ „‘†‹•ƒ††‡†ƒ ”‘••ƒ—•ƒ–—”ƒ–‹‘Ǥ͵͵ǡ͵͸ –Š‹• ƒ•‡Š›†”‘•‹Žƒ‡• ƒ”‡—•‡†ƒ•Š›†”‹†‡†‘‘”•ǡ™Š‹ Š‘”ƒŽŽ›‹•ƒ•ƒˆ‡”ƒŽ–‡”ƒ–‹˜‡–Šƒǡ ˆ‘”‹•–ƒ ‡ǡ–Š‡—•‡‘ˆŠ›†”‹†‡”‡ƒ‰‡–•Ǥ‘”‡‘˜‡”ǡ–Š‡—•‡‘ˆ•‹Žƒ‡• ‰‡‡”ƒŽŽ› ƒŽŽ‘™• ˆ‘” ‹Ž† ”‡ƒ –‹‘ ‘†‹–‹‘• ƒ† ‹• –Š‡”‡ˆ‘”‡ —•‡† ‹ Š‡‘•‡Ž‡ –‹˜‡ ƒ‹†‡ ”‡†— –‹‘•Ǥ  ˜ƒ”‹‡–› ‘ˆ †‹ˆˆ‡”‡– ‘‡” ‹ƒŽŽ› ƒ˜ƒ‹Žƒ„Ž‡•‹Žƒ‡••— Šƒ•Šʹ‹ ʹǡŠ‹ ͵ǡͳǡʹǦ„‹•ȋ†‹‡–Š›Ž•‹Ž›ŽȌ„‡œ‡‡ ȋȌǡ ȋ‡Ȍ͵‹ ǡ ȋ–Ȍʹ‡‹ ǡ –͵‹ ǡ ͳǡͳǡ͵ǡ͵Ǧ–‡–”ƒ‡–Š›Ž†‹•‹Ž‘šƒ‡ ȋȌǡƒ†’‘Ž›ȋ‡–Š›ŽŠ›†”‘•‹Ž‘šƒ‡Ȍȋ Ȍƒ”‡ˆ”‡“—‡Ž›—•‡†‹ Š›†”‘•‹Ž›Žƒ–‹‘•ȋ ‹‰—”‡ʹȌǤŠ‡‹Ȃ „‘†‹•™‡ƒŽ›Š›†”‹†‹ ǡƒ††—‡ –‘–Š‡ ‘’”‘‹•‡†”‡ƒ –‹˜‹–›‘•–‘ˆ–Š‡•‹Žƒ‡•”‡“—‹”‡ƒ –‹˜ƒ–‹‘„› ‡‹–Š‡”ƒ ƒ–ƒŽ›•–‘”ƒ”‡ƒ‰‡–‹‘”†‡”–‘„‡—•‡†‹”‡†— –‹‘•Ǥ͵͵ ‘™Ǧ ‡˜‡”ǡ–Š‹•ˆ‡ƒ–—”‡ƒ‡•–Š‡Š›†”‘•‹Žƒ‡Ǧ„ƒ•‡†”‡†— –ƒ–•‘”‡•‡Ž‡ Ǧ –‹˜‡‹ ‘’ƒ”‹•‘–‘–”ƒ†‹–‹‘ƒŽŠ›†”‹†‡”‡ƒ‰‡–•ǡ•— Šƒ•‹Ž Ͷǡ„‘Ǧ ͵͹ ”ƒ‡ǡ Ǧ ƒ†ƒ ͶǤ  —”–Š‡”‘”‡ǡ–Š‡‡Ž‡ –”‘‹ ’”‘’‡”–‹‡•ƒ† •–‡”‹ •‘ˆ–Š‡•‹Žƒ‡ ƒ‡ƒ•‹Ž›„‡‘†‹ˆ‹‡†„› Šƒ‰‹‰–Š‡•—„•–‹–—‡– ‘–Š‡•‹Ž‹ ‘ǡ–Š—•ƒˆˆ‡ –‹‰–Š‡”‡ƒ –‹˜‹–›ƒ†•‡Ž‡ –‹˜‹–›Ǥ ‘”‹•–ƒ ‡ǡ ƒŽ‘š›•‹Žƒ‡•ǡ•— Šƒ•ȋ–Ȍ͵‹ ǡƒ”‡ƒ••‘ ‹ƒ–‡†™‹–Š–Š‡’‘–‡–‹ƒŽˆ‘”Ǧ ͵ͺ ƒ–‹‘‘ˆ‘‘•‹Žƒ‡ǡ‹ Ͷǡ™Š‹ Š‹•ƒ’›”‘’Š‘”‹ ƒ†‡š’Ž‘•‹˜‡‰ƒ•Ǥ  –Š‡‘–Š‡”Šƒ†ǡ‹••–ƒ„Ž‡–‘‘‹•–—”‡ǡƒ‹”ƒ†Š‡ƒ–ƒ–‡—–”ƒŽ ’ ǡ‹–‹•ƒŽ•‘‹‡š’‡•‹˜‡ƒ† ‘•‹†‡”‡†•—‹–ƒ„Ž‡ˆ‘”• ƒŽ‡Ǧ—’Ǥ͵͹  –‡”• ‘ˆ ‘•– –Š‡”‡ ‹• ‘Ž› ‘‡ Š›†”‘•‹Žƒ‡ –Šƒ– ”‹˜ƒŽ• ǡ ƒ‡Ž›  ǡ™Š‹ Š‹•ˆ‘”‡†ƒ•ƒ•‹†‡’”‘†— –‹–Š‡•‹Ž‹ ‘‡‹†—•–”›Ǥ͵ͻ

 Figure2.StructuresofafewcommerciallyavailablesilanesusedinhydrosilylaǦ tions.

Š‡ Š‘‹ ‡‘ˆƒ –‹˜ƒ–‘”‘”‡–ƒŽ ƒ–ƒŽ›•–ˆ‘”Š›†”‘•‹Ž›Žƒ–‹‘”‡ƒ –‹‘•‹• –‘ƒ‰”‡ƒ–‡š–‡–ƒˆˆ‡ –‹‰–Š‡”‡•—Ž–‹‰ Š‡‘•‡Ž‡ –‹˜‹–›Ǥ —”–Š‡”‘”‡ǡ Š›†”‘•‹Ž›Žƒ–‹‘‘ˆƒ‹†‡•‹•Š‹‰ŠŽ›‹ˆŽ—‡ ‡†„›–Š‡•—„•–‹–—–‹‘‘–Š‡ ƒ‹†‡Ǧ‹–”‘‰‡Ǥ ‡ ‡ǡ –‡”–‹ƒ”› ƒ‹†‡• ƒ”‡ ‘•– ”‡ƒ –‹˜‡ ˆ‘ŽŽ‘™‡† „› •‡ ‘†ƒ”›ƒ‹†‡•ǡ™Š‡”‡ƒ•’”‹ƒ”›ƒ‹†‡•ƒ”‡Ž‡••’”‘‡–‘—†‡”‰‘ ”‡†— –‹‘Ǥ͵͹ – Šƒ• „‡‡ †‡‘•–”ƒ–‡† –Šƒ– –Š‡ •Ž‹‰Š–Ž› ƒ ‹†‹  ’”‘–‘• •‹–—ƒ–‡†‘–Š‡‹–”‘‰‡ƒ–‘ƒˆˆ‡ ––Š‡”‡ƒ –‹‘ƒ†–Š—•‘”‡Šƒ”•Š ‘†‹–‹‘•ƒ”‡”‡“—‹”‡†ǡ™Š‹ Š—Ž–‹ƒ–‡Ž›ƒˆˆ‡ –•–Š‡ Š‡‘•‡Ž‡ –‹˜‹–›‘ˆ –Š‡”‡†— –‹‘Ǥ 

ͷ  

›†”‘•‹Ž›Žƒ–‹‘‘ˆƒ‹†‡•‹•ƒ‡š’ƒ†‹‰ƒ”‡ƒ‘ˆ”‡•‡ƒ” Šƒ†•‡˜‡”ƒŽ ‰”‘—’•Šƒ˜‡†‡˜‡Ž‘’‡†’”‘–‘ ‘Ž•„ƒ•‡†‘’Žƒ–‹—Ǧ‰”‘—’‡–ƒŽ•ǡͶͲƒ• ™‡ŽŽ ƒ• ‹”‘ǡͶͳœ‹ ǡͶʹ‰‘Ž†ǡͶ͵ ‘„ƒŽ–ǡͶͶ‹†‹—ǡͶͷƒ‰‡•‹—Ͷ͸ƒ†„‘Ǧ ”‘ǤͶ͹ ‡‡”ƒŽŽ›ǡ ‡•–‡”ǡ ›ƒ‘ ƒ† ‹–”‘ ˆ— –‹‘ƒŽ‹–‹‡• ƒ”‡ –‘Ž‡”ƒ–‡† ‹ –Š‡•‡ ”‡†— –‹‘•ǡ ƒŽ„‡‹– –Š‡ •‡Ž‡ –‹˜‡ ”‡†— –‹‘ ‘ˆ ƒ‹†‡• ‹ –Š‡ ’”‡•Ǧ ‡ ‡‘ˆ‡–‘‡•ƒ†ƒŽ†‡Š›†‡•‹•”ƒ–Š‡”— ‘‘Ǥ

 Scheme 4. Reaction mechanisms suggested for the hydrosilylation; a)ChalkǦHarrod,b)modifiedChalkǦHarrod,c)ɐǦbondmetathesisand,d)Lewis acidcatalyzed.

Š‡‹– ‘‡•–‘–Š‡‡ Šƒ‹•ˆ‘”–Š‡‡–ƒŽǦ ƒ–ƒŽ›œ‡†Š›†”‘•‹Ž›ŽƒǦ –‹‘• ‘ˆ ƒ”„‘›Ž ‘’‘—†• –Š‡”‡ ƒ”‡ –™‘ Žƒ••‹ ƒŽ ‡ Šƒ‹••Ǣ ŠƒŽǦ ƒ””‘†ͶͺȋƒȌƒ†‘†‹ˆ‹‡†ŠƒŽǦ ƒ””‘†ͶͻǡͷͲȋ„Ȍȋ Š‡‡ͶȌǤŠ‡ › Ž‡‹•‹‹–‹ƒ–‡†„›‘š‹†ƒ–‹˜‡ƒ††‹–‹‘‘ˆ–Š‡•‹Žƒ‡–‘–Š‡‡–ƒŽǡˆ‘”‹‰ ƒ‡–ƒŽǦŠ›†”‹†‡•’‡ ‹‡•ǤͷͳŠ‡•—„•–”ƒ–‡‹•–Š‡ ‘‘”†‹ƒ–‡†–‘–Š‡‡–Ǧ ƒŽƒ†‡‹–Š‡”–Š‡Š›†”‹†‡ȋƒȌ‘”–Š‡•‹Ž‹ ‘‘‹‡–›ȋ„Ȍ‰‡–•‹•‡”–‡†‹–‘ –Š‡ α „‘† ƒ† –Š‡ ’”‘†— – ‹• —Ž–‹ƒ–‡Ž› ‰‡‡”ƒ–‡† ƒˆ–‡” ”‡†— –‹˜‡ ‡Ž‹‹ƒ–‹‘ǤŠ‡•‡–™‘‡ Šƒ‹••ƒ”‡ ‘‘ˆ‘”‰”‘—’ͺǦͳͲ–”ƒ•‹Ǧ –‹‘ ‡–ƒŽ• ƒ† ‡ Šƒ‹•–‹  ‹˜‡•–‹‰ƒ–‹‘• Šƒ• •Š‘™ –Šƒ– ”ǡͷʹǡͷ͵ŠͷͲ ƒ† ‘Ǧ ƒ–ƒŽ›œ‡†Ͷͻ Š›†”‘•‹Ž›Žƒ–‹‘ ‘ —”• –Š”‘—‰Š ‘†‹ˆ‹‡†

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ŠƒŽǦ ƒ””‘† ™Š‹Ž•– –Ǧ ƒ–ƒŽ›œ‡†ͶͺǡͷͶ ”‡ƒ –‹‘• ƒ”‡ ’”‘’‘•‡† –‘ ˆ‘ŽŽ‘™ –Š‡ Žƒ••‹ ‡ Šƒ‹•Ǥ ‘”•‘‡‡–ƒŽ•ǡ–›’‹ ƒŽŽ›‡ƒ”Ž›–”ƒ•‹–‹‘‡–Ǧ ƒŽ•ǡ•— Šƒ•‹ƒ†”ǡ‹–‹•‘–’‘••‹„Ž‡–‘’‡”ˆ‘”–Š‡‘š‹†ƒ–‹˜‡ƒ††‹Ǧ –‹‘Ǥͷͳ  –Š‡•‡ ƒ•‡• ɐǦ„‘† ‡–ƒ–Š‡•‹• ‘ˆ –Š‡ ‹Ȃ  „‘† ‘ —”• –‘ –”ƒ•ˆ‡”–Š‡Š›†”‹†‡ˆ”‘–Š‡•‹Žƒ‡–‘–Š‡ ƒ–ƒŽ›•–ȋ Š‡‡Ͷ ȌǤ‘”‡‘Ǧ ˜‡”ǡ ‡™‹• ƒ ‹†• ‹ •–‘‹ Š‹‘‡–”‹  ƒ‘—–• ƒ”‡ ‘™ –‘ ƒ –‹˜ƒ–‡ ƒ”Ǧ „‘›Ž•ǡͷͷƒŽ–Š‘—‰Š–Š‡›Šƒ˜‡ƒŽ•‘„‡‡•Š‘™–‘ƒ –‹˜ƒ–‡–Š‡‹Ȃ „‘† ͷ͸ ȋ‡Ǥ‰Ǥ ™‹–Š ƒ–ƒŽ›–‹  ƒ‘—–• ‘ˆ ȋ͸ ͷȌ͵Ȍ ȋ Š‡‡ Ͷ†ȌǤ  – ™ƒ• †‡–‡”Ǧ ‹‡† –Šƒ– –Š‡ ‡™‹• ƒ ‹† ƒ –‹˜ƒ–‡• –Š‡ •‹Žƒ‡ ˆ‘”‹‰ ƒ •‹Ž›Ž‹—Ǧ „‘”‘Š›†”‹†‡‹‘Ǧ’ƒ‹”•’‡ ‹‡•ǡ–Š‡’”‘†— –‹•‘„–ƒ‹‡†ƒˆ–‡”ƒ––ƒ ‘ˆ–Š‡ Š›†”‹†‡‘–‘–Š‡ƒ –‹˜ƒ–‡† ƒ”„‘›ŽǤ ‘•– ‘ˆ –Š‡ ”‡’‘”–‡† Š‡‘•‡Ž‡ –‹˜‡ ƒ‹†‡ ”‡†— –‹‘ ’”‘–‘ ‘Ž• †‡‘•–”ƒ–‡ –Š‡ –”ƒ•ˆ‘”ƒ–‹‘ ‘ˆ ƒ‹†‡• ‹–‘ ƒ‹‡•Ǣ Š‘™‡˜‡”ǡ –Š‡ •›•–‡• ƒ’ƒ„Ž‡ ‘ˆ ‰‡‡”ƒ–‹‰ ƒŽ†‡Š›†‡• ƒ”‡ Ž‹‹–‡†Ǥ ‡‰ƒ”†‹‰ •‡Ž‡ Ǧ –‹˜‡ƒ‹†‡”‡†— –‹‘ǡ–Š‡ˆ‹‡Ž†‘ˆŠ›†”‘•‹Ž›Žƒ–‹‘‹••—’‡”‹‘”‹–‡”•‘ˆ Š‡‘•‡Ž‡ –‹˜‹–›™‹–Šƒ—„‡”‘ˆ”‡’‘”–‡†’”‘–‘ ‘Ž•Ǥ͵͵ –Š‡ˆ‘ŽŽ‘™‹‰ •‡ –‹‘•ȋͳǤʹǤͶƒ†ͳǤʹǤͷȌ–Š‡‘•–’”‘‹‡–ƒ†‹’‘”–ƒ–’”‘–‘ ‘Ž• ˆ‘”–Š‡ Š‡‘•‡Ž‡ –‹˜‡ƒ‹†‡”‡†— –‹‘‹–‘ƒ‹‡ƒ†ƒŽ†‡Š›†‡’”‘†Ǧ — –•™‹ŽŽ„‡†‹• —••‡†Ǥ

1.2.4ChemoselectiveReductionofAmidestoAmines

‘”ƒ‡•Šƒ˜‡„‡‡—•‡†ƒ•‹Ž†”‡ƒ‰‡–•ˆ‘”–Š‡”‡†— –‹‘‘ˆ’”‹ƒ”›ǡ •‡ ‘†ƒ”› ƒ† –‡”–‹ƒ”› ƒ‹†‡•Ǥ  –Š‡ Žƒ––‡” ƒ•‡ǡ –Š‡ ”‡ƒ –‹‘ ƒ„‡ ’‡”ˆ‘”‡†‹–Š‡’”‡•‡ ‡‘ˆ‹–”‘‰”‘—’Ǥͷ͹‘”‡–etal.•Š‘™‡†–Šƒ– ƒ‹†‡• ‘—Ž†„‡”‡†— ‡†•‡Ž‡ –‹˜‡Ž›‘˜‡”ƒ‡•–‡”ˆ— –‹‘ƒŽ‹–›ǡ™Š‹ Š ƒŽŽ‘™‡†ˆ‘”–Š‡‹•‘Žƒ–‹‘‘ˆƒ—„‡”‘ˆƒ‹‘Ǧ‡•–‡”•ǤʹͶŠ‡‹Ž†‡••‘ˆ „‘”ƒ‡•ǡ ‡•’‡ ‹ƒŽŽ› ‹ –Š‡ ˆ‘” ‘ˆ  ͵ή‡ʹǡ ™ƒ• †‡‘•–”ƒ–‡† „› ”‘‘‡•ƒ† ‘Ǧ™‘”‡”•‹–Š‡‹”•›–Š‡•‹•‘ˆȋRȌǦ‡”ƒ’ƒ‹Žǡ ȋ—•‡† ‹ ͷͺ –Š‡–”‡ƒ–‡–ˆ‘” ƒ”†‹‘˜ƒ• —Žƒ”ƒ‹Ž‡–• Ȍǡ™Š‡”‡ ͵ή‡ʹ™ƒ•‡Ǧ ’Ž‘›‡†‹–Š‡ˆ‹ƒŽ•–‡’ȋ Š‡‡ͷȌǤͷͻ—”‹‰–Š‡‡˜ƒŽ—ƒ–‹‘‘ˆ†‹ˆˆ‡”‡– ”‡†— ‹‰ ƒ‰‡–• –Š‡ ƒ—–Š‘”• ‘„•‡”˜‡† Ȃ Ž‡ƒ˜ƒ‰‡ ™Š‡ —•‹‰  ǡ ƒ† Ž‘™ •‡Ž‡ –‹˜‹–› „‡–™‡‡ ƒ‹†‡ ƒ† ›ƒ‘ ‘‹‡–‹‡• ™ƒ• ‘„–ƒ‹‡† ™‹–Š  ͵ή Ǥ Š‡ ‹–”‹Ž‡ ˆ— –‹‘ƒŽ‹–› ™ƒ• ‘– •—„•–ƒ–‹ƒŽŽ› ƒˆˆ‡ –‡† ™Š‡—•‹‰ ͵ή‡ʹƒ–”‘‘–‡’‡”ƒ–—”‡ƒ†ȋRȌǦ‡”ƒ’ƒ‹Ž™ƒ•‘„Ǧ –ƒ‹‡†‹͹͵Ψ›‹‡Ž†ȋ͹͹‰ȌǤŠ‡†”ƒ™„ƒ •ƒ••‘ ‹ƒ–‡†™‹–Š—•‹‰„‘Ǧ ”ƒ‡•ƒ”‡–Šƒ––Š‡”‡ƒ‰‡–‹•—•‡†‹‡š ‡••ƒ†–Šƒ––Š‡“—‡ Š‹‰’”‘Ǧ ‡†—”‡‹•“—‹–‡Šƒ”•Š‹‘”†‡”–‘Š›†”‘Ž›œ‡–Š‡„‘”‘”‡•‹†—‡•ƒ•™‡ŽŽƒ• –Š‡ˆ‘”‡†ƒ‹‡Ǧ„‘”‘ ‘’Ž‡š‡•Ǥ͵͵

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 Scheme 5. Chemoselective reduction as final step in the synthesis of (R)ǦVerapamil.

Š‡‰”‘—’‘ˆŠƒ”‡––‡†‡˜‡Ž‘’‡†ƒŠ‹‰ŠŽ› Š‡‘•‡Ž‡ –‹˜‡•–‘‹ Š‹‘‡–”‹  ’”‘–‘ ‘Žˆ‘”ƒ‹†‡”‡†— –‹‘–‘ƒ‹‡•ȋ Š‡‡͸ƒȌǤ͸Ͳ‡”–‹ƒ”›ƒ‹†‡• ™‡”‡‹‹–‹ƒŽŽ›ƒ –‹˜ƒ–‡†™‹–Šˆʹ–‘‰‡‡”ƒ–‡‡Ž‡ –”‘’Š‹Ž‹ ‹‹‹—–”‹Ǧ ˆŽƒ–‡ ‹–‡”‡†‹ƒ–‡ ȋAȌǡ™Š‹ Š™ƒ••—„•‡“—‡–Ž›”‡†— ‡†™‹–Šƒ ƒ–œ• Š ‡•–‡” ȋ†‹‡–Š›Ž ͳǡͶǦ†‹Š›†”‘Ǧʹǡ͸Ǧ†‹‡–Š›ŽǦ͵ǡͷǦ ’›”‹†‹‡†‹ ƒ”„‘š›Žƒ–‡ǡ  ȌǤŠ‡’”‘–‘ ‘Ž†‡‘•–”ƒ–‡†Š‹‰Šˆ— –‹‘Ǧ ƒŽ ‰”‘—’ –‘Ž‡”ƒ ‡ ƒ† –‡”–‹ƒ”› ƒ‹†‡• ‘–ƒ‹‹‰ ƒŽ‡‡•ǡ ƒŽ›‡•ǡ ‡’‘š‹†‡•ǡ‹–”‹Ž‡•ǡ‡•–‡”•ƒ†‡–‘‡•™‡”‡•— ‡••ˆ—ŽŽ›”‡†— ‡†–‘–Š‡ ‘””‡•’‘†‹‰ˆ— –‹‘ƒŽ‹œ‡†ƒ‹‡•ǤŠ‡ˆʹȀ  Ǧ„ƒ•‡†•›•–‡™ƒ• ˆ—”–Š‡”‹˜‡•–‹‰ƒ–‡†ƒ†ƒ‹’”‘˜‡†’”‘–‘ ‘Žˆ‘”–Š‡”‡†— –‹‘‘ˆ•‡ Ǧ ‘†ƒ”› ƒ‹†‡• –‘ ‹‹‡•ǡ ƒŽ†‡Š›†‡• ƒ† ƒ‹‡• ™ƒ• †‡˜‡Ž‘’‡† ȋ Š‡‡ ͸„ȌǤ͸ͳ ‘ ”‡†— ‡ –Š‡ •‡ ‘†ƒ”› ƒ‹†‡•ǡ ʹǦˆŽ—‘”‘’›”‹†‹‡ ȋʹǦ ›”Ȍ™ƒ•ƒ††‡†–‘‰‡–Š‡”™‹–Š–͵‹ ƒ•ƒ™‡ƒŠ›†”‹†‡†‘‘”ǡ™Š‹ Š ‰‡‡”ƒ–‡†–Š‡ ‘””‡•’‘†‹‰‹‹‹—•ƒŽ–•ȋBȌ ‹ ‰‘‘† –‘ ‡š ‡ŽŽ‡– ›‹‡Ž†•Ǥ Š‡   ™ƒ• ƒ††‡† –Š‡ ‘””‡•’‘†‹‰ ƒ‹‡• ‘—Ž† „‡ ‘„Ǧ –ƒ‹‡†Ǥ ‰ƒ‹ǡ ‡š ‡ŽŽ‡– ˆ— –‹‘ƒŽ ‰”‘—’ –‘Ž‡”ƒ ‡ ™ƒ• ‘„•‡”˜‡† ƒ† ƒŽ‡‡•ǡƒŽ›‡•ǡ‡’‘š‹†‡•‹–”‹Ž‡•ǡ‡•–‡”•ƒ†‡˜‡ƒŽ†‡Š›†‡•™‡”‡–‘ŽǦ ‡”ƒ–‡†Ǥ



Scheme6.ChemoselectivereductionbyprioractivationoftheamidewithTf2O.

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Š‡’”‘–‘ ‘Ž™ƒ•ˆ—”–Š‡”‡˜ƒŽ—ƒ–‡†‹–Š‡•›–Š‡•‹•‘ˆ‘‡’‡œ‹Ž™Š‡”‡ –Š‡ƒ‹†‡‘‹‡–›™ƒ••‡Ž‡ –‹˜‡Ž›”‡†— ‡†‹–‘ƒ‹‡‹–Š‡’”‡•‡ ‡‘ˆ ƒ‡–‘‡ǡ ‰‹˜‹‰ ‘‡’‡œ‹Ž‹ͶͻΨ‹•‘Žƒ–‡†›‹‡Ž†ȋ Š‡‡͹ȌǤŠ‡”‡ƒǦ ‰‡–•—•‡†ƒ”‡‡š’‡•‹˜‡ƒ†—•‡†‹•–‘‹ Š‹‘‡–”‹ ƒ‘—–•ǢŠ‘™‡˜‡”ǡ –Š‡’”‘–‘ ‘Ž•ƒ”‡ƒ‘‰–Š‡‘•–‘—–•–ƒ†‹‰ Š‡‘•‡Ž‡ –‹˜‡•›•–‡• ˆ‘”ƒ‹†‡”‡†— –‹‘Ǥ —”–Š‡”‘”‡ǡ–Š‡•ƒ‡”‡•‡ƒ” Š‰”‘—’‡’Ž‘›‡† –Š‡ ’”‘–‘ ‘Ž ˆ‘” ƒ‹†‡ ƒ –‹˜ƒ–‹‘ „‘–Š ‹ –Š‡ ‘˜‡”•‹‘ ‘ˆ ƒ‹†‡• –‘ ƒŽ†‡Š›†‡•ƒ†‹”‡†— –‹˜‡ˆ— –‹‘ƒŽ‹œƒ–‹‘‘ˆƒ‹†‡•ǤŠ‡•‡–‘’‹ •ƒ”‡ †‹• —••‡†Žƒ–‡”‹–Š‹•–Š‡•‹•ȋ•‡ –‹‘•ͳǤʹǤͷƒ†ͳǤ͵ǤͳȌǤ

 Scheme7.SynthesisofDonepezil.

ƒ‰ƒ† —ƒ‰ƒŽ•‘†‡˜‡Ž‘’‡†ƒ‘‡Ǧ’‘–’”‘–‘ ‘Žˆ‘”–Š‡”‡†— –‹‘‘ˆ ͸ʹ •‡ ‘†ƒ”› ƒ‹†‡• –‘ ƒ‹‡• „ƒ•‡† ‘ ˆʹȀʹǦ ›” ƒ –‹˜ƒ–‹‘Ǥ  ‡”‡ǡ –”‹•ȋ’‡–ƒˆŽ—‘”‘’Š‡›ŽȌ„‘”ƒ‡ ȋȋ͸ ͷȌ͵Ȍ ƒ†  ™‡”‡ —•‡† ‹ –Š‡ •—„•‡“—‡– ”‡†— –‹‘ •–‡’•Ǥ – ™ƒ• ’‘••‹„Ž‡ –‘ ‡ˆˆ‹ ‹‡–Ž› ”‡†— ‡ •‡ Ǧ ‘†ƒ”›ƒ‹†‡•–‘ƒ‹‡•‹–Š‡’”‡•‡ ‡‘ˆƒŽ‡‡•ǡ‡•–‡”•ǡ‹–”‹Ž‡•ǡ˜‹Ǧ ›Ž ŠŽ‘”‹†‡•ǡ–‡”‹ƒŽƒŽ›‡•ƒ†‹–”‘‰”‘—’•ǤŠ‡’”‘–‘ ‘Ž™ƒ•ƒ’Ǧ ’Ž‹‡†‹–Š‡•›–Š‡•‹•‘ˆȋ–ȌǦʹǦepiǦ’•‡—†‘ ‘Š›†”‹‡ǡ™Š‹ Š‹•ƒƒŽƒǦ Ž‘‹† ‹•‘Žƒ–‡† ˆ”‘ ’‘‹•‘ Š‡Ž‘  ȋConium maculatumȌ͸͵ȋ Š‡‡ͺȌǤ Š‡ ƒ‹†‡ ‘‹‡–› ™ƒ• •‡Ž‡ –‹˜‡Ž› ”‡†— ‡† ‹ –Š‡ ’”‡•‡ ‡ ‘ˆ –Š‡Žƒ Ǧ –‘‡ǡ›‹‡Ž†‹‰–Š‡ ‘””‡•’‘†‹‰ƒ‹‡‹͸ͻΨ›‹‡Ž†ǤŠ‡•ƒ‡”‡•‡ƒ” Š ‰”‘—’ Šƒ• ƒŽ•‘ †‡˜‡Ž‘’‡† ’”‘–‘ ‘Ž• „ƒ•‡† ‘ ˆʹȀƒ Ͷƒ† ’ʹ” ŽȀƒ Ͷ ˆ‘” –Š‡ Š‡‘•‡Ž‡ –‹˜‡ ”‡†— –‹‘ ‘ˆ •‡ ‘†ƒ”› ƒǦ ‹†‡•Ǥ͸Ͷ — –‹‘ƒŽ‰”‘—’••— Šƒ•ƒŽ‡‡ǡ‡•–‡”ǡ‹–”‹Ž‡ƒ†‹–”‘‰”‘—’• ™‡”‡–‘Ž‡”ƒ–‡†™‹–Š–Š‡•‡•›•–‡•Ǥ

 Scheme8.Synthesisof(–)Ǧ2ǦepiǦpseudoconhydrine.

ͻ  

Š‡ ‰”‘—’ ‘ˆ ƒ‰ƒ•Š‹ƒ Šƒ• ‘–”‹„—–‡† •—„•–ƒ–‹ƒŽŽ› –‘ –Š‡ ˆ‹‡Ž† ‘ˆ Š‡‘•‡Ž‡ –‹˜‡ ƒ‹†‡ ”‡†— –‹‘ ƒ† †‡˜‡Ž‘’‡† •‡˜‡”ƒŽ ƒ–ƒŽ›–‹  •›•Ǧ –‡• †‹•’Žƒ›‹‰ Š‹‰Š •‡Ž‡ –‹˜‹–›Ǥ Š‡ ‹”‘Ǧ„ƒ•‡† ’”‘–‘ ‘Ž —•‹‰ ‡ȋȌͷȀ ‡͵ȋȌͳʹ ƒ• ƒ–ƒŽ›•– •— ‡••ˆ—ŽŽ› ”‡†— ‡† ƒ”‘ƒ–‹  ƒ† ƒŽ‹Ǧ ’Šƒ–‹  –‡”–‹ƒ”› ƒ‹†‡• —†‡” ‹Ž† Š›†”‘•‹Ž›Žƒ–‹‘ ‘†‹–‹‘• ȋ Š‡‡ ͻƒȌǤͶͳƒ ‘™‡˜‡”ǡ‘Ž›•—„•–”ƒ–‡• ‘–ƒ‹‹‰ƒŽ‹‹–‡†•‡Ž‡ –‹‘‘ˆƒ††‹Ǧ –‹‘ƒŽˆ— –‹‘ƒŽ‰”‘—’••— Šƒ•„‡œ›Ž‹  ŠŽ‘”‹†‡ƒ†‡•–‡”™‡”‡‡˜ƒŽ—Ǧ ƒ–‡†Ǥ Š‡ ”‡•‡ƒ” Š ‰”‘—’ Žƒ–‡” ‹˜‡•–‹‰ƒ–‡† –Š‡ —•‡ ‘ˆ ƒ Š‡’–ƒ— Ž‡ƒ” ‹”‘ ƒ”„‘›Ž Ž—•–‡”ǡ ƒ† –Š‹• ƒ–ƒŽ›•– ƒŽŽ‘™‡† ˆ‘” •Š‘”–‡” ”‡ƒ –‹‘ –‹‡•ǡƒŽ„‡‹––Š‡•ƒ‡ Š‡‘•‡Ž‡ –‹˜‹–›™ƒ•‘„•‡”˜‡†ǤͶͳ 

 Scheme9.HydrosilylationprotocolsdevelopedbytheNagashimagroup.

ƒ‰ƒ•Š‹ƒ ƒ† ‘Ǧ™‘”‡”• Šƒ˜‡ ƒŽ•‘ †‡˜‡Ž‘’‡† ƒ–ƒŽ›–‹  ’”‘–‘ ‘Ž• „ƒ•‡† ‘ ‘„Ž‡ ‡–ƒŽ•Ǣ ʹ–Ž͸ȉ͸ ʹ ™ƒ• —•‡† ‹ ‘„‹ƒ–‹‘ ™‹–Š ‘” –‘”‡†— ‡ƒ—„‡”‘ˆ–‡”–‹ƒ”›ƒ‹†‡•™‹–ŠŠ‹‰Š Š‡‘•‡Ž‡ –‹˜‹–›ȋ Š‡‡ͻ„ȌǤͶͲ Š‡–Ǧ„ƒ•‡†•›•–‡–‘Ž‡”ƒ–‡†ƒ™‹†‡ ˜ƒ”‹‡–› ‘ˆ ˆ— –‹‘ƒŽ ‰”‘—’•Ǣ ‹–”‹Ž‡•ǡ ƒŽ‡‡•ǡ ‡•–‡”• ƒ† ‹–”‘ ‰”‘—’•Ǥ —”–Š‡”‘”‡ǡ™Š‡—•‹‰ –Š‡ƒ‹‡• ‘—Ž†„‡‹•‘Žƒ–‡†„›ˆ‹Ž–”ƒǦ –‹‘‘ˆ–Š‡ ”‘••ǦŽ‹‡†•‹Ž‹ ‘’‘Ž›‡”–Šƒ–ƒŽ•‘‡ ƒ’•—Žƒ–‡†–Š‡ ƒ–ƒǦ Ž›•–ǡ ”‡‘˜‹‰ —’ –‘ ͻͺǤͻΨ ‘ˆ –Š‡ ’Žƒ–‹— •’‡ ‹‡•Ǥ Š‡ ˆ‘ŽŽ‘™‹‰ ‡ Šƒ‹•–‹  ‹˜‡•–‹‰ƒ–‹‘ ”‡˜‡ƒŽ‡† –Šƒ– –Š‡ ’”‘š‹‹–› ‘ˆ –™‘ ‹Ȃ  ‰”‘—’•‹–Š‡•‹Žƒ‡”‡ƒ‰‡–Šƒ†ƒ•–”‘‰‡ˆˆ‡ –‘–Š‡”‡ƒ –‹‘”ƒ–‡Ǥ͸ͷǡͷͶ  —Ǧ ƒ–ƒŽ›œ‡† ’”‘–‘ ‘Ž ™ƒ• ƒŽ•‘ ‡•–ƒ„Ž‹•Š‡† „› –Š‡ ƒ‰ƒ•Š‹ƒ ‰”‘—’ǤͶͲ„›—•‹‰ƒ–”‹”—–Š‡‹— Ž—•–‡”ƒ• ƒ–ƒŽ›•–‹ ‘„‹ƒ–‹‘™‹–Š Š‡ʹ‹ ƒŽŽ‘™‡†ˆ‘”•‡Ž‡ –‹˜‡”‡†— –‹‘‘ˆƒŽ‹’Šƒ–‹ ƒ†ƒ”‘ƒ–‹ –‡”Ǧ –‹ƒ”›ƒ‹†‡•ƒ–”‘‘–‡’‡”ƒ–—”‡ȋ Š‡‡ͻ ȌǤŠ‡’”‘–‘ ‘Ž–‘Ž‡”ƒ–‡† ‡•–‡”‰”‘—’•ǡƒ†ˆ‘”–Š‡ˆ‹”•––‹‡ǡ–Š‡‡–‘‡ˆ— –‹‘ƒŽ‹–›Ǥ‘‘„–ƒ‹ Š‹‰Š Š‡‘•‡Ž‡ –‹˜‹–›ǡ–Š‡ ƒ–ƒŽ›•–™ƒ•’‘‹•‘‡†™‹–Šƒ‡š ‡••‘ˆ–”‹Ǧ ‡–Š›Ž ƒ‹‡ ȋ–͵ȌǤ ‘”‡‘˜‡”ǡ –Š‹• ’”‘–‘ ‘Ž ‡šŠ‹„‹–• ƒ —’ƒ”ƒŽŽ‡Ž‡† Š‡‘•‡Ž‡ –‹˜‹–› ƒ‘‰ –Š‡ Š›†”‘•‹Ž›Žƒ–‹‘ ’”‘–‘ ‘Ž• „ƒ•‡† ‘ ‘„Ž‡ –”ƒ•‹–‹‘‡–ƒŽ•Ǥ͵͵ ƒ††‹–‹‘ǡ–Š‡•ƒ‡”‡•‡ƒ” Š‰”‘—’ƒŽ•‘ˆ‘—†–Šƒ–

ͳͲ  

ƒ •›•–‡ „ƒ•‡† ‘ ƒ–ƒŽ›–‹  ƒ‘—–• ‘ˆ ‹”‹†‹— ‹ ‘„‹ƒ–‹‘ ™‹–Š ƒ•–Š‡”‡†— –ƒ–†‹•’Žƒ›‡†Š‹‰Š Š‡‘•‡Ž‡ –‹˜‹–›‹–Š‡–”ƒ•ˆ‘”Ǧ ƒ–‹‘‘ˆƒ‹†‡•‹–‘‡ƒ‹‡•ǤͳͶŠ‡•›•–‡‡šŠ‹„‹–‡†Š‹‰Š Š‡‘•‡Ǧ Ž‡ –‹˜‹–› ƒ† ™ƒ• ƒ’’Ž‹‡† „› Š‹†ƒƒ†ƒ–‘‹–Š‡•›–Š‡•‹•‘ˆ ȋΪȌǦ‡‘•–‡‹‡ǡ ƒ ƒ–—”ƒŽ ’”‘†— – ‘™ –‘ Šƒ˜‡ ƒ–‹–—••‹˜‡ ƒ –‹˜‹–› ȋ Š‡‡ ͳͲȌǤ͸͸ Š‡ ’”‘–‘ ‘Ž †‡˜‡Ž‘’‡† „› ƒ‰ƒ•Š‹ƒ –‘‰‡–Š‡” ™‹–Š ‘–Š‡” ‡ƒ‹‡ ‰‡‡”ƒ–‹‰ ‡–Š‘†‘Ž‘‰‹‡• ™‹ŽŽ „‡ ˆ—”–Š‡” †‹• —••‡† ‹ Šƒ’–‡”͵Ǥ

 Scheme 10. Application of the hydrosilylation protocol developed by the NaǦ gashimagroupinthesynthesisof(+)ǦNeostenine.

’ƒ”ƒŽŽ‡Ž™‹–Š–Š‡™‘”‘ˆƒ‰ƒ•Š‹ƒǡ‡ŽŽ‡”ƒ† ‘Ǧ™‘”‡”•†‡˜‡ŽǦ ‘’‡†ƒ”‡†— –‹‘•›•–‡ˆ‘”–‡”–‹ƒ”›ƒ‹†‡•„ƒ•‡†‘–Š‡—•‡‘ˆ Ͷͳˆ ‡͵ȋȌͳʹƒ• ƒ–ƒŽ›•–™‹–Š ƒ•”‡†— ‹‰ƒ‰‡–Ǥ Š‡•ƒ‡ ƒ–ƒŽ›•– ‹š–—”‡‹ ‘„‹ƒ–‹‘™‹–ŠŠ‹ ͵ƒ•Š›†”‹†‡•‘—” ‡™ƒ••— ‡••ˆ—ŽŽ› ‡’Ž‘›‡†‹–Š‡”‡†— –‹‘‘ˆ•‡ ‘†ƒ”›ƒ‹†‡•ǤŠ‡‹– ‘‡•–‘ˆ— Ǧ –‹‘ƒŽ‰”‘—’–‘Ž‡”ƒ ‡ǡ‹‘†‹†‡•ǡƒŽ‡‡•ƒ†‡•–‡”•”‡ƒ‹‡†—”‡ƒ –‹˜‡ ‹–Š‡ ƒ•‡‘ˆ–‡”–‹ƒ”›ƒ‹†‡•ǡˆ‘”•‡ ‘†ƒ”›ƒ‹†‡•‘ Š‡‘•‡Ž‡ –‹˜‹–› •–—†›™ƒ•”‡’‘”–‡†Ǥ Š‡ ”‡•‡ƒ” Š ‰”‘—’ ‘ˆ ‡ŽŽ‡” ƒŽ•‘ †‡˜‡Ž‘’‡† ƒ •›•–‡ „ƒ•‡† ‘ ȋ Ȍʹƒ†ȋ–Ȍ͵‹ ˆ‘”–Š‡”‡†— –‹‘‘ˆ–‡”–‹ƒ”›ƒ‹†‡•ƒ†™‡”‡ ƒ„Ž‡–‘‘„–ƒ‹ƒ‹‡• ‘–ƒ‹‹‰Š‹‰ŠŽ›”‡†— ‹„Ž‡‰”‘—’•ǡ‹ Ž—†‹‰‡Ǧ –‘‡ˆ— –‹‘ƒŽ‹–›ȋ Š‡‡ͳͳƒȌǤͶʹƒ‡ Šƒ‹•–‹ ‹˜‡•–‹‰ƒ–‹‘™ƒ• ’‡”ˆ‘”‡†ǡ ™Š‹ Š •Š‘™‡† –Šƒ– –Š‡ ƒ–ƒŽ›•– ƒ –‹˜ƒ–‡† –Š‡ Š›†”‘•‹Žƒ‡ ”ƒ–Š‡”–Šƒ–Š‡ ƒ”„‘›Ž‰”‘—’‘ˆ–Š‡ƒ‹†‡ǤͶʹ„Š‡•›•–‡™ƒ•ˆ—”–Š‡” ‹˜‡•–‹‰ƒ–‡† ƒ† –™‘ ‹’”‘˜‡† ’”‘–‘ ‘Ž• ™‡”‡ ’”‡•‡–‡†Ǣ ȋ ȌʹȀ‡ȋ–Ȍʹ‹ ˆ‘”–‡”–‹ƒ”›ƒ‹†‡•ƒ†ȋˆȌʹȀˆ‘”•‡ Ǧ ‘†ƒ”›ƒ‹†‡•ǤŠ‡ˆ— –‹‘ƒŽ‰”‘—’–‘Ž‡”ƒ ‡™ƒ•‡˜ƒŽ—ƒ–‡†ƒ†‹–”‘ǡ ‹–”‹Ž‡ǡƒœ‘ǡƒŽ‡‡ƒ†‡•–‡”ˆ— –‹‘ƒŽ‹–‹‡•™‡”‡•Š‘™–‘•—”˜‹˜‡–Š‡ ”‡ƒ –‹‘ ‘†‹–‹‘•Ǥ —ȋ ȌǦ„ƒ•‡†•›•–‡ˆ‘”–Š‡”‡†— –‹‘‘ˆ•‡ ‘†ƒ”›ƒ‹†‡•™ƒ• ƒŽ•‘†‡˜‡Ž‘’‡†„›–Š‡‡ŽŽ‡”‰”‘—’Ǥ͸͹ –Š‹• ƒ•‡ǡ™ƒ•—•‡†ƒ•–Š‡ Š›†”‹†‡•‘—” ‡ƒ†–Š‡‡•–‡”ˆ— –‹‘ƒŽ‹–› ‘—Ž†„‡–‘Ž‡”ƒ–‡†Ǥ —”–Š‡”Ǧ ‘”‡ǡ ‡ŽŽ‡” ƒ† ‘Ǧ™‘”‡”• ’—„Ž‹•Š‡† ƒ ’”‘–‘ ‘Ž „ƒ•‡† ‘ ͷǦ”Ǧ„‡œ‘–Š‹‘’Š‡‡†‡”‹˜‡†„‘”‘‹ ƒ ‹†‹ ‘„‹ƒ–‹‘™‹–ŠŠ‹ ͵

ͳͳ  

ˆ‘” –Š‡ ”‡†— –‹‘ ‘ˆ ƒ‹†‡•ǤͶ͹ƒ ‡”‡ǡ –‡”–‹ƒ”› ƒ‹†‡• ™‡”‡ •‡Ž‡ –‹˜‡Ž› ”‡†— ‡†‹–Š‡’”‡•‡ ‡‘ˆ‹–”‘ǡ‹–”‹Ž‡ƒ†‡•–‡”ˆ— –‹‘ƒŽ‹–‹‡•Ǥ

 Scheme11.HydrosilylationprotocolsdevelopedbytheBellergroup.

Š‡ •ƒ‡ ”‡•‡ƒ” Š ‰”‘—’ ƒŽ•‘ ”‡’‘”–‡† ‘ ƒ •›•–‡ „ƒ•‡† ‘ Šȋ ‘†Ȍʹ Ͷƒ†ͳǡ͵Ǧ„‹•ȋ†‹’Š‡›Ž’Š‘•’Š‹‘Ȍ’”‘’ƒ‡ȋ†’’’Ȍ‹ ‘„‹Ǧ ƒ–‹‘™‹–ŠŠ‹ ͵ˆ‘”–Š‡”‡†— –‹‘‘ˆ–‡”–‹ƒ”›ƒ†•‡ ‘†ƒ”›ƒ‹†‡• ȋ Š‡‡ ͳͳ„ȌǤͶͲ‡ Š‡ Š‡‘•‡Ž‡ –‹˜‹–› ‘ˆ –Š‹• ’”‘–‘ ‘Ž ™ƒ• ‘– –Š‘”Ǧ ‘—‰ŠŽ› ‡š’Ž‘”‡†ǡ ƒŽ–Š‘—‰Š –Š‡ ‡•–‡” ˆ— –‹‘ƒŽ‹–› ™ƒ• –‘Ž‡”ƒ–‡†Ǥ Š‡ ‡–Š‘†™ƒ•ƒŽ•‘ƒ’’Ž‹‡†‹–Š‡”‡†— –‹‘‘ˆ–Š‡ › Ž‹ ’‘Ž›’‡’–‹†‡ ›Ǧ Ž‘•’‘”‹‡ǡ™Š‡”‡‹–‡”‡•–‹‰Ž›‘Ž›‘‡•’‡ ‹ˆ‹ ƒ‹†‡‘‹‡–›ȋ‘—–‘ˆ ‡Ž‡˜‡‹–‘–ƒŽȌ™ƒ•”‡†— ‡†ǡƒ†–Šƒ–‹–Š‡’”‡•‡ ‡‘ˆƒ‡•–‡”ˆ— Ǧ –‹‘ƒŽ‹–›Ǥ Š‡ •›•–‡ ™ƒ• ˆ—”–Š‡” †‡˜‡Ž‘’‡† ƒ† –Š‡ Š‡‘•‡Ž‡ –‹˜‹–› ™ƒ• ‡˜ƒŽ—ƒ–‡† ‹ –Š‡ ”‡†— –‹‘ ‘ˆ •‡ ‘†ƒ”› ƒ‹†‡• ȋ Š‡‡ ͳͳ ȌǤ͸ͺ ‡”‡ǡ ‹–”‘ǡ ‹–”‹Ž‡ǡ ƒœ‘ǡ ƒŽ‡‡ ƒ† ƒŽ›‡ ƒ• ™‡ŽŽ ƒ• –Š‡ ‡–‘‡ ˆ— Ǧ –‹‘ƒŽ‹–›™‡”‡–‘Ž‡”ƒ–‡†Ǥ‘ ‘ Ž—†‡ǡ–Š‡ŠǦ ƒ–ƒŽ›œ‡†’”‘–‘ ‘Ž•Š‘™• •—’‡”‹‘” Š‡‘•‡Ž‡ –‹˜‹–›™Š‡‹– ‘‡•–‘–Š‡”‡†— –‹‘‘ˆ•‡ ‘†ƒ”› ƒ‹†‡• ‘’ƒ”‡†–‘‘–Š‡”ƒ˜ƒ‹Žƒ„Ž‡ ƒ–ƒŽ›–‹ ‡–Š‘†•Ǥ͵͵

 Scheme12.AmidereductiondevelopedbytheBrookhartgroup.

”‘‘Šƒ”–ƒ† ‘Ǧ™‘”‡”•†‡˜‡Ž‘’‡†ƒ ƒ–ƒŽ›–‹ •›•–‡„ƒ•‡†‘‹”‹†‹Ǧ —ˆ‘”–Š‡Š›†”‘•‹Ž›Žƒ–‹‘‘ˆ•‡ ‘†ƒ”›ƒ‹†‡•™‹–Š–ʹ‹ ʹƒ•”‡†— ‹‰ ƒ‰‡–ȋ Š‡‡ͳʹȌǤͶͲ†Š‡ ƒ–ƒŽ›•–™ƒ•ƒ„Ž‡–‘”‡†— ‡„‘–ŠƒŽ‹’Šƒ–‹ ƒ• ™‡ŽŽ ƒ• ƒ”‘ƒ–‹  •‡ ‘†ƒ”› ƒ‹†‡•ǡ ƒŽ–Š‘—‰Š –Š‡ •›•–‡ ™ƒ• ”‡ƒ –‹˜‡ –‘™ƒ”†•„‘–Š‹–”‹Ž‡ƒ†‹–”‘‰”‘—’•ǡ”‡•—Ž–‹‰‹‹š–—”‡•‘ˆ’”‘†— –• ƒ† ’‘‘” ›‹‡Ž†•ǡ ƒŽ–Š‘—‰Š –Š‡ •›•–‡ –‘Ž‡”ƒ–‡† „‡œ›Ž‹  ŠƒŽ‹†‡•ǡ ƒœ‘Ǧ ‰”‘—’•ƒ†ƒŽ‡‡•Ǥ  ͳʹ  

Š‡”‡•‡ƒ” Š‰”‘—’‘ˆ†‘Žˆ••‘Šƒ•†‡˜‡Ž‘’‡†ƒǦ ƒ–ƒŽ›œ‡†’”‘–‘ ‘Ž —•‹‰ ˆ‘”–Š‡ Š‡‘•‡Ž‡ –‹˜‡”‡†— –‹‘‘ˆ–‡”–‹ƒ”›ƒ‹†‡• ȋ Š‡‡ ͳ͵ƒȌǤͶʹ  Š‡ ‘•– ‡ˆˆ‹ ‹‡– •›•–‡ ‘•‹•–‡† ‘ˆ ƒ ‹š–—”‡ ‘ˆ –ʹƒ†‹Žǡƒ™‹†‡”ƒ‰‡‘ˆˆ— –‹‘ƒŽ‰”‘—’•™ƒ•–‘Ž‡”ƒ–‡†‹–Š‡ ”‡†— –‹‘ǡ •— Š ƒ• ‹–”‘ǡ ‹–”‹Ž‡ǡ ƒŽ‡‡ǡ ‘Ǧ ‘Œ—‰ƒ–‡† ƒŽ›‡ ƒ† BocǦ’”‘–‡ –‡†ƒ‹‡ǡƒŽ„‡‹–•‘‡ˆ— –‹‘ƒŽ‰”‘—’•™‡”‡‘– ‘’ƒ–‹Ǧ „Ž‡ȋ ‘Œ—‰ƒ–‡†ƒŽ›‡ǡ‡•–‡”ƒ†‡–‘‡ȌǤ

 Scheme13.HydrosilylationprotocolsdevelopedbytheAdolfssongroup(aand b)andbyKeinanandPerez(c).

‡ ‡–Ž›ǡƒ”‡†— –‹‘•›•–‡„ƒ•‡†‘‘ȋȌ͸ƒ• ƒ–ƒŽ›•–ƒ†ƒ• Š›†”‹†‡•‘—” ‡™ƒ•†‡˜‡Ž‘’‡†ˆ‘”–Š‡”‡†— –‹‘ȽǡȾǦ—•ƒ–—”ƒ–‡†–‡”Ǧ –‹ƒ”› ƒ† •‡ ‘†ƒ”› ƒ‹†‡• –‘ –Š‡ ‘””‡•’‘†‹‰ ƒŽŽ›Ž‹  ƒ‹‡• ȋ Š‡‡ ͳ͵„ȌǤ͸ͻŠ‡†‡˜‡Ž‘’‡†’”‘–‘ ‘ŽŠƒ•‘”–Š‘‰‘ƒŽ•‡Ž‡ –‹˜‹–› ‘’ƒ”‡†–‘–Š‡‘Ǧ„ƒ•‡†”‡†— –‹‘’”‘–‘ ‘Ž’—„Ž‹•Š‡†„›‡‹ƒƒ† ‡”‡œ™Š‡”‡–Š‡—•ƒ–—”ƒ–‹‘‹•”‡†— ‡†‹•–‡ƒ†‘ˆ–Š‡ƒ‹†‡‘‹‡–›ǡ ™Š‹ Š ‹• ’‘••‹„Ž› ƒ ”‡•—Ž– ˆ”‘ —•‹‰ –‡”‹ƒŽ ‘Ž‡ˆ‹• ƒ• ™‡ŽŽ ƒ• –Š‡ Š‘‹ ‡‘ˆ•‹Žƒ‡ȋ Š‡‡ͳ͵ ȌǤ͹Ͳ –Š‡†‘Žˆ••‘‡–Š‘†–Š‡ ‘Œ—‰ƒ–‡† ƒ‹†‡•™‡”‡•‡Ž‡ –‹˜‡Ž›”‡†— ‡†ƒ†–Š‡‡–Š‘†‘Ž‘‰›™ƒ•‡’Ž‘›‡†‹ –Š‡•›–Š‡•‹•‘ˆ–Š‡’Šƒ”ƒ ‡—–‹ ƒŽ†”—‰ƒˆ–‹ˆ‹‡ȋ Š‡‡ͳͶȌǤŠ‡ ‘–‹—ƒ–‹‘ ‘ˆ –Š‡ ‘ȋȌ͸Ǧ„ƒ•‡† ”‡†— –‹‘ •›•–‡ ‹• †‹• —••‡† ‹ Šƒ’–‡”•ʹƒ†͵‘ˆ–Š‹•–Š‡•‹•Ǥ

 Scheme14.SynthesisofNaftifinebyhydrosilylation.

ͳ͵  

 ‹–‡”‡•–‹‰ ’”‘–‘ ‘Ž ˆ‘” –Š‡ Š‡‘•‡Ž‡ –‹˜‡ Š›†”‘•‹Ž›Žƒ–‹‘ ‘ˆ –‡”Ǧ –‹ƒ”›ƒ‹†‡• ƒ–ƒŽ›œ‡†„›ƒ„‘”‹‹ ƒ ‹†™ƒ•†‡˜‡Ž‘’‡†„›Žƒ Š‡–ƒ† ‘Ǧ™‘”‡”•ȋ Š‡‡ͳͷȌǤ͹ͳ –Š‹•‡–ƒŽǦˆ”‡‡ƒ†‹Ž†’”‘–‘ ‘Žǡƒ‹†‡• ‘–ƒ‹‹‰ ‹–”‘ǡ ƒŽ‡‡ǡ ƒŽ›‡ǡ ‡•–‡” ƒ† ‡˜‡ ‡–‘‡ ˆ— –‹‘ƒŽ‹–‹‡• ™‡”‡ Š‡‘•‡Ž‡ –‹˜‡Ž›”‡†— ‡†Ǥ

 Scheme15.HydrosilylationprotocoldevelopedbyBlanchet.

Š‡‡–Š‘†‘Ž‘‰‹‡•†‡• ”‹„‡†‹–Š‹•–Š‡•‹•†‡ƒŽ•™‹–Š–Š‡ Š‡‘•‡Ž‡ Ǧ –‹˜‡ ”‡†— –‹‘ ‘ˆ ƒ‹†‡•Ǣ ƒŽ–Š‘—‰Šǡ ‘•– ’”‘–‘ ‘Ž• ‘ ‡” –Š‡”‡†— Ǧ –‹‘‘ˆ–‡”–‹ƒ”›ƒ‹†‡•Ǥ –Š‡ ƒ•‡‘ˆ•‡ ‘†ƒ”›ƒ‹†‡•‘Ž›ƒˆ‡™’”‘Ǧ –‘ ‘Ž•Šƒ˜‡†‡‘•–”ƒ–‡†ˆ— –‹‘ƒŽ‰”‘—’–‘Ž‡”ƒ ‡ƒ†™Š‡‹– ‘‡• –‘ –Š‡ ”‡†— –‹‘ ‘ˆ ’”‹ƒ”› ƒ‹†‡• –Š‡ —„‡” ‘ˆ ’”‘–‘ ‘Ž• ƒ”‡ ‡˜‡ ‘”‡Ž‹‹–‡†Ǥ

1.2.5ChemoselectiveReductionofAmidestoAldehydes

Š‡”‡†— –‹‘‘ˆƒ‹†‡•‹–‘ƒ‹‡•‹•ƒˆ‘”ƒŽ†‡‘š›‰‡ƒ–‹‘’”‘ ‡•• ƒ†Š‡ ‡”‡“—‹”‡• Ž‡ƒ˜ƒ‰‡‘ˆ–Š‡ƒ‹†‡Ȃ„‘†Ǥ ‘™‡˜‡”ǡ‹ˆ–Š‡ ”‡†— –‹˜‡’”‘ ‡••‹˜‘Ž˜‡•Ȃ„‘† Ž‡ƒ˜ƒ‰‡ǡƒŽ†‡Š›†‡•ƒ†ƒŽ ‘Š‘Ž• ƒ „‡ ‰‡‡”ƒ–‡†Ǥ ‡‘”‰ ƒ† ‘Ǧ™‘”‡”• ”‡’‘”–‡† ƒ ’”‘–‘ ‘Ž ˆ‘” –Š‡ ’ƒ”–‹ƒŽ ”‡†— –‹‘ ‘ˆ –‡”–‹ƒ”› ƒ‹†‡• –‘ ƒŽ†‡Š›†‡• ‡’Ž‘›‹‰ –Š‡ ͹ʹǡ͹͵  Š™ƒ”–œ”‡ƒ‰‡–ȋ”’ʹ ŽȌȋ Š‡‡ͳ͸ƒȌǤ Š‡”‡ƒ –‹‘ǡhydrozirǦ conationǡ™ƒ•‡ˆˆ‹ ‹‡–ƒ†ƒ‹†‡•™‡”‡ ‘˜‡”–‡†‹–‘ƒŽ†‡Š›†‡•—†‡” ‹Ž† ‘†‹–‹‘•Ǥƒ–‡”ǡ–Š‡• ‘’‡‘ˆ–Š‡–”ƒ•ˆ‘”ƒ–‹‘™ƒ•‡š’ƒ†‡†–‘ ‹ Ž—†‡•‡ ‘†ƒ”›ƒ†’”‹ƒ”›ƒ‹†‡•ǡƒ†ƒ††‹–‹‘ƒŽŽ›–Š‡‡ Šƒ‹• ™ƒ•‹˜‡•–‹‰ƒ–‡†Ǥ͹ͶŠ‡ƒ‹†‡‹•”‡†— ‡†„›–Š‡ Š™ƒ”–œ”‡ƒ‰‡–ǡˆ‘”Ǧ ‹‰ ƒ œ‹” ‘ƒ › Ž‡ ƒ• ‹–‡”‡†‹ƒ–‡ǡ ™Š‹ Š —’‘ ƒ“—‡‘—• ™‘”Ǧ—’ ‘ŽǦ Žƒ’•‡•–‘–Š‡ƒŽ†‡Š›†‡ȋ Š‡‡ͳ͸„ȌǤ —”–Š‡”‘”‡ǡ—•‹‰–Š‡ ‘‡”Ǧ ‹ƒŽŽ›ƒ˜ƒ‹Žƒ„Ž‡†‡—–‡”ƒ–‡†”‡ƒ‰‡–ǡ”’ʹŽǡ‹–™ƒ•’‘••‹„Ž‡–‘‘„–ƒ‹ –Š‡†‡—–‡”‹—ǦŽƒ„‡ŽŽ‡†ƒŽ†‡Š›†‡•‹‡š ‡ŽŽ‡–›‹‡Ž†•ǤŠ‡’”‘–‘ ‘Ž™ƒ• Š‹‰ŠŽ› Š‡‘•‡Ž‡ –‹˜‡ƒ†ƒ‹†‡••—„•–‹–—–‡†™‹–Š‡•–‡”•ǡ ›ƒ‘ǡ‹–”‘ǡ  ǦBoc ƒ† ‘Œ—‰ƒ–‡† ƒŽ‡‡• ‘—Ž† „‡ ”‡†— ‡† ™‹–Š‘—– ƒˆˆ‡ –‹‰ –Š‡•‡ ˆ— –‹‘ƒŽ ‰”‘—’•Ǥ ˆ‘”–—ƒ–‡Ž›ǡ –Š‡ ’”‘–‘ ‘Ž †‹† ‘– –‘Ž‡”ƒ–‡ ‡–‘‡• ƒ† ƒŽ†‡Š›†‡•ǡ ™Š‹ Š ™‡”‡ ”‡†— ‡† ‹–‘ –Š‡‹” ‘””‡•’‘†‹‰ ƒŽ ‘Š‘Ž•Ǥ‹ ‡–Š‡ Š™ƒ”–œ”‡ƒ‰‡–‹•‘™–‘„‡•‡•‹–‹˜‡–‘™ƒ”†• ƒ‹”ǡŽ‹‰Š–ƒ†‘‹•–—”‡ǡ–Š‡‰”‘—’‘ˆ‹‡ —•†‡˜‡Ž‘’‡†ƒ’”‘–‘ ‘Žˆ‘” –Š‡insituˆ‘”ƒ–‹‘‘ˆ–Š‡”‡ƒ‰‡–Ǥ͹ͷ ‘’ƒ”‹•‘‘ˆ–Š‹•’”‘–‘ ‘Ž™‹–Š ͳͶ  

–Š‡‘‡•†‡˜‡Ž‘’‡†‡ƒ”Ž‹‡”„› ‡‘”‰•Š‘™‡†–Šƒ––Š‡insituˆ‘”‡†”‡ƒǦ ‰‡– ”‡“—‹”‡† •Š‘”–‡” ”‡ƒ –‹‘ –‹‡• ƒ† •‘‡ ›‹‡Ž†• ™‡”‡ ‹’”‘˜‡†Ǥ ‘–Š‡–Š‘†‘Ž‘‰‹‡••Š‘™‡†–Š‡•ƒ‡†‡‰”‡‡‘ˆ Š‡‘•‡Ž‡ –‹˜‹–›Ǥ

 Scheme16.HydrozirconationofamidesintoaldehydesdevelopedbyGeorg.

Š‡Šƒ”‡––‡‰”‘—’†‡˜‡Ž‘’‡†’”‘–‘ ‘Ž•ˆ‘”–Š‡ Š‡‘•‡Ž‡ –‹˜‡ƒ‹†‡ ͸Ͳǡ͸ͳ ”‡†— –‹‘„›–Š‡—•‡‘ˆˆʹƒ•ƒƒ –‹˜ƒ–‹‰”‡ƒ‰‡–ȋ•‡ –‹‘ͳǤʹǤͶȌǤ  › –”‡ƒ–‹‰ ‹–‡”‡†‹ƒ–‡ B ƒˆ–‡” –Š‡ ƒ –‹˜ƒ–‹‘Ȁ”‡†— –‹‘ ™‹–Š ‡‹–Š‡” ‹–”‹ ƒ ‹†‘”ƒ“—‡‘—•ƒ ͵ ‹– ™ƒ• ’‘••‹„Ž‡ –‘ ‘„–ƒ‹ ƒŽ†‡Š›†‡• ‘” ‹‹‡• ƒ• –Š‡ ˆ‹ƒŽ ’”‘†— –• ȋ Š‡‡ ͳ͹ȌǤ͸ͳŠ‡•›•–‡•Š‘™‡†Š‹‰Š Š‡‘•‡Ž‡ –‹˜‹–›ƒ†•‡ ‘†ƒ”›ƒ‹†‡•™‡”‡•— ‡••ˆ—ŽŽ›–”ƒ•ˆ‘”‡† ‹–‘ƒŽ†‡Š›†‡•ƒ†‹‹‡•‹–Š‡’”‡•‡ ‡‘ˆ ›ƒ‘ǡ‹–”‘ǡƒœ‹†‘ǡƒŽ‡‡ǡ ƒŽ›‡ǡ‡•–‡”ƒ†‡˜‡ƒŽ†‡Š›†‡ˆ— –‹‘ƒŽ‹–‹‡•Ǥ

 Scheme17.ChemoselectiveamidereductiondevelopedbytheCharettegroup.

Š‡ˆ‹”•–’”‘–‘ ‘Žˆ‘”–Š‡’ƒ”–‹ƒŽŠ›†”‘•‹Ž›Žƒ–‹‘‘ˆƒ‹†‡•™ƒ•”‡’‘”–‡† ‹ ͳͻͻ͸ „› — Š™ƒŽ† ȋ Š‡‡ ͳͺȌǤ͹͸ –‘‹ Š‹‘‡–”‹  ƒ‘—–• ‘ˆ i ‹ȋ ”ȌͶ™ƒ•—•‡†–‘‰‡–Š‡”™‹–ŠŠʹ‹ ʹˆ‘”–Š‡”‡†— –‹‘‘ˆ–‡”–‹ƒ”› ƒ‹†‡• ‹–‘ ‡ƒ‹‡•ǡ ™Š‹ Š ™‡”‡ •—„•‡“—‡–Ž› Š›†”‘Ž›œ‡† ‹–‘ –Š‡ ‘””‡•’‘†‹‰ƒŽ†‡Š›†‡•ǤŠ‡’”‘–‘ ‘Ž–‘Ž‡”ƒ–‡†ƒ™‹†‡”ƒ‰‡‘ˆˆ— Ǧ –‹‘ƒŽ ‰”‘—’•ǡ •— Š ƒ• ‹–”‹Ž‡•ǡ •‹Ž›Ž ‡–Š‡”•ǡ ‡’‘š‹†‡•ǡ ƒŽ‡‡• ƒ† ƒŽǦ ›‡•Ǥ ‘–Š –Š‡ ’ƒ”–‹ƒŽ ”‡†— –‹‘ –‘ ƒŽ†‡Š›†‡• ƒ† –Š‡ ‡ƒ‹‡•ƒ”‡ ˆ—”–Š‡”†‹• —••‡†‹–Š‹•–Š‡•‹•ȋ Šƒ’–‡”•ʹƒ†͵ȌǤ

 Scheme 18. Hydrosilylation of tertiary amides followed by hydrolysis of the formedenaminesresultedinaldehydesasfinalproducts.

ͳͷ  

1.3ReductiveFunctionalizationofAmides

 –‹˜ƒ–‹‘ ƒ† ˆ— –‹‘ƒŽ‹œƒ–‹‘ ‘ˆ ƒ‹†‡• Šƒ• „‡‡ ‘™ ˆ‘” ‘˜‡” ƒ ‡–—”›Ǥ͹͹ ‘‡ Žƒ••‹ ƒŽ ƒ‹†‡ ƒ –‹˜ƒ–‹‘ ”‡ƒ‰‡–• –Šƒ– Šƒ˜‡ „‡‡ ͹ͺ ͹ͻ ͺͲ ͺͳ ͺʹ ™‹†‡Ž›—•‡†ƒ”‡Žʹǡ Ž͵ǡ Ž͵ǡ Žͷ ƒ†ȋŽȌʹǤ ‡ ‡–”‡Ǧ •‡ƒ” Š ™‹–Š‹ –Š‡ ˆ‹‡Ž† ‘ˆ ”‡†— –‹˜‡ ˆ— –‹‘ƒŽ‹œƒ–‹‘ ‘ˆ ƒ‹†‡• Šƒ• •Š‘™–Šƒ–ƒ‹†‡• ƒ—†‡”‰‘‹Ž†‡Ž‡ –”‘’Š‹Ž‹ ƒ –‹˜ƒ–‹‘—•‹‰ˆʹǡ ‡•’‡ ‹ƒŽŽ›‹ ‘„‹ƒ–‹‘™‹–Š†‹ˆˆ‡”‡–’›”‹†‹‡Ǧ„ƒ•‡† ‘’‘—†•Ǥͺƒǡͺ͵ Š‡ƒŠ›†”‹†‡ƒ –‹˜ƒ–‹‘Ž‡ƒ†•–‘ƒŠ‹‰ŠŽ›‡Ž‡ –”‘’Š‹Ž‹ ‹‹‹—–”‹ˆŽƒ–‡ •’‡ ‹‡•ƒ†„›–”‡ƒ–‹‰–Š‡•‡insitu‰‡‡”ƒ–‡†‡Ž‡ –”‘’Š‹Ž‡•™‹–Š•—‹–ƒǦ „Ž‡— Ž‡‘’Š‹Ž‡•ǡƒƒ””ƒ›‘ˆ†‹ˆˆ‡”‡–ˆ— –‹‘ƒŽ‹œ‡† ‘’‘—†• ƒ„‡ ‘„–ƒ‹‡†ˆ”‘–Š‡•–ƒ”–‹‰ƒ‹†‡ȋ Š‡‡ͳͻƒȌǤ‡†— –‹˜‡ˆ— –‹‘ƒŽ‹Ǧ œƒ–‹‘‘ˆƒ‹†‡• ƒƒŽ•‘„‡ƒ Š‹‡˜‡†–Š”‘—‰Š— Ž‡‘’Š‹Ž‹ ƒ –‹˜ƒ–‹‘Ǣ‹ –Š‹• ƒ•‡ƒŠ›†”‹†‡ƒ––ƒ ‘–Š‡ ƒ”„‘›Ž‹‹–‹ƒŽŽ›‰‡‡”ƒ–‡•ƒŠ‡‹ƒ‹Ǧ ƒŽȋ Š‡‡ͳͻ„ƒ† ȌǤ

 Scheme19.Generalschemeshowing(a)electrophilicand(bandc)nucleophilic activationandfunctionalizationofamides.

Š‡ ‘ŽŽƒ’•‡‘ˆ–Š‹•–‡–”ƒŠ‡†”ƒŽ‹–‡”‡†‹ƒ–‡‰‹˜‡•ƒ‹‹‹—•’‡ ‹‡•ǡ ™Š‹ Šǡ‹Ž‹‡™‹–Š–Š‡‹‹‹—–”‹ˆŽƒ–‡•’‡ ‹‡•ǡ ƒ„‡–”‡ƒ–‡†™‹–Š†‹ˆǦ ˆ‡”‡–— Ž‡‘’Š‹Ž‡•Ǥ ‘™‡˜‡”ǡ–Š‡ ŠƒŽŽ‡‰‡‹•–‘ƒ˜‘‹†ƒƒ††‹–‹‘ƒŽ Š›†”‹†‡ ƒ––ƒ  ‘ –Š‡ ‹‹‹— •’‡ ‹‡• –Šƒ– ™‘—Ž† ‰‡‡”ƒ–‡ –Š‡ ‘””‡Ǧ •’‘†‹‰ ƒ‹‡Ǥ ‡’‡†‹‰ ‘ –Š‡ ƒ–—”‡ ‘ˆ –Š‡ ƒ‹†‡ •—„•–”ƒ–‡ǡ–Š‡ — Ž‡‘’Š‹Ž‹ ƒ –‹˜ƒ–‹‘ ƒƒŽ•‘’”‘†— ‡‡ƒ‹‡•ȋ Š‡‡ͳͻ ȌǤŠ‡•‡ •’‡ ‹‡• ƒ”‡ — Ž‡‘’Š‹Ž‹ ǡ –Š—• ”‡†— –‹˜‡ ˆ— –‹‘ƒŽ‹œƒ–‹‘ ƒ ƒŽ•‘ „‡ ’‡”ˆ‘”‡†„›–Š‡ƒ††‹–‹‘‘ˆ‡Ž‡ –”‘’Š‹Ž‡•Ǥ 

ͳ͸  

1.3.1ElectrophilicActivationofAmides

”‹ˆŽ‹ ƒŠ›†”‹†‡‹• ‘•‹†‡”‡†ƒ•ƒ‹Ž†”‡ƒ‰‡–ƒ†Šƒ•„‡‡—•‡†‹ –Š‡ ‡Ž‡ –”‘’Š‹Ž‹  ƒ –‹˜ƒ–‹‘ ‘ˆ ƒ‹†‡•Ǥ Š‡ ƒ‹†‡ ”‡ƒ –• ™‹–Š •–‘‹ Š‹‘Ǧ ‡–”‹ ƒ‘—–•‘ˆˆʹ–‘‰‡‡”ƒ–‡ƒŠ‹‰ŠŽ›‡Ž‡ –”‘’Š‹Ž‹ ‹‹‹—–”‹Ǧ ˆŽƒ–‡•’‡ ‹‡•Aȋ Š‡‡ʹͲȌǤͺͶŠ‡ƒ††‹–‹‘‘ˆ†‹ˆˆ‡”‡–’›”‹†‹‡„ƒ•‡•‹ ‘„‹ƒ–‹‘ ™‹–Š ˆʹ ‰‹˜‡• ”‹•‡ –‘ ‡˜‡ ‘”‡ ”‡ƒ –‹˜‡ ‹–‡”‡†‹ƒ–‡• †‡’‡†‹‰‘–Š‡•–”— –—”‡‘ˆ–Š‡ƒ‹†‡Ǥͺƒǡͺͷ ‘” ƒ‹†‡• ‘–ƒ‹‹‰ ȽǦ’”‘–‘•–Š‡‡–‡‹‹‹—‹‘C ƒ„‡ˆ‘”‡†„›†‡’”‘–‘ƒ–‹‘ǤŠ‹• •’‡ ‹‡•‹•‹‡“—‹Ž‹„”‹—™‹–Š–Š‡‡–‡‡Ǧƒ‹ƒŽ‹–‡”‡†‹ƒ–‡Bǡ™Š‹ Š ‹•Š‹‰ŠŽ›”‡ƒ –‹˜‡ƒ†ƒ•›–Š‡–‹ ƒŽŽ›˜‡”•ƒ–‹Ž‡‹–‡”‡†‹ƒ–‡Ǥͺ͸ –‹•‹Ǧ ’‘”–ƒ––‘’‘‹–‘—––Šƒ––Š‡ƒ –‹˜ƒ–‹‘‘ˆƒ‹†‡•’”‘ ‡‡†•„‘–Š‹–Š‡ ’”‡•‡ ‡ ƒ† ƒ„•‡ ‡ ‘ˆ –Š‡ ’›”‹†‹‡ „ƒ•‡ǡ ƒŽ–Š‘—‰Š –Š‡ ‡“—‹Ž‹„”‹— „‡–™‡‡–Š‡‡–‡‹‹‹—‹‘Cƒ†–Š‡ƒ‹ƒŽƒƒŽ‘‰—‡B‹••–”‘‰Ž› ƒˆˆ‡ –‡†„›„‘–Š–Š‡•–‡”‹ ƒ†‡Ž‡ –”‘‹ ’”‘’‡”–‹‡•‘ˆ–Š‡—•‡†’›”‹†‹‡ „ƒ•‡Ǥ

 Scheme20.Differentintermediatesthatcanbeformedbyactivationofamides withtriflicanhydride.

Š‡ƒ„•‡ ‡‘ˆȽǦ’”‘–‘•Ž‡ƒ†•–‘–Š‡ˆ‘”ƒ–‹‘‘ˆ†‹ˆˆ‡”‡–’›”‹†‹‹— ‹–‡”‡†‹ƒ–‡•ȋ’›”‹†‹‹—‹–‡”‡†‹ƒ–‡•ǡDƒ†EȌ„›— Ž‡‘’Š‹Ž‹ •—„Ǧ •–‹–—–‹‘ ‘ˆ –Š‡ –”‹ˆŽƒ–‡ ™‹–Š –Š‡ ’›”‹†‹‡ „ƒ•‡Ǥ ‘” •‡ ‘†ƒ”›ƒ‹†‡• –Š‹••’‡ ‹‡•‹•‹‡“—‹Ž‹„”‹—™‹–Š–Š‡Š‹‰ŠŽ›”‡ƒ –‹˜‡‹–”‹Ž‹—‹‘•’‡Ǧ ‹‡•Fǡ™Š‹ ŠŠƒ•„‡‡•—’’‘”–‡†„› ‡ƒ•—”‡‡–•”‡’‘”–‡†„›‘Ǧ ˜ƒ••ƒ‰Š‹ƒ† ‘Ǧ™‘”‡”•Ǥͺ͹

ͳ͹  

a) b) c) d) e) f) Citric acid 1. R4 MX Reduction or aqueous R4(SO)R5 m n + 2. H3O NaHCO3

Scheme21.TransformationsofamidesusingTf2O/2ǦFPyrasactivatingreagent.

Š‡ˆ‘”‡†‹‹‹—•’‡ ‹‡• ƒ„‡ˆ—”–Š‡””‡†— ‡†–‘–Š‡ ‘””‡•’‘†Ǧ ‹‰ƒ‹‡•ȋ•‡ –‹‘ͳǤʹǤͶƒ† Š‡‡ʹͳƒȌǤ͸Ͳǡ͸ͳ›™‘”Ǧ—’™‹–Š‡‹–Š‡” ‹–”‹  ƒ ‹† ‘” ƒ“—‡‘—• ƒ ͵‹–‹•’‘••‹„Ž‡–‘‘„–ƒ‹ƒŽ†‡Š›†‡•‘” ‹‹‡• ˆ”‘ –Š‡ ‹–‡”‡†‹ƒ–‡ ‹‹‹— ‘’‘—†• ȋ•‡ –‹‘ ͳǤʹǤͷǡ  Š‡‡ͳ͹ƒ† Š‡‡ʹͳ„ȌǤ͸ͳ— Ž‡‘’Š‹Ž‡• ƒƒŽ•‘ƒ††–‘–Š‡•‡•’‡Ǧ ‹‡• ƒ† –Š‹• ‡–Š‘†‘Ž‘‰› Šƒ• „‡‡ —•‡† ‡š–‡•‹˜‡Ž›ǡ •‘‡ ‡šƒ’Ž‡• ƒ”‡ ȽǦƒ”›Žƒ–‹‘ ȋ Š‡‡ ʹͳ ȌǡͺͺȽǦƒŽ›Žƒ–‹‘ǡͺͻ ȽǦƒ‹ƒ–‹‘ ȋ Š‡‡ ʹͳ†ȌͻͲƒ†‹–Š‡•›–Š‡•‹•‘ˆ‡–‘‡•ǡͻͳǡͻʹƒŽ†‡Š›†‡•ͻʹȋ Š‡‡ʹͳ‡ƒ† ͻ͵  Š‡‡ ʹͳˆȌ ƒ† ‡–‹‹‡•Ǥ  —ƒ‰—•‡†ˆʹ –‘ ƒ –‹˜ƒ–‡ Žƒ –ƒ• ˆ‘” –Š‡ƒŽ›Žƒ–‹‘‘ˆ–Š‡ ƒ”„‘›Ž ƒ”„‘™‹–Š•–‡’™‹•‡ƒ††‹–‹‘‘ˆ†‹ˆˆ‡”‡– ‘”‰ƒ‘‡–ƒŽŽ‹  ”‡ƒ‰‡–•ǡ ™Š‹ Š ”‡•—Ž–‡† ‹ –Š‡ ˆ‘”ƒ–‹‘ ‘ˆ ͻͶ †‹Ǧ•—„•–‹–—–‡†ƒ‹‡•Ǥ ›ƒ††‹–‹‘‘ˆ‡Ž͵–‘‰‡–Š‡”™‹–Š–Š‡‘”‰ƒ‘Ǧ ‡–ƒŽŽ‹ ”‡ƒ‰‡–ǡ–Š‡‘‘Ǧ•—„•–‹–—–‡†ƒ‹‡™ƒ•‘„–ƒ‹‡†ƒˆ–‡””‡†— Ǧ ͻͷ –‹‘™‹–Šƒ ͶǤ 

Š‡Šƒ”‡––‡‰”‘—’—•‡†ˆʹ ‹ ‘„‹ƒ–‹‘ ™‹–Š ʹǦ‡–Š‘š›’›”‹†‹‡ ȋʹǦ‡›”Ȍ –‘ ˆ‘” –‘•›ŽŠ›†”ƒœ‘ƒ‹†‡•ǡ ™Š‹ Š –Š”‘—‰Š†Ǧ ƒ–ƒŽ›œ‡†Ȃ ƒ –‹˜ƒ–‹‘›‹‡Ž†‡†͵Ǧƒ‹‘‹†ƒœ‘Ž‡•ȋ Š‡‡ ʹʹƒȌǤͻ͸•‹‹Žƒ”‡–ƒŽǦˆ”‡‡”‡ƒ –‹‘ˆ‘”–Š‡‹–”ƒ‘Ž‡ —Žƒ” › Ž‹œƒ–‹‘ ™ƒ•’—„Ž‹•Š‡†„›–Š‡ƒ—Ž‹†‡‰”‘—’ȋ Š‡‡ʹʹ„ȌǤͻ͹Šƒ”‡––‡ ˆ—”–Š‡” ‡š’Ž‘”‡†–Š‹•’”‘–‘ ‘Žˆ‘”ƒ‹–”ƒ‘Ž‡ —Žƒ” › Ž‹œƒ–‹‘‹–Š‡•›–Š‡•‹• ‘ˆ͵Ǧƒ‹‘‹‹†ƒœ‘ǦȏͳǡʹǦaȐ’›”‹†‹‡•ȋ Š‡‡ʹʹ ȌǤͻͺ —ƒ‰ ‘–”‹„—–‡† –‘ –Š‡ ƒ’’Ž‹ ƒ–‹‘• ƒ† ™‡”‡ ƒ„Ž‡ –‘ •›–Š‡•‹œ‡ ‡ƒ‹‘‡• ȋ Š‡‡ ʹʹ†ȌǤͻͻ‹Ž†ƒ –‹˜ƒ–‹‘™‹–Š–”‹ˆŽ‹ ƒŠ›†”‹†‡Šƒ•ˆ—”–Š‡”„‡‡ƒ’’Ž‹‡†‹ –Š‡ –‘–ƒŽ •›–Š‡•‹• ‘ˆ †‹ˆˆ‡”‡– ƒŽƒŽ‘‹†•ǡ ™Š‹ Š †‡‘•–”ƒ–‡• –Š‡ —•‡Ǧ ˆ—Ž‡•• ‘ˆ –Š‹• ‡–Š‘†‘Ž‘‰›ǤͳͲͲ —”–Š‡”‘”‡ǡ –Š‡ ˆ‘”‡† ‹‹‹— –”‹Ǧ ˆŽƒ–‡• ƒƒŽ•‘„‡—•‡†‹ͳǡ͵Ǧ › Ž‘ƒ††‹–‹‘•™‹–Š†‹’‘Žƒ”‘’Š‹Ž‡•ǤͳͲͳ

ͳͺ  



Scheme22.SelectedapplicationsoftheTf2Oactivationofamides.

1.3.2NucleophilicActivationofAmides

— Ž‡‘’Š‹Ž‹ ƒ –‹˜ƒ–‹‘‘ˆƒ‹†‡• ƒ„‡’‡”ˆ‘”‡†™‹–ŠŠ›†”‹†‡ ‘Ǧ –ƒ‹‹‰ ‘’‘—†•ǡ •— Š ƒ• –Š‡  Š™ƒ”–œ ”‡ƒ‰‡– ȋ”’ʹ ŽȌǤ Š‡ Š›Ǧ †”‹†‡ ‹•‡”–‹‘ ‰‡‡”ƒ–‡• ƒ œ‹” ‘ƒ › Ž‡ǡ ƒ •–ƒ„Ž‡ ‹–‡”‡†‹ƒ–‡ȋ•‡ Ǧ –‹‘ͳǤʹǤͷȌǤ͹ʹǡ͹͵ǡ͹Ͷǡ͹ͷŠ‡ˆ‘”‡†•’‡ ‹‡• ƒǡ„›–”‡ƒ–‡–™‹–Šƒ ‹† ‘ŽǦ Žƒ’•‡‹–‘–Š‡‹‹‡ȋ‘”‹‹‹—‹‘Ȍǡ™Š‹ Š ƒ‡‹–Š‡”„‡“—‡ Š‡† ™‹–Š™ƒ–‡”–‘‰‡‡”ƒ–‡ƒŽ†‡Š›†‡•ȋ Š‡‡ͳ͸Ȍǡ‘””‡ƒ –‡†™‹–Š†‹ˆˆ‡”‡– — Ž‡‘’Š‹Ž‡•Ǥ Š‡Š‹†ƒ‰”‘—’†‡˜‡Ž‘’‡†’”‘–‘ ‘Ž•ˆ‘”–Š‡ Š‡‘•‡Ž‡ –‹˜‡”‡Ǧ †— –‹˜‡— Ž‡‘’Š‹Ž‹ ƒ††‹–‹‘–‘–‡”–‹ƒ”›ǡ•‡ ‘†ƒ”›ƒ†NǦ‡–Š‘š›ƒǦ ‹†‡•ȋ Š‡‡ʹ͵ȌǤͳͲʹŠ‡›—•‡†–Š‡ Š™ƒ”–œ”‡ƒ‰‡––‘”‡†— ‡–Š‡ƒǦ ‹†‡•ǡ ˆ‘”‹‰ †‹ˆˆ‡”‡– ”Ǧƒ††— –•ǡ ™Š‹ Š –Š‡ „› ƒ††‹–‹‘ ‘ˆ †‹ˆˆ‡”‡– ƒ ‹†‹  ƒ††‹–‹˜‡• ƒ† — Ž‡‘’Š‹Ž‡• ’”‘†— ‡ –Š‡ ƒŽ›Žƒ–‡† ƒ‹‡•ǤŠ‡ ”‡†— –‹‘‘ˆ•‡ ‘†ƒ”›ƒ‹†‡•™ƒ•‘”‡†‹ˆˆ‹ —Ž–ǡ”‡“—‹”‹‰Š‹‰Š‡” Ž‘ƒ†‹‰•‘ˆ–Š‡ Š™ƒ”–œ”‡ƒ‰‡–ȋʹ‡“—‹˜ȌǤ ‹ƒŽŽ›ǡ–Š‡‘”‡”‡ƒ –‹˜‡ ƒŽŽ›Žœ‹  „”‘‹†‡ ™ƒ• —•‡† ‹ –Š‡ ƒŽŽ›Žƒ–‹‘ ƒ† ‰ƒ˜‡ –Š‡ „‡•– —–‘ˆˆ „‡–™‡‡•‡Ž‡ –‹˜‹–›ƒ†›‹‡Ž†Ǥ

ͳͻ  

 Scheme23.ChemoselectivereductivenucleophilicadditiondevelopedbyChida.

Š‡—•‡ ‘ˆ ‹Ž†— Ž‡‘’Š‹Ž‡•™ƒ• ”— ‹ƒŽ–‘ƒ˜‘‹†—™ƒ–‡†”‡ƒ –‹‘• ™‹–Š‘–Š‡”ˆ— –‹‘ƒŽ‰”‘—’•’”‡•‡–ȋ Š‡‡ʹͶȌǤ ‹‰Š Š‡‘•‡Ž‡ –‹˜‹Ǧ –›™ƒ•‘„•‡”˜‡†ˆ‘”–Š‡”‡†— –‹˜‡— Ž‡‘’Š‹Ž‹ ƒŽ›Žƒ–‹‘ǡƒŽ–Š‘—‰Šǡ–Š‡ • ‘’‡‘ˆ–Š‡•‡ ‘†ƒ”›ƒ‹†‡•™ƒ•‘”‡Ž‹‹–‡†–Šƒˆ‘”–Š‡–‡”–‹ƒ”› ƒ‹†‡•ǤŠ‡”‡†— –‹˜‡ƒŽ›Žƒ–‹‘‘ˆNǦ‡–Š‘š›ƒ‹†‡•ƒˆˆ‘”†‡†•‹‰‹ˆ‹Ǧ ƒ–Ž› ‹’”‘˜‡† ”‡•—Ž–•ǡ ™Š‹ Š ™‡”‡ ‡š’Žƒ‹‡† „› –Š‡ ‡–Š‘š› ‰”‘—’ –Šƒ– ˆ‘”• ƒ ˆ‹˜‡Ǧ‡„‡”‡† ‹–‡”‡†‹ƒ–‡Ǥ Š‹• ƒ‡• –Š‡ ”‡†— –‹‘ ‘”‡Ž‹‡Ž›–‘‘ —”ȋ Š‡‡ʹ͵ Ȍǡƒ†ƒ††‹–‹‘ƒŽŽ›–Š‡ˆ‘”‡†‹‹‹— ‹‘Šƒ•ƒŠ‹‰Š‡Ž‡ –”‘’Š‹Ž‹ ‹–›†—‡–‘–Š‡‡Ž‡ –”‘Ǧ†‡ˆ‹ ‹‡ ›‘ˆ–Š‡‹Ǧ –”‘‰‡ƒ–‘Ǥ



  TMS-CN  

    

     Scheme 24. Different nucleophiles used in the reductive functionalization of amidesbytheChidagroup.

Š‡ Š‡‘•‡Ž‡ –‹˜‡”‡†— –‹˜‡ƒŽŽ›Žƒ–‹‘‘ˆNǦ‡–Š‘š›ƒ‹†‡•Šƒ•ƒŽ•‘ „‡‡—•‡†‹–Š‡–‘–ƒŽ•›–Š‡•‹•‘ˆȋάȌǦ ‡’Š›”‘–‘š‹ǡƒ ‘’‘—†’‘•Ǧ •‡••‹‰ ‡—”‘Ž‘‰‹ ƒŽ ƒ –‹˜‹–› ȋ Š‡‡ ʹͷȌǤͳͲ͵ ‡”‡ǡ–Š‡ƒ‹†‡™ƒ•”‡Ǧ †— ‡†™‹–Š–Š‡ Š™ƒ”–œ”‡ƒ‰‡–ƒ†—†‡”™‡–•—„•‡“—‡–ƒŽŽ›Žƒ–‹‘

ʹͲ  

™‹–Š ƒŽŽ›Ž–”‹„—–›Ž•–ƒƒ‡ ‹ –Š‡ ’”‡•‡ ‡ ‘ˆ ƒ–ƒŽ›–‹  ƒ‘—–•‘ˆ  ȋˆȌ͵Ǥ

 Scheme25.ActivationandallylationofaNǦmethoxyamideinthesynthesisof (±)ǦGephyrotoxin.

Š‡ ƒ„ƒ ‰”‘—’ †‡˜‡Ž‘’‡† ƒ ’”‘–‘ ‘Ž ˆ‘” –Š‡ ”‡†— –‹‘ ‘ˆ NǦ•—Žˆ‘›Ž ƒ‹†‡• ‹–‘ ‹‹‹— ‹‘• ™‹–Š •—„•‡“—‡– –”ƒ’’‹‰ ™‹–Š ‡‹–Š‡” •‹Ž›Ž ›ƒ‹†‡ ‘” •‹Ž›Ž ‡‘Žƒ–‡• ȋ Š‡‡ ʹ͸ȌǤͳͲͶŠ‡‹– ‘‡•–‘ˆ— –‹‘ƒŽ ‰”‘—’–‘Ž‡”ƒ ‡ǡ–Š‡•›•–‡•Š‘™••‘‡ Š‡‘•‡Ž‡ –‹˜‹–› ƒ†ƒ‹†‡• ‘–ƒ‹‹‰–‡”‹ƒŽƒŽ‡‡•ǡƒŽ›‡•ƒ†ˆ”‡‡Š›†”‘š›Ž‘‹‡–‹‡•™‡”‡ –‘Ž‡”ƒ–‡†‹–Š‡”‡†— –‹‘Ǥ

 Scheme26.Alkylationofamidesbypriorformationofiminiumions.

•‹‹Žƒ”–›’‡‘ˆ”‡†— –‹˜‡ˆ— –‹‘ƒŽ‹œƒ–‹‘’”‘–‘ ‘Ž™ƒ•”‡ ‡–Ž›’—„Ǧ Ž‹•Š‡† „› –Š‡ ‹š‘ ‰”‘—’ ȋ Š‡‡ ʹ͹ƒȌǤͳͲͷ –Š‹• ƒ•‡ǡ–Š‡ ”Ǧ„ƒ•‡† ”‡†— –‹‘ ’”‘–‘ ‘Ž †‡˜‡Ž‘’‡† „› ƒ‰ƒ•Š‹ƒ ˆ‘” –Š‡ Š›†”‘•‹Ž›Žƒ–‹‘ ‘ˆ ƒ‹†‡•ͳͶ ™ƒ• ‡’Ž‘›‡† ƒ† –Š‡ ›ƒƒ–‹‘ ™ƒ• ’‡”ˆ‘”‡† —•‹‰ ǦǤŠ‡‡–Š‘†‘Ž‘‰›•Š‘™‡†Š‹‰Šˆ— –‹‘ƒŽ‰”‘—’–‘Ž‡”ƒ ‡ƒ† ™ƒ•ƒ’’Ž‹ ƒ„Ž‡‘ƒ„”‘ƒ†”ƒ‰‡‘ˆ–‡”–‹ƒ”›ƒ‹†‡•Ǣˆ—”–Š‡”‘”‡ǡ‹–™ƒ• ƒ’’Ž‹‡†‹–Š‡ ›ƒƒ–‹‘‘ˆƒ‹†‡ ‘–ƒ‹‹‰†”—‰•ǤŠ‡”‡†— –‹˜‡ˆ— Ǧ –‹‘ƒŽ‹œƒ–‹‘™ƒ•ƒŽ•‘—•‡†‹–Š‡–‘–ƒŽ•›–Š‡•‹•‘ˆAspidospermaƒŽƒǦ Ž‘‹†•ͳͲ͸ƒ†–Š‡ƒŽƒŽ‘‹†ȋάȌǦepiǦ‡’‹“—‹ƒ‹†‡™ƒ•‘„–ƒ‹‡†‹‘Ž›ˆ‘—” •–‡’•ǤͳͲ͹ ʹͳ  

 Scheme 27. Alkylation of amides by the prior activation/reduction with IrCl(CO)(PPh3)2.

—ƒ‰ƒ† ‘Ǧ™‘”‡”•Šƒ˜‡†‡‘•–”ƒ–‡†‡ˆˆ‹ ‹‡–ƒŽ››Žƒ–‹‘‘ˆƒǦ ‹†‡•ǡˆ—”‹•Š‹‰ȽǦƒŽ››Žƒ–‡†ƒ‹‡•ƒ•–Š‡ˆ‹ƒŽ’”‘†— –•ȋ Š‡‡ ʹ͹„ȌǤͳͲͺŠ‡•›•–‡ǡƒŽ•‘„ƒ•‡†‘ƒ‰ƒ•Š‹ƒǯ•Š›†”‘•‹Ž›Žƒ–‹‘’”‘–‘Ǧ ‘Žǡ †‹•’Žƒ›• Š‹‰Š Š‡‘•‡Ž‡ –‹˜‹–› ƒ† •‡˜‡”ƒŽ •‡•‹–‹˜‡ ˆ— –‹‘ƒŽ ‰”‘—’•ǡ•— Šƒ•ƒŽ†‡Š›†‡ǡ ›ƒ‘ǡ‡•–‡”ƒ†‹–”‘‰”‘—’•™‡”‡–‘Ž‡”ƒ–‡†Ǥ Š‡Š‹†ƒ‰”‘—’—•‡†–Š‡ ”Ǧ„ƒ•‡†”‡†— –‹‘’”‘–‘ ‘Ž†‡˜‡Ž‘’‡† „›ƒ‰ƒ•Š‹ƒ–‘ˆ‘”•‹Ž›ŽŠ‡‹ƒ‹ƒŽ•ˆ”‘NǦ‡–Š‘š›ƒ‹†‡•ǡ™Š‹ Š ͳͲͻ ™‡”‡–”‡ƒ–‡†™‹–Š ͵ȉ–ʹƒ†— Ž‡‘’Š‹Ž‡•ȋ Š‡‡ʹͺƒȌǤ Š‡”‡Ǧ †— –‹˜‡ ˆ— –‹‘ƒŽ‹œƒ–‹‘ ™ƒ• Š‹‰ŠŽ› Š‡‘•‡Ž‡ –‹˜‡ ƒ† –Š‡ •ƒ‡ —Ǧ Ž‡‘’Š‹Ž‡• ‘—Ž†„‡—•‡†ƒ•‹–Š‡ˆ— –‹‘ƒŽ‹œƒ–‹‘™‹–Š–Š‡ Š™ƒ”–œ ”‡ƒ‰‡–ȋ Š‡‡ʹͶȌǤŠ‡”‡†— –‹‘‘ˆNǦŠ›†”‘š›ƒ‹†‡•’”‘†— ‡•†‹•Ǧ ‹Ž›Žƒ–‡†NǡOǦƒ ‡–ƒŽ•ƒ•‹–‡”‡†‹ƒ–‡•ǡ™Š‹ Š—’‘–”‡ƒ–‡–™‹–Š‡‹–Š‡” ’›”‹†‹‹—pǦ–‘Ž—‡‡•—Žˆ‘ƒ–‡ȋȌ‘”–‡–”ƒ„—–›Žƒ‘‹—ˆŽ—‘”‹†‡ ȋ Ȍ ƒˆˆ‘”†• ˆ— –‹‘ƒŽ‹œ‡† ‹–”‘‡• ƒ• –Š‡ ˆ‹ƒŽ ’”‘†— –• ȋ Š‡‡ ʹͺ„ȌǤͳͳͲ

 Scheme28.ReductivefunctionalizationdevelopedbytheChidagroup,employǦ ingtheIrCl(CO)(PPh3)2Ǧbasedreductionprotocolfortheinitialreduction.

‘†ƒ›ǡƒŽ‹‹–‡†—„‡”‘ˆ‡–ƒŽǦ ƒ–ƒŽ›œ‡†’”‘–‘ ‘Ž•ˆ‘”–Š‡‹Ž†ƒ† Š‡‘•‡Ž‡ –‹˜‡”‡†— –‹˜‡ˆ— –‹‘ƒŽ‹œƒ–‹‘‘ˆƒ‹†‡•Šƒ˜‡„‡‡†‡˜‡ŽǦ ‘’‡†ǡ ƒ† –Š‡ ƒŒ‘”‹–› ‘ˆ –Š‡ ’”‘–‘ ‘Ž• ƒ”‡ „ƒ•‡† ‘ –Š‡ ‹”‹†‹—Ǧ ƒ–ƒŽ›œ‡† Š‡‘•‡Ž‡ –‹˜‡ Š›†”‘•‹Ž›Žƒ–‹‘ •›•–‡ ”‡’‘”–‡† „› ƒ‰ƒ•Š‹Ǧ ƒƒ† ‘Ǧ™‘”‡”•Ǥ 

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1.4ObjectivesoftheThesis

Š‡ƒ‹‘ˆ–Š‹•–Š‡•‹•™ƒ•–Š‡†‡˜‡Ž‘’‡–‘ˆ‡ˆˆ‹ ‹‡– ƒ–ƒŽ›–‹ •›•–‡• „ƒ•‡†‘‘ȋȌ͸ˆ‘”–Š‡Š›†”‘•‹Ž›Žƒ–‹‘‘ˆƒ‹†‡•ǤŠ‡ˆ‹”•–’ƒ”–ǡ’”‡Ǧ •‡–‡†‹ Šƒ’–‡”ʹǡ‹•†‡˜‘–‡†–‘–Š‡‹Ž†ƒ†•‡Ž‡ –‹˜‡–”ƒ•ˆ‘”ƒ–‹‘ ‘ˆƒ‹†‡•‹–‘ƒ‹‡•ƒ†ƒŽ†‡Š›†‡•ǤŠ‡ Š‡‘•‡Ž‡ –‹˜‹–›‘ˆ–Š‡’”‘Ǧ –‘ ‘Ž™ƒ•‹˜‡•–‹‰ƒ–‡†ƒ•™‡ŽŽƒ•–Š‡ƒ„‹Ž‹–›–‘• ƒŽ‡Ǧ—’–Š‡”‡ƒ –‹‘•Ǣ ˆ—”–Š‡”‘”‡–Š‡•›•–‡™ƒ•‡˜ƒŽ—ƒ–‡†‹–Š‡•›–Š‡•‹•‘ˆ’Šƒ”ƒ ‡—–‹Ǧ ƒŽ†”—‰‘‡’‡œ‹ŽǤ

 Šƒ’–‡”͵ǡ–Š‡‘ȋȌ͸•›•–‡™ƒ•‘’–‹‹œ‡†ˆ‘”–Š‡ˆ‘”ƒ–‹‘ ‘ˆ ‡ƒ‹‡• ˆ”‘ ƒ‹†‡ ”‡†— –‹‘ǡ ™‹–Š –Š‡ ƒ‹ ‘ˆ †‡˜‡Ž‘’‹‰ ƒ Š‡‘•‡Ž‡ –‹˜‡™ƒ›–‘’”‘†— ‡‡ƒ‹‡•ǤŠ‡”‡•—Ž–•’”‡•‡–‡†‹–Š‹• Šƒ’–‡” ƒ”‡ ƒ •—ƒ”› ‘ˆ –Š‡ ˆ‹†‹‰• ‹ ƒ’‡”•  Ȃ  ”‡‰ƒ”†‹‰ ‡ƒ‹‡ˆ‘”ƒ–‹‘Ǥ

‘–Š‡” ˆ‘ —• ™ƒ• –‘ ‡š’Ž‘”‡ –Š‡ ‘ȋȌ͸Ǧ ƒ–ƒŽ›œ‡† •›•–‡ ˆ‘” ”‡†— –‹˜‡ ˆ— –‹‘ƒŽ‹œƒ–‹‘ ‘ˆ ƒ‹†‡• ‹–‘ ‘–Š‡” ˜ƒŽ—ƒ„Ž‡ ‘’‘—†•Ǥ Š—•ǡ–Š‡–Š‹”†’ƒ”–‘ˆ–Š‹•–Š‡•‹•†‡• ”‹„‡•–Š‡†‹”‡ ––”ƒ•ˆ‘”ƒ–‹‘‘ˆ ƒ‹†‡• ‹–‘ ƒ ˜ƒ”‹‡–› ‘ˆ Š‡–‡”‘ › Ž‹  ‘’‘—†• •— Š ƒ• –”‹ƒœ‘Ž‹‡•ǡ –”‹ƒœ‘Ž‡•ǡ ͶǡͷǦ†‹Š›†”‘‹•‘šƒœ‘Ž‡•ǡ ’›”‹‹†‹‡†‹‘‡• ƒ• ™‡ŽŽ ƒ• NǦ•—Žˆ‘›Žˆ‘”ƒ‹†‹‡•  ƒ† –Š‹‘ƒ ”›Žƒ‹†‡•Ǥ Š‡ ’”‘–‘ ‘Ž• ˆ‘” –Š‡ ˆ‘”ƒ–‹‘ ‘ˆ –”‹ƒœ‘Ž‹‡•ǡ –”‹ƒœ‘Ž‡• ƒ† NǦ•—Žˆ‘›Žˆ‘”ƒ‹†‹‡• ™‡”‡ ƒŽ•‘‡˜ƒŽ—ƒ–‡†‘’”‡’ƒ”ƒ–‹˜‡• ƒŽ‡ǡŠ‹‰ŠŽ‹‰Š–‹‰–Š‡’”ƒ –‹ ƒŽ‹–›‘ˆ–Š‡ †‡˜‡Ž‘’‡† ƒ–ƒŽ›–‹ ’”‘–‘ ‘Ž•Ǥ 

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ʹͶ  

2. Chemoselective Reduction of Tertiary AmidesunderThermalControl(PaperI)

”‡˜‹‘—•Ž›ǡ –Š‡ †‘Žˆ••‘ ‰”‘—’ Šƒ• †‡˜‡Ž‘’‡† ƒ ‘ȋȌ͸Ǧ ƒ–ƒŽ›œ‡† ’”‘–‘ ‘Ž ˆ‘” –Š‡ ”‡†— –‹‘ ‘ˆ ȽǡȾǦ—•ƒ–—”ƒ–‡† ƒ‹†‡• ‹–‘ –Š‡ ‘””‡Ǧ •’‘†‹‰ ƒŽŽ›Ž‹  ƒ‹‡• ȋ Š‡‡ ͳ͵ ƒ†  Š‡‡ ʹͻƒȌǤ͸ͻŠ‡•›•–‡ –‘Ž‡”ƒ–‡† ‹–‡”ƒŽ ‘Ž‡ˆ‹•Ǣ Š‘™‡˜‡”ǡ ‘ ‘–Š‡” ”‡†— ‹„Ž‡ ˆ— –‹‘ƒŽ ‰”‘—’•™‡”‡‡˜ƒŽ—ƒ–‡†Ǥ —”–Š‡”‹˜‡•–‹‰ƒ–‹‘‘ˆ–Š‡‘ȋȌ͸Ǧ ƒ–ƒŽ›œ‡† •›•–‡•Š‘™‡†–Šƒ–„‡œƒ‹†‡1a™ƒ•”‡†— ‡†‹–‘ƒ‹‡3aƒˆ–‡”͵Š ƒ– ͺͲ ι ™‹–Š ͷ ‘ŽΨ ‘ȋȌ͸ǡ ƒŽ–Š‘—‰Š ƒ Žƒ”‰‡” ƒ‘—– ‘ˆ  ȋͶ ‡“—‹˜Ȍ ™ƒ• ”‡“—‹”‡† ȋ Š‡‡ ʹͻ„ȌǤ Š‡ –Š‡ ”‡ƒ –‹‘ ’”‘‰”‡•• ™ƒ• ‘‹–‘”‡†„›ͳ •’‡ –”‘• ‘’›ƒ–”‘‘–‡’‡”ƒ–—”‡•‹Ž›ŽŠ‡‹ƒ‹Ǧ ƒŽ1a´™ƒ•‘„•‡”˜‡†ƒ•–Š‡ƒŒ‘”’”‘†— –Ǥͳͳͳ

 Scheme29.a)Previouswork.b)TemperatureǦcontrolledhydrosilylationprotoǦ col.

‹Ž›ŽŠ‡‹ƒ‹ƒŽ1a’‹•ƒ‹–‡”‡†‹ƒ–‡‹–Š‡–™‘Ǧ•–‡’”‡†— –‹‘‘ˆƒǦ ‹†‡•–‘™ƒ”†•ƒ‹‡•ƒ†Šƒ˜‡’”‡˜‹‘—•Ž›„‡‡”‡’‘”–‡†„›ƒ‡ŽŽƒ† ‘Ǧ™‘”‡”•‹ƒ‡ Šƒ‹•–‹ •–—†›™Š‡”‡–Š‡›—•‡†‘ȋȌ͸‹–Š‡”‡Ǧ †— –‹‘‘ˆNǡNǦ†‹‡–Š›Žˆ‘”ƒ‹†‡ȋ Ȍƒ†NǡNǦ†‹‡–Š›Žˆ‘”ƒ‹†‡Ǥͳͳʹ ––Š‡•ƒ‡–‹‡”‘‘Šƒ”–ƒ†ƒ”‘„•‡”˜‡†–Š‹•‹–‡”‡†‹ƒ–‡ƒ•™‡ŽŽ ™Š‡‹˜‡•–‹‰ƒ–‹‰–Š‡‹”‹†‹—Ǧ ƒ–ƒŽ›œ‡†”‡†— –‹‘‘ˆƒ‹†‡•Ǥͷʹ„Š‡ ’‘••‹„‹Ž‹–›–‘•–‘’ƒ––Š‡•‹Ž›ŽŠ‡‹ƒ‹ƒŽ•–ƒ‰‡‘ˆ–Š‡”‡†— –‹‘‹•“—‹–‡ ”ƒ”‡•‹ ‡–Š‹••’‡ ‹‡•‡ƒ•‹Ž› ‘ŽŽƒ’•‡•‹–‘–Š‡‹‹‹—‹‘‹–Š‡’”‡•Ǧ ‡ ‡ ‘ˆ ‡™‹• ƒ ‹†• ‘” ‡–ƒŽǦ ƒ–ƒŽ›•–• ƒ† –Š‡”‡ƒˆ–‡” —†‡”‰‘‡• ”ƒ’‹†

ʹͷ  

”‡†— –‹‘‹–‘ƒ‹‡Ǥ‹ ‡ƒŠ‹‰Š ‘˜‡”•‹‘‘ˆƒ‹†‡‹–‘•‹Ž›ŽŠ‡‹Ǧ ƒ‹ƒŽ™ƒ•‘„•‡”˜‡†ƒ–Ž‘™–‡’‡”ƒ–—”‡ƒ†‹–™ƒ•Š›’‘–Š‡•‹œ‡†–Šƒ– ƒŽ†‡Š›†‡• ‘—Ž†„‡‘„–ƒ‹‡†ƒˆ–‡”ƒ ‹†‹ ™‘”Ǧ—’‘ˆ–Š‡•‡•’‡ ‹‡•Ǥ—‡ –‘–Š‡Ž‘™„‘‹Ž‹‰’‘‹–‘ˆ„‡œƒŽ†‡Š›†‡ȋ2aȌǡpǦ‡–Š‘š›„‡œƒ‹†‡1b ™ƒ•‹•–‡ƒ†‡˜ƒŽ—ƒ–‡†ƒ†”‡†— ‡†ǡ™Š‹ Š’”‘˜‹†‡†–Š‡ ‘””‡•’‘†‹‰ ƒŽ†‡Š›†‡2b‹ͺͲΨ‹•‘Žƒ–‡†›‹‡Ž†ƒˆ–‡”™‘”Ǧ—’ȋ Š‡‡͵ͲȌǤ‹ˆˆ‡”‡– NǦ•—„•–‹–—‡–•™‡”‡‡˜ƒŽ—ƒ–‡†ǡ’”‘˜‹†‹‰–Š‡ƒŽ†‡Š›†‡2b‹ͺ͸Ψƒ† ͺ͵Ψ›‹‡Ž†•ǡ”‡•’‡ –‹˜‡Ž›ǡ•–ƒ”–‹‰ˆ”‘–Š‡†‹„‡œ›Žƒ†–Š‡‘”’Š‘Ž‹‡ †‡”‹˜‡†ƒ‹†‡•Ǥ Š‡• ‘’‡‘ˆ–Š‡”‡ƒ –‹‘™ƒ•ˆ—”–Š‡”‹˜‡•–‹‰ƒ–‡†ƒ†‹–™ƒ•‘„Ǧ •‡”˜‡† –Šƒ– ‡Ž‡ –”‘‹  ’”‘’‡”–‹‡• ‘ˆ –Š‡ ƒ”‘ƒ–‹  ”‹‰ ‘ˆ –Š‡ ƒ‹†‡ •–”‘‰Ž›‹ˆŽ—‡ ‡†–Š‡”‡ƒ –‹‘ǡ™Š‡”‡‹’ƒ”–‹ —Žƒ”‡Ž‡ –”‘Ǧ’‘‘”•—„Ǧ •–”ƒ–‡•”‡“—‹”‡†Šƒ”•Š‡” ‘†‹–‹‘•ǡ‘ˆ–‡‹ ‘„‹ƒ–‹‘™‹–Š‡š–‡†‡† ”‡ƒ –‹‘–‹‡•–‘ƒ Š‹‡˜‡Š‹‰Š ‘˜‡”•‹‘•‘ˆ–Š‡•–ƒ”–‹‰ ‘’‘—†•Ǥ Š‡ ‹‘†‘Ǧ ‘–ƒ‹‹‰ ƒŽ†‡Š›†‡ 2d ™ƒ• ‹•‘Žƒ–‡† ™‹–Š‘—– ƒ› †‡–‡ –ƒ„Ž‡ †‡ŠƒŽ‘‰‡ƒ–‹‘Ǥ Š‡ ƒ†ƒƒ–›ŽǦ„ƒ•‡† ƒŽ†‡Š›†‡ 2e™ƒ•‘„–ƒ‹‡†‹ ͺͳΨ›‹‡Ž†ƒˆ–‡”ͶͺŠ‘—”•”‡ƒ –‹‘–‹‡ƒ–ȂͷιǤŽ‘™”‡ƒ –‹‘–‡’‡”ƒǦ –—”‡™ƒ•‡ ‡••ƒ”›†—‡–‘’”‘„Ž‡•™‹–Š‘˜‡”Ǧ”‡†— –‹‘‘ˆ–Š‡ƒ‹†‡ ‹–‘ƒ‹‡™Š‹ Š‘ —””‡†ƒ–Š‹‰Š‡”–‡’‡”ƒ–—”‡ǤŠ‡ˆ—”ƒƒ†–Š‹‘Ǧ ’Š‡‡ ƒ‹†‡• ™‡”‡ ƒŽ•‘ ‘’ƒ–‹„Ž‡ ƒ† ‰ƒ˜‡ ƒŽ†‡Š›†‡• 2fƒ†2g‹ ͸ͻΨƒ†ͻͷΨͳ ›‹‡Ž†ǡ”‡•’‡ –‹˜‡Ž›Ǥ —”–Š‡”‘”‡ǡ–Š‡pǦ‹–”‘•—„Ǧ •–‹–—–‡† ƒ‹†‡ ȋͶǦ‹–”‘’Š‡›ŽȌȋ’‹’‡”‹†‹ǦͳǦ›ŽȌ‡–Šƒ‘‡ ‘—Ž† ‘– „‡ ”‡†— ‡†ƒ–Ž‘™–‡’‡”ƒ–—”‡ƒ†™Š‡–Š‡‘”‡‡Ž‡ –”‘Ǧ”‹ Šƒ‹†‡ ȋ͵Ǧ‡–Š‘š›ǦͶǦ‹–”‘’Š‡›ŽȌȋ’‹’‡”‹†‹ǦͳǦ›ŽȌ‡–Šƒ‘‡ 1h™ƒ•‡šƒǦ ‹‡†ǡ–Š‡ ‘””‡•’‘†‹‰‹–”‘ǦƒŽ†‡Š›†‡2h™ƒ•‹•‘Žƒ–‡†‹ͺͳΨ›‹‡Ž†Ǥ ‹†‡•™‹–Š˜ƒ”‹‘—•”‡†— ‹„Ž‡ˆ— –‹‘ƒŽ‰”‘—’•™‡”‡‡˜ƒŽ—ƒ–‡† ƒ† ƒŽ†‡Š›†‡• ‘–ƒ‹‹‰ ˜‹›ŽǦ ȋ2iȌǡ ƒ”„ƒƒ–‡Ǧ ȋ2jȌǡ ƒ”„‘š›Ž‹  ƒ ‹†Ǧ ȋ2kȌƒ† ›ƒ‘‰”‘—’•ȋ2lȌ™‡”‡‘„–ƒ‹‡†‹ͺͺΨǡ͸ʹΨǡ͹ͻΨƒ†͹ͻΨǡ ”‡•’‡ –‹˜‡Ž›Ǥ‡†— –‹‘‘ˆ–Š‡BocǦ’”‘–‡ –‡†ƒ‹†‡1j ‘—Ž†‘–„‡’‡”Ǧ ˆ‘”‡†™‹–Š‘—–’ƒ”–‹ƒŽƒ‹‡ˆ‘”ƒ–‹‘ǡ™Š‹ Šƒˆˆ‡ –‡†–Š‡›‹‡Ž†‘ˆ–Š‡ ƒŽ†‡Š›†‡Ǥ‘”‡‘˜‡”ǡ‘”‡†— –‹‘‘ˆ‡•–‡”ǡ‡–‘‡ƒ†ƒŽ†‡Š›†‡‘‹‡Ǧ –‹‡• ™‡”‡ ‘„•‡”˜‡† ƒ† –Š‡ ‘””‡•’‘†‹‰ ƒŽ†‡Š›†‡• ȋ2mȂ2qȌ ™‡”‡ ‘„–ƒ‹‡†‹Š‹‰Š›‹‡Ž†•Ǥ††‹–‹‘ƒŽŽ›ǡˆ‘”–Š‡‡•–‡”Ǧˆ— –‹‘ƒŽ‹œ‡†ƒ‹†‡ 1m –Š‡ ”‡†— –‹‘ ‹–‘ –Š‡ •‹Ž›ŽŠ‡‹ƒ‹ƒŽ ‘—Ž† „‡ ’‡”ˆ‘”‡† —†‡” ‹Ž†‡””‡ƒ –‹‘ ‘†‹–‹‘•‹–Š‡ ƒ•‡‘ˆNǡNǦ†‹‡–Š›Ž•—„•–‹–—–‡†ƒǦ ‹†‡ ‘’ƒ”‡† –‘ –Š‡ ’‹’‡”‹†‹‡ †‡”‹˜ƒ–‡Ǥ ˜‡ ƒ‹†‡• ‘–ƒ‹‹‰ ‡–‹‹‡ƒ†ƒŽ†‹‹‡•—„•–‹–—‡–•™‡”‡ Š‡‘•‡Ž‡ –‹˜‡Ž›”‡†— ‡†ƒ† –Š‡ ‘””‡•’‘†‹‰ƒŽ†‡Š›†‡•ȋ2rƒ†2sȌ™‡”‡‘„–ƒ‹‡†‹Š‹‰Š›‹‡Ž†•Ǥ

ʹ͸  

2b,80% 2c, 67% 2d,92% 2e, 81% 2 h, 0 °C 6 h, 65 °C 3 h, r.t. 48 h, –5 °C 3 h, r.t., 86%a 13 h, r.t., 83%b

2f,c 69% 2g,c 95% 2h,d 81% 2i, 88% 5 h, 0 °C 24 h, –5 °C 5 h, 50 °C 3 h, r.t.

2j, 62% 2k,e,f 79% 2l, 74% 2m,81% 5 h, 40 °C 9 h, 40 °C 16 h, 50 °C 10 h, 60 °C 2 h, r.t., 88%g

2n, 83% 2o, 86% 2p,h 82% 2q,88% 3 h, 60 °C 3 h, r.t. 5 h, 65 °C 4 h, 50 °C O

N

MeO 2r,f 81% 2s,f 80% 24 h, r.t. 1 h, 40 °C Scheme30.ChemoselectiveformationofaldehydesfrompiperidinederivedamǦ ides 1 (1.0mmol), isolated yields. aDibenzyl derived amide 1b’. b Morpholine derived amide 1b’’. c 1H NMR yields using 1,3,5Ǧtrimethoxybenzene as internal d e f standard. Mo(CO)6(10mol%),TMDS(6.0equiv). TMDS(8.0equiv). Isolation g h wasperformedon0.5mmolscale. N,NǦdimethylderivedamide1m’. Mo(CO)6 (10mol%).



ʹ͹  

‡”ˆ‘”‹‰–Š‡”‡†— –‹‘•ƒ–‡Ž‡˜ƒ–‡†–‡’‡”ƒ–—”‡Ž‡†–‘ˆ—ŽŽ”‡†— –‹‘ ‹–‘–Š‡ ‘””‡•’‘†‹‰ƒ‹‡•ȋ Š‡‡͵ͳȌǤŠ‡‡–Š‘†‹•ƒ’’Ž‹ ƒ„Ž‡ –‘ „‘–Š ‡Ž‡ –”‘Ǧ”‹ Š ƒ† ‡Ž‡ –”‘Ǧ’‘‘” ƒ‹†‡• ȋ1bƒ†1cȌǡ ƒŽ–Š‘—‰Š –Š‡ ‡Ž‡ –”‘Ǧ’‘‘” ƒ‹†‡• ”‡“—‹”‡† Ž‘‰‡” ”‡ƒ –‹‘ –‹‡Ǥ ‹†‡• ™‹–Š ˜ƒ”‹‘—• NǦ•—„•–‹–—‡–• ™‡”‡ ‡˜ƒŽ—ƒ–‡† ƒ† ’‹’‡”‹†‹‡ǡ NǡNǦ†‹„‡œ›Žƒ‹‡ ȋ3b’Ȍǡ ‘”’Š‘Ž‹‡ ȋ3b’’Ȍǡ NǡNǦ†‹‡–Š›Žƒ‹‡ ȋ3m’ ƒ†3kȌƒ†’›””‘Ž‹†‹‡ȋ3uȌ†‡”‹˜‡†ƒ‹‡•™‡”‡‘„–ƒ‹‡†‹‰‘‘†–‘ ‡š ‡ŽŽ‡– ›‹‡Ž†•Ǥ ‰ƒ‹ǡ ‘ †‡ŠƒŽ‘‰‡ƒ–‹‘ ™ƒ• ‘„•‡”˜‡† ˆ‘” –Š‡ ‹‘†‘Ǧ ‘–ƒ‹‹‰ƒ‹†‡1dƒ†ƒ‹‡3d™ƒ•‹•‘Žƒ–‡†‹‡š ‡ŽŽ‡–›‹‡Ž†Ǥ ‡–Ǧ ‡”‘ƒ”›Ž ‘–ƒ‹‹‰ƒ‹‡•3fƒ†3gƒŽ‘‰™‹–ŠƒŽ‹’Šƒ–‹ ƒ‹‡3t™‡”‡ ƒŽ•‘‘„–ƒ‹‡†‹Š‹‰Š›‹‡Ž†•ǤŠ‹”ƒŽƒ‹†‡1u™ƒ•”‡†— ‡†–‘–Š‡ ‘””‡Ǧ •’‘†‹‰ƒ‹‡3u‹Š‹‰Š‹•‘Žƒ–‡†›‹‡Ž†™‹–Šˆ—ŽŽ”‡–‡–‹‘‘ˆ–Š‡•–‡Ǧ ”‡‘ Š‡‹•–”›Ǥ —‡”‘—• ˆ— –‹‘ƒŽ ‰”‘—’• ™‡”‡ ”‡ƒ‹‡† —–‘— Š‡†ǡ •— Š ƒ• ‹–”‘ȋ3hȌǡ‘Ž‡ˆ‹ȋ3iƒ†3vȌǡ ƒ”„ƒƒ–‡ȋ3jȌǡ‡•–‡”ȋ3mǡ3wƒ†3m’Ȍ ƒ† ƒ”„‘š›Ž‹  ƒ ‹† ȋ3kȌǤ  —”’”‹•‹‰Ž›ǡ ‡–‹‹‡ ƒ† ƒŽ†‹‹‡ ‰”‘—’• ™‡”‡‡ƒ•‹Ž›–‘Ž‡”ƒ–‡†‡˜‡ƒ–Š‹‰Š‡”–‡’‡”ƒ–—”‡•ƒ†–Š‡ ‘””‡•’‘†Ǧ ‹‰ƒ‹†‡•ȋ1rƒ†1sȌ™‡”‡ Š‡‘•‡Ž‡ –‹˜‡Ž›”‡†— ‡†–‘ƒˆˆ‘”† ‘Ǧ ’‘—†•3rƒ†3sǤ 

ʹͺ  

3a, 97% 3b, 95% 3b’, 94% 5 h, 80 °C 2 h, 70 °C 3 h, 80 °C

3b’’, 77% 3c, 74% 3d, 92% 5 h, 80 °C 24 h, 80 °C 3 h, 80 °C

3t, 81% 3f: X = O, 82%a 3u,c 68% 3 h, 80 °C 3g: X = S, 78%b 4 h, 80 °C

3h,d 74% 3i, 78% 3v, 79% 4 h, 80 °C 3 h, 80 °C 3 h, 80 °C

e 3j, 76% 3m: 4-CO2Me, 86% 3m’, 70% f 4 h, 80 °C 3w: 2-CO2Me, 81% 5 h, 80 °C

3k,g 68% 3r,g 79% 3s,g 88% 24 h, 80 °C 1 h, 80 °C 1 h, 80 °C Scheme31.Chemoselectiveformationofaminesfromamides(1.0mmol),isolatǦ  a b  c d ed yields.  2 h, 65 °C. 5h, 65 °C.  99% ee.  Mo(CO)6 (10mol%), TMDS (2.0mmol).eTMDS(2.0equiv),9h,80°C.f24h,65°C.gIsolationwasperformed on0.5mmolscale. 

ʹͻ  

—‡ –‘ –Š‡ Šƒ”•Š‡” ”‡ƒ –‹‘ ‘†‹–‹‘• ”‡“—‹”‡† ˆ‘” –Š‡ ”‡†— –‹‘ ‘ˆ ƒ‹†‡•‹–‘ƒ‹‡•ǡ ‘’‘—†• ‘–ƒ‹‹‰‡–‘‡ƒ†ƒŽ†‡Š›†‡ˆ— Ǧ –‹‘ƒŽ ‰”‘—’• •—ˆˆ‡”‡† ˆ”‘ ’ƒ”–‹ƒŽ —™ƒ–‡† ”‡†— –‹‘ ‘ˆ –Š‡ ‘–Š‡” ƒ”„‘›Žˆ— –‹‘ƒŽ‹–‹‡•ȋ Š‡‡͵ʹȌǤ‡š–‡•‹˜‡• ”‡‡‹‰™ƒ•’‡”Ǧ ˆ‘”‡†ƒ†‹–™ƒ•‘„•‡”˜‡†–Šƒ––Š‡ ƒ–ƒŽ›•–„‡ ƒ‡‘”‡ƒ –‹˜‡‹ˆ–Š‡ ”‡ƒ –‹‘˜‡••‡Ž™ƒ•’—”‰‡†™‹–Šʹƒˆ–‡”–Š‡–Š‡”ƒŽƒ –‹˜ƒ–‹‘‘ˆ–Š‡ ƒ–ƒŽ›•–Ǥͳͳͳ ‹–Š –Š‹• ‡™ ˆ‹†‹‰ǡ –Š‡ ‡–‘‡ ƒ† ƒŽ†‡Š›†‡ ‘–ƒ‹‹‰ •‹Ž›ŽŠ‡‹ƒ‹ƒŽ• ‘—Ž†„‡‰‡‡”ƒ–‡†ƒ–Ž‘™‡”–‡’‡”ƒ–—”‡ȋͷͲιȌǤ —”Ǧ –Š‡”‘”‡ǡ‹–™ƒ•†‡ ‹†‡†–‘‡˜ƒŽ—ƒ–‡–Š‡ƒ††‹–‹‘‘ˆ‘š‘’Š‹Ž‹ ‡™‹• ƒ ‹†•ǡ‹‘”†‡”–‘’”‘‘–‡–Š‡ ‘ŽŽƒ’•‡‘ˆ–Š‡–‡–”ƒŠ‡†”ƒŽ‹–‡”‡†‹ƒ–‡ –‘–Š‡ ‘”‡ ‡ƒ•‹Ž›”‡†— ‡†‹‹‹— ‹‘Ǥ‡”‡ƒ•‘‡†–Šƒ––Š‹•™‘—Ž† ‡ƒ„Ž‡–Š‡ˆ—ŽŽ”‡†— –‹‘‘ˆ–Š‡ƒ‹†‡•‹–‘ƒ‹‡•ƒ–Ž‘™‡”–‡’‡”ƒǦ –—”‡ǡ™Š‹Ž‡‡‡’‹‰–Š‡‡–‘‡ƒ†ƒŽ†‡Š›†‡‘‹‡–‹‡•‹–ƒ –Ǥ ”ƒ–‹ˆ›‹‰Ǧ Ž›ǡ ƒ–ƒŽ›–‹ ƒ‘—–•‘ˆ‹Ž’”‘‘–‡†–Š‡ ‘ŽŽƒ’•‡‘ˆ–Š‡•‹Ž›ŽŠ‡‹ƒ‹Ǧ ƒŽ‹–‡”‡†‹ƒ–‡ǡ”‡•—Ž–‹‰‹‹•‘Žƒ–‹‘‘ˆ‡–‘‡ƒ†ƒŽ†‡Š›†‡ ‘–ƒ‹Ǧ ‹‰ƒ‹‡•3nƒ†3p‹‰‘‘†›‹‡Ž†•Ǥ

 Scheme32.Chemoselectivereductionofamidestoamines.

‘‡ Ž‹‹–ƒ–‹‘• ™‡”‡ ‘„•‡”˜‡† †—”‹‰ –Š‡ • ‘’‡ ‡˜ƒŽ—ƒ–‹‘Ǣ ›ƒ‘ ‘–ƒ‹‹‰ ƒ‹†‡ 1lƒ†pǦ‹–”‘ •—„•–‹–—–‡† ƒ‹†‡ǡ ȋͶǦ‹–”‘’Š‡›ŽȌȋ’‹’‡”‹†‹ǦͳǦ›ŽȌ‡–Šƒ‘‡ǡ ‘—Ž†‘–„‡”‡†— ‡†•‡Ž‡ Ǧ –‹˜‡Ž›–‘–Š‡ ‘””‡•’‘†‹‰ƒ‹‡Ǥ‘”‡‘˜‡”ǡ’‡”ˆ‘”‹‰–Š‡”‡†— –‹‘ ‘ƒƒ‹†‡ ‘–ƒ‹‹‰ƒ–‡”‹ƒŽƒŽ›‡”‡•—Ž–‡†‹–Š‡ˆ‘”ƒ–‹‘‘ˆƒ ‘’Ž‡š‹š–—”‡‘ˆ’”‘†— –•‡˜‡ƒ–Ž‘™–‡’‡”ƒ–—”‡Ǥ‡ ‘†ƒ”› ƒ† ’”‹ƒ”›ƒ‹†‡•ƒ”‡‘™–‘„‡Ž‡••”‡ƒ –‹˜‡ƒ†™‡”‡‘–”‡†— ‡† —†‡”–Š‡”‡ƒ –‹‘ ‘†‹–‹‘•‹–Š‹•’”‘–‘ ‘ŽǤͳͳ͵ ‘”†‹‰–‘ ͳ  ƒƒŽ›•‹•ǡ –Š‡ ƒŒ‘” ’”‘†— –• ‹ –Š‡•‡ ”‡ƒ –‹‘• ™‡”‡ –Š‡ •‹Ž›Žƒ–‡† ƒǦ ‹†‡•ǡ™Š‹ Š’”‡˜‹‘—•Ž›™‡”‡”‡’‘”–‡†„›ƒ‰ƒ•Š‹ƒƒ† ‘Ǧ™‘”‡”•ǤͳͳͶ ††‹–‹‘ƒŽŽ›ǡ–Š‡–‡”–‹ƒ”›ƒ‹†‡•”‡“—‹”‡†•—„•–‹–—–‹‘ƒ––Š‡ȽǦ ƒ”„‘ –‘–Š‡ ƒ”„‘›Žˆ— –‹‘ƒŽ‹–›–‘ƒ˜‘‹†‡ƒ‹‡ˆ‘”ƒ–‹‘ȋ•‡‡ Šƒ’–‡”͵ ˆ‘” ‘ȋȌ͸Ǧ ƒ–ƒŽ›œ‡† ‡ƒ‹‡ ˆ‘”ƒ–‹‘ȌǤ ‡†— –‹‘ ‘ˆ –Š‡ ƒŽ‹’Šƒ–‹  ƒ‹†‡ʹǦ’Š‡›ŽǦͳǦȋ’‹’‡”‹†‹ǦͳǦ›ŽȌ‡–Šƒ‘‡ȋ6aǡvideinfraȌ‰ƒ˜‡ƒ‹šǦ –—”‡‘ˆ‡ƒ‹‡ƒ†ƒ‹‡Ǥ  ͵Ͳ  

2.1CompetitiveStudy–Chemoselectivity

Š‡ Š‡‘•‡Ž‡ –‹˜‹–›‘ˆ–Š‡•›•–‡™ƒ•ƒŽ•‘‡˜ƒŽ—ƒ–‡†„›ƒ ‘’‡–‹–‹˜‡ ”‡†— –‹‘‡š’‡”‹‡–—•‹‰ƒ‹š–—”‡‘ˆƒ‹†‡ǡ‡–‘‡ƒ†ƒŽ†‡Š›†‡ •—„•–”ƒ–‡•ȋͳǣͳǣͳ”ƒ–‹‘Ȍȋ Š‡‡͵͵ȌǤŠ‡‘’–‹‹œ‡† ‘†‹–‹‘•ˆ‘”ƒǦ ‹†‡1b™‡”‡—•‡†ƒ†ˆ—ŽŽ ‘˜‡”•‹‘‘ˆ–Š‡ƒ‹†‡‹–‘ƒ‹‡3b™ƒ• ‘„•‡”˜‡†™‹–Š‹–™‘Š‘—”•Ǥ ‡”‡ǡ–Š‡‡–‘‡ȋ4Ȍƒ†–Š‡ƒŽ†‡Š›†‡ȋ2bȌ ”‡ƒ‹‡†—ƒˆˆ‡ –‡†ǤŽ‡ –”‘Ǧ”‹ Š ƒ”„‘›Ž ‘’‘—†•ƒ”‡ ‘™–‘ „‡ Ž‡•• ’”‘‡ –‘™ƒ”†• ”‡†— –‹‘ †—‡ –‘ –Š‡ †‡ ”‡ƒ•‡† ‡Ž‡ –”‘’Š‹Ž‹  Šƒ”ƒ –‡”‘ˆ–Š‡ ƒ”„‘›Ž ƒ”„‘Ǥ ‘™‡˜‡”ǡ‹–Š‹•’”‘–‘ ‘Ž‹–™ƒ•‘„Ǧ •‡”˜‡†–Šƒ–ƒ‹†‡•„‡ƒ”‹‰‡Ž‡ –”‘Ǧ†‘ƒ–‹‰ ‰”‘—’• ™‡”‡ ‡ƒ•‹‡”–‘ ”‡†— ‡Ǥ  ’Žƒ—•‹„Ž‡ ‡š’Žƒƒ–‹‘ ˆ‘” –Š‹• ‘—– ‘‡ ƒ „‡ –Š‡ ‹ ”‡ƒ•‡† ‘‘”†‹ƒ–‹‰ ƒ„‹Ž‹–› ‘ˆ –Š‡ ƒ‹†‡ –‘™ƒ”†• –Š‡ ƒ–ƒŽ›•–ǡ ™Š‹ Š –Š‡ ™‘—Ž†ƒŽŽ‘™–Š‡”‡†— –‹‘–‘‘ —”Ǥ

 Scheme33.Competitivereductionbetweenamide1b,ketone4andaldehyde2b.

2.2ApplicationsoftheReductionProtocol

‘Š‹‰ŠŽ‹‰Š––Š‡—•‡ˆ—Ž‡••‘ˆ–Š‡’”‘–‘ ‘Ž‹–™ƒ•†‡ ‹†‡†–‘’‡”ˆ‘” ‰”ƒǦ• ƒŽ‡‡š’‡”‹‡–•ǡ„‘–Šˆ‘”–Š‡ƒŽ†‡Š›†‡ƒ†–Š‡ƒ‹‡ˆ‘”ƒ–‹‘ ȋ Š‡‡ ͵ͶȌǤ ‹†‡ 1d ™ƒ• ”‡†— ‡† ‘ ƒ ͳͲ ‘Ž • ƒŽ‡ ȋ͵Ǥͳͷ ‰Ȍ ƒ– ”‘‘ –‡’‡”ƒ–—”‡ ‹ ʹǦ‡–Š›Ž–‡–”ƒŠ›†”‘ˆ—”ƒ ȋʹǦ‡Ǧ Ȍǡ ™Š‹ Š ‹• ‘•‹†‡”‡† ƒ ‰”‡‡ •‘Ž˜‡–ǡͳͳͷƒˆˆ‘”†‹‰ƒŽ†‡Š›†‡2d ‹ ͻͲΨ ‹•‘Žƒ–‡† ›‹‡Ž†ȋʹǤͳͲ‰ȌǤŠ‡ ‘””‡•’‘†‹‰ƒ‹‡™ƒ•‹•‘Žƒ–‡†ƒˆ–‡””‡ˆŽ—šˆ‘”ͳǤͷ Š‘—”•‹ͻͳΨ›‹‡Ž†ȋʹǤ͹ͷ‰ȌǤ

 Scheme34.ScaleǦupreactionsofthechemoselectiveandtunableamidereducǦ tionintoaldehydeandamine. ͵ͳ  

‘ˆ—”–Š‡”†‡‘•–”ƒ–‡–Š‡ Š‡‘•‡Ž‡ –‹˜‹–›ƒ†˜‡”•ƒ–‹Ž‹–›‘ˆ–Š‡’”‘Ǧ –‘ ‘Ž ™‡ ’”‡’ƒ”‡† ƒ‹†‡ 5ǡ ƒ ’”‡ —”•‘” ‹ –Š‡ •›–Š‡•‹• ‘ˆ ‘‡’‡œ‹Ž ȋ Š‡‡͵ͷȌǤ‘‡’‡œ‹Ž‹•ƒ’Šƒ”ƒ ‡—–‹ ƒŽ ‘’‘—†—•‡†‹–Š‡’ƒŽŽ‹Ǧ ƒ–‹˜‡–”‡ƒ–‡–‘ˆŽœŠ‡‹‡”Ʋ•†‹•‡ƒ•‡Ǥͳͳ͸”‡ —”•‘”5™ƒ••—„‹––‡†–‘ –Š‡ ”‡ƒ –‹‘ ‘†‹–‹‘• ƒ† ƒˆˆ‘”†‡† ‘‡’‡œ‹Ž ‹ ͺʹΨ ‹•‘Žƒ–‡† ›‹‡Ž†Ǥ Š‹•ˆ—”–Š‡”’”‘˜‡•–Š‡Š‹‰Š Š‡‘•‡Ž‡ –‹˜‹–›‘ˆ–Š‡•›•–‡™Š‡”‡ ƒ ƒ‹†‡ ‹• ”‡†— ‡† ‘˜‡” ƒ ‡–‘‡ ‘‹‡–› ƒ† –Šƒ– –Š‹• ’”‘–‘ ‘Ž ƒ „‡ —•‡†‹Žƒ–‡Ǧ•–ƒ‰‡”‡†— –‹‘•Ǥ

 Scheme35.EmployingtheMo(CO)6ǦcatalyzedprotocolforlateǦstagefunctionalǦ izationinthesynthesisofDonepezil.

2.3Conclusions

 ‡–Š‘†‘Ž‘‰› ˆ‘” –Š‡ ‹Ž† ƒ† Š‡‘•‡Ž‡ –‹˜‡ ”‡†— –‹‘ ‘ˆ –‡”–‹ƒ”› ƒ‹†‡•™ƒ•†‡˜‡Ž‘’‡†Ǥ›–—‹‰–Š‡”‡ƒ –‹‘–‡’‡”ƒ–—”‡‹–™ƒ•’‘•Ǧ •‹„Ž‡–‘–”ƒ•ˆ‘”–Š‡ƒ‹†‡•‹–‘„‘–ŠƒŽ†‡Š›†‡•ƒ†ƒ‹‡•ǡŠ‡ ‡ ‘–”‘ŽŽ‹‰ –Š‡ •‡Ž‡ –‹˜‡ „”‡ƒƒ‰‡ ‘ˆ –Š‡ Ȃ ‘” –Š‡ Ȃ „‘† ‘ˆ –Š‡ ƒ‹†‡ǤŽ‡ –”‘Ǧ’‘‘”ƒ‹†‡•™‡”‡ˆ‘—†–‘„‡‘”‡†‹ˆˆ‹ —Ž––‘”‡†— ‡ —†‡” ‹Ž† ‘†‹–‹‘•ǡ ™Š‹ Š ‘–”ƒ†‹ – •–ƒ†ƒ”† ƒ”„‘›Ž Š‡‹•–”› ™Š‡”‡ –Š‡ ‡Ž‡ –”‘ †‡ˆ‹ ‹‡– ƒ”„‘›Ž —•—ƒŽŽ› ‹• ‡ƒ•‹‡” –‘ ”‡†— ‡Ǥ Š‡ ’”‘–‘ ‘Ž •Š‘™‡† —’”‡ ‡†‡–‡† Š‡‘•‡Ž‡ –‹˜‹–› ™Š‡ ‹– ‘‡• –‘ ˆ— –‹‘ƒŽ‰”‘—’–‘Ž‡”ƒ ‡ƒ†–Š‡ƒ‹†‡‘‹‡–› ‘—Ž†„‡–”ƒ•ˆ‘”‡† ‹–Š‡’”‡•‡ ‡‘ˆ ›ƒ‘ǡ‡•–‡”ǡ‡–‘‡ǡƒŽ†‡Š›†‡ǡ‡–‹‹‡ƒ•™‡ŽŽ ƒ• ƒŽ†‹‹‡‘‹‡–‹‡•Ǥ‘–Š‡„‡•–‘ˆ‘—”‘™Ž‡†‰‡ǡ–Š‹•‹•–Š‡•‘Ž‡‡–ŠǦ ‘†‘Ž‘‰›™Š‡”‡–Š‡ƒŽ†‡Š›†‡ˆ— –‹‘ƒŽ‹–›‹•–‘Ž‡”ƒ–‡†‹–Š‡”‡†— –‹‘ ‘ˆƒ‹†‡•–‘™ƒ”†•ƒ‹‡•Ǥ Š‡ Š‡‘•‡Ž‡ –‹˜‹–›™ƒ•‡˜ƒŽ—ƒ–‡†‹ƒ ‘’‡–‹–‹˜‡‡š’‡”‹‡– ™‹–Šƒ‹†‡ǡ‡–‘‡ƒ†ƒŽ†‡Š›†‡”‡•—Ž–‹‰‹”‡†— –‹‘‘ˆ‘Ž›–Š‡ƒǦ ‹†‡ ‘’‘—†ǤŠ‡’”‘–‘ ‘Ž™ƒ•• ƒŽƒ„Ž‡ƒŽŽ‘™‹‰ˆ‘”–Š‡•›–Š‡•‹•‘ˆ ͶǦ‹‘†‘„‡œƒŽ†‡Š›†‡ ȋ2dȌ ƒ† ͳǦȋͶǦ‹‘†‘„‡œ›ŽȌ’‹’‡”‹†‹‡ ȋ3dȌ ‘ ƒ ͳͲ‘Ž • ƒŽ‡Ǥ ‘”‡‘˜‡”ǡ –Š‡ ‡–Š‘†‘Ž‘‰› ™ƒ• ‡’Ž‘›‡† ƒ• ƒ Žƒ–‡Ǧ•–ƒ‰‡ˆ— –‹‘ƒŽ‹œƒ–‹‘•–‡’‹–Š‡•›–Š‡•‹•‘ˆ–Š‡’Šƒ”ƒ ‡—–‹ ƒŽ ‘’‘—†‘‡’‡œ‹ŽǤ 

͵ʹ  

3. Mo(CO)6ǦCatalyzed Enamine Formation fromAmides(PapersII–V)

3.1Introduction

ƒ‹‡• ƒ”‡ ‹’‘”–ƒ– ‹–‡”‡†‹ƒ–‡• –Šƒ– ƒ”‡ ‡••‡–‹ƒŽ ‹ —‡”‘—• –”ƒ•ˆ‘”ƒ–‹‘•ǡ •— Š ƒ• ƒŽ›Žƒ–‹‘•ǡ ƒ ›Žƒ–‹‘•ǡ ‘Œ—‰ƒ–‡ ƒ††‹–‹‘•ǡ ˆ‘”ƒ–‹‘‘ˆŠ‡–‡”‘ › Ž‡•ƒ† › Ž‘ƒ††‹–‹‘”‡ƒ –‹‘•Ǥͳͳ͹ —”–Š‡”‘”‡ǡ ‡ƒ‹‡• ƒǡ –Š”‘—‰Š ƒ•›‡–”‹  ”‡†— –‹‘ ‰‹˜‡ ”‹•‡ –‘ Š‹”ƒŽ ƒ‹‡•ǤͳͳͺŠ‡•‡ƒ”‡‘ˆŠ‹‰Š‹’‘”–ƒ ‡ƒ† ƒ„‡—•‡†ƒ• Š‹”ƒŽŽ‹‰Ǧ ƒ†•ǡ ‘”‰ƒ‘ ƒ–ƒŽ›•–• ƒ† ƒ• „—‹Ž†‹‰ „Ž‘ • ‹ –Š‡ ˆ‹‡Ǧ Š‡‹ ƒŽ ƒ† ’Šƒ”ƒ ‡—–‹ ƒŽ‹†—•–”›Ǥ Š‡ ˆ‹”•– ’”ƒ –‹ ƒŽ •›–Š‡•‹• ‘ˆ ‡ƒ‹‡• ™ƒ• ƒ ‘’Ž‹•Š‡† „› ƒ‹ Šƒ†ƒ˜‹†•‡ǡ™Š‘‹š‡† ƒ‹‡•ƒ† ƒŽ†‡Š›†‡•—†‡”„ƒ•‹  ‘†‹–‹‘•ǡ ™Š‹ Š ’”‘˜‹†‡† ‡ƒ‹‡• ƒ• ’—”‡ ’”‘†— –• ƒˆ–‡” †‹•–‹ŽŽƒǦ –‹‘Ǥͳͳͻ‘†ƒ›–Š‡ƒ‹”‘—–‡ˆ‘”–Š‡ˆ‘”ƒ–‹‘‘ˆ‡ƒ‹‡•‹•„› ‘Ǧ †‡•ƒ–‹‘‘ˆƒƒŽ†‡Š›†‡‘”‡–‘‡™‹–Šƒ•‡ ‘†ƒ”›ƒ‹‡’”‘‘–‡† „› ‡‹–Š‡” ”ސ•–‡† ‘” ‡™‹• ƒ ‹† ƒ–ƒŽ›•‹• ȋ Š‡‡ ͵͸ƒȌǤͳͳ͹ ‘ ‘„–ƒ‹ ‰‘‘†›‹‡Ž†•ǡŠ‹‰Š–‡’‡”ƒ–—”‡‹ ‘„‹ƒ–‹‘™‹–Š™ƒ–‡”• ƒ˜‡‰‡”•‘” ƒœ‡‘–”‘’‹ †‹•–‹ŽŽƒ–‹‘‹•—•—ƒŽŽ›”‡“—‹”‡†ƒ†–Š‡ˆ— –‹‘ƒŽ‰”‘—’–‘ŽǦ ‡”ƒ ‡‹•–Š‡”‡ˆ‘”‡”‡•–”‹ –‡†ǤŠ‡—•‡‘ˆ‘Ž‡ —Žƒ”•‹‡˜‡•ƒ•†‡Š›†”ƒǦ –‹‘ƒ‰‡–• ƒ‡ˆˆ‹ ‹‡–Ž›”‡‘˜‡™ƒ–‡”ƒ†ˆ—”‹•Š‡ƒ‹‡•ƒ–‹Ž† ‘†‹–‹‘• ™Š‡”‡ ƒŽ‡‡ǡ ‡•–‡”ǡ ƒ”„‘š›Ž‹  ƒ ‹†ǡ ƒ ‡–ƒŽǡ ‡–‘‡ƒ†•‹Ǧ Ž›Ž‡–Š‡”‘‹‡–‹‡•™‡”‡–‘Ž‡”ƒ–‡†ǤͳʹͲ‘–Š‡””‘—–‡–‘ˆ‘”‡ƒ‹‡•‹• „› ’ƒŽŽƒ†‹—Ǧ ‘” ‘’’‡”Ǧ ƒ–ƒŽ›œ‡† — Š™ƒŽ†Ǧ ƒ”–™‹‰Ǧ–›’‡ ƒ‹ƒ–‹‘ ‘ˆ˜‹›ŽŠƒŽ‹†‡•ƒ†ƒ‹‡•ǡƒŽ„‡‹–ǡ–Š‡ˆ‘”ƒ–‹‘‘ˆ‡ƒ‹‡• ‘–ƒ‹‹‰ ƒ††‹–‹‘ƒŽ ŠƒŽ‹†‡• ‹• –Š‡”‡ˆ‘”‡ ŠƒŽŽ‡‰‹‰ ȋ Š‡‡ ͵͸„ȌǤͳʹͳ —”–Š‡”Ǧ ‘”‡ǡ ƒ–ƒŽ›–‹ ƒ‘—–•‘ˆŠȋȌʹȋƒ ƒ ȌŠƒ•ƒŽ•‘„‡‡—•‡†‹ ‘„‹Ǧ ƒ–‹‘ ™‹–Š ʹǡʹǯǦ„‹•ȋ†‹’Š‡›Ž’Š‘•’Šƒ›Ž‡–Š›ŽȌǦͳǡͳǯǦ„‹ƒ’Š–Š›Ž ȋƒǦ ’Š‘•Ȍˆ‘”–Š‡Š›†”‘ƒ‹‘‡–Š›Žƒ–‹‘‘ˆ˜ƒ”‹‘—•ƒŽ‡‡•„›–Š‡‡ŽŽ‡” ͳʹʹ ‰”‘—’ ȋ Š‡‡ ͵͸ ȌǤ  ‹‰Š ’”‡••—”‡ ‘ˆ Ȁ ʹ ™ƒ• ‡‡†‡† ƒ† –Š‡ ‡ƒ‹‡•™‡”‡‘„–ƒ‹‡†‹Š‹‰Š›‹‡Ž†ƒ†•‡Ž‡ –‹˜‹–›Ǥ

͵͵  

 Scheme 36.Enamine formation a) withacid catalysis, b) PdǦcatalyzed aminaǦ tionofvinylhalides,andc)hydroaminomethylationofalkenes.

ƒ–ƒŽ›–‹ Š›†”‘•‹Ž›Žƒ–‹‘‘ˆƒ‹†‡•ˆ‘”–Š‡ˆ‘”ƒ–‹‘‘ˆƒ‹‡•‹•™‡ŽŽ ‘™ ƒ† Šƒ• „‡‡ ‡š–‡•‹˜‡Ž› •–—†‹‡† ȋ•‡ –‹‘ ͳǤʹǤ͵ȌǢ Š‘™‡˜‡”ǡ –Š‡ †‹”‡ – –”ƒ•ˆ‘”ƒ–‹‘ ‘ˆ ƒ‹†‡• ‹–‘ ‡ƒ‹‡• ‹• Ž‡•• ‡š’Ž‘”‡†Ǥ— ŠǦ ™ƒŽ† ƒ† ‘Ǧ™‘”‡”• ™‡”‡ ƒ„Ž‡ –‘ ‘˜‡”– ƒ‹†‡• ‹–‘ ƒŽ†‡Š›†‡• via i ‡ƒ‹‡ ‹–‡”‡†‹ƒ–‡• —•‹‰ •–‘‹ Š‹‘‡–”‹  ƒ‘—–• ‘ˆ ‹ȋ ”ȌͶ‹ ͹͸ ‘„‹ƒ–‹‘ ™‹–Š †‹’Š‡›Ž•‹Žƒ‡ ȋŠʹ‹ ʹȌ ȋ Š‡‡ ͵͹ƒȌǤ Š‡ ‡ƒ‹‡• ™‡”‡ ‘– ‹•‘Žƒ–‡† „—– Š›†”‘Ž›œ‡† –‘ ƒŽ†‡Š›†‡•ǡ ™Š‹ Š ™‡”‡ ‹•‘Žƒ–‡†‹‰‘‘†–‘‡š ‡ŽŽ‡–›‹‡Ž†•Ǥ

 Scheme 37. Enamine synthesis by hydrosilylation a) employing stoichiometric i amountsofTi(O Pr)4,b)IrǦcatalysis,andc)baseǦmediatedamidehydrosilylation.

Š‡ƒ‰ƒ•Š‹ƒ‰”‘—’’—„Ž‹•Š‡†ƒ’”‘–‘ ‘Ž„ƒ•‡†‘ƒ‹”‹†‹— ƒ–ƒŽ›•– ˆ‘” –Š‡ –”ƒ•ˆ‘”ƒ–‹‘ ‘ˆ ƒ‹†‡• ‹–‘ ‡ƒ‹‡• —•‹‰  ȋ Š‡‡ ͵͹„ȌǤͳͶŠ‡’”‘–‘ ‘Ž™ƒ•Š‹‰ŠŽ› Š‡‘•‡Ž‡ –‹˜‡ƒ†‡ƒ‹‡• ‘–ƒ‹Ǧ ‹‰ ‘Ž‡ˆ‹ǡ ‡•–‡” ƒ† ‡–‘‡ ‘‹‡–‹‡• ‘—Ž† „‡ ‘„–ƒ‹‡†Ǥ Š‡ •ƒ‡ ”‡Ǧ •‡ƒ” Š‰”‘—’”‡ ‡–Ž›†‡˜‡Ž‘’‡†ƒ‘–Š‡”’”‘–‘ ‘Žˆ‘”–Š‡‡ƒ‹‡ˆ‘”Ǧ ƒ–‹‘—•‹‰ƒ•‡”‹‡•‘ˆ‹”‹†‹— ƒ–ƒŽ›•–•‹•’‹”‡†„›–Š‡ƒ•ƒ ‘Ǧ ͷ͵ ’Ž‡šǡ ”ŽȋȌȋŠ͵Ȍʹǡ –‘ ‡ˆˆ‹ ‹‡–Ž› ‘˜‡”– ƒ‹†‡• ‹–‘ ‡ƒ‹‡•Ǥ  ‘”‡‘˜‡”ǡ –Š‡ †‘Žˆ••‘ ‰”‘—’ Šƒ• ”‡’‘”–‡† ‘ ƒ t—Ǧ ƒ–ƒŽ›œ‡† ”‡Ǧ ͵Ͷ  

†— –‹‘’”‘–‘ ‘Ž‘ˆƒ‹†‡•‹–‘‡ƒ‹‡•—•‹‰–”‹ƒŽ‘š›•‹Žƒ‡•ƒ•–Š‡ Š›†”‹†‡•‘—” ‡ȋ Š‡‡͵͹ ȌǤͳʹ͵ ™ƒ„— Š‹ƒ† ‘Ǧ™‘”‡”••›–Š‡•‹œ‡†–Š‡ƒ–—”ƒŽ’”‘†— –—”‹Ǧ ›‡‹‡ȋ‹”ƒ ‡‹ ˆ‘”Ȍ„›ƒ’’Ž›‹‰–Š‡ ”ŽȋȌȋŠ͵ȌʹǦ ƒ–ƒŽ›œ‡†”‡Ǧ †— –‹‘’”‘–‘ ‘Žǡ™Š‹ Š™‡”‡†‡˜‡Ž‘’‡†‹–Š‡ƒ‰ƒ•Š‹ƒ‰”‘—’ǡ‹–Š‡ Žƒ•–•–‡’‘ˆ–Š‡•›–Š‡•‹•ȋ Š‡‡͵ͺȌǤͳʹͶŠ‡ƒ‹†‡‘‹‡–›™ƒ••‡Ž‡ Ǧ –‹˜‡Ž› ”‡†— ‡† ‹ –Š‡ ’”‡•‡ ‡ ‘ˆ ƒ ‡–‘‡ ƒ† –Š‡ †‡•‹”‡† ‡ƒ‹‡ ’”‘†— – ‘—Ž†„‡‘„–ƒ‹‡†‹ͺͳΨ‹•‘Žƒ–‡†›‹‡Ž†Ǥ

 Scheme38.ApplicationofthehydrosilylationprotocolinthesynthesisofTurkiǦ yenine.

Š‡ˆ‘”ƒ–‹‘‘ˆ‡ƒ‹‡•ˆ”‘ƒ‹†‡•„› ƒ–ƒŽ›–‹ Š›†”‘•‹Ž›Žƒ–‹‘Šƒ• „‡‡•—‰‰‡•–‡†–‘‘ —”via–™‘†‹ˆˆ‡”‡–’ƒ–Š™ƒ›•ƒˆ–‡”–Š‡‹‹–‹ƒŽ”‡Ǧ †— –‹‘‘ˆ–Š‡ƒ‹†‡‹–‘•‹Ž›ŽŠ‡‹ƒ‹ƒŽAȋ Š‡‡͵ͻȌǤ‹–Š‡”„› ‘ŽǦ Žƒ’•‡‘ˆ–Š‡–‡–”ƒŠ‡†”ƒŽ‹–‡”‡†‹ƒ–‡‹–‘–Š‡‹‹‹—•’‡ ‹‡•Bˆ‘ŽǦ Ž‘™‡†„›†‡’”‘–‘ƒ–‹‘‘”„›•‹—Ž–ƒ‡‘—•†‡’”‘–‘ƒ–‹‘Ȁ‡Ž‹‹ƒ–‹‘ •–‡’–Šƒ–†‹”‡ –Ž›†‡Ž‹˜‡”•–Š‡‡ƒ‹‡ǤͳͶǡͷ͵

O H OM R1 R3 M-H R1 R3 -OSiR R1 R3 N N 3 N Reduction H R2 H R2 H R2 Amide Hemiaminal Iminium ion A B

Deprotonation

H Deprotonation R1 R3 Elimination N R2 Enamine  Scheme39.SuggestedpathwaysfortheformationofenaminesbyhydrosilylaǦ tion.

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3.2Optimization

—”‹‰ –Š‡ ’”‡˜‹‘—• ’”‘Œ‡ – ‘ ‡”‹‰ –Š‡ Š‡‘•‡Ž‡ –‹˜‡ ƒ‹†‡”‡Ǧ †— –‹‘ȋ Šƒ’–‡”ʹȌ‹–™ƒ•‘„•‡”˜‡†–Šƒ–trans‡ƒ‹‡•™‡”‡ˆ‘”‡†–‘ ƒŠ‹‰Š‡š–‡–™Š‡‡’Ž‘›‹‰ƒŽ‹’Šƒ–‹ ƒ‹†‡•™‹–Š‘—–•—„•–‹–—–‹‘ƒ– –Š‡ȽǦ ƒ”„‘Ǥͳʹͷ‡–Š‡”‡ˆ‘”‡†‡ ‹†‡†–‘ˆ—”–Š‡”‘’–‹‹œ‡–Š‡”‡ƒ –‹‘ ‘†‹–‹‘•ƒ†‹‹–‹ƒ–‡†ƒ• ”‡‡‹‰‘ˆ•‘Ž˜‡–•ȋƒ„Ž‡ͳǡ‡–”‹‡•ͳȂͺȌǤ Table1.Optimizationofreactionconditionsfortheenamineformation.a

 Entry Solvent Time[h] Enamine7a[%]b ͳ  ͵ εͻͷ ʹ ‘Ž—‡‡ ͵ ʹͲ ͵ ‡ ͵ ͵ Ͷ  ͵ ͳͶ ͷ  ͵ Ͳ ͸ ‹‡–Š›Ž‡–Š‡” ͵ ͹ͺ ͹  ‡–‘‡ ͵ ͸ ͺ –Š›Žƒ ‡–ƒ–‡ ͵ ͺ͵ ͻ  –Š›Žƒ ‡–ƒ–‡ ͵ εͻͷ ͳͲ ǡ† –Š›Žƒ ‡–ƒ–‡ ͵ εͻͷ ͳͳ ǡ† –Š›Žƒ ‡–ƒ–‡ ͳ εͻͷ ͳʹ ǡ† –Š›Žƒ ‡–ƒ–‡ ͲǤͷ ͻͶ ͳ͵ ǡ† –Š›Žƒ ‡–ƒ–‡ ͲǤʹͷ ͸ͺ ͳͶ ǡ†ǡ‡ –Š›Žƒ ‡–ƒ–‡ ͳ εͻͷ ͳͷ ǡˆ –Š›Žƒ ‡–ƒ–‡ ͵ ʹͲ ƒ‘ȋȌ͸ȋͲǤͲʹ‘ŽȌǡƒ‹†‡6a ȋͳǤͲ‘ŽȌǡ†”‹‡†•‘Ž˜‡–ȋʹǡ ͲǤͷȌǡ  ȋʹǤͲ ‡“—‹˜ȌǤ „ ͳ   ›‹‡Ž†• —•‹‰ ͳǡ͵ǡͷǦ–”‹‡–Š‘š›„‡œ‡‡ ƒ• ‹–‡”ƒŽ •–ƒ†ƒ”†Ǥ  –Š›Ž ƒ ‡–ƒ–‡ ȋͲǤͷǡʹȌǤ†ȋͳǤͷ‡“—‹˜Ȍ™ƒ•—•‡†Ǥ‡‘Ǧ†”‹‡†‡–Š›Žƒ ‡–ƒ–‡ ™ƒ•—•‡†Ǥˆ ȋ͵ǤͲ‡“—‹˜Ȍ™ƒ•—•‡†Ǥ –™ƒ•‘„•‡”˜‡†–Šƒ––Š‡”‡ƒ –‹‘’”‘˜‹†‡†„‡––‡””‡•—Ž–•‹’‘Žƒ”ƒ’”‘Ǧ –‹ •‘Ž˜‡–•ǡ•— Šƒ• ƒ†‡–Š›Žƒ ‡–ƒ–‡ǡƒŽ–Š‘—‰Š†‹‡–Š›Ž‡–Š‡”™ƒ• ˆ‘—†–‘‰‹˜‡Š‹‰Š›‹‡Ž†•‘ˆ‡ƒ‹‡ƒ•™‡ŽŽǤ‡™‡”‡•—”’”‹•‡†„›–Š‡ ˆƒ ––Šƒ––Š‡”‡†— –‹‘–‘‘’Žƒ ‡‹‡–Š›Žƒ ‡–ƒ–‡•‹ ‡–Š‹• •‘Ž˜‡–‹• ”‡†— ‹„Ž‡ ƒ† –Š‡”‡ˆ‘”‡ ‘—Ž† ‘’‡–‡ ™‹–Š –Š‡ •—„•–”ƒ–‡Ǥ ‹ ‡‡–Š›Ž ƒ ‡–ƒ–‡‹• ‘•‹†‡”‡†ƒ•ƒ‰”‡‡•‘Ž˜‡–ͳʹ͸‹–™ƒ•†‡ ‹†‡†–‘—•‡‹–‹–Š‡ ‘–‹—ƒ–‹‘‘ˆ–Š‡‘’–‹‹œƒ–‹‘Ǥ —ŽŽ ‘˜‡”•‹‘‹–‘–Š‡‡ƒ‹‡™ƒ• ‘„–ƒ‹‡†„›‹ ”‡ƒ•‹‰–Š‡ ‘ ‡–”ƒ–‹‘‘ˆ–Š‡•–ƒ”–‹‰ƒ‹†‡ȋ‡–”›ͻȌ ƒ†ƒ––Š‡•ƒ‡–‹‡‹–™ƒ•ƒŽ•‘’‘••‹„Ž‡–‘†‡ ”‡ƒ•‡–Š‡ƒ‘—– ‘ˆ  –‘ ͳǤͷ ‡“—‹˜ƒŽ‡–• ȋ‡–”› ͳͲȌǤ —”–Š‡”‘”‡ǡ ™‡ †‹• ‘˜‡”‡† –Šƒ– –Š‡”‡ƒ –‹‘–‹‡™ƒ•„‡–™‡‡͵Ͳ‹—–‡•ƒ†‘‡Š‘—”ȋ‡–”‹‡•ͳͳȂ

͵͸  

ͳ͵Ȍǡ ƒ† –Š‡ ”‡ƒ –‹‘ ‘—Ž† „‡ ’‡”ˆ‘”‡† ‹ ‘Ǧ†”‹‡† ‡–Š›Ž ƒ ‡–ƒ–‡ǡ ›‹‡Ž†‹‰ƒŽ‘•––Š‡•ƒ‡ ‘˜‡”•‹‘‹–‘‡ƒ‹‡ȋ‡–”›ͳͶȌǤŠ‡Š›Ǧ †”‘•‹Žƒ‡‹•‹‡š’‡•‹˜‡ǡ•–ƒ„Ž‡–‘‘‹•–—”‡ǡƒ‹”ƒ†Š‡ƒ–ǡ„—–‹ –‡”•‘ˆ ‘•––Š‡”‡‹•‘Ž›‘‡Š›†”‘•‹Žƒ‡–Šƒ–•—”’ƒ••‡•ǡƒ‡Ž›  Ǥ ˆ‘”–—ƒ–‡Ž› –Š‡ —•‡ ‘ˆ –Š‹• •‹Žƒ‡ ”‡•—Ž–‡† ‹ Ž‘™ ‘˜‡”•‹‘ ȋ‡–”›ͳͷȌǤ

3.3Scope

‹–Š–Š‡‘’–‹‹œ‡† ‘†‹–‹‘•‹Šƒ†ǡ–Š‡Ž‹‹–ƒ–‹‘•‘ˆ–Š‡• ‘’‡™‡”‡ ‹˜‡•–‹‰ƒ–‡†ȋ Š‡‡ͶͲȌǤ‘–Š‡Ž‡ –”‘Ǧ’‘‘”ƒ†‡Ž‡ –”‘Ǧ”‹ Šƒ‹†‡• ™‡”‡‡ˆˆ‡ –‹˜‡Ž› ‘˜‡”–‡†‹–‘–Š‡ ‘””‡•’‘†‹‰‡ƒ‹‡•ȋ7bȂ7hȌǡ ƒŽ–Š‘—‰Š‡Ž‡ –”‘†‡ˆ‹ ‹‡–ƒ‹†‡•™‡”‡‘”‡†‹ˆˆ‹ —Ž––‘–”ƒ•ˆ‘”ƒ† ”‡“—‹”‡†Ž‘‰‡””‡ƒ –‹‘–‹‡ȋ6bǡ6cǡ6fǡ6gƒ†6hȌǤŠ‡‹–”‘ ‘–ƒ‹Ǧ ‹‰ƒ‹†‡ȋ6gȌ™ƒ•’ƒ”–‹ —Žƒ”†‹ˆˆ‹ —Ž––‘”‡†— ‡ƒ†”‡“—‹”‡†„‘–Š‡šǦ –‡†‡†”‡ƒ –‹‘–‹‡‹ ‘„‹ƒ–‹‘™‹–ŠƒŠ‹‰Š‡” ƒ–ƒŽ›•–Ž‘ƒ†‹‰ǤŠ‡ –Š‹‘’Š‡‡ ‘–ƒ‹‹‰ƒ‹†‡•ȋ6iƒ†6jȌ™‡”‡•— ‡••ˆ—ŽŽ›–”ƒ•ˆ‘”‡† ‹–‘‡ƒ‹‡•ǡƒŽ–Š‘—‰Š–Š‡’‹’‡”‹†‹‡ƒƒŽ‘‰—‡”‡“—‹”‡†Ž‘‰‡””‡ƒ Ǧ –‹‘–‹‡ǡvideinfraǤŠ‡ȽǦ ƒ”„‘•—„•–‹–—–‡†ƒ‹†‡ȋ6kȌ™ƒ•†‹ˆˆ‹ —Ž– –‘ ”‡†— ‡ ƒ† †‡•’‹–‡ ƒ Ž‘‰‡” ”‡ƒ –‹‘ –‹‡ǡ ‘Ž› ͸͹Ψ ͳ   ›‹‡Ž† ‘—Ž†„‡‘„–ƒ‹‡†Ǥ‘”‡‘˜‡”ǡ–Š‹•‹•–Š‡‘Ž›‡ƒ‹‡’”‘†— –™Š‡”‡ƒ ‹š–—”‡ ‘ˆ ‹•‘‡”• ™ƒ• ‘„•‡”˜‡† ȋͺ͹ǣͳ͵ ”ƒ–‹‘ȌǤ – ™ƒ• ’”‘„Ž‡ƒ–‹  –‘ †‡–‡”‹‡ –Š‡ •–”— –—”‡ ‘ˆ –Š‡ ƒŒ‘” ‹•‘‡” •‹ ‡ ‘Ž› •‹‰Ž‡–•™‡”‡ ‘„•‡”˜‡†‹–Š‡ ͳ •’‡ –”—ƒ†‘ ‘ Ž—•‹‘• ‘—Ž†„‡†”ƒ™ „ƒ•‡†‘–Š‡ ‘—’Ž‹‰ ‘•–ƒ–•Ǥ 

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7a, >95% 7b, >95% 7c, >95% 1 h 3 h 3 h

7d, >95% 7e, >95% 7f, >95% 7g,a 85% 1 h 1 h 2 h, 75 °C 24 h

7h, 80% 7i, >95% 7j,a >95% 7k,b 67% 2 h 3 h 2 h 7 h

7l, 70% 7m, >95% 7n, 89% 7o, >95% 2 h, 80 °C 1 h 5 h, 40 °C 4 h

7p, >95% 7q, >95% 7r, >95% 7s, >95% 0.5 h 3 h 1 h 2 h

7t, >95% 7u, >95% 7v, >95% 7w,c 88% 1 h 5 h 1 h 3 h

7x,a >95% 7y,d >95% 7z,a >95% 24 h 15 h 9 h Scheme 40. Chemoselective formation of enamines from amides (0.5 mmol). 1 a HNMR yields using 1,3,5Ǧtrimethoxybenzene as internal standard. Mo(CO)6 (5mol%). b1,4Ǧdimethoxybenzenewasusedasinternalstandard. cUnpublished d results. Et3N(10mol%)added.

͵ͺ  

Š‡”‡†— –‹‘‘ˆ–Š‡ƒŽ‹’Šƒ–‹ ƒ‹†‡6l™ƒ•‘–•‡Ž‡ –‹˜‡ƒ†ƒ‹š–—”‡ ‘ˆ‡ƒ‹‡ƒ†ƒ‹‡™ƒ•‘„–ƒ‹‡†ǢŠ‘™‡˜‡”ǡƒ–ͺͲ陇™‡”‡ƒ„Ž‡–‘ ‘„–ƒ‹ ‡ƒ‹‡ 7l ‹ ͹ͲΨ ͳ ›‹‡Ž†Ǥ ”ƒ–‹ˆ›‹‰Ž›ǡ–Š‡–”ƒ•ˆ‘”Ǧ ƒ–‹‘‘ˆƒ‹†‡•‹–‘‡ƒ‹‡•™ƒ• Š‡‘•‡Ž‡ –‹˜‡ƒ†‡•–‡”•ǡ‡–‘‡• ƒ†‹‹‡• ‘—Ž†„‡–‘Ž‡”ƒ–‡†ǡ—Ž–‹ƒ–‡Ž›Ž‡ƒ†‹‰–‘ ‘’‘—†•7mǡ7n ƒ†7oǤŠ‡•‡–›’‡•‘ˆ’”‘†— –•‹‰Š–‘–„‡’‘••‹„Ž‡–‘ˆ‘”™‹–Š‘–ŠǦ ‡” –›’‡• ‘ˆ ‡ƒ‹‡ •›–Š‡•‹•Ǣ Š‘™‡˜‡”ǡ ƒ• ‡–‹‘‡† ƒ„‘˜‡ –Š‡”‡ ‹• ‘‡‡šƒ’Ž‡‹–Š‡Ž‹–‡”ƒ–—”‡‘ˆ‹Ž†ƒ† Š‡‘•‡Ž‡ –‹˜‡‡ƒ‹‡•›Ǧ –Š‡•‹•ˆ”‘ƒ‹‡•ƒ†ƒŽ†‡Š›†‡•ǤͳʹͲ Š‡”‡†— –‹‘‘ˆƒ‹†‡• ‘–ƒ‹‹‰†‹ˆˆ‡”‡–•—„•–‹–—‡–•‘–Š‡ ‹–”‘‰‡™ƒ••—„•‡“—‡–Ž›‡˜ƒŽ—ƒ–‡†ƒ†‹–™ƒ•†‹• ‘˜‡”‡†–Šƒ––Š‡ ‘”’Š‘Ž‹‡ ‘–ƒ‹‹‰ƒ‹†‡6q™ƒ•‘”‡†‹ˆˆ‹ —Ž––‘”‡†— ‡–Šƒ–Š‡ ’‹’‡”‹†‹‡ ‘–ƒ‹‹‰ ƒ‹†‡ 6aǤ ƒ‹‡• ‘–ƒ‹‹‰ ‘–Š‡” NǦ•—„•–‹–—‡–••— Šƒ•ʹǡ͸Ǧ†‹‡–Š›Ž’‹’‡”‹†‹‡ȋ7sȌǡƒ ‡–ƒŽȋ7tȌƒ†ƒŽ‹Ǧ ’Šƒ–‹ ƒ › Ž‹ ƒ‹‡ȋ7uƒ†7vȌ ‘—Ž†„‡‘„–ƒ‹‡†ǤŠ‡ƒŽŽ›Ž‹ ‘‹‡–› •—”˜‹˜‡†–Š‡”‡†— –‹˜‡ ‘†‹–‹‘•ƒ•™‡ŽŽƒ†‡ƒ‹‡7w™ƒ•‘„–ƒ‹‡† ‹Š‹‰Š ͳ ›‹‡Ž†ǤŠ‡NǡNǦ†‹„‡œ›Žƒ‹†‡6x™ƒ•†‹ˆˆ‹ —Ž––‘ ‘Ǧ ˜‡”–‹–‘–Š‡ ‘””‡•’‘†‹‰‡ƒ‹‡„—–™ƒ•—Ž–‹ƒ–‡Ž›ˆ‘”‡†™‹–Šƒ ‹ ”‡ƒ•‡† ƒ–ƒŽ›•–Ž‘ƒ†‹‰‹ ‘„‹ƒ–‹‘™‹–ŠŽ‘‰‡””‡ƒ –‹‘–‹‡ǤŠ‡ NǦ‡–Š›Ž ƒ‹Ž‹‡ ‘–ƒ‹‹‰ ƒ‹†‡ 6y’”‘˜‡†–‘„‡‘”‡†‹ˆˆ‹ —Ž––‘ ”‡†— ‡ƒ†ƒ‹š–—”‡‘ˆ‡ƒ‹‡ǡƒ‹‡ƒ†’”‘†— –•ˆ”‘Ȃ„‘† Ž‡ƒ˜ƒ‰‡ ™ƒ• ‘„•‡”˜‡† ƒ– –Š‡ Šƒ”•Š ‘†‹–‹‘• ”‡“—‹”‡† ȋεʹͶ Š ƒ– ͸ͷ ιȌǤ Š‹• ’”‘„Ž‡ ™ƒ• ‹” —˜‡–‡† „› –Š‡ ƒ††‹–‹‘ ‘ˆ ƒ ƒ–ƒŽ›–‹  ƒ‘—–‘ˆ–”‹‡–Š›Žƒ‹‡ȋͳͲ‘ŽΨȌ–‘–Š‡•–ƒ†ƒ”† ‘†‹–‹‘•ƒ† ’”‘˜‹†‡† –Š‡ †‡•‹”‡† ‡ƒ‹‡ •‡Ž‡ –‹˜‡Ž› ‹ εͻͷΨ ͳ ›‹‡Ž† ƒˆ–‡” ͳͷŠ‘—”•ǤŠ‡‡š’Žƒƒ–‹‘ ƒ„‡–Šƒ––Š‡’”‘’‘•‡†•‹Ž›ŽŠ‡‹ƒ‹ƒŽ ‹–‡”‡†‹ƒ–‡ ”‡“—‹”‡• ƒ „ƒ•‡ –‘ ˆƒ ‹Ž‹–ƒ–‡ –Š‡ ”‡‘˜ƒŽ ‘ˆ –Š‡ ȽǦ’”‘–‘ ƒ† ˆ‘”ƒ–‹‘ ‘ˆ –Š‡ ‡ƒ‹‡ǡ ™Š‹ Š ƒ „‡ ƒ Š‹‡˜‡† „› ƒ‘–Š‡” •‹Ǧ Ž›ŽŠ‡‹ƒ‹ƒŽ‘”„›–Š‡‡ƒ‹‡’”‘†— –Ǥ –Š‡ ƒ•‡‘ˆ–Š‡ƒ‹Ž‹‡ ‘Ǧ –ƒ‹‹‰ƒ‹†‡–Š‹•†‡’”‘–‘ƒ–‹‘‹‰Š–‘–„‡‡ˆˆ‹ ‹‡–†—‡–‘’‘‘”„ƒǦ •‹ ‹–›‘ˆ–Š‡‹–”‘‰‡ƒ†–Š‡”‡ˆ‘”‡‡‡†ƒ••‹•–ƒ ‡ˆ”‘ƒƒ††‡†‡šǦ –‡”ƒŽ „ƒ•‡Ǥ ‹ƒŽŽ›ǡ –Š‡ ‹†‘Ž‹‡ ‘–ƒ‹‹‰ ‡ƒ‹‡ 7z ‘—Ž†„‡‘„Ǧ –ƒ‹‡†„›‹ ”‡ƒ•‹‰„‘–Š–Š‡ ƒ–ƒŽ›•–Ž‘ƒ†‹‰ƒ†–Š‡”‡ƒ –‹‘–‹‡Ǥ ‡‰ƒ”†‹‰–Š‡”‡†— –‹‘‘ˆƒ‹†‡• ‘–ƒ‹‹‰†‹ˆˆ‡”‡–•—„•–‹–—Ǧ ‡–•‘–Š‡‹–”‘‰‡™‡ ‘’ƒ”‡†–Š‡”‡†— –‹‘‘ˆƒ‹†‡•†‡”‹˜‡†ˆ”‘ ’‹’‡”‹†‹‡ȋ6aȌǡ’›””‘Ž‹†‹‡ȋ6pȌƒ††‹‡–Š›Žƒ‹‡ȋ6rȌȋƒ„Ž‡ʹȌǤ – ™ƒ•‘„•‡”˜‡†–Šƒ––Š‡”‡†— –‹‘‘ —””‡†ˆƒ•–‡”ˆ‘”–Š‡’›””‘Ž‹†‹‡ƒ† †‹‡–Š›Ž ƒ‹‡ •—„•–‹–—–‡† ƒ‹†‡• –Šƒ ˆ‘” –Š‡ ’‹’‡”‹†‹‡ ƒƒŽ‘‰—‡Ǥ Š‹• ƒ„‡‡š’Žƒ‹‡†„›–Š‡†‹ˆˆ‡”‡ ‡‹‘˜‡”Žƒ’‘ˆ–Š‡Ž‘‡’ƒ‹” ‘ ‹–”‘‰‡ ™‹–Š –Š‡ ƒ–‹Ǧ„‘†‹‰ ‘”„‹–ƒŽ ‘ˆ –Š‡ ƒ”„‘›Ž ƒ”„‘ ‘ –Š‡ ƒ‹†‡Ǥ͹ǡͳʹ͹

͵ͻ  

Table 2. Comparison between amides with different NǦsubstituents in the forǦ mationofenamines.a

 Entry Amide Enamine [%]

ͳ ͸ͺ

6a 7a

ʹ ͻʹ 6p 7p

͵ ͺͻ 6r 7r

ƒ‹†‡6 ȋͲǤͷ ‘ŽȌǡ ‘ȋȌ͸ ȋʹ ‘ŽΨȌǡ  ȋͲǤ͹ͷ ‘ŽȌǡ ‡–Š›Ž ƒ ‡–ƒ–‡ ȋͲǤʹͷ ǡ ʹȌǤ ͳ   ›‹‡Ž†• —•‹‰ ͳǡ͵ǡͷǦ–”‹‡–Š‘š›„‡œ‡‡ ƒ•‹–‡”ƒŽ•–ƒ†ƒ”†Ǥ

—”‹‰ –Š‡ ‹˜‡•–‹‰ƒ–‹‘ ‘ˆ –Š‡ • ‘’‡ •‘‡ Ž‹‹–ƒ–‹‘• ™‡”‡ ‘„•‡”˜‡† ȋ Š‡‡ ͶͳȌǤ ‘” ƒ‹†‡• ‘–ƒ‹‹‰ Š‡–‡”‘ƒ–‘• ƒ†Œƒ ‡– –‘ –Š‡ ȽǦ’”‘–‘ȋ6aaȂ6adȌǡ’‘‘”‘”‘ ‘˜‡”•‹‘‹–‘‡ƒ‹‡™ƒ•†‡–‡ –Ǧ ‡†Ǥ ‘”ƒ‹†‡6ae‘Ž›ƒ‹‡ˆ‘”ƒ–‹‘™ƒ•‘„•‡”˜‡†ƒ†–Š‡‡˜ƒŽ—ƒǦ –‹‘‘ˆ–Š‡„”ƒ Š‡†ƒ‹†‡6af•Š‘™‡†‘‡ƒ‹‡ˆ‘”ƒ–‹‘ǡƒ†‹Ǧ •–‡ƒ†ƒ‹‡ˆ‘”ƒ–‹‘™ƒ•‘„•‡”˜‡†Ǥ–Š‡‘–Š‡”Šƒ†ǡ”‡†— –‹‘ ‘ˆ ƒ‹†‡ 6ag”‡•—Ž–‡†‹‡ƒ‹‡ˆ‘”ƒ–‹‘ǡƒŽ„‡‹–ƒ–„‡•–͵ͺΨͳ  ›‹‡Ž†Ǥ•‹‹Žƒ”‘„•‡”˜ƒ–‹‘™ƒ•ƒ†‡ˆ‘”–Š‡„”ƒ Š‡†ƒ‹†‡6ahƒ† ‘Ž›͵ͲΨ‡ƒ‹‡™ƒ•‰‡‡”ƒ–‡†ǤŠ‡ȽǦ ŠŽ‘”‘•—„•–‹–—–‡†ƒ‹†‡•6ai ƒ†6aj™‡”‡ ‘•—‡†‹–Š‡”‡ƒ –‹‘„—–‘‡ƒ‹‡ˆ‘”ƒ–‹‘™ƒ• ‘„•‡”˜‡† ƒ† –Š‡ •‹†‡ ’”‘†— –• ‘—Ž† —ˆ‘”–—ƒ–‡Ž› ‘– „‡ ‹†‡–‹ˆ‹‡†Ǥ ›”‹†‹‡ ‘–ƒ‹‹‰ƒ‹†‡6ak•Š‘™‡†‘ ‘˜‡”•‹‘–‘‡ƒ‹‡ƒˆ–‡” ͹ʹŠ‘—”•ƒ†–Š‡ ƒ–ƒŽ›•–™ƒ•’”‘„ƒ„Ž›‹Š‹„‹–‡†„›–Š‡Š‹‰Š ‘‘”†‹ƒ–Ǧ ‹‰ ƒ„‹Ž‹–› ‘ˆ –Š‡ •—„•–”ƒ–‡Ǥ ‘” –Š‡ ƒŽ†‡Š›†‡ ‘–ƒ‹‹‰ ƒ‹†‡ 6alǡ ‡ƒ‹‡™ƒ•‹†‡‡†ˆ‘”‡†ǢŠ‘™‡˜‡”ǡ‹–”‡ƒ –‡†‹ƒ•‡ŽˆǦ ‘†‡•ƒ–‹‘ ”‡ƒ –‹‘™‹–Š–Š‡ƒŽ†‡Š›†‡Ǥ‡šƒ’Ž‡‘Š‘™–Š‹•ƒ‹†‡ȋ6alȌ •–‹ŽŽ ‘—Ž†„‡—•‡†‹•†‡• ”‹„‡†‹ Šƒ’–‡”ͶǤ 

ͶͲ  

6aa 6ab 6ac 6ad

6ae 6af 6ag 6ah

6ai 6aj 6ak 6al Scheme41.Amidesthatdidnotsuccessfullyundergoenamineformationusing theMo(CO)6Ǧcatalyzedprotocol.

‘–Š‡„‡•–‘ˆ‘—”‘™Ž‡†‰‡–Š‡‡ƒ‹‡•ˆ‘”‡†‹–Š‡”‡ƒ –‹‘ƒ”‡ –Š‡trans‹•‘‡”•ȋ‡š ‡’–ˆ‘”7kȌǡ„—–—ˆ‘”–—ƒ–‡Ž›ǡƒ––‡’–•–‘‹•‘Žƒ–‡ –Š‡•‡’ƒ”–‹ —Žƒ”‡ƒ‹‡•™‡”‡—•— ‡••ˆ—Ž†—‡–‘–Š‡‹Š‡”‡–”‡ƒ Ǧ –‹˜‹–›–‘™ƒ”†•Š›†”‘Ž›•‹•Ǥͳʹͺ ‡–Š‡”‡ˆ‘”‡†‡ ‹†‡†–‘—•‡–Š‡‹”‡ƒ Ǧ –‹‘•™Š‡”‡‡ƒ‹‡•†‡ ‘”ƒ–‡†™‹–Š•‡•‹–‹˜‡ˆ— –‹‘ƒŽ‰”‘—’• ‘—Ž† „”‘ƒ†‡–Š‡• ‘’‡‘ˆ–Š‡–”ƒ•ˆ‘”ƒ–‹‘•ȋ Šƒ’–‡”•ͶȂ͹ȌǤ—”‹‰‘—” †‡˜‡Ž‘’‡–‘ˆ–Š‡’”‘–‘ ‘Ž†‡• ”‹„‡†‹–Š‹• Šƒ’–‡”‡‹–Š‡”•‹Ž›ŽŠ‡‹Ǧ ƒ‹ƒŽ‘”‹‹‹—‹–‡”‡†‹ƒ–‡•™‡”‡‘„•‡”˜‡†ǡ‘–‡˜‡ƒ–Ž‘™–‡Ǧ ’‡”ƒ–—”‡Ǥ —”–Š‡”‘”‡ǡ –Š‹• Šƒ’–‡” ™‹ŽŽ ™‘” ƒ• ƒ ˆ‘—†ƒ–‹‘ ˆ‘” –Š‡ ˆ‘ŽŽ‘™‹‰ Šƒ’–‡”•Ǥ 

Ͷͳ  

3.4Conclusions

‰‡‡”ƒŽƒ†‹Ž†’”‘–‘ ‘Žˆ‘”–Š‡‘ȋȌ͸Ǧ ƒ–ƒŽ›œ‡†Š›†”‘•‹Ž›Žƒ–‹‘ ‘ˆƒ‹†‡•‹–‘‡ƒ‹‡•™ƒ•†‡˜‡Ž‘’‡†ǤŠ‡”‡†— –‹‘™ƒ•Š‹‰ŠŽ› Š‡‘•‡Ž‡ –‹˜‡ǡ ›‹‡Ž†‹‰ ‡ƒ‹‡• Š‘Ž†‹‰ •‡•‹–‹˜‡ ˆ— –‹‘ƒŽ ‰”‘—’• ȋ ‘–ƒ‹‹‰‡–‘‡ǡƒŽ†‡Š›†‡ƒ†‹‹‡Ȍǡ•‘‡‘ˆ™Š‹ Šƒ”‡‘–ƒ ‡••‹Ǧ „Ž‡„› ‘†‡•ƒ–‹‘”‡ƒ –‹‘•ǤŠ‡‘„–ƒ‹‡†‡ƒ‹‡•™‡”‡‘–‹•‘Žƒ–‡† „—–—•‡†ˆ—”–Š‡”‹ƒ’’Ž‹ ƒ–‹‘•ǡ™Š‹ Š™‹ŽŽ„‡†‡• ”‹„‡†‹–Š‡ˆ‘ŽŽ‘™Ǧ ‹‰ Šƒ’–‡”•†‡˜‘–‡†–‘”‡†— –‹˜‡ˆ— –‹‘ƒŽ‹œƒ–‹‘‘ˆƒ‹†‡•Ǥ Š‡ƒ„‹Ž‹–›–‘–”ƒ•ˆ‘”•–ƒ„Ž‡ƒ‹†‡‘‹‡–‹‡•—†‡”‹Ž† ‘†‹Ǧ –‹‘•‘’‡•—’ˆ‘”–Š‡’‘••‹„‹Ž‹–›–‘‡’Ž‘›•— Šƒ††— –•‹–‘–ƒŽ•›Ǧ –Š‡•‹•ǡ e.gǤ ƒ• ’”‘–‡ –‹‘ ‰”‘—’• –Šƒ– ƒ „‡ –”ƒ•ˆ‘”‡† ‹ –Š‡ Žƒ•– •–‡’•ǤŠ‹•’”‘˜‹†‡•–Š‡‘’’‘”–—‹–›–‘ ”‡ƒ–‡‘˜‡Žƒ†’‘••‹„Ž›‘”‡ ‡ˆˆ‹ ‹‡–’ƒ–Š™ƒ›•ˆ‘”–Š‡•›–Š‡•‹•‘ˆ ‘’Ž‡š–ƒ”‰‡–‘Ž‡ —Ž‡•Ǥ

Ͷʹ  

4.ReductiveFunctionalizationofAmidesinto TriazolinesandTriazoles(PaperII)

4.1Introduction

ȟʹǦͳǡʹǡ͵Ǧ–”‹ƒœ‘Ž‹‡• ȋƒŽ•‘ ƒŽŽ‡† ͶǡͷǦ†‹Š›†”‘ǦͳHǦͳǡʹǡ͵Ǧ–”‹ƒœ‘Ž‡•Ȍ ƒ† ͳǡʹǡ͵Ǧ–”‹ƒœ‘Ž‡•i ƒ”‡ ‹’‘”–ƒ– Žƒ••‡• ‘ˆ ˆ‹˜‡Ǧ‡„‡”‡† Š‡–‡”‘ › Ž‹  ‘’‘—†• ȋ ‹‰—”‡ ͵ȌǤ Š‡› ƒ”‡ ‘™ –‘ ‡šŠ‹„‹– „‹‘Ž‘‰‹ ƒŽ ƒ –‹˜‹Ǧ –›ͳʹͻǡͳ͵Ͳƒ†ƒ”‡‹’‘”–ƒ–‹–‡”‡†‹ƒ–‡•‹•›–Š‡•‹•Ǥͳ͵ͳ‹‰‹ˆ‹ ƒ–ƒ–Ǧ –‡–‹‘Šƒ•„‡‡†‡˜‘–‡†ˆ‘”–Š‡‰‡‡”ƒ–‹‘‘ˆ–”‹ƒœ‘Ž‡•ƒ†–Š‡•–ƒ†Ǧ ƒ”†”‘—–‡–‘™ƒ”†•–Š‡•‡ ‘’‘—†•‹•–Š”‘—‰Š–Š‡—Ǧ ƒ–ƒŽ›œ‡†ƒœ‹†‡Ǧ ƒŽ›‡ › Ž‘ƒ††‹–‹‘ ”‡ƒ –‹‘ ȋ–Š‡ DzŽ‹ dz ”‡ƒ –‹‘ǡ  Š‡‡ ͶʹȌǤͳ͵ʹ –Š‡‘–Š‡”Šƒ†ǡŽ‹––Ž‡ˆ‘ —•Šƒ•„‡‡’—–‹–‘–Š‡†‡˜‡Ž‘’‡–‘ˆ’”‘–‘Ǧ ‘Ž•ˆ‘”–Š‡’”‡’ƒ”ƒ–‹‘‘ˆ–”‹ƒœ‘Ž‹‡•Ǥ

 Figure3.Structuresoftriazolineandtriazole.

 Scheme42.CuǦcatalyzed“Click”reactionbetweenanalkyneandanazideformǦ ingtriazoleasproduct.

‡‰ƒ”†‹‰ –Š‡ •›–Š‡•‹• ‘ˆ –”‹ƒœ‘Ž‹‡•ǡ ‘Žˆˆ †‹• ‘˜‡”‡† ‹ ͳͻͳʹ –Šƒ– –Š‡•‡ ‘’‘—†• ™‡”‡ ˆ‘”‡† „› –Š‡ ͳǡ͵Ǧ†‹’‘Žƒ” › Ž‘ƒ††‹–‹‘ ‘ˆƒœǦ

    i –Š‹•–Š‡•‹•ƒ†‹–Š‡’—„Ž‹ ƒ–‹‘ȋǤŽƒ‰„”ƒ†ǡǤ‘Ž‘˜ǡǤ”‹ŽŽ‘ǡ Ǥ‹‹•ǡ Ǥ†‘Žˆ••‘ǡACSCatalysisǡ2017ǡ7ǡͳ͹͹ͳǦͳ͹͹ͷȌ–Š‡ ‘’‘—†•ƒ”‡”‡ˆ‡””‡†–‘ ƒ•triazolinesƒ†triazoles. Ͷ͵  

‹†‡•ͳ͵͵™‹–Š‘Ž‡ˆ‹•ȋ Š‡‡Ͷ͵ƒȌǤͳ͵Ͷƒ–‡” —‹•‰‡ƒ†̵„„±†‡‘Ǧ •–”ƒ–‡†–Šƒ––Š‡”‡ƒ –‹˜‹–›‘ˆ–Š‡‘Ž‡ˆ‹‹–Š‡”‡ƒ –‹‘™ƒ•Š‹‰ŠŽ› ‘Ǧ ‡ –‡† –‘ ‹–• ‡Ž‡ –”‘‹  ’”‘’‡”–‹‡•Ǥͳ͵ͷ – ™ƒ• ‡•–ƒ„Ž‹•Š‡† –Šƒ– ‡Ž‡ –”‘ †‡ˆ‹ ‹‡– ƒŽ‡‡• ™‡”‡ Ž‡•• ”‡ƒ –‹˜‡ǡ ”‡“—‹”‹‰ †ƒ›• ‘” ‡˜‡ ™‡‡• –‘ ”‡ƒ –ǤŠ‹• ‘—Ž†„‡‘˜‡” ‘‡„›‡’Ž‘›‹‰ƒŠ‹‰Š’”‡••—”‡ȋͳʹ„ƒ”Ȍ ƒ•Žƒ–‡”•Š‘™„›‡‹”‡„ƒ† ‘Ǧ™‘”‡”•Ǥͳ͵͸ ‘”‡ ‡Ž‡ –”‘Ǧ”‹ Š ‘Ž‡Ǧ ˆ‹•ȋe.gǤ‡ƒ‹‡•Ȍ”‡ƒ –‘”‡”‡ƒ†‹Ž›ƒ†Šƒ˜‡„‡‡•Š‘™–‘—†‡”‰‘ –Š‡ › Ž‘ƒ††‹–‹‘ ”‡ƒ –‹‘ ”‡‰‹‘•’‡ ‹ˆ‹ ƒŽŽ› —†‡” ‹Ž† ”‡ƒ –‹‘ ‘†‹Ǧ –‹‘•Ǥͳ͵͹ ‘™‡˜‡”ǡ –Š‡ ‘˜‡”ƒŽŽ ›‹‡Ž† ™ƒ• •–”‘‰Ž› ‘””‡Žƒ–‡† ™‹–Š –Š‡ •— ‡••‹–Š‡’”‡’ƒ”ƒ–‹‘‘ˆ–Š‡‡ƒ‹‡’”‹‘”–‘—•‡ǤŠ‡”‡‡š‹•–‘Ž› ƒ ˆ‡™ ‡šƒ’Ž‡• ™‡”‡ –Š‡ ‡ƒ‹‡ ‹• ˆ‘”‡† in situƒ†•—„•‡“—‡–Ž› —•‡†‹ƒͳǡ͵Ǧ › Ž‘ƒ††‹–‹‘”‡ƒ –‹‘Ǥ‹ƒ Š‡––‹etal.’”‡’ƒ”‡†‡ƒ‹‡• ˆ”‘ƒ ‡–‘‡ƒ††‹ˆˆ‡”‡–ƒŽ‹’Šƒ–‹ ƒ‹‡•ǡ™Š‹ Š–Š‡›”‡ƒ –‡†‹ƒ –ƒ†‡”‡ƒ –‹‘™‹–Šƒ”›Žƒœ‹†‡•ǡƒŽ„‡‹–‘Ž›ƒˆ‡™–”‹ƒœ‘Ž‹‡’”‘†— –• ™‡”‡ ‘„–ƒ‹‡†Ǥͳ͵ͺ  ’”‘–‘ ‘Ž ™‹–Š ƒ „”‘ƒ†‡” ‡ƒ‹‡ • ‘’‡ ™ƒ• ’—„Ǧ Ž‹•Š‡†„›–”ƒ†‹ƒ†‘ ƒ”™Š‡”‡†‹ˆˆ‡”‡–ƒŽ†‡Š›†‡•ƒ†‡–‘‡•™‡”‡ —•‡†‹ ‘„‹ƒ–‹‘™‹–Š„‘–Š’”‹ƒ”›ƒ†•‡ ‘†ƒ”› ƒ‹‡•ˆ‘” –Š‡ •›–Š‡•‹•‘ˆ–”‹ƒœ‘Ž‹‡•ȋ Š‡‡Ͷ͵„ȌǤͳ͵ͻŠ‡‘„–ƒ‹‡†–”‹ƒœ‘Ž‹‡•™‡”‡ ‹•‘Žƒ–‡†‹Ž‘™–‘‡š ‡ŽŽ‡–›‹‡Ž†•ǡƒŽ–Š‘—‰Šǡ‘Ž›pǦ‹–”‘ ’Š‡›Ž ƒœ‹†‡ ™ƒ•‡’Ž‘›‡†ƒ•–Š‡•‡ ‘† ‘’‘‡–‹–Š‡ › Ž‹œƒ–‹‘Ǥ

 Scheme43.Synthesisoftriazolinesthrougha)1,3Ǧcycloadditionofazideswith activatedolefins,b)cycloadditionwithinsituformedenamines,c)triazoleforǦ mationviatriazolineintermediates.

ƒ–ƒŽ›–‹  ƒ‘—–• ‘ˆ ƒ‹‡ Šƒ˜‡ „‡‡ —•‡† –‘ ‰‡‡”ƒ–‡ ƒ–ƒŽ›–‹  ƒ‘—–• ‘ˆ ‡ƒ‹‡ in situ ˆ‘ŽŽ‘™‡† „› ͳǡ͵Ǧ › Ž‘ƒ††‹–‹‘ ™‹–Š ƒœ‹†‡ ȋ Š‡‡Ͷ͵ ȌǤͳͶͲŠ‹•‡–Š‘†‘Ž‘‰›†‘‡•‘–”‡•—Ž–‹–Š‡–”‹ƒœ‘Ž‹‡ƒ• –Š‡ˆ‹ƒŽ’”‘†— –ǡ„—–”ƒ–Š‡”ƒ•ƒ‹–‡”‡†‹ƒ–‡–‘™ƒ”†•–”‹ƒœ‘Ž‡ ƒˆ–‡” •’‘–ƒ‡‘—•‡Ž‹‹ƒ–‹‘‘ˆ–Š‡ƒ‹‡ ƒ–ƒŽ›•–Ǥ‘–Š‡””‘—–‡–‘™ƒ”†• –Š‡ˆ‘”ƒ–‹‘‘ˆ–”‹ƒœ‘Ž‹‡•‹•–Š‡ › Ž‘ƒ††‹–‹‘”‡ƒ –‹‘‘ˆ†‹ƒœ‘ ‘Ǧ ’‘—†•™‹–Š Š‹ˆˆ„ƒ•‡•ǤͳͶͳ

ͶͶ  

4.2Results

Š‡ †‡˜‡Ž‘’‡– ‘ˆ –Š‡ ‘ȋȌ͸Ǧ ƒ–ƒŽ›œ‡† ’”‘–‘ ‘Ž ˆ‘” ƒ‹†‡ ”‡†— Ǧ –‹‘‡ƒ„Ž‡†–Š‡‹Ž†ƒ† Š‡‘•‡Ž‡ –‹˜‡ˆ‘”ƒ–‹‘‘ˆ‡ƒ‹‡•ȋ Šƒ’Ǧ –‡”͵ȌǤ‹ ‡–Š‡”‡†— –‹‘•›•–‡–‘Ž‡”ƒ–‡•ƒ’Ž‡–Š‘”ƒ‘ˆ†‹ˆˆ‡”‡–ˆ— Ǧ –‹‘ƒŽ‰”‘—’•™‡‡˜‹•‹‘‡†–Šƒ–•–ƒ„Ž‡ƒ‹†‡• ‘—Ž†„‡—•‡†‹‘‡Ǧ’‘– •›–Š‡•‹• ‹–‘ ˜ƒŽ—ƒ„Ž‡ ‘’‘—†•Ǥ ‡ ˆ‘—† –Šƒ– –Š‡ Ž‹–‡”ƒ–—”‡Šƒ† ‘Ž› • ƒ” ‡Ž› †‡• ”‹„‡† –Š‡ ‡ƒ‹‡Ǧƒœ‹†‡ › Ž‘ƒ††‹–‹‘ ”‡ƒ –‹‘ ˆ‘” –Š‡•›–Š‡•‹•‘ˆ–”‹ƒœ‘Ž‹‡•ƒ†‹–™ƒ•†‡ ‹†‡†–‘‡˜ƒŽ—ƒ–‡‘—”•›•–‡ ˆ‘”†‡˜‡Ž‘’‹‰ƒ‰‡‡”ƒŽ‡–Š‘†Ǥ ”ƒ–‹ˆ›‹‰Ž›ǡ„›ƒ††‹‰ͳǤͷ‡“—‹˜ƒŽ‡–• ‘ˆ’Š‡›Žƒœ‹†‡ȋ8aȌ–‘–Š‡’”‡Ǧˆ‘”‡†‡ƒ‹‡ȋ7aȌˆ‘”ƒ–‹‘‘ˆ–”‹ƒǦ œ‘Ž‹‡ 9a ‘—Ž† „‡ ‘„•‡”˜‡† ȋ Š‡‡ ͶͶȌǤ Š‹• ‘’‘—† ™ƒ• Žƒ–‡” ‹•‘Žƒ–‡†‹ͻͳΨ›‹‡Ž†ƒ†™‡‹˜‡•–‹‰ƒ–‡†‹ˆ–Š‡”‡ƒ –‹‘ ‘—Ž†„‡’‡”Ǧ ˆ‘”‡†ƒ•ƒ–ƒ†‡”‡ƒ –‹‘Ǥ‡”‡ƒŽ‹œ‡†–Šƒ––Š‡ƒ‹†‡”‡†— –‹‘™ƒ• Š‹‰ŠŽ›ƒˆˆ‡ –‡†ƒ•ƒ‹Ž›•–ƒ”–‹‰ƒ–‡”‹ƒŽ™ƒ•”‡–ƒ‹‡†ƒŽ‘‰™‹–Š–”ƒ Ǧ ‡•‘ˆ–”‹ƒœ‘Ž‹‡’”‘†— –Ǥ –™ƒ••—‰‰‡•–‡†–Šƒ––Š‡ƒ††‹–‹‘‘ˆƒœ‹†‡™ƒ• ‘––Š‡•‘—” ‡‘ˆ–Š‡’‘‹•‘‹‰‘ˆ–Š‡ ƒ–ƒŽ›•–„—–”ƒ–Š‡”–Š‡ˆ‹ƒŽ’”‘†Ǧ — –ȋ–”‹ƒœ‘Ž‹‡ȌǤŠ‹•™ƒ••—’’‘”–‡†„›ƒ‡š’‡”‹‡–‹™Š‹ Šͷ‘ŽΨ ‘ˆ–”‹ƒœ‘Ž‹‡™ƒ•ƒ††‡†–‘–Š‡•–ƒ†ƒ”†ƒ‹†‡”‡†— –‹‘”‡ƒ –‹‘ǡ Ž‡ƒ”Ǧ Ž›•Š‘™‹‰–Šƒ––Š‡‡ƒ‹‡ˆ‘”ƒ–‹‘™ƒ•‹’‡†‡†Ǥ

 Scheme44.OneǦpotformationoftriazolinesfromamides.

Š‡ ”‡ƒ –‹‘ ‘ˆ ‡ƒ‹‡• ™‹–Š ƒœ‹†‡• ™ƒ• ’”‡˜‹‘—•Ž› ‹˜‡•–‹‰ƒ–‡† „› — ƒ† ‘Ǧ™‘”‡”• ƒ† ™ƒ• ‘„•‡”˜‡† –‘ „‡ ”‡‰‹‘•’‡ ‹ˆ‹ ǡ ˆ‘”‹‰ ‘Ž› ‘‡ ”‡‰‹‘‹•‘‡” ƒ• ’”‘†— –Ǥͳ͵͹„ ˜‹†‡ ‡ ˆ‘” –Š‡ ”‡ƒ –‹‘ „‡‹‰ ‘ ‡”–‡†™ƒ••—’’‘”–‡†„›–Š‡‰”‘—’‘ˆ ‘—Ǥͳ͵͹ ‡•—‰‰‡•–‡†–Šƒ– –Š‡•–”— –—”‡‘ˆ–Š‡’”‘†— –‹•ƒ•†‡’‹ –‡†‹ Š‡‡ͶͶǡƒ†–Š‹•™ƒ• ‘ˆ‹”‡†„›ͳ ‡š’‡”‹‡–•‘–”‹ƒœ‘Ž‹‡9dǤ ‹–Šƒ•— ‡••ˆ—Ž’”‘–‘ ‘Žˆ‘”–Š‡–”‹ƒœ‘Ž‹‡•›–Š‡•‹•™‡†‡ ‹†‡† –‘ ˆ—”–Š‡” ‹˜‡•–‹‰ƒ–‡ –Š‡ • ‘’‡ ‘ˆ –Š‡ ”‡ƒ –‹‘ •–ƒ”–‹‰ „› ‡˜ƒŽ—ƒ–‹‰ †‹ˆˆ‡”‡–‡ƒ‹‡•ȋ Šƒ’–‡”͵ƒ† Š‡‡ͶͷȌǤ‘–Š‡Ž‡ –”‘Ǧ’‘‘”ȋ7bȌ ƒ†‡Ž‡ –”‘Ǧ”‹ Šȋ7cȌ‡ƒ‹‡• ‘—Ž†„‡—•‡†‰‡‡”ƒ–‹‰–Š‡’”‘†— –• ‹Š‹‰Š‹•‘Žƒ–‡†›‹‡Ž†•Ǥ —”–Š‡”‘”‡ǡ–Š‡–Š‹‘’Š‡‡ ‘–ƒ‹‹‰–”‹ƒœ‘Ž‹‡ 9d™ƒ•‘„–ƒ‹‡†‹ͺ͵ΨǤŠ‡‡ƒ‹‡ˆ”‘–Š‡„”ƒ Š‡†ƒ‹†‡6k ȋ‘„–ƒ‹‡†‹ͺ͹ǣͳ͵”ƒ–‹‘‘ˆ‹•‘‡”•Ȍˆ‘”‡†–™‘†‹ƒ•–‡”‡‘‡”•ȋ9eȌ‹

Ͷͷ  

–Š‡ › Ž‘ƒ††‹–‹‘”‡ƒ –‹‘‹ƒʹǣͳ”ƒ–‹‘ȋ Š‡‡Ͷ͸ȌǤŠ‡ƒŒ‘” ‘Ǧ ’‘—†™ƒ••— ‡••ˆ—ŽŽ›•‡’ƒ”ƒ–‡†ƒ†–Š‡•–‡”‡‘ Š‡‹•–”›™ƒ•†‡–‡”Ǧ ‹‡†„›ͳ ‡š’‡”‹‡–•ǤŠ‡‡–Š›Ž‰”‘—’™ƒ•ˆ‘—†–‘„‡ cis–‘–Š‡–”‹ƒœ‘Ž‹‡’”‘–‘ǤŠ‡ƒŽ‹’Šƒ–‹ ƒ‹†‡6l ‰ƒ˜‡ ƒ ‹š–—”‡ ‘ˆ ‡ƒ‹‡ƒ†ƒ‹‡ǡ›‹‡Ž†‹‰–Š‡–”‹ƒœ‘Ž‹‡9f‹‘†‡”ƒ–‡›‹‡Ž†Ǥ‘”‡‘Ǧ ˜‡”ǡŠ‹‰Šˆ— –‹‘ƒŽ‰”‘—’–‘Ž‡”ƒ ‡™ƒ•‘„•‡”˜‡†ƒ†–”‹ƒœ‘Ž‹‡• ‘Ǧ –ƒ‹‹‰‡•–‡”ȋ9gȌǡ‡–‘‡ȋ9hȌƒ†ƒŽ†‹‹‡ȋ9iȌ‘‹‡–‹‡• ‘—Ž†„‡‘„Ǧ –ƒ‹‡†‹Š‹‰Š–‘‡š ‡ŽŽ‡–›‹‡Ž†•Ǥ

9a, 91% 9b, 86% 9c, 88% 2 h 2 h 2 h

9d, 83% 9e,a,b 61% 9f, 66% 2.5 h 15 h 3 h

9g, 94% 9h, 84% 9i, 88% 2 h 2.5 h 3 h Scheme45.Evaluationoftertiaryamides6inthechemoselectivereductionand subsequent cycloaddition reaction with enamines from amides (1mmol) with organicazide8a,isolatedyields.aReactionperformedat60°C.bDiastereomers wereobtainedina2:1ratio.

Ͷ͸  

 Scheme46.Distributionofdiastereomersforcompound9e.

•‡–‹‘‡†‹ Šƒ’–‡”͵ǡ–Š‡”‡†— –‹‘‘ˆ–Š‡ƒŽ†‡Š›†‡ ‘–ƒ‹‹‰ ƒ‹†‡6al™ƒ•’”‘„Ž‡ƒ–‹ †—‡–‘—†‡•‹”‡†•‹†‡Ǧ”‡ƒ –‹‘•Ǥ‘ ‹” —Ǧ ˜‡––Š‹•’”‘„Ž‡ǡ‹–™ƒ•‡˜‹•‹‘‡†–Šƒ–‹–‹‰Š–„‡’‘••‹„Ž‡–‘—•‡–Š‡ insituˆ‘”‡†‡ƒ‹‡‹ƒ–ƒ†‡”‡ƒ –‹‘ȋ Š‡‡Ͷ͹ȌǤ ‹‰Š‡”Ž‘ƒ†Ǧ ‹‰‘ˆ‘ȋȌ͸ȋ͵Ͳ‘ŽΨȌ™ƒ•”‡“—‹”‡†–‘’—•Š–Š‡”‡ƒ –‹‘–‘™ƒ”†• ’”‘†— –†—‡–‘‹Š‹„‹–‹‘‘ˆ–Š‡ ƒ–ƒŽ›•–‹ ‘„‹ƒ–‹‘™‹–Š‡š–‡†‡† ”‡ƒ –‹‘–‹‡ȋ͹ʹŠȌƒ•™‡ŽŽƒ•‡’Ž‘›‹‰–Š‡‘”‡”‡ƒ –‹˜‡pǦ ͵’Š‡Ǧ ›Žƒœ‹†‡8bǤ –Š‡’”‡•‡ ‡‘ˆƒœ‹†‡ǡ–Š‡ˆ‘”‡†‡ƒ‹‡†‹†‘–•‡ŽˆǦ ‘†‡•ƒ–‡™‹–Š–Š‡ƒŽ†‡Š›†‡‘‹‡–›ƒ†–”‹ƒœ‘Ž‹‡9j ‘—Ž†—Ž–‹ƒ–‡Ž› „‡‹•‘Žƒ–‡†‹ͺͲΨ›‹‡Ž†ǤŠ‹•‡š’‡”‹‡–ˆ—”–Š‡”†‡‘•–”ƒ–‡•–Š‡‡šǦ ‡ŽŽ‡– Š‡‘•‡Ž‡ –‹˜‹–›‘ˆ–Š‡”‡†— –‹‘’”‘–‘ ‘ŽǤ

 Scheme47.Tandemreactionforthealdehydecontainingamide6al(0.5mmol) intothecorrespondingtriazoline9j.

Ͷ͹  

Table 3. Comparison between enamines containing different NǦsubstituents in thecyclizationwithphenylazide(8).a

 Entry Enamine Triazoline [%]

ͳ ͳͶ

7a 9a

ʹ Ͷʹ

7p 9k

͵ ͳ͸ 7r 9n ƒ ƒ‹‡• ˆ”‘ ƒ‹†‡• 6 ȋͲǤͷ ‘ŽȌǤ ͳ   ›‹‡Ž†• —•‹‰ ͳǡ͵ǡͷǦ–”‹‡–Š‘š›„‡œ‡‡ƒ•‹–‡”ƒŽ•–ƒ†ƒ”†Ǥ

ƒ‹‡•†‡”‹˜‡†ˆ”‘’‹’‡”‹†‹‡ȋ7aȌǡ’›””‘Ž‹†‹‡ȋ7pȌƒ††‹‡–Š›ŽǦ ƒ‹‡ȋ7rȌ™‡”‡‡˜ƒŽ—ƒ–‡†‹–Š‡ › Ž‹œƒ–‹‘”‡ƒ –‹‘ȋƒ„Ž‡͵Ȍƒ†‹– ™ƒ• ˆ‘—† –Šƒ– –Š‡ ’›””‘Ž‹†‹‡ ‘–ƒ‹‹‰ ‡ƒ‹‡ 7p”‡ƒ –‡†ˆƒ•–‡” –Šƒ–Š‡‘–Š‡”–™‘ǤŠ‡”‡•—Ž–‹•‹Ž‹‡™‹–Š‡ƒ”Ž‹‡”‘„•‡”˜ƒ–‹‘•™Š‡”‡ –Š‡ ‡ƒ‹‡ ™‹–Š ƒ ‘”‡ ’Žƒƒ” ‘ˆ‘”ƒ–‹‘ ™ƒ• ˆ‘—† –‘ „‡ ‘”‡ ”‡ƒ –‹˜‡ǤŠ‹•ƒŽŽ‘™•ˆ‘”ƒ‰‘‘†‘˜‡”Žƒ’™‹–Š–Š‡ƒŽ‡‡†‘—„Ž‡„‘†ǡ ƒ† ‰‹˜‡• ƒ ‘”‡ ”‡ƒ –‹˜‡ ‡ƒ‹‡Ǥ͹ǡͳͶʹ —”–Š‡”‡˜ƒŽ—ƒ–‹‘‘ˆƒ‹†‡• ™‹–Š†‹ˆˆ‡”‡–NǦ•—„•–‹–—‡–•Ž‡†–‘–Š‡‹•‘Žƒ–‹‘‘ˆ ‘’‘—†•9k–‘9q •Š‘™‹ Š‡‡ͶͺǤ 

Ͷͺ  

9k, 90% 9l, 72% 9m, 78% 9n, 92% 3 h 3 h 1 h 3 h

9o, 90% 9p,a 82% 9q,a 60% 5 h 5 h 3 h Scheme48.Evaluationoftertiaryamides6inthechemoselectivereductionand subsequent cycloaddition reaction of enamines from amides (1mmol), isolated a yields. pǦCF3phenylazide(8b)wasused.

Š‡‹Ž†ƒ† Š‡‘•‡Ž‡ –‹˜‡”‡†— –‹‘•›•–‡ƒŽŽ‘™‡†ˆ‘”–Š‡‘‡Ǧ’‘– ƒ††‹–‹‘”‡ƒ –‹‘‘ˆƒœ‹†‡•„‡ƒ”‹‰ƒ™‹†‡”ƒ‰‡‘ˆ”‡†— ‹„Ž‡ˆ— –‹‘ƒŽ ‰”‘—’•ȋ Š‡‡ͶͻȌǤ”‹ƒœ‘Ž‹‡••—„•–‹–—–‡†™‹–ŠƒŽ†‹‹‡ȋ9rȌǡ–‡”‹Ǧ ƒŽ‘Ž‡ˆ‹ȋ9sȌǡ–‡”‹ƒŽƒŽ›‡ȋ9tȌǡƒœ‹†‡ȋ9vȌǡ ›ƒ‘ȋ9aaȌǡ‡•–‡”ȋ9yǡ 9xƒ†9aiȌǡ‡–‘‡ȋ4ajȌƒ†ƒŽ†‡Š›†‡ȋ4akȌ‘‹‡–‹‡•™‡”‡‘„–ƒ‹‡†‹ ‰‘‘†–‘Š‹‰Š›‹‡Ž†•ǤŠ‡Š›†”‘š›Ž ‘–ƒ‹‹‰–”‹ƒœ‘Ž‹‡9ah™ƒ•‹•‘Žƒ–‡† ‹’‘‘”›‹‡Ž†ȋ͵ͷΨȌǡ™Š‹ Š™ƒ•‘–‹’”‘˜‡†—’‘ƒ††‹–‹‘‘ˆ‘”‡ ƒœ‹†‡ǡ‡š–‡†‹‰–Š‡”‡ƒ –‹‘–‹‡‘”‹ ”‡ƒ•‹‰–Š‡”‡ƒ –‹‘–‡’‡”ƒǦ –—”‡Ǥ 

Ͷͻ  

9r, 92% 9s, 85% 9t, 93% 9u, 88% 3 h 3 h 3 h 2 h

9v, 78% 9w, 75% 9x, 88% 9y, 79% 3 h, 65 °C 15 h, 65 °C 3 h, r.t. 22 h, 50 °C

9z, 95% 9aa, 82% 9ab, 80% 9ac, 85% 3 h 3 h 2 h 3 h

9ad, 92% 9ae, 89% 9af, 97% 9ag, 85% 2 h 20 h 3 h 7 h

9ah, 35% 9ai, 91% 9aj, 90% 9ak, 93% 3 h 3 h 3 h 3 h Scheme49.Evaluationoforganicazides8inthechemoselectivereductionand subsequentcycloadditionreactionwithenaminesfromamides6(1mmol),isolatǦ edyields.

‡ ‘„•‡”˜‡† –Šƒ– ‡Ž‡ –”‘Ǧ’‘‘” ‡ƒ‹‡ 7gȋpǦʹȌ ”‡ƒ –‡† ‘”‡ •Ž‘™Ž› ‹ –Š‡ › Ž‘ƒ††‹–‹‘ ƒ† –Š‡ ‘”‡ ”‡ƒ –‹˜‡ pǦ ͵’Š‡›Ž ƒœ‹†‡ ȋ8bȌ Šƒ† –‘ „‡ ‡’Ž‘›‡†Ǥ ‘ ‘—” •—”’”‹•‡ –”‹ƒœ‘Ž‡ 10a ™ƒ• ‘„–ƒ‹‡†ǡ ’”‘„ƒ„Ž› †—‡ –‘ –Š‡ ‹•–ƒ„‹Ž‹–› ‘ˆ–Š‡ˆ‘”‡†–”‹ƒœ‘Ž‹‡ȋ Š‡‡ ͷͲȌǤ ‡œ›Žƒœ‹†‡”‡ƒ –‡†’‘‘”Ž›™‹–Š‡ƒ‹‡•—†‡”•–ƒ†ƒ”† ‘†‹–‹‘•ǡ ™Š‡”‡ƒ•‹ ”‡ƒ•‹‰–‡’‡”ƒ–—”‡ƒ†–‹‡‘ˆ–Š‡”‡ƒ –‹‘Ž‡†–‘–Š‡ˆ‘”Ǧ ƒ–‹‘‘ˆ–”‹ƒœ‘Ž‡10b‹Š‹‰Š‹•‘Žƒ–‡†›‹‡Ž†ǤŠ‡•ƒ‡ ‘†‹–‹‘•™‡”‡ ”‡“—‹”‡† ˆ‘” –Š‡ ƒŽ‹’Šƒ–‹  ƒœ‹†‡ –‘ —†‡”‰‘ –”ƒ•ˆ‘”ƒ–‹‘ǡ ƒŽ–Š‘—‰Š ‡˜‡Ž‘‰‡”–‹‡™ƒ•”‡“—‹”‡†–‘†‡Ž‹˜‡”–Š‡ ‘””‡•’‘†‹‰–”‹ƒœ‘Ž‡10c ‹“—ƒ–‹–ƒ–‹˜‡›‹‡Ž†Ǥ –‹•‘™–Šƒ––”‹ƒœ‘Ž‹‡•ƒ”‡–Š‡”ƒŽŽ›Žƒ„‹Ž‡ƒ† –Š‡Š‹‰Š–‡’‡”ƒ–—”‡”‡“—‹”‡†ˆ‘”–Š‡•‡ƒœ‹†‡•–‘”‡ƒ –‹‰Š–ƒŽ•‘’”‘Ǧ ‘–‡ –Š‡ ‡Ž‹‹ƒ–‹‘ ”‡ƒ –‹‘ –‘ ‰‡‡”ƒ–‡ –Š‡ –”‹ƒœ‘Ž‡•Ǥ •’‹”‡† „› ͷͲ  

— ƒ† ‹ǡ ™Š‘ •Š‘™‡† –Šƒ– –”‹ƒœ‘Ž‡• ƒ „‡ ˆ‘”‡† „› –”‡ƒ–‹‰ –”‹ƒœ‘Ž‹‡•™‹–Šƒ‡š ‡••‘ˆ„ƒ•‡ȋ Ȁ‡ Ȍ—†‡””‡ˆŽ—š ‘†‹–‹‘•ǡ ™‡ †‡ ‹†‡† –‘ ‡˜ƒŽ—ƒ–‡ –Š‡ ‡Ž‹‹ƒ–‹‘ ”‡ƒ –‹‘Ǥͳ͵͹ƒ – ™ƒ• ˆ‘—† –Šƒ– –Š‡ ‘ŽŽƒ’•‡‘ˆ–Š‡–”‹ƒœ‘Ž‹‡‘Ž›”‡“—‹”‡† ƒ–ƒŽ›–‹ ƒ‘—–‘ˆ„ƒ•‡ȋʹͷ ‘ŽΨȌƒ†–Šƒ––”‹ƒœ‘Ž‡•10dƒ†10e ‘—Ž†„‡‘„–ƒ‹‡†‹Š‹‰Š›‹‡Ž†• ‹ƒ–Š”‡‡Ǧ•–‡’‘‡Ǧ’‘–ˆƒ•Š‹‘Ǥ —”–Š‡”‘”‡ǡ–Š‡ƒ„‹Ž‹–›–‘ˆ‘”–”‹ƒœ‘Ž‡ ‘–ƒ‹‹‰ƒƒœ‹†‡‘‹‡–›ȋ10eȌ‹•‘ˆ‰”‡ƒ–˜ƒŽ—‡•‹ ‡–Š‹• ‘’‘—† ‹•˜‡”› ŠƒŽŽ‡‰‹‰–‘ˆ‘”„›DzŽ‹ dz Š‡‹•–”›Ǥ

10a,a 58% 10b,b,c 79% 10c,b 96% 15 h, r.t. 24 h, 80 °C 65 h, 80 °C

10d,a,d 92% 10e,b,d 78% 3 h, 65 °C 2 h, r.t. Scheme50.Evaluationoftertiaryamides6andazides8inthechemoselective reduction and subsequent cycloaddition reaction with enamines from amides (1mmol),isolatedyields. aPiperidinederivedamidewasused. bPyrrolidinedeǦ rived amide was used. c Isolation was performed on 0.5 mmol scale. d KOH in methanol(2M,0.25equiv)wasaddedandreactionwasleftforadditional3hat 65°C.

‘”‡‘˜‡”ǡ –Š‡ ’”‘–‘ ‘Ž ™ƒ• ‡˜ƒŽ—ƒ–‡† ‘ ƒ ’”‡’ƒ”ƒ–‹˜‡ • ƒŽ‡ —•‹‰ ƒ –™‘Ǧ‡ ‡† ”‘—†Ǧ„‘––‘ ˆŽƒ• ˆ‹––‡† ™‹–Š ƒ ‘†‡•‡” ȋ Š‡‡ ͷͳȌǤ Š‹•”‡•—Ž–‡†‹–Š‡‹•‘Žƒ–‹‘‘ˆ–Š‡‡–‘‡ ‘–ƒ‹‹‰–”‹ƒœ‘Ž‹‡9aj‹ ͻʹΨ›‹‡Ž†‘ͷ‘Ž• ƒŽ‡ƒ†–”‹ƒœ‘Ž‡10f ™ƒ• Ž‹‡™‹•‡ ‘„–ƒ‹‡† ‹ Š‹‰Š›‹‡Ž†ǡ™Š‹ Š†‹•’Žƒ›•–Šƒ––Š‡ ›ƒ‘‘‹‡–›‹•™‡ŽŽ–‘Ž‡”ƒ–‡†‹–Š‹• ’”‘–‘ ‘ŽǤ 

ͷͳ  

 Scheme51.ScaleǦupreactionsoftheprotocolsfor(a)triazolineand(b)triazole formation.

4.3Conclusions

Š‡ˆƒ ‹Ž‡ˆ‘”ƒ–‹‘‘ˆ–”‹ƒœ‘Ž‹‡•ƒ†–”‹ƒœ‘Ž‡•™‡ŽŽ‹ŽŽ—•–”ƒ–‡•–Šƒ––Š‡ ‘ȋȌ͸Ǧ ƒ–ƒŽ›œ‡†•›•–‡‹••—‹–ƒ„Ž‡‹”‡†— –‹˜‡ˆ— –‹‘ƒŽ‹œƒ–‹‘•‘ˆ ƒ‹†‡•Ǥ  ™‹†‡ ˜ƒ”‹‡–› ‘ˆ ˆ— –‹‘ƒŽ ‰”‘—’• ƒ”‡ –‘Ž‡”ƒ–‡†ǡ ‡‹–Š‡” •‹–—ƒ–‡†‘–Š‡ƒ‹†‡•—„•–”ƒ–‡‘”ƒœ‹†‡”‡ƒ‰‡–ǤŠ‡”‡ƒ –‹‘• ‘—Ž†„‡ ’‡”ˆ‘”‡†‹–Š‡‰”‡‡•‘Ž˜‡–‡–Š›Žƒ ‡–ƒ–‡—•‹‰–Š‡ƒ‹”ǡ‘‹•–—”‡ƒ† Š‡ƒ–•–ƒ„Ž‡ǡ™Š‹ Š‹–‡”•‘ˆ•‹Žƒ‡•‹•ƒ‹‡š’‡•‹˜‡Š›†”‹†‡ •‘—” ‡Ǥ —”–Š‡”‘”‡ǡ ‹– ™ƒ• ’‘••‹„Ž‡ –‘ ‘„–ƒ‹ „‘–Š –Š‡ –”‹ƒœ‘Ž‹‡ ƒ† –”‹ƒœ‘Ž‡’”‘†— –•‘ƒ’”‡’ƒ”ƒ–‹˜‡• ƒŽ‡Ǥ 

ͷʹ  

5.ReductiveFunctionalizationofAmidesinto NǦSulfonylformamidines(PaperIII)

5.1Introduction

‹†‹‡• ƒ”‡ ‘ˆ–‡ ˆ‘—† ‹ „‹‘Ž‘‰‹ ƒŽŽ› ƒ –‹˜‡ ‘’‘—†• –Šƒ– Šƒ˜‡ ƒ–‹Ǧ‹ˆŽƒƒ–‘”›ǡ ƒ–‹„ƒ –‡”‹ƒŽǡ ƒ–‹˜‹”ƒŽǡ ƒ–‹„‹‘–‹  ƒ† ƒ‡•–Š‡–‹  ’”‘’‡”–‹‡•ǤͳͶ͵ǡͳͶͶŠ‡› ƒƒŽ•‘„‡—•‡†ƒ•’”‘–‡ –‹‘‰”‘—’•ˆ‘”’”‹ƒ”› ƒ‹‡•ƒ†ƒ•Ž‹‰ƒ†•‹‡–ƒŽ ‘’Ž‡š‡•ǤͳͶͷ‘”‡‘˜‡”ǡ–Š‡›ƒ”‡—•‡†ƒ• ‹–‡”‡†‹ƒ–‡•ƒ†’”‡ —”•‘”•‹–Š‡•›–Š‡•‹•‘ˆ‹’‘”–ƒ–Š‡–‡”‘ › Ž‹  ‘’‘—†•ǡ•— Šƒ•’›”‹‹†‹‡•ǡ‹•‘“—‹‘Ž‹‡•ǡ“—‹ƒœ‘Ž‹‡•ƒ†‹‹†Ǧ ƒœ‘Ž‡•ǤͳͶ͸ ‡†— –‹˜‡ˆ— –‹‘ƒŽ‹œƒ–‹‘‘ˆƒ‹†‡•‹•ƒ‡‡”‰‹‰ˆ‹‡Ž†™‹–Š‹ ‘”‰ƒ‹  Š‡‹•–”› ȋ•‡ –‹‘ ͳǤ͵ȌǤ Š‡ ‰”‘—’ ‘ˆ Šƒ”‡––‡ Šƒ• —•‡†–”‹ˆŽ‹  ƒŠ›†”‹†‡ƒ•ƒ‹Ž†ƒ‹†‡ƒ –‹˜ƒ–‹‰ƒ‰‡–‹–Š‡•›–Š‡•‹•‘ˆƒ‹†‹‡• ͳͶ͹ ȋ Š‡‡ͷʹƒȌǤ ‡Žƒ˜ƒetal.”‡’‘”–‡†–Š‡—•‡‘ˆŽ‡͵ƒ•ƒ –‹˜ƒ–‹‘ ”‡ƒ‰‡– ‹ –Š‡ •—„•‡“—‡– ƒ‹†‹‡ ˆ‘”ƒ–‹‘ ˆ”‘ ’”‹ƒ”› ƒ‹†‡• ͳͶͺ ȋ Š‡‡ͷʹ„Ȍ ƒ†ŠƒŠ‘†‡‡etalǤ—•‡†Š͵Ȁ ʹ–‘•›–Š‡•‹œ‡ƒ‹Ǧ †‹‡•ˆ”‘•‡ ‘†ƒ”›ƒ‹†‡•ȋ Š‡‡ͷʹ ȌǤͳͶͻ a) R4 R4 R5 O N N 1. Tf2O 1.3 equiv 3 3 3 1 R 1 R or 1 R R N 2. H R N R N 2 2 R 4 N 5 R R R R2 = alkyl R2 =H R5 =H b) 2 NH2 R R2 O N AlMe3 2.8 equiv 1 1 R NH2 R NH2

c) 1. Ph P/I 1.5 equiv R3 R4 O 3 2 N Et3N 5.0 equiv R2 R2 R1 N 2. H R1 N H N R3 R4 d) Ts TsN 1.5 equiv N R3 3 R1 N R3 R1 N R2 CH2Cl2, r.t., 20 min R2  Scheme 52. Preparation of amidines through electrophilic amide activation a)byCharetteandGrenon,b)Velavanetal.andc)Phakhodeeetal.

ͷ͵  

‹†‹‡• ƒ ƒŽ•‘ „‡ ‘„–ƒ‹‡† „› –Š‡ †‹”‡ – ‘†‡•ƒ–‹‘ ‘ˆ NǡNǦ†‹‡–Š›Žˆ‘”ƒ‹†‡ †‹‡–Š›Ž ƒ ‡–ƒŽ ™‹–Š •—Žˆ‘ƒ‹†‡ͳͷͲ‘”ˆ”‘ –Š‡ ”‡ƒ –‹‘ ‘ˆ ‡ƒ‹‡• ™‹–Š •—Žˆ‘›Ž ƒœ‹†‡• ȋ Š‡‡ ͷʹ†ȌǤͳͷͳ —”Ǧ ͺͲ ͹ͻ –Š‡”‘”‡ǡ Žƒ••‹  ƒ‹†‡ ƒ –‹˜ƒ–‹‘ ”‡ƒ‰‡– •— Š ƒ• Žͷǡ Ž͵  ͹ͺ ͳͷʹ Žʹ ƒ•™‡ŽŽƒ•‘šƒŽ›ŽŠƒŽ‹†‡• Šƒ˜‡ƒŽ•‘„‡‡—•‡†‹ƒ‹†‹‡•›Ǧ –Š‡•‹•Ǥ

5.2Results

—”‹‰–Š‡• ‘’‡‡˜ƒŽ—ƒ–‹‘‹–Š‡–”‹ƒœ‘Ž‹‡’”‘Œ‡ –ȋ Šƒ’–‡”ͶȌ™‡†‹•Ǧ ‘˜‡”‡†–Šƒ––Š‡—•‡‘ˆ•—Žˆ‘›Žƒœ‹†‡11a†‹†‘–‰‡‡”ƒ–‡–Š‡‡š’‡ –‡† –”‹ƒœ‘Ž‹‡ ’”‘†— – 9ǡ ‹•–‡ƒ† NǦ•—Žˆ‘›Žˆ‘”ƒ‹†‹‡ 12a ™ƒ• ˆ‘”‡† ȋ Š‡‡ͷ͵ȌǤŠ‡ ‘†‹–‹‘•ˆ‘”–Š‡ˆ‘”ƒ–‹‘‘ˆ–Š‹•’ƒ”–‹ —Žƒ”’”‘†— – ™‡”‡‘’–‹‹œ‡†ƒ†‹–™ƒ•ˆ‘—†–Šƒ––™‘‡“—‹˜ƒŽ‡–•‘ˆ•—Žˆ‘›Žƒœ‹†‡ 11a™‡”‡”‡“—‹”‡†ˆ‘”–Š‡”‡ƒ –‹‘–‘”‡ƒ Š ‘’Ž‡–‹‘™‹–Š‹͵Ͳ ‹—–‡•ƒ–ͶͲιǤ –Š‡ˆ‘”ƒ–‹‘‘ˆƒ‹†‹‡’”‘†— –12a–Š‡„‡œ›Ž ’ƒ”–‘ˆ–Š‡ƒ‹†‡‹• Ž‡ƒ˜‡†‘ˆˆǤ‘‹’”‘˜‡–Š‡ƒ••„ƒŽƒ ‡‘ˆ–Š‡’”‘Ǧ –‘ ‘Ž‹–™‘—Ž†„‡†‡•‹”ƒ„Ž‡–‘—•‡ƒ ‡–ƒ‹†‡•ǡƒŽ–Š‘—‰Šƒ––‡’–•–‘”‡Ǧ †— ‡ ƒ ‡–ƒ‹†‡ ȋ6aeȌ–‘‡ƒ‹‡”‡•—Ž–‡†‹–Šƒ–ƒ‹Ž›ƒ‹‡™ƒ• ‘„–ƒ‹‡†ȋ Šƒ’–‡”͵ȌǤ‘•‡“—‡–Ž›ǡ‹–™ƒ•‡ ‡••ƒ”›–‘—•‡’Š‡›ŽƒǦ ‡–ƒ‹†‡•–Š”‘—‰Š‘—––Š‡‡˜ƒŽ—ƒ–‹‘‘ˆ–Š‡• ‘’‡Ǥ

 Scheme53.OneǦpotformationofNǦsulfonylformamidinebyreductivefunctionǦ alizationofamides.

‹ ‡–Š‡„‡œ›Ž’ƒ”–‘ˆ–Š‡ƒ‹†‡‹• Ž‡ƒ˜‡†‘ˆˆ‹–Š‡”‡ƒ –‹‘‘Ž›ƒǦ ‹†‡• ™‹–Š †‹ˆˆ‡”‡– ƒ‹‘ ‘‹‡–‹‡• ™‡”‡ ‡˜ƒŽ—ƒ–‡† ‹ –Š‡ •›–Š‡•‹• ‘ˆ NǦ•—Žˆ‘›Žˆ‘”ƒ‹†‹‡•ȋ Š‡‡ͷͶȌǤŠ‡insitu‰‡‡”ƒ–‡†‡ƒ‹‡•7 ™‡”‡–”‡ƒ–‡†™‹–Š•—Žˆ‘›Žƒœ‹†‡11a—†‡”‹Ž† ‘†‹–‹‘•ƒ†–ƒ”‰‡– ‘’‘—†••—„•–‹–—–‡†™‹–ŠNǡNǦ†‹‡–Š›Žƒ‹‡ȋ12bƒ†12cȌǡ’‹’‡”Ǧ ‹†‹‡ ȋ12dƒ†12eȌǡ NǡNǦ†‹„—–›Žƒ‹‡ȋ12fȌǡ NǡNǦ†‹‹•‘’”‘’›Ž ƒ‹‡ ȋ12gȌǡ ‹†‘Ž‹‡ ȋ12hȌǡ ‘”’Š‘Ž‹‡ ȋ12iȌǡ ʹǡ͸Ǧ†‹‡–Š›Ž’‹’‡”‹†‹‡ ȋ12jȌ ƒ† NǦ‡–Š›ŽǦNǦ’Š‡›Ž ƒ‹‡ ȋ12kȌ™‡”‡‘„–ƒ‹‡†‹ˆƒ‹”–‘‰‘‘† ›‹‡Ž†•Ǥ 

ͷͶ  

12a, 78% 12b, 64% 12c,a 60%

12d, 68% 12e,a 57% 12f, 75% O O S iPr N N iPr 12g, 72% 12h, 66% 12i, 58%

12j, 39% 12k, 63% Scheme54.Evaluationoftertiaryamides6inthechemoselectivereductionand subsequentreactionofenaminesfromamides(1mmol)withsulfonylazide11a, a isolatedyields. pǦNO2sulfonylazide11bwasused.

—”–Š‡”‘”‡ǡ†‹ˆˆ‡”‡–•—Žˆ‘›Žƒœ‹†‡•™‡”‡‡˜ƒŽ—ƒ–‡†‹–Š‡”‡ƒ –‹‘ ƒ†ƒ™‹†‡˜ƒ”‹‡–›‘ˆNǦ•—Žˆ‘›Žˆ‘”ƒ‹†‹‡•™‡”‡‘„–ƒ‹‡†‹›‹‡Ž†• ”ƒ‰‹‰ˆ”‘Ͷ͹Ψ–‘͹ͻΨȋ Š‡‡ͷͷȌǤ‘–Š‡„‡•–‘ˆ‘—”‘™Ž‡†‰‡ –Š‡”‡ƒ –‹‘™ƒ•‘–ƒˆˆ‡ –‡†„›‡Ž‡ –”‘‹ ‡ˆˆ‡ –•ƒ†ˆ— –‹‘ƒŽ‰”‘—’• •— Šƒ•‹–”‘ȋ12oƒ†12tȌǡ ›ƒ‘ȋ12pȌǡ‡•–‡”ȋ12xȌǡ•‡ ‘†ƒ”›ƒ‹†‡ ȋ12wȌƒ•™‡ŽŽƒ•ƒŽ†‡Š›†‡ȋ12vȌǡ™‡”‡–‘Ž‡”ƒ–‡†Ǥ‡œ›Žƒ†ƒŽ‹’Šƒ–‹  •—Žˆ‘›Ž ƒœ‹†‡• ™‡”‡ ƒŽ•‘ ‘’ƒ–‹„Ž‡ ƒ† ƒˆˆ‘”†‡† –Š‡ ‘””‡•’‘†‹‰ NǦ•—Žˆ‘›Žˆ‘”ƒ‹†‹‡•12zƒ†12aaǤ 

ͷͷ  

12l, 50% 12m, 57% 12n, 50%

12o, 70% 12p, 49% 12q, 61%

12r, 63% 12s, 55% 12t, 60%

12u, 54% 12v, 79% 12w, 60%

12x, 47% 12y, 69%

12z, 83% 12aa, 58% Scheme55.Evaluationofsulfonylazides(11)inthechemoselectivereduction andsubsequentreactionofenaminefromamide6p(1mmol)withsulfonylazǦ ides,isolatedyields.



ͷ͸  

‘ ‹ŽŽ—•–”ƒ–‡ –Š‡ ƒ’’Ž‹ ƒ„‹Ž‹–› ‘ˆ –Š‡ ’”‘–‘ ‘Žǡ –Š‡ ’”‡’ƒ”ƒ–‹‘ ‘ˆ NǦ•—Žˆ‘›Žˆ‘”ƒ‹†‹‡12a™ƒ•’‡”ˆ‘”‡†‘ƒ’”‡’ƒ”ƒ–‹˜‡• ƒŽ‡—•‹‰ ƒ–™‘Ǧ‡ ‡†”‘—†Ǧ„‘––‘ˆŽƒ•—†‡”‹‡”–ƒ–‘•’Š‡”‡ȋ Š‡‡ͷ͸ȌǤ Š‹•ƒŽŽ‘™‡†ˆ‘”–Š‡‹•‘Žƒ–‹‘‘ˆ–Š‡†‡•‹”‡† ‘’‘—†‹͹ͲΨȋͳǤ͸͸‰Ȍ ‘ƒͳͲ‘Ž• ƒŽ‡Ǥ

 Scheme56.SynthesisofNǦsulfonylformamidine12aonapreparativescale.

”‹ƒœ‘Ž‹‡•ƒ”‡‘™–‘†‡ ‘’‘•‡‹–‘ƒ˜ƒ”‹‡–›‘ˆ’”‘†— –•ǡ•— Šƒ• –”‹ƒœ‘Ž‡• ȋ Šƒ’–‡” ͶȌǡ ƒœ‹”‹†‹‡• ƒ† ƒ‹†‹‡•Ǥͳ͵͹‡ǡͳͷ͵  Šƒ’–‡” Ͷ ™‡ •— ‡••ˆ—ŽŽ› ‹•‘Žƒ–‡† ƒ ™‹†‡ ˜ƒ”‹‡–› ‘ˆ –”‹ƒœ‘Ž‹‡•ǡ ƒŽ–Š‘—‰Šǡ ‡Ž‡ –”‘ †‡ˆ‹ ‹‡– –”‹ƒœ‘Ž‹‡• ȋ9Ȍ ™‡”‡ ‘”‡ —•–ƒ„Ž‡ ƒ† ‹ •‘‡ ƒ•‡• –Š‡ ƒ‹‡ ‘‹‡–› ‡Ž‹‹ƒ–‡† •’‘–ƒ‡‘—•Ž›ǡ ˆ‘”‹‰ –Š‡ –”‹ƒœ‘Ž‡ ’”‘†— – ȋ10ȌǤ”‹ƒœ‘Ž‹‡•ˆ‘”‡†ˆ”‘•—Žˆ‘›Žƒœ‹†‡•ƒ”‡‘™–‘„‡—•–ƒ„Ž‡Ǣ Š‘™‡˜‡”ǡ –Š‡ †‡ ‘’‘•‹–‹‘ ‘ˆ –Š‡•‡ •’‡ ‹‡• †‘‡• ‘– ƒŽ™ƒ›• ›‹‡Ž† NǦ•—Žˆ‘›Žˆ‘”ƒ‹†‹‡•Ǥ ‘” ‡šƒ’Ž‡ǡ NǦ—•—„•–‹–—–‡† ͳHǦͳǡʹǡ͵Ǧ–”‹ƒœ‘Ž‡•ȋ10ȌŠƒ˜‡„‡‡”‡’‘”–‡†–‘„‡ˆ‘”‡†ˆ”‘–Š‡”‡ƒ Ǧ –‹‘‘ˆ‡ƒ‹‡•™‹–Š•—Žˆ‘›Žƒœ‹†‡•Ǥͳͷ͵„ —”–Š‡”‘”‡ǡ†‹ˆˆ‡”‡–’ƒ–ŠǦ ™ƒ›•ˆ‘”–Š‡†‡ ‘’‘•‹–‹‘‘ˆ–Š‡–”‹ƒœ‘Ž‹‡•Šƒ˜‡„‡‡•—‰‰‡•–‡†Ǥ ‘—ƒ† ‘Ǧ™‘”‡”•‹˜‡•–‹‰ƒ–‡†–Š‡—•‡‘ˆ’‡”ˆŽ—‘”‹ƒ–‡†ƒ”›Žƒœ‹†‡• ‹ –Š‡ › Ž‹œƒ–‹‘ ”‡ƒ –‹‘ ™‹–Š ‡ƒ‹‡•ǡ ™Š‹ Š ‰ƒ˜‡ ƒ ‡•• –‘ȽǦ •—„•–‹–—–‡†ƒ‹†‹‡•„›–Š‡Ž‘••‘ˆʹˆ”‘–Š‡–”‹ƒœ‘Ž‹‡‹–‡”‡†‹ƒ–‡• ȋ Š‡‡ͷ͹ƒȌǤͳͷͶNǦ•—Žˆ‘›Žˆ‘”ƒ‹†‹‡•™‡”‡’”‡’ƒ”‡†„›‹ƒ† ‘Ǧ ™‘”‡”•„› ‘„‹‹‰–‡”–‹ƒ”›ƒ‹‡•ƒ†•—Žˆ‘›Žƒœ‹†‡•™‹–Š•–‘‹ Š‹Ǧ ‘‡–”‹ ƒ‘—–•‘ˆ†‹‡–Š›Žƒœ‘†‹ ƒ”„‘š›Žƒ–‡ȋȌȋ Š‡‡ͷ͹„ȌǤͳͷͷ ƒ‹‡• Šƒ˜‡ ƒŽ•‘ „‡‡ ‰‡‡”ƒ–‡† —•‹‰ ƒ–ƒŽ›–‹  ƒ‘—– ‘ˆ ‘’’‡” •ƒŽ–• ˆ‘” –Š‡ ’”‡’ƒ”ƒ–‹‘ ‘ˆ ƒ‹†‹‡•Ǥͳͷ͸Š‡†‡ ‘’‘•‹–‹‘‘ˆ–Š‡ ˆ‘”‡†–”‹ƒœ‘Ž‹‡‹–‡”‡†‹ƒ–‡•‹–Š‹• ƒ•‡‰ƒ˜‡ˆ‘”ƒ‹†‹‡•12ƒ† –Š‡ƒ—–Š‘”••–ƒ–‡†–Šƒ–†‹ƒœ‘‡–Šƒ‡™ƒ•ƒ„›’”‘†— –ǤŠ‹•™ƒ•ˆ—”Ǧ –Š‡”‘”‡ ‘ˆ‹”‡†„›–”ƒ’’‹‰‘ˆ–Š‡†‹ƒœ‘‡–Šƒ‡™‹–Šƒ ƒ”„‘š›Ž‹  ƒ ‹†Ǥͳͷ͹

ͷ͹  

 Scheme 57. Proposed mechanism for the cleavage of the formed triazoline by a)Ramström,YanandHouk,b)LiandcoǦworkers.

‘‡˜ƒŽ—ƒ–‡‹ˆ–”‹ƒœ‘Ž‹‡9™ƒ•‹†‡‡†ˆ‘”‡†ƒ•ƒ”‡ƒ –‹˜‡‹–‡”‡†‹ƒ–‡ —†‡”‘—””‡ƒ –‹‘ ‘†‹–‹‘•™‡ƒ––‡’–‡†–‘–”ƒ’–Š‡’Š‡›Ž†‹ƒœ‘‡Ǧ –Šƒ‡13–Šƒ–™‘—Ž†„‡‰‡‡”ƒ–‡†—’‘–Š‡ ‘ŽŽƒ’•‡‘ˆ–Š‡Š‡–‡”‘ › Ž‡ ȋ Š‡‡ͷͺȌǤ›ƒ††‹–‹‘‘ˆ„‡œ‘‹ ƒ ‹†™‡™‡”‡ƒ„Ž‡–‘‘„–ƒ‹–Š‡ ‘””‡•’‘†‹‰‡•–‡”14ȋʹʹΨͳ ›‹‡Ž†ǡͳ͵Ψ‹•‘Žƒ–‡†›‹‡Ž†Ȍǡ™Š‹ Š •—’’‘”–• –Šƒ– –Š‡ ”‡ƒ –‹‘ ’ƒ–Š™ƒ› ’”‘ ‡‡†• via–Š‡–”‹ƒœ‘Ž‹‡ˆ‘”Ǧ ƒ–‹‘™‹–Š•—„•‡“—‡–‰‡‡”ƒ–‹‘‘ˆ’Š‡›Ž†‹ƒœ‘‡–Šƒ‡ȋ13ȌǤ

 Scheme 58. Proposed mechanism of triazoline decomposition leading to NǦsulfonylformamidine and aryldiazomethane (13) and trapping experiment withbenzoicacidtoformester14.



ͷͺ  

5.3Conclusions

‹Ž†ƒ† Š‡‘•‡Ž‡ –‹˜‡’”‘–‘ ‘Žˆ‘”–Š‡‘‡Ǧ’‘–ˆ‘”ƒ–‹‘‘ˆ NǦ•—Žˆ‘›Žˆ‘”ƒ‹†‹‡• –Š”‘—‰Š ”‡†— –‹˜‡ ˆ— –‹‘ƒŽ‹œƒ–‹‘ ‘ˆ ƒ‹†‡• ™ƒ•†‡˜‡Ž‘’‡†Ǥ™‹†‡”ƒ‰‡‘ˆ•—Žˆ‘›Žƒœ‹†‡•ƒ†ƒ‹†‡•™‡”‡‡˜ƒŽ—Ǧ ƒ–‡†ƒ†–Š‡ƒŒ‘”‹–›‘ˆ–Š‡NǦ•—Žˆ‘›Žˆ‘”ƒ‹†‹‡•Šƒ˜‡‘–’”‡˜‹‘—•Ǧ Ž›„‡‡’—„Ž‹•Š‡†Ǥ —”–Š‡”‘”‡ǡ‹–™ƒ•’‘••‹„Ž‡–‘• ƒŽ‡Ǧ—’–Š‡’”‘–‘ ‘Ž ƒ† NǦ•—Žˆ‘›Žˆ‘”ƒ‹†‹‡ 12a ™ƒ• •›–Š‡•‹œ‡† ‘ ƒ ͳͲ‘Ž • ƒŽ‡Ǥ ”ƒ’’‹‰‡š’‡”‹‡–•™‹–Š„‡œ‘‹ ƒ ‹†•—’’‘”–•–Šƒ––Š‡”‡ƒ –‹‘’”‘Ǧ ‡‡†•via–Š‡ ‘ŽŽƒ’•‡‘ˆ–”‹ƒœ‘Ž‹‡ƒ†ˆ‘”•’Š‡›Ž†‹ƒœ‘‡–Šƒ‡ȋ13Ȍ ƒ•ƒ„›’”‘†— –Ǥ

ͷͻ  



͸Ͳ  

6.ReductiveFunctionalizationofAmidesinto 4,5ǦDihydroisoxazoles(PaperIV)

6.1Introduction

ͶǡͷǦ†‹Š›†”‘‹•‘šƒœ‘Ž‡•ii ƒ”‡ ‘™ –‘ ‡šŠ‹„‹– „‹‘Ž‘‰‹ ƒŽ ƒ –‹˜‹–›ͳͷͺƒ† ƒ”‡ —•‡ˆ—Ž ‹–‡”‡†‹ƒ–‡• ‹ –Š‡ ’”‡’ƒ”ƒ–‹‘ ‘ˆ ƒ ™‹†‡ ˜ƒ”‹‡–› ‘ˆ ˆ— Ǧ –‹‘ƒŽ ‰”‘—’•ǡͳͷͻ•— Šƒ•ȾǦƒ‹‘‡–‘‡•ǡͳ͸ͲȾǦŠ›†”‘š›‡–‘‡•ǡͳ͸ͳ ȾǦƒ‹‘ƒŽ ‘Š‘Ž•ǡͳ͸ͲȾǦƒ‹‘ƒ ‹†•ǡͳ͸ʹ’›””‘Ž‡•ͳ͸͵ƒ†ƒ ›Žƒœ‹”‹†‹‡•Ǥͳ͸Ͷ Š‡”‡ˆ‘”‡ǡ†‡˜‡Ž‘’‹‰‡–Š‘†‘Ž‘‰‹‡•ˆ‘”–Š‡•›–Š‡•‹•‘ˆʹǦ‹•‘šƒœ‘Ž‹‡• ‹•‘ˆŠ‹‰Š‹’‘”–ƒ ‡ǤŠ‡‘•– ‘‘’”‘ ‡†—”‡–‘‘„–ƒ‹–Š‡•‡Š‡–Ǧ ‡”‘ › Ž‹  ‘’‘—†•‹•„›–Š‡ͳǡ͵Ǧ†‹’‘Žƒ” › Ž‘ƒ††‹–‹‘”‡ƒ –‹‘‘ˆ‘Ž‡Ǧ ˆ‹•™‹–Š‹–”‹Ž‡‘š‹†‡•Ǥͳ͸Ͷƒǡͳ͸ͷ‹–”‹Ž‡‘š‹†‡•ƒ”‡Š‹‰ŠŽ›”‡ƒ –‹˜‡ƒ†ƒ”‡ –Š‡”‡ˆ‘”‡ ˆ‘”‡† in situǡ ‡‹–Š‡” „› ȋƒȌ ‘š‹†ƒ–‹˜‡ †‡Š›†”ƒ–‹‘ ‘ˆ ƒŽ†‘šǦ ‹‡•ǡȋ„Ȍ†‡Š›†”ƒ–‹‘‘ˆ‹–”‘ ‘’‘—†•‘”ȋ Ȍ„ƒ•‡Ǧ’”‘‘–‡††‡Š›Ǧ †”‘ŠƒŽ‘‰‡ƒ–‹‘ ‘ˆ Š›†”‘š‹‹‘›Ž ŠƒŽ‹†‡• ȋ Š‡‡ ͷͻȌǤ ŽŽ –Š‡•‡ƒ’Ǧ ’”‘ƒ Š‡• Šƒ˜‡ „‡‡ —•‡† ‹ –Š‡ ”‡ƒ –‹‘• ™‹–Š‘Ž‡ˆ‹• ˆ‘” –Š‡ ‘‡Ǧ’‘– •›–Š‡•‹•‘ˆʹǦ‹•‘šƒœ‘Ž‹‡•ȋ Š‡‡͸ͲƒȌǤͳ͸͸

 Scheme59.Insitupreparationofnitrileoxides.

    ii –Š‹•–Š‡•‹•ƒ†‹–Š‡’—„Ž‹ ƒ–‹‘ȋǤŽƒ‰„”ƒ†ǡ Ǥ‡”˜‡ˆ‘”•ǡ Ǥ‹‹•ǡ Ǥ†‘Žˆ••‘ǡ Adv. Synth. Catal.ǡ 2017ǡ 359ǡ ͳͻͻͲǦͳͻͻͷȌ –Š‡ ‘’‘—†• ƒ”‡ ”‡ˆ‡””‡†–‘ƒ•2Ǧisoxazoline. ͸ͳ  

 Scheme 60. Synthesis of 4,5Ǧdihydroisoxazoles from (a) alkenes, (b) isolated enaminesand(c)insitupreparedenamines.

Š‡”‡ƒ”‡ ˆ‡™’”‘–‘ ‘Ž• ƒ˜ƒ‹Žƒ„Ž‡—•‹‰ ‡ƒ‹‡•‹ ͳǡ͵Ǧ › Ž‘ƒ††‹–‹‘ ”‡ƒ –‹‘• ™‹–Š ‹–”‹Ž‡ ‘š‹†‡• ˆ‘” –Š‡ ˆ‘”ƒ–‹‘ ‘ˆ ͷǦƒ‹‘Ǧ ͶǡͷǦ†‹Š›†”‘‹•‘šƒœ‘Ž‡•Ǥ—‡Š‡ƒ† ‘Ǧ™‘”‡”•ƒ•™‡ŽŽƒ•ƒ•ƒ‹ǡ‘•Š‹Ǧ ‘ƒ ƒ† ”‹ƒ” ‘ ‰”‘—’• ‘„–ƒ‹‡† –Š‡ ƒ‹‘Ǧ•—„•–‹–—–‡† ’”‘†— –•‹ ”‡ƒ –‹‘• „‡–™‡‡ ‡ƒ‹‡• ƒ† Š›†”‘š‹‹‘›Ž ŠŽ‘”‹†‡• ȋ Š‡‡ ͸Ͳ„ȌǤͳ͸͹ǡͳ͸ͺ‘”‡‘˜‡”ǡƒ”ƒ‡ŽŽƒƒ†Ž„‹‹‡˜ƒŽ—ƒ–‡†–Š‡—•‡‘ˆ‹†‘Ž‡• ‹–Š‡”‡ƒ –‹‘™‹–Š„‡œ‘‹–”‹Ž‡Ǧƒ†‡•‹–‘‹–”‹Ž‡‘š‹†‡•ƒ†‘„–ƒ‹‡† –Š‡ ‘””‡•’‘†‹‰ʹǦ‹•‘šƒœ‘Ž‹‡•ǡƒŽ„‡‹–‹Ž‘™‹•‘Žƒ–‡†›‹‡Ž†ƒˆ–‡”–™‘ ‘–Š•”‡ƒ –‹‘–‹‡Ǥͳ͸ͻ—‡–‘–Š‡ˆƒ ‹Ž‡Š›†”‘Ž›•‹•‘ˆ‡ƒ‹‡•ǡƒ‰ ƒ†—ƒ––‡’–‡†–‘‹’”‘˜‡–Š‡›‹‡Ž†‘ˆʹǦ‹•‘šƒœ‘Ž‹‡•„›‰‡‡”ƒ–‹‰ „‘–Š ‡ƒ‹‡• ƒ† ‹–”‹Ž‡ ‘š‹†‡• insitu, ”‡•—Ž–‹‰ ‹ ƒ ™‹†‡ •—„•–”ƒ–‡ • ‘’‡ ˆ‘” –Š‡ •›–Š‡•‹• ‘ˆ ͷǦƒ‹‘ǦͶǡͷǦ†‹Š›†”‘‹•‘šƒœ‘Ž‡• ȋ Š‡‡ ͸Ͳ ȌǤͳ͹Ͳ Š‡ › Ž‘ƒ††‹–‹‘ ”‡ƒ –‹‘ ™ƒ• ˆ—”–Š‡”‘”‡ ƒ’’Ž‹‡† ƒ• ƒ ‡› •–‡’‹–Š‡•›–Š‡•‹•‘ˆƒŽ†‡ ‘š‹„ǡƒƒ–‹Ǧ‹ˆŽƒƒ–‘”›†”—‰ȋ Š‡‡ ͸ͳȌǤͳ͹ͳ OH N

Cl 0.8 equiv O N N O Et3N 1.1 equiv N N DCM, 25 °C, 2 - 3 h SO NH 89% GC yield Valdecoxib 2 2 Yield: 60% 69% GC yield  Scheme61.ReportedsynthesisofValdecoxib,anonsteroidalantiǦinfammatory drug. 

͸ʹ  

6.2Results

‡ƒ‹‡†ƒ–†‡˜‡Ž‘’‹‰ƒ‘‡Ǧ’‘–’”‘–‘ ‘Žˆ‘”–Š‡ˆ‘”ƒ–‹‘‘ˆ‹•‘šƒǦ œ‘Ž‹‡• „› –Š‡ in situ ‰‡‡”ƒ–‹‘ ‘ˆ „‘–Š ‡ƒ‹‡ ƒ† ‹–”‹Ž‡ ‘š‹†‡ ȋƒ„Ž‡ͶȌǤ‹ ‡‡ƒ‹‡7p‹•‘™–‘„‡‘”‡”‡ƒ –‹˜‡ȋ Šƒ’–‡”ͶȌ ™‡†‡ ‹†‡†–‘—•‡‹–ƒ•–Š‡•–ƒ†ƒ”†•—„•–”ƒ–‡‹–Š‡‡˜ƒŽ—ƒ–‹‘‘ˆ–Š‡ ‘†‹–‹‘•Ǥ ˆ‘”–—ƒ–‡Ž›ǡ –Š‡ †‡•‹”‡† ’”‘†— – 16a™ƒ•‘–ˆ‘”‡† ™Š‡ƒ††‹‰ͳǤͷ‡“—‹˜ƒŽ‡–•‘ˆŠ›†”‘š‹‹‘›Ž ŠŽ‘”‹†‡ȋ15aȌ‡‹–Š‡”ƒ– ”‘‘–‡’‡”ƒ–—”‡‘”ƒ–͸ͷιȋ‡–”‹‡•ͳȂʹȌǤ •’‹”‡†„›ƒ‰ǡ — ƒ† ‘Ǧ™‘”‡”•™‡†‡ ‹†‡†–‘ƒ††„ƒ•‡–‘–Š‡”‡ƒ –‹‘‹‘”†‡”–‘’”‘Ǧ ‘–‡ –Š‡ in situ †‡ŠƒŽ‘‰‡ƒ–‹‘ ‘ˆ –Š‡ Š›†”‘š‹‹‘›Ž ŠŽ‘”‹†‡ 15a–‘ –Š‡‹–”‹Ž‡‘š‹†‡ȋ‡–”‹‡•͵ȂͷȌǤͳ͹Ͳ’‘ƒ††‹–‹‘‘ˆ„ƒ•‡™‡ ‘—Ž†‹Ǧ †‡‡†•‡‡–Š‡ˆ‘”ƒ–‹‘‘ˆʹǦ‹•‘šƒœ‘Ž‹‡16aƒ†–”‹‡–Š›Žƒ‹‡‰ƒ˜‡–Š‡ „‡•– ”‡•—Ž–•Ǥ —”–Š‡” ‘’–‹‹œƒ–‹‘ •Š‘™‡† –Šƒ– ‹– ™ƒ• ‘– ’‘••‹„Ž‡ –‘ †‡ ”‡ƒ•‡–Š‡ƒ‘—–‘ˆŠ›†”‘š‹‹‘›Ž ŠŽ‘”‹†‡‘”–”‹‡–Š›Žƒ‹‡™‹–ŠǦ ‘—–ƒˆˆ‡ –‹‰–Š‡›‹‡Ž†ȋ‡–”‹‡•͸ȂͺȌǤ Table4.Optimizationofreactionconditionsfortheformationof2Ǧisoxazoline.a

 Entry 15a[equiv] Additive[equiv] 2ǦIsoxazoline16a[%]b ͳ ͳǤͷ Ǧ Ǧ Ǧ ʹ ͳǤͷǦ Ǧ Ǧ ͵ ͳǤͷ ƒ ͳǤͷ ͹Ͷ Ͷ ͳǤͷ ƒʹ͵ ͳǤͷ Ͷͺ ͷ ͳǤͷ –͵ ͳǤͷ εͻͷ ͸ ͳǤͷ –͵ͳǤͳͺͻ ͹ ͳǤͳ –͵ͳǤͷ͹͸ ͺ ͳǤͷ –͵ͳǤʹͷͻ͵ ƒ ›†”‘š‹‹‘›Ž ŠŽ‘”‹†‡ 15a™ƒ•ƒ††‡†ƒˆ–‡”–Š‡ ƒ–ƒŽ›–‹ ”‡†— –‹‘‘ˆƒ‹†‡6p–‘ ‡ƒ‹‡7p™ƒ• ‘’Ž‡–‡ȋͲǤͷ‘ŽȌǤ„ͳ ›‹‡Ž†•—•‹‰ͳǡ͵ǡͷǦ–”‹‡–Š‘š›„‡œ‡‡ ƒ•‹–‡”ƒŽ•–ƒ†ƒ”†Ǥ ‡ƒ –‹‘’‡”ˆ‘”‡†ƒ–͸ͷιǤ

–Š‡‡˜ƒŽ—ƒ–‹‘‘ˆ–Š‡• ‘’‡™‡‹‹–‹ƒŽŽ›ˆ‘ —•‡†‘‡ƒ‹‡• ‘–ƒ‹Ǧ ‹‰†‹ˆˆ‡”‡–ƒ‹‘‘‹‡–‹‡•ƒ†™‡™‡”‡ƒ„Ž‡–‘‹•‘Žƒ–‡ʹǦ‹•‘šƒœ‘Ž‹‡• •—„•–‹–—–‡† ™‹–Š ’›””‘Ž‹†‹‡ ȋ16aȌǡ ’‹’‡”‹†‹‡ ȋ16bȌǡ ʹǡ͸Ǧ†‹‡–Š›Ž ’‹Ǧ ’‡”‹†‹‡ȋ16cȌǡ‘”’Š‘Ž‹‡ȋ16dȌǡ†‹‡–Š›Žƒ‹‡ȋ16eȌǡ†‹„—–›Žƒ‹‡ ȋ16fȌǡ NǦ‡–Š›ŽǦNǦ’Š‡›Ž ƒ‹‡ ȋ16gȌ ƒ† ‹†‘Ž‹‡ ȋ16hȌ ƒ• ™‡ŽŽ ƒ• †‹„‡œ›Ž ƒ‹‡ ȋ16iȌ ‹ Š‹‰Š ›‹‡Ž†• ȋ Š‡‡ ͸ʹȌǤ Ž–Š‘—‰Š –Š‡ NǡNǦ†‹ƒŽŽ›Ž •—„•–‹–—–‡† ƒ‹†‡ 6w ™ƒ• ‡ˆˆ‹ ‹‡–Ž› –”ƒ•ˆ‘”‡† ‹–‘ –Š‡ ͸͵  

‘””‡•’‘†‹‰ ‡ƒ‹‡ ‹ ͵ Š‘—”• ȋ Šƒ’–‡” ͵Ȍǡ ƒ ‹š–—”‡ ‘ˆ ’”‘†— –• ™ƒ•‘„–ƒ‹‡†ƒˆ–‡”–Š‡”‡ƒ –‹‘™‹–Š‹–”‹Ž‡‘š‹‡ǡ™Š‹ Š‘•–Ž‹‡Ž›‹• ”‡Žƒ–‡† –‘ –Š‡ ”‡ƒ –‹˜‹–› ‘ˆ –Š‡ ƒŽŽ›Ž‹  ‰”‘—’• ’ƒ”–‹ ‹’ƒ–‹‰ ‹ –Š‡ ͳǡ͵Ǧ › Ž‘ƒ††‹–‹‘”‡ƒ –‹‘Ǥ

16a, 84% 16b, 94% 16c, 84% 16d, 85%

16e, 93% 16f, 84% 16g,a 92% 16h, 79%

16i, 81% 16j, 93% 16k, 80% 16l, 91%

16m, 80% 16n, 55% 16o, 91%

16p, 93% 16q, 96% 16r,a 74% Scheme62.Evaluationoftertiaryamides6inthechemoselectivereductionand subsequentcycloadditionreactionwithenaminesfromamides(1mmol),isolated yields.aIsolationwasperformedon0.5mmolscale.

͸Ͷ  

Š‡• ‘’‡‘ˆ–Š‡”‡ƒ –‹‘™ƒ•‘–ƒˆˆ‡ –‡†„›‡Ž‡ –”‘‹ ‡ˆˆ‡ –•ƒ†„‘–Š ‡Ž‡ –”‘Ǧ”‹ Š ȋ16lȌ ƒ• ™‡ŽŽ ƒ• ‡Ž‡ –”‘Ǧ’‘‘” ʹǦ‹•‘šƒœ‘Ž‹‡• ȋ16jǡ 16k ƒ† 16oȌ™‡”‡‘„–ƒ‹‡†‹Š‹‰Š–‘‡š ‡ŽŽ‡–›‹‡Ž†•Ǥ —”–Š‡”‘”‡ǡ–Š‡ ŠƒŽ‘‰‡ ‘–ƒ‹‹‰ ƒ‹†‡• 6c ƒ† 6h ™‡”‡ ‘– †‡ŠƒŽ‘‰‡ƒ–‡† †—”‹‰ –Š‡ ”‡†— –‹‘Ǥ ‡ ‘—Ž† ˆ—”–Š‡”‘”‡ ‘„–ƒ‹ –Š‡ –Š‹‘’Š‡‡ ‘–ƒ‹‹‰ ʹǦ‹•‘šƒœ‘Ž‹‡16m‹ͺͲΨ›‹‡Ž†ƒˆ–‡”‹•‘Žƒ–‹‘ǡ™Š‹ Š†‡‘•–”ƒ–‡•–Šƒ– –Š‹• ’”‘–‘ ‘Ž ‹• ‘’ƒ–‹„Ž‡ ™‹–Š ‘’‘—†• ‘–ƒ‹‹‰ Š‡–‡”‘ › Ž‹  ˆ— –‹‘ƒŽ‹–‹‡•ǤŠ‡ʹǦ‹•‘šƒœ‘Ž‹‡’”‘†— –16n †‡”‹˜‡† ˆ”‘ ƒŽ‹’Šƒ–‹  ƒ‹†‡6l™ƒ•‘„–ƒ‹‡†‹‘†‡”ƒ–‡›‹‡Ž†ȋͷͷΨȌ†—‡–‘•‡Ž‡ –‹˜‹–›‹••—‡• †—”‹‰–Š‡”‡†— –‹‘ȋ Šƒ’–‡”͵ȌǤŠ‡‹Ž†‡••ƒ†–Š‡ Š‡‘•‡Ž‡ –‹˜‡ ’”‘’‡”–‹‡•‘ˆ–Š‡‘ȋȌ͸Ǧ ƒ–ƒŽ›œ‡†’”‘–‘ ‘ŽƒŽŽ‘™‡†ˆ‘”ƒ‰”‡ƒ–ˆ— Ǧ –‹‘ƒŽ‰”‘—’–‘Ž‡”ƒ ‡ƒ†™‡™‡”‡ƒ„Ž‡–‘‹•‘Žƒ–‡ʹǦ‹•‘šƒœ‘Ž‹‡• ‘Ǧ –ƒ‹‹‰‹–”‘ȋ16oȌǡ ›ƒ‘ȋ16pȌǡ‡•–‡”ȋ16qȌƒ†‡–‘‡ȋ16rȌ‘‹‡–‹‡•Ǥ ʹǦ •‘šƒœ‘Ž‹‡ ‘–ƒ‹‹‰ƒŽ†‹‹‡‰”‘—’ˆ”‘–Š‡”‡†— –‹‘‘ˆƒ‹†‡6o ™ƒ• ‘„–ƒ‹‡† ‹ ͸ʹΨ ͳ   ›‹‡Ž†Ǣ Š‘™‡˜‡”ǡ –Š‡ ‘’‘—† †‡ ‘Ǧ ’‘•‡††—”‹‰™‘”Ǧ—’ƒ† ‘—Ž†‘–„‡‹•‘Žƒ–‡†Ǥ ‡†‡ ‹†‡†–‘‡˜ƒŽ—ƒ–‡†‹ˆˆ‡”‡–Š›†”‘š‹‹‘›Ž ŠŽ‘”‹†‡•‹–Š‡ ͳǡ͵Ǧ › Ž‘ƒ††‹–‹‘ ȋ Š‡‡ ͸͵ȌǤ – ™ƒ• †‹• ‘˜‡”‡† –Šƒ– –Š‡ ‡Ž‡ –”‘‹  ‡ˆˆ‡ –•‘–Š‡Š›†”‘š‹‹‘›Ž ŠŽ‘”‹†‡•Ž‹‡™‹•‡•‡‡•–‘Šƒ˜‡ƒ‹‘” ‹ˆŽ—‡ ‡ ‘ –Š‡ ”‡ƒ –‹‘ ƒ† ʹǦ‹•‘šƒœ‘Ž‹‡• ‘–ƒ‹‹‰ pǦ‹–”‘ ȋ16sȌǡ ’Š‡›Ž ȋ16tȌǡ pǦ‡–Š›Ž ȋ16uȌ ƒ† pǦ ŠŽ‘”‘ ȋ16vȌ •—„•–‹–—‡–• ™‡”‡ ‘„–ƒ‹‡†‹•‹‹Žƒ”›‹‡Ž†•ǤŠ‡•–›”›Ž ‘–ƒ‹‹‰ʹǦ‹•‘šƒœ‘Ž‹‡16w™ƒ• ‘„–ƒ‹‡†‹ͺͲΨ›‹‡Ž†ƒ†ƒŽ‹’Šƒ–‹ Š›†”‘š‹‹‘›Ž ŠŽ‘”‹†‡• ‘—Ž†ƒŽ•‘ „‡‡’Ž‘›‡†ƒ•™‡ŽŽǡ‰‡‡”ƒ–‹‰’”‘†— –•16xƒ†16yǤ

16s, 89% 16t, 91% 16u, 90% 16v, 87%

16w, 80% 16x, 89% 16y, 83% Scheme63.Evaluationofhydroximinoylchlorides15inthechemoselectivereǦ duction and subsequent cycloaddition reaction with enamine from amide 6p (1mmol),isolatedyields.

͸ͷ  

‡ ‘„•‡”˜‡† ˆ‘”ƒ–‹‘ ‘ˆ ‘Ž› ‘‡ ‘—– ‘ˆ –™‘ ’‘••‹„Ž‡ ”‡‰‹‘‹•‘‡”• †—”‹‰–Š‡• ‘’‡‹˜‡•–‹‰ƒ–‹‘ǡ™Š‹ Š‹•‹Ž‹‡™‹–Šƒ‰ǡ—ƒ† ‘Ǧ ™‘”‡”• •–—†› ‘ ͳǡ͵Ǧ › Ž‘ƒ††‹–‹‘ ”‡ƒ –‹‘• „‡–™‡‡ ‡Ž‡ –”‘Ǧ”‹ Š ‘Ž‡ˆ‹•ǡ•— Šƒ•‡ƒ‹‡•ǡƒ†‹–”‹Ž‡‘š‹†‡•Ǥͳ͹Ͳ ƒ ‘’—–ƒ–‹‘ƒŽ•–—†› ’‡”ˆ‘”‡†„›ƒ‰—•‘ƒ†”ƒƒ–ƒ–Š‡›†‹• ‘˜‡”‡†–Šƒ–‘Ž‡ˆ‹•™‹–Š ‡Ž‡ –”‘Ǧ†‘ƒ–‹‰•—„•–‹–—‡–•‰ƒ˜‡ʹǦ‹•‘šƒœ‘Ž‹‡•17‹–Š‡ › Ž‘ƒ††‹Ǧ –‹‘ ȋ Š‡‡ ͸ͶƒȌǤ ͳ͹ʹ‡–”‹‡†–‘‡Ž— ‹†ƒ–‡–Š‡”‡‰‹‘ Š‡‹•–”›‘ˆ–Š‡ ‘„–ƒ‹‡† ʹǦ‹•‘šƒœ‘Ž‹‡• —•‹‰ ͳ    ‡š’‡”‹‡–•ǡ „—– —ˆ‘”–—Ǧ ƒ–‡Ž›ǡ –Š‡•‡ ‡š’‡”‹‡–• ‰ƒ˜‡ ‘ ‘ Ž—•‹˜‡ ”‡•—Ž–Ǥ Š‡ †‹ˆˆ‡”‡ ‡ ‹ •Š‹ˆ–„‡–™‡‡–Š‡–™‘’‘••‹„Ž‡”‡‰‹‘‹•‘‡”••Š‘—Ž†„‡“—‹–‡•—„•–ƒ–‹ƒŽǡ „—–™‡™‡”‡‘–ƒ„Ž‡–‘ˆ‹†ƒ›•’‡ –”‘• ‘’‹ †ƒ–ƒ‘ˆͶǦƒ‹‘ǦͶǡͷǦ †‹Š›†”‘‹•‘šƒœ‘Ž‡• ‹ –Š‡ Ž‹–‡”ƒ–—”‡Ǥ ‡‹–Š‡” ™‡”‡ ™‡ ƒ„Ž‡ –‘ ‘’ƒ”‡ ‘—”•’‡ –”‘• ‘’‹ †ƒ–ƒ™‹–Š–Š‡™‘”‘ˆƒ‰ƒ†—•‹ ‡‘Ž›‘‡‘ˆ –Š‡‹” ’”‘†— –• ™ƒ• ˆ—ŽŽ› Šƒ”ƒ –‡”‹œ‡†Ǥͳ͹Ͳ ͵ǡͶǦ†‹•—„•–‹–—–‡† ‹•‘šƒœ‘Ž‡• Šƒ˜‡„‡‡•Š‘™–‘„‡ƒ ‡••‹„Ž‡ˆ”‘ͶǦƒ‹‘ǦͶǡͷǦ†‹Š›†”‘‹•‘šƒœ‘Ž‡• –Š”‘—‰Š„ƒ•‡Ǧ’”‘‘–‡†‡Ž‹‹ƒ–‹‘‘ˆ–Š‡ƒ‹‡‘‹‡–›Ǥͳ͹͵‘’‘—† 16a™ƒ•–Š‡”‡ˆ‘”‡–”‡ƒ–‡†™‹–Šƒ•‘Ž—–‹‘‘ˆ ‹‡–Šƒ‘Žǡ™Š‹ Š ‰ƒ˜‡ ‹•‘šƒœ‘Ž‡ 19‹ͺͳΨ‹•‘Žƒ–‡†›‹‡Ž†ȋ Š‡‡͸Ͷ„ȌǤŠ‡ͳ   ƒƒŽ›•‹•‘ˆ 19ƒ– Š‡†–Š‡‘‡•ˆ‘—†‹–Š‡Ž‹–‡”ƒ–—”‡ǡͳ͹Ͷ™Š‹ Š•—’Ǧ ’‘”–•–Šƒ––Š‡‹•‘šƒœ‘Ž‹‡•‹–Š‹•’”‘–‘ ‘Žƒ”‡•—„•–‹–—–‡†™‹–Š–Š‡ƒ‹Ǧ ‘‘‹‡–›‹–Š‡ͷǦ’‘•‹–‹‘Ǥ

 Scheme64.a)Differentregioisomersthatcanbeformedinthe1,3ǦdipolarcyǦ cloaddition. b) Determination of the regioisomer formed under the developed reactionconditions.

6.3Conclusions

‡ˆˆ‹ ‹‡–’”‘–‘ ‘Žˆ‘”–Š‡‘‡Ǧ’‘–ˆ‘”ƒ–‹‘‘ˆʹǦ‹•‘šƒœ‘Ž‹‡•via”‡Ǧ †— –‹˜‡ˆ— –‹‘ƒŽ‹œƒ–‹‘‘ˆ ƒ”„‘šƒ‹†‡•™‹–ŠŠ›†”‘š‹‹‘›Ž ŠŽ‘”‹†‡• ™ƒ•†‡˜‡Ž‘’‡†ǤŠ‡Š‹‰Š Š‡‘•‡Ž‡ –‹˜‹–›‘ˆ–Š‡‘ȋȌ͸Ǧ ƒ–ƒŽ›œ‡† ”‡†— –‹‘’”‘–‘ ‘Ž–‘Ž‡”ƒ–‡†ƒ™‹†‡•—„•–”ƒ–‡• ‘’‡ƒ†ƒƒŒ‘”‹–› ‘ˆ –Š‡’”‘†— –•™‡”‡‘„–ƒ‹‡†‹Š‹‰Š›‹‡Ž†•Ǥ  ͸͸  

7.ReductiveFunctionalizationofAmidesinto Pyrimidinediones and Thioacrylamides (PaperV)

7.1Introduction

›”‹‹†‹‡†‹‘‡• ƒ”‡ ƒ ‹’‘”–ƒ– Žƒ•• ‘ˆ ‘’‘—†• ‘ˆ „‹‘Ž‘‰‹ ƒŽ •‹‰‹ˆ‹ ƒ ‡ ƒ† ƒ „‡ ˆ‘—† ‹ — Ž‡‹  ƒ ‹†•ǡ •— Š ƒ• —”ƒ ‹Ž ȋ Š‡‡ ͸ͷƒȌǤŠ‡•‡•’‡ ‹‡•Šƒ˜‡’”‘˜‡–‘’‘••‡••ƒ–‹„ƒ –‡”‹ƒŽǡƒ–‹‡‘’Žƒ•–‹  ƒ†ƒ–‹˜‹”ƒŽ’”‘’‡”–‹‡•Ǥͳ͹ͷ›”‹‹†‹‡†‹‘‡•Šƒ˜‡‡ƒ”Ž‹‡”„‡‡•›–Š‡Ǧ •‹œ‡† „› › Ž‹œƒ–‹‘ ”‡ƒ –‹‘ ‘ˆ –Š‡ ƒ”„ƒƒ–‡ ƒ ‘”†‹‰ –‘  Š‡‡ ͸ͷ„Ǥͳ͹͸ —”–Š‡”‘”‡ǡ—••Ž‡”etal.™‡”‡ƒ„Ž‡–‘’”‡’ƒ”‡‡‹‰Š–†‹ˆˆ‡”‡– ’›”‹‹†‹‡†‹‘‡•‹’‘‘”–‘‘†‡”ƒ–‡›‹‡Ž†•ȋʹͲΨȂͶͻΨȌˆ”‘insitu ‰‡‡”ƒ–‡†‡ƒ‹‡•—•‹‰–͵ƒ†ƒ”›Ž‹•‘ ›ƒƒ–‡•—†‡”Šƒ”•Š”‡ˆŽ—š ‘†‹–‹‘•ȋͳͶͲιȌǤͳ͹͹Š‡‹––ƒ‰”‘—’Šƒ•ƒŽ•‘†‡˜‡Ž‘’‡†ƒ’”‘–‘ ‘Ž ˆ‘”–Š‡•›–Š‡•‹•‘ˆ’›”‹‹†‹‡†‹‘‡•„›†‹‡”‹œƒ–‹‘‘ˆƒŽ››Žƒ‹†‡• ‹–Š‡’”‡•‡ ‡‘ˆ„ƒ•‡ȋ Š‡‡͸ͷ ȌǤͳ͹ͺ

 Scheme65.(a)Generalstructureofpyrimidinedione.SynthesisofpyrimidinediǦ onesby(b)cyclizationand(c)dimerizationofynamides.

Š‹‘ƒ ”›Žƒ‹†‡• ƒ”‡ ˜‡”•ƒ–‹Ž‡ •›–Š‘• ‹ –‘–ƒŽ •›–Š‡•‹•ͳ͹ͻƒ†Šƒ˜‡ „‡‡•›–Š‡•‹œ‡†„›”‡ƒ –‹‰‡ƒ‹‡•™‹–Š‹•‘–Š‹‘ ›ƒƒ–‡•ǡƒŽ–Š‘—‰Šǡ ‹–Š‹• ƒ•‡–Š‡‡ƒ‹‡•‡‡†‡†–‘„‡’”‡’ƒ”‡†ƒ†‹•‘Žƒ–‡†„‡ˆ‘”‡—•‡ǡ ™Š‹ Š ƒ„‡’”‘„Ž‡ƒ–‹ ƒ†ƒˆˆ‡ ––Š‡‘˜‡”ƒŽŽ›‹‡Ž†•ȋ Š‡‡͸͸ƒȌǤͳͺͲ ͸͹  

Š‡”‡‹•ƒŽ•‘ƒ–™‘Ǧ•–‡’’”‘–‘ ‘Žˆ‘”–Š‡ƒ –‹˜ƒ–‹‘ƒ†ˆ— –‹‘ƒŽ‹œƒ–‹‘ ‘ˆ ƒ‹†‡• ›‹‡Ž†‹‰ –Š‹‘ƒ ”›Žƒ‹†‡• ƒ• –Š‡ ˆ‹ƒŽ ’”‘†— –• ȋ Š‡‡ ͸͸„ȌǤͳͺͳ‡”–‹ƒ”›ƒ‹†‡•™‡”‡–”ƒ•ˆ‘”‡†‹–‘–Š‡ ‘””‡•’‘†‹‰ ŠŽ‘Ǧ ”‘Ǧ•—„•–‹–—–‡† ‹‹‹— ’‡” ŠŽ‘”ƒ–‡•ǡ ™Š‹ Š ™‡”‡ ‹•‘Žƒ–‡† ƒ† –Š‡ –”‡ƒ–‡†™‹–Šƒƒ“—‡‘—••‘Ž—–‹‘‘ˆ•‘†‹—•—Žˆ‹†‡ȋƒʹȌǤ

 Scheme66.Thesynthesisofthioacrylamidesfromenamines(a)and(b)amides.

7.2Results

Š‡”‡ƒ –‹‘„‡–™‡‡‡ƒ‹‡•ƒ†‘”‰ƒ‹ ‹•‘ ›ƒƒ–‡•Šƒ•ƒŽ•‘„‡‡ †‡‘•–”ƒ–‡†–‘ˆ‘”ȾǦƒ‹‘ǦȾǦŽƒ –ƒ•ȋ Š‡‡͸͹ȌǤͳͺʹŠ‡ƒ††‹–‹‘ ‘ˆͳǤͷ‡“—‹˜ƒŽ‡–•‘ˆ’Š‡›Ž‹•‘ ›ƒƒ–‡20a–‘‡ƒ‹‡7p†‹†‘–”‡•—Ž– ‹ˆ‘”ƒ–‹‘‘ˆ21aǤ •–‡ƒ†ǡ ’›”‹‹†‹‡†‹‘‡ 22a™ƒ•ˆ‘”‡†ƒ•–Š‡ •‘Ž‡’”‘†— –ǤŠ‡ › Ž‹œƒ–‹‘”‡ƒ –‹‘‹–‘22a”‡“—‹”‡•ƒ‹‹—‘ˆ –™‘‡“—‹˜ƒŽ‡–•‘ˆ–Š‡‹•‘ ›ƒƒ–‡ƒ†ƒˆ–‡”‘’–‹‹œƒ–‹‘™‡ˆ‘—†–Šƒ– ʹǤʹ‡“—‹˜ƒŽ‡–•‘ˆ20a™‡”‡‡‡†‡†–‘”‡ƒ Šˆ—ŽŽ ‘˜‡”•‹‘ǤŠ‡”‡ƒ Ǧ –‹‘•™‡”‡’‡”ˆ‘”‡†ƒ–͸ͷιˆ‘”ͶŠƒ† ‘—Ž†ƒŽ•‘„‡’‡”ˆ‘”‡†ƒ– ”‘‘–‡’‡”ƒ–—”‡™‹–Šƒ‡š–‡†‡†”‡ƒ –‹‘–‹‡Ǥ–ƒ†‡•‡–Ǧ—’™ƒ• ƒ––‡’–‡† ˆ‘” –Š‡ ”‡†— –‹˜‡ ˆ— –‹‘ƒŽ‹œƒ–‹‘ ‘ˆ ƒ‹†‡ 6p ƒ† ͶͲΨ ͳ  ›‹‡Ž† ‘ˆ ’›”‹‹†‹‡†‹‘‡ 22a™ƒ•‘„•‡”˜‡†ǡƒŽ–Š‘—‰Šǡ™‹–Šƒ ‹š–—”‡‘ˆ—‹†‡–‹ˆ‹‡†•‹†‡’”‘†— –•Ǥ

 Scheme67.Formationofpyrimidinedione22afromenamine7p.

—”–Š‡”‘”‡ǡ™‡ ‘’ƒ”‡†–Š‡”‡ƒ –‹˜‹–›‘ˆ‡ƒ‹‡••—„•–‹–—–‡†™‹–Š †‹ˆˆ‡”‡– ƒ‹‡ ‘‹‡–‹‡• ȋ’‹’‡”‹†‹‡ ȋ7aȌǡ’›””‘Ž‹†‹‡ȋ7pȌ ƒ†

͸ͺ  

NǡNǦ†‹‡–Š›Žȋ7rȌȌƒ†ˆ‘—†–Šƒ–ƒŽŽ‰ƒ˜‡–Š‡•ƒ‡ƒ‘—–‘ˆ’”‘†— – 22aȋƒ„Ž‡ͷȌǤ ”ƒ–‹ˆ›‹‰ǡ–Š‡’‘‘”•‘Ž—„‹Ž‹–›‘ˆ–Š‡’”‘†— –•‡ƒ„Ž‡† ˆƒ ‹Ž‡’”‘†— –‹•‘Žƒ–‹‘„›’”‡ ‹’‹–ƒ–‹‘™‹–Š’‡–ƒ‡Ǥ Table 5. Comparison between enamines containing different NǦsubstituents in thecyclizationwithphenylisocyanate(20a).a

 Entry Enamine Pyrimidinedione22a[%]

ͳ ͹Ͷ

7a

ʹ ͹ͷ 7p

͵ ͹ͳ 7r ƒƒ‹‡‰‡‡”ƒ–‡†ˆ”‘ƒ‹†‡6ȋͲǤͷ‘ŽȌǤͳ ›‹‡Ž†• —•‹‰ͳǡ͵ǡͷǦ–”‹‡–Š‘š›„‡œ‡‡ƒ•‹–‡”ƒŽ•–ƒ†ƒ”†Ǥ

‹ˆˆ‡”‡–ƒ‹†‡•™‡”‡‡˜ƒŽ—ƒ–‡†‹–Š‡‘‡Ǧ’‘–ˆ‘”ƒ–‹‘‘ˆ’›”‹Ǧ ‹†‹‡†‹‘‡• ƒ† ™‡ ™‡”‡ ƒ„Ž‡ –‘ ‘„–ƒ‹ ’”‘†— –• †‡”‹˜‡† ˆ”‘ „‘–Š ‡Ž‡ –”‘Ǧ”‹ Šȋ22bȌƒ†‡Ž‡ –”‘Ǧ’‘‘”ȋ22cȌƒ‹†‡•ȋ Š‡‡͸ͺȌǤ—‡ –‘‹••—‡•ƒ••‘ ‹ƒ–‡†™‹–Š•‡Ž‡ –‹˜‹–›‹–Š‡‡ƒ‹‡ˆ‘”ƒ–‹‘ˆ‘”ƒ‹†‡ 6lȋ Šƒ’–‡”͵ȌƒŽ‘™‡”›‹‡Ž†™ƒ•‘„–ƒ‹‡†ˆ‘”’›”‹‹†‹‡†‹‘‡22dǤŠ‡ –Š‹‘’Š‡‡ ‘–ƒ‹‹‰’›”‹‹†‹‡†‹‘‡22e ‘—Ž†ƒŽ•‘„‡’”‡’ƒ”‡†ƒ† ™ƒ•‹•‘Žƒ–‡†‹ͺͷΨ›‹‡Ž†Ǥƒ‹‡• ‘–ƒ‹‹‰˜ƒ”‹‘—•”‡†— ‹„Ž‡ˆ— Ǧ –‹‘ƒŽ‰”‘—’•™‡”‡ƒŽ•‘‡˜ƒŽ—ƒ–‡†ƒ†‹–™ƒ•‹†‡‡†’‘••‹„Ž‡–‘‘„–ƒ‹ ’›”‹‹†‹‡†‹‘‡• ‘–ƒ‹‹‰ ›ƒ‘ȋ22fȌǡ‡•–‡”ȋ22gȌǡ‡–‘‡ȋ22hȌƒ† ƒŽ†‹‹‡ȋ22iȌˆ— –‹‘ƒŽ‹–‹‡•Ǥ‡‘„•‡”˜‡†–Šƒ––Š‡‡Ž‡ –”‘†‡ˆ‹ ‹‡– ›ƒ‘ ‡ƒ‹‡ 7f ”‡ƒ –‡† •Ž‘™Ž› ‹ –Š‡ › Ž‘ƒ††‹–‹‘ ƒ† ™‡”‡ ‘Ž› ƒ„Ž‡–‘‘„–ƒ‹Ͷ͸Ψ‹•‘Žƒ–‡†›‹‡Ž†‘ˆ’›”‹‹†‹‡†‹‘‡†‡”‹˜‡†ˆ”‘’Š‡Ǧ ›Ž ‹•‘ ›ƒƒ–‡ 20aǤ‘‹’”‘˜‡–Š‡›‹‡Ž†–Š‡‘”‡”‡ƒ –‹˜‡pǦˆŽ—‘”‘ ’Š‡›Ž‹•‘ ›ƒƒ–‡ȋ20bȌ™ƒ•—•‡†‹ ‘„‹ƒ–‹‘™‹–Šƒ‡š–‡†‡†”‡ƒ Ǧ –‹‘–‹‡ȋ͹ʹŠȌǡ™Š‹ Š”‡•—Ž–‡†‹ͺͷΨ‹•‘Žƒ–‡†›‹‡Ž†‘ˆ22fǤŠ‡Ž‘™ ”‡ƒ –‹˜‹–›‘ˆ‡Ž‡ –”‘†‡ˆ‹ ‹‡–‡ƒ‹‡•™ƒ• ‘ˆ‹”‡†„›–Š‡‡˜ƒŽ—ƒǦ –‹‘‘ˆpǦʹ ‘–ƒ‹‹‰‡ƒ‹‡7gǡ™Š‹ Šƒˆˆ‘”†‡†‘’›”‹‹†‹‡†‹Ǧ ‘‡’”‘†— –Ǥ

͸ͻ  



22a,a 75% 22b, 92% 22c, 76%

22d, 57% 22e,a 85% 22f,a,b 85%

22g,a,c 64% 22h,d 71% 22i,d,e 76% Scheme68.Evaluationofamides6inthechemoselectivereductionandsubseǦ quent functionalization with enamines from piperidine derivated amides (1mmol),isolatedyields. aEnaminefrompyrrolidinederivatedamidewasused. bpǦFluorophenylisocyanate20b(3.5equiv)wasused,65°C,72h.c65°C,16h. dIsolationwasperformedon0.5mmolscale.ePhenylisocyanate20a(3.0equiv) wasused.

‡š–ǡ™‡‡˜ƒŽ—ƒ–‡†–Š‡—•‡‘ˆ†‹ˆˆ‡”‡–‹•‘ ›ƒƒ–‡•ȋ20Ȍƒ†™‡”‡ƒ„Ž‡ –‘‘„–ƒ‹†‹ˆˆ‡”‡–NǦ•—„•–‹–—–‡†’›”‹‹†‹‡†‹‘‡•ȋ Š‡‡͸ͻȌǤ›”‹Ǧ ‹†‹‡†‹‘‡22j™ƒ•ƒˆˆ‘”†‡†‹ƒŽ‘™›‹‡Ž†ǡ’”‘„ƒ„Ž›†—‡–‘–Š‡•–‡”‹  Š‹†”ƒ ‡‹’‘•‡†„›–Š‡‡–Š›Ž‰”‘—’•‹–Š‡‘”–Š‘’‘•‹–‹‘ǤŠ‡•–‡Ǧ ”‹ „—Ž‹–Š‡’”‘†— –ƒŽ•‘‰‡‡”ƒ–‡†”‘–ƒ‡”•ǡ™Š‹ Š™‡”‡‘„•‡”˜‡† „› ͳ  ƒ† ͳ͵  ƒƒŽ›•‹•Ǥ ƒ’Š–›ŽǦ ȋ22kȌǡŠƒŽ‘‰‡ȋ22lƒ†22mȌǡ ›ƒ‘ ȋ22nȌ ƒ† ‡–‘ ȋ22oȌ •—„•–‹–—–‡† ’Š‡›Ž ‹•‘ ›ƒƒ–‡• ™‡”‡ ƒŽŽ –‘Ž‡”ƒ–‡†‹–Š‡”‡ƒ –‹‘ǤpǦ‹–”‘•—„•–‹–—–‡†’Š‡›Ž‹•‘ ›ƒƒ–‡ǡ„‡œ›Ž‹  ƒ†ƒŽ‹’Šƒ–‹ ȋ„”ƒ Š‡†ƒ†Ž‹‡ƒ”Ȍ‹•‘ ›ƒƒ–‡•™‡”‡‡˜ƒŽ—ƒ–‡†ƒ•™‡ŽŽǡ ƒŽ–Š‘—‰Š–Š‡†‡•‹”‡†’”‘†— –•™‡”‡‘–ˆ‘”‡†Ǥ

͹Ͳ  



22j, 40% 22k,a 83% 22l,b 75%

CN O Ph N

N O

CN

22m, 94% 22n,a,c 86% 22o, 84% Scheme 69. Evaluation of aryl isocyanates 20 in the chemoselective reduction andsubsequentfunctionalizationwithenaminefromamide6p(1mmol),isolated yields.a65°C,16h.bIsocyanate(3.0equiv),65°C,16h. Isolationwasperformed on0.5mmolscale.

‡ˆ—”–Š‡”–‡•–‡†‹ˆ’Š‡›Ž‹•‘–Š‹‘ ›ƒƒ–‡23a ‘—Ž†„‡—•‡†‹ƒ•‹‹Ǧ Žƒ” ™ƒ› –‘ ˆ‘” ’›”‹‹†‹‡†‹–Š‹‘‡ 24aȋ Š‡‡͹ͲȌǤ •–‡ƒ†‘ˆ–Š‡ †‡•‹”‡†’”‘†— –ǡ–Š‹‘ƒ ”›Žƒ‹†‡25a™ƒ•ˆ‘”‡†ǡ™Š‹ Š‹•‘™–‘„‡ ˆ‘”‡† ˆ”‘ –Š‡ ”‡ƒ –‹‘ ‘ˆ ‡ƒ‹‡• ™‹–Š ‹•‘–Š‹‘ ›ƒƒ–‡•ǤͳͺͲ ‘—” ƒ•‡ƒ‹‘”‘’–‹‹œƒ–‹‘”‡˜‡ƒŽ‡†–Šƒ–‹–™ƒ•’‘••‹„Ž‡–‘”‡†— ‡ –Š‡ ƒ‘—– ‘ˆ ’Š‡›Ž ‹•‘–Š‹‘ ›ƒƒ–‡ 23aˆ”‘ʹǤʹ–‘ͳǤͳ‡“—‹˜ƒŽ‡–•Ǥ› ’‡”ˆ‘”‹‰–Š‡”‡ƒ –‹‘ƒ–͸ͷιˆ‘”ͳ͸Šǡ–Š‹‘ƒ ”›Žƒ‹†‡25a™ƒ••— Ǧ ‡••ˆ—ŽŽ›‰‡‡”ƒ–‡†‹ͻͶΨ‹•‘Žƒ–‡†›‹‡Ž†Ǥ‰ƒ‹ǡƒ–ƒ†‡•‡–Ǧ—’ˆ‘”–Š‡ ”‡†— –‹˜‡ ˆ— –‹‘ƒŽ‹œƒ–‹‘ ‘ˆ ƒ‹†‡ 6p ™ƒ• ’‡”ˆ‘”‡†Ǥ Ž„‡‹– ƒ ’‘‘” ͳ ›‹‡Ž†‘ˆ–Š‹‘ƒ ”›Žƒ‹†‡25aȋͷΨȌ™ƒ•‘„–ƒ‹‡†ƒŽ‘‰™‹–Š”‡Ǧ ƒ‹‹‰•–ƒ”–‹‰ƒ–‡”‹ƒŽȋƒ‹†‡6pȌǤ –Š‡•ƒ‡™ƒ›ƒ•ˆ‘”–Š‡’›”‹Ǧ ‹†‹‡†‹‘‡•22™‡™‡”‡ƒ„Ž‡–‘‹•‘Žƒ–‡–Š‡–Š‹‘ƒ ”›Žƒ‹†‡’”‘†— –•„› ’”‡ ‹’‹–ƒ–‹‘™‹–Š’‡–ƒ‡Ǥ

͹ͳ  

 Scheme70.Evaluationofphenylisothiocyanate23ainthesynthesisofpyrimǦ idinethione24a.Formationofpyrimidinedione22afromenamine7p.

‡•‡–‘—––‘‡˜ƒŽ—ƒ–‡†‹ˆˆ‡”‡–ƒ‹†‡•ƒ†‹•‘–Š‹‘ ›ƒƒ–‡•ǡ™Š‹ ŠŽ‡† –‘–Š‡‹•‘Žƒ–‹‘‘ˆƒ˜ƒ”‹‡–›‘ˆ–Š‹‘ƒ ”›Žƒ‹†‡•ȋ25aȂ25gȌ‹‰‘‘†–‘ ‡š ‡ŽŽ‡–›‹‡Ž†•ȋ Š‡‡͹ͳȌǤ‡‘„•‡”˜‡††‡ ”‡ƒ•‡†”‡ƒ –‹˜‹–›ˆ‘”‡Ž‡ Ǧ –”‘Ǧ’‘‘”‡ƒ‹‡•ƒ†pǦ‹–”‘‡ƒ‹‡7g†‹†‘–Ž‡ƒ†–‘ƒ›’”‘†— – ˆ‘”ƒ–‹‘Ǥ‘‘—”†‡Ž‹‰Š–ǡ™‡™‡”‡ƒ„Ž‡–‘‘„–ƒ‹–Š‡‡•–‡”•—„•–‹–—–‡† –Š‹‘ƒ ”›Žƒ‹†‡ 25e ‹ ͺͻΨ ‹•‘Žƒ–‡† ›‹‡Ž†Ǥ ƒ‹‡• ™‹–Š †‹ˆˆ‡”‡– NǦ •—„•–‹–—‡–• ™‡”‡ • ”‡‡‡† ƒ† ͵Ǧƒ‹‘–Š‹‘ƒ ”›Žƒ‹†‡• ‘–ƒ‹‹‰ ’‹’‡”‹†‹‡ȋ25fȌǡ‘”’Š‘Ž‹‡ȋ25gȌƒ†NǡNǦ†‹‡–Š›Žƒ‹‡ȋ25hȌ™‡”‡ ƒˆˆ‘”†‡†‹‘†‡”ƒ–‡–‘‰‘‘†›‹‡Ž†•ǤŠ‡›‹‡Ž†•‘„–ƒ‹‡† ‘””‡Žƒ–‡™‡ŽŽ ™‹–Š–Š‡”‡ƒ –‹˜‹–›‘ˆ–Š‡—•‡†‡ƒ‹‡•Ǣ†‡ ”‡ƒ•‹‰ˆ”‘–Š‡‘•–”‡ƒ Ǧ –‹˜‡ǡ’›””‘Ž‹†‹‡ȋ7pȌǡNǡNǦ†‹‡–Š›Žƒ‹‡ȋ7rȌǡ’‹’‡”‹†‹‡ȋ7aȌ–‘‘”Ǧ ’Š‘Ž‹‡ ȋ7qȌǡ–Š‡Ž‡ƒ•–”‡ƒ –‹˜‡Ǥ͹ǡͳͶʹ  ”‡‰ƒ”†• –‘ ‹•‘–Š‹‘ ›ƒƒ–‡• ™‡ ™‡”‡ƒ„Ž‡–‘‘„–ƒ‹–Š‹‘ƒ‹†‡••—„•–‹–—–‡†™‹–Šƒ’Š–Š›Žȋ25iȌƒ•™‡ŽŽ ƒ•„‘–Š‡Ž‡ –”‘Ǧ”‹ Šȋ25jȌƒ†‡Ž‡ –”‘Ǧ’‘‘”ȋ25kƒ†25lȌ‘‹‡–‹‡•‹ Š‹‰Š–‘‡š ‡ŽŽ‡–›‹‡Ž†•Ǥˆ‘”–—ƒ–‡Ž›ǡpǦ‹–”‘’Š‡›Ž‹•‘ ›ƒƒ–‡ƒ†ʹǦ ‹•‘–Š‹‘ ›ƒƒ–‘ǦʹǦ‡–Š›Ž’”‘’ƒ‡ ȋtertǦ„—–›Ž ‹•‘–Š‹‘ ›ƒƒ–‡Ȍ †‹† ‘– ”‡ƒ –•— ‡••ˆ—ŽŽ›™‹–Š‡ƒ‹‡7pǤ 

͹ʹ  



25a, 94% 25b, 94% 25c, 75% 25d, 60%

25e, 89% 25f, 67% 25g, 39% 25h, 71%

25i, 83% 25j, 82%

25k, 94% 25l, 97% Scheme71.Evaluationofamides(6)andisothiocyanates(23)inthechemoseǦ lective reduction and subsequent functionalization of enamines from amides (1mmol),isolatedyields.

–‡”‡•–‹‰Ž›ǡ–Š‡‘„–ƒ‹‡†’”‘†— –•ȋ25Ȍ”‡’”‡•‡–ƒ†‹ˆˆ‡”‡––›’‡‘ˆ ‡ƒ‹‡•™Š‹ Š•Š‘™ƒ‹ ”‡ƒ•‡†•–ƒ„‹Ž‹–›‹ ‘’ƒ”‹•‘™‹–Š7ǤŠ‡ •–ƒ„‹Ž‹–›‘ˆ–Š‡’”‘†— –‡ƒ‹‡•‹•Ž‹‡Ž›†—‡–‘–Š‡ ‘Œ—‰ƒ–‹‘‘ˆ–Š‡ •›•–‡Ǥͳͺ͵‡˜‡”–Š‡Ž‡••ǡŠ›†”‘Ž›•‹•‘ˆ25a‹–‘–Š‡ ‘””‡•’‘†‹‰ƒŽ†‡Ǧ Š›†‡26 ‘—Ž†„‡ƒ Š‹‡˜‡†—•‹‰Š›†”‘ ŠŽ‘”‹ ƒ ‹†ȋ Š‡‡͹ʹȌǤŽ› –Š‡‡‘Žˆ‘”‘ˆ–Š‡ƒŽ†‡Š›†‡™ƒ•‘„•‡”˜‡†‹–Š‡ ͳ •’‡ –”ƒ‹ 6 Ž͵ǡƒŽ–Š‘—‰Šǡ„›•™‹– Š‹‰•‘Ž˜‡––‘d Ǧƒ‹š–—”‡‘ˆƒŽ†‡Š›†‡ ƒ† ‡‘Ž ‘—Ž† „‡ †‡–‡ –‡†Ǥ Š‡ ‡“—‹Ž‹„”‹— „‡–™‡‡ ‡–‘ ƒ† ‡‘Ž ˆ‘”ˆ‘”ƒ•‹‹Žƒ”–Š‹‘ƒ‹†‡™ƒ•”‡’‘”–‡†„›ƒ ‡etalǤƒ†–Š‡›†‡Ǧ –‡”‹‡†–Š‡”ƒ–‹‘–‘„‡ͳǣͳǤʹ‡–‘ǣ‡‘Žȋˆ‘” ͵Ǧ‘š‘ǦNǡ͵Ǧ†‹’Š‡›Ž’”‘’ƒ‡–Š‹‘ƒ‹†‡ȌǤͳͺͶ

͹͵  

 Scheme72.Hydrolysisofthioacrylamide25aintothecorrespondingaldehyde 26.

7.3Conclusions

 ’”‘–‘ ‘Ž ˆ‘” –Š‡ ‘‡Ǧ’‘– ”‡†— –‹˜‡ ˆ— –‹‘ƒŽ‹œƒ–‹‘ ‘ˆ ƒ‹†‡• ‹–‘ ’›”‹‹†‹‡†‹‘‡•ƒ†–Š‹‘ƒ ”›Žƒ‹†‡•™ƒ•†‡˜‡Ž‘’‡†„›–”‡ƒ–‹‰–Š‡in situ‰‡‡”ƒ–‡†‡ƒ‹‡•™‹–Š‡‹–Š‡”‘”‰ƒ‹ ‹•‘ ›ƒƒ–‡•‘”‹•‘–Š‹‘ ›ƒǦ ƒ–‡•Ǥ‘–Š‡„‡•–‘ˆ‘—”‘™Ž‡†‰‡ǡƒŽŽ‘ˆ–Š‡ ‘’‘—†•’”‡’ƒ”‡†‹ –Š‹•’”‘Œ‡ –ƒ”‡‘˜‡Žƒ†Šƒ˜‡‘–„‡‡•›–Š‡•‹œ‡†„‡ˆ‘”‡Ǥ ‡‡”ƒŽŽ›ǡ –Š‡’”‘†— –•™‡”‡‘„–ƒ‹‡†‹Š‹‰Š›‹‡Ž†•ƒ†–Š‡’”‘–‘ ‘Ž‡šŠ‹„‹–•Š‹‰Š Š‡‘•‡Ž‡ –‹˜‹–›Ǥ – •Š‘—Ž† „‡ ’‘‹–‡† ‘—– –Šƒ– •‘‡ ‘ˆ –Š‡ ‡ƒ‹‡• —•‡†‹–Š‹•’”‘–‘ ‘Ž™‘—Ž†„‡†‹ˆˆ‹ —Ž––‘ˆ‘”insituˆ”‘–Š‡ ‘””‡Ǧ •’‘†‹‰ƒŽ†‡Š›†‡•ǡƒ‹‰–Š‡†‡˜‡Ž‘’‡†•–”ƒ–‡‰›ƒƒ––”ƒ –‹˜‡ ‘Ǧ ’Ž‡‡––‘’”‡˜‹‘—•Ž›”‡’‘”–‡†‡–Š‘†•Ǥ 

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ConcludingRemarks

–Š‹•–Š‡•‹•ǡ‘˜‡Ž ƒ–ƒŽ›–‹ ‡–Š‘†•ˆ‘”–Š‡Š›†”‘•‹Ž›Žƒ–‹‘‘ˆƒ‹†‡• „ƒ•‡†‘‘ȋȌ͸ƒ†Šƒ˜‡„‡‡†‡˜‡Ž‘’‡†ƒ•™‡ŽŽƒ•–Š‡”‡†— Ǧ –‹˜‡ˆ— –‹‘ƒŽ‹œƒ–‹‘‘ˆƒ‹†‡•ǤŠ‡ˆ‹”•–’ƒ”–‹•†‡˜‘–‡†–‘–Š‡†‡˜‡ŽǦ ‘’‡– ‘ˆ ’”‘–‘ ‘Ž• ˆ‘” Š‡‘•‡Ž‡ –‹˜‡ ”‡†— –‹‘ ‘ˆ ƒ‹†‡• –‘ ƒŽ†‡Ǧ Š›†‡•ǡƒ‹‡•ƒ†‡ƒ‹‡•ǤŠ‡”‡†— –‹‘•›•–‡•Š‘™‡†ƒ—’”‡ Ǧ ‡†‡–‡† Š‡‘•‡Ž‡ –‹˜‹–› ƒ† ƒ‹†‡ ”‡†— –‹‘ –‘‘ ’Žƒ ‡ ‹ –Š‡ ’”‡•Ǧ ‡ ‡‘ˆ‘–Š‡””‡†— ‹„Ž‡ˆ— –‹‘ƒŽ‰”‘—’•ǡ‹ Ž—†‹‰‡–‘‡•ǡƒŽ†‡Š›†‡•ǡ ƒ† ‹‹‡•Ǥ Š‡ ’”‘–‘ ‘Ž• ™‡”‡ • ƒŽƒ„Ž‡ ƒ† ‘—Ž† „‡ ’‡”ˆ‘”‡† ‘ ‡‹–Š‡” ͷ ‘” ͳͲ ‘Ž • ƒŽ‡Ǥ —”–Š‡”‘”‡ǡ –Š‡ ’Šƒ”ƒ ‡—–‹ ƒŽ †”—‰ ‘‡’‡œ‹Ž™ƒ••›–Š‡•‹œ‡†–Š”‘—‰ŠƒŽƒ–‡Ǧ•–ƒ‰‡”‡†— –‹‘‘ˆ–Š‡–‡”–‹ƒ”› ƒ‹†‡ ˆ— –‹‘ƒŽ‹–› –‘ –Š‡ ‘””‡•’‘†‹‰ ƒ‹‡ ‹ –Š‡ ’”‡•‡ ‡ ‘ˆ ƒ ‡–‘‡Ǥ –Š‡•‡ ‘†ŠƒŽˆ‘ˆ–Š‡–Š‡•‹• Š‡‘•‡Ž‡ –‹˜‡”‡†— –‹˜‡ˆ— –‹‘Ǧ ƒŽ‹œƒ–‹‘‘ˆƒ‹†‡•ƒ†ƒ’’Ž‹ ƒ–‹‘•‘ˆ–Š‡‡ƒ‹‡ˆ‘”ƒ–‹‘’”‘–‘ ‘Ž• ƒ”‡†‹• —••‡†ǤŠ‡ˆ‘”‡†‡ƒ‹‡•™‡”‡”‡ƒ –‡†™‹–Šƒ™‹†‡˜ƒ”‹‡–›‘ˆ ‡Ž‡ –”‘’Š‹Ž‡•ǡ ˆ‘”‹‰ –”‹ƒœ‘Ž‹‡•ǡ –”‹ƒœ‘Ž‡•ǡ NǦ•—Žˆ‘›Žˆ‘”ƒ‹†‹‡•ǡ ͶǡͷǦ†‹Š›†”‘‹•‘šƒœ‘Ž‡•ǡ ’›”‹‹†‹‡†‹‘‡•ǡ ƒ• ™‡ŽŽ ƒ• –Š‹‘ƒ ”›Žƒ‹†‡•Ǥ Š‡ ’”‘–‘ ‘Ž• ˆ‘” –Š‡ •›–Š‡•‹• ‘ˆ –”‹ƒœ‘Ž‹‡•ǡ –”‹ƒœ‘Ž‡• ƒ† NǦ•—Žˆ‘›Žˆ‘”ƒ‹†‹‡• ‘—Ž† ˆ—”–Š‡”‘”‡ „‡ ’‡”ˆ‘”‡† ‘ ’”‡’ƒ”ƒǦ –‹˜‡• ƒŽ‡•Š‘™‹‰–Š‡’”ƒ –‹ ƒŽ‹–›‘ˆ–Š‡†‡˜‡Ž‘’‡†’”‘–‘ ‘Ž•Ǥ

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AppendixA:ContributionList

Š‡ƒ—–Š‘”ǯ• ‘–”‹„—–‹‘–‘’—„Ž‹ ƒ–‹‘• Ȃǣ

 I. ‡”ˆ‘”‡†ƒ–Š‹”†‘ˆ–Š‡‡š’‡”‹‡–ƒŽ™‘”ƒ†–‘‘’ƒ”–‹–Š‡ ’”‡’ƒ”ƒ–‹‘‘ˆ–Š‡ƒ—• ”‹’–ƒ†–Š‡•—’’‘”–‹‰‹ˆ‘”ƒ–‹‘Ǥ

II. ‡”ˆ‘”‡†ƒ–Š‹”†‘ˆ–Š‡‡š’‡”‹‡–ƒŽ™‘”ƒ†–‘‘’ƒ”–‹–Š‡ ’”‡’ƒ”ƒ–‹‘‘ˆ–Š‡ƒ—• ”‹’–ƒ†–Š‡•—’’‘”–‹‰‹ˆ‘”ƒ–‹‘Ǥ

III. ‡”ˆ‘”‡†ƒ‹‘”’ƒ”–‘ˆ–Š‡‡š’‡”‹‡–ƒŽ™‘”ƒ†–‘‘’ƒ”– ‹ ’”‡’ƒ”ƒ–‹‘ ‘ˆ –Š‡ ƒ—• ”‹’– ƒ† –Š‡ •—’’‘”–‹‰ ‹ˆ‘”Ǧ ƒ–‹‘Ǥ

IV. ‡”ˆ‘”‡† ŠƒŽˆ ‘ˆ –Š‡ ‡š’‡”‹‡–ƒŽ ™‘” ƒ† –‘‘ ’ƒ”– ‹ –Š‡ ’”‡’ƒ”ƒ–‹‘‘ˆ–Š‡ƒ—• ”‹’–ƒ†–Š‡•—’’‘”–‹‰‹ˆ‘”ƒ–‹‘Ǥ

V. ‡”ˆ‘”‡† ŠƒŽˆ ‘ˆ –Š‡ ‡š’‡”‹‡–ƒŽ ™‘” ƒ† –‘‘ ’ƒ”– ‹ –Š‡ ’”‡’ƒ”ƒ–‹‘‘ˆ–Š‡ƒ—• ”‹’–ƒ†–Š‡•—’’‘”–‹‰‹ˆ‘”ƒ–‹‘Ǥ



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AppendixB:ReprintPermissions

‡’”‹– ’‡”‹••‹‘• ™‡”‡ ‹†Ž› ‰”ƒ–‡† ˆ‘” ‡ƒ Š ’—„Ž‹ ƒ–‹‘ „›–Š‡ ˆ‘ŽŽ‘™‹‰’—„Ž‹•Š‡”•ǣ  I. Ǥ‹‹•ǡȗǤ‘Ž‘˜ǡǤŽƒ‰„”ƒ†ǡ Ǥ†‘Žˆ••‘ȗ Angew.Chem.Int.Ed.,2016ǡ55ǡͶͷ͸ʹǦͶͷ͸͸ ‘’›”‹‰Š–̹ʹͲͳ͸‹Ž‡›Ǧ ‡”Žƒ‰ „ Ƭ‘Ǥ  ƒǡ‡‹Š‡‹  II. ǤŽƒ‰„”ƒ†ǡǤ‘Ž‘˜ǡǤ”‹ŽŽ‘ǡ Ǥ‹‹•ǡȗ Ǥ†‘Žˆ••‘ȗ ACSCatalysisǡ2017ǡ7ǡͳ͹͹ͳǦͳ͹͹ͷ ‘’›”‹‰Š–̹ʹͲͳ͹‡”‹ ƒŠ‡‹ ƒŽ‘ ‹‡–›  III. Ǥ”‹ŽŽ‘ǡǤŽƒ‰„”ƒ†ǡ Ǥ‹‹•ǡȗ Ǥ†‘Žˆ••‘ȗ ChemistryOpenǡ2017ǡ6ǡͶͺͶǦͶͺ͹ ‘’›”‹‰Š–̹ʹͲͳ͹‹Ž‡›Ǧ ‡”Žƒ‰ „ Ƭ‘Ǥ  ƒǡ‡‹Š‡‹  IV. ǤŽƒ‰„”ƒ†ǡ Ǥ‡”˜‡ˆ‘”•ǡ Ǥ‹‹•ǡȗ Ǥ†‘Žˆ••‘ȗ Adv.Synth.Catal.ǡ2017ǡ359ǡͳͻͻͲǦͳͻͻͷ ‘’›”‹‰Š–̹ʹͲͳ͹‹Ž‡›Ǧ ‡”Žƒ‰ „ Ƭ‘Ǥ  ƒǡ‡‹Š‡‹  V. Ǥ”‹ŽŽ‘ǡᑽǤŽƒ‰„”ƒ†ǡᑽ Ǥ‹‹•ǡȗ Ǥ†‘Žˆ••‘ȗ Chem.Commun.ǡ2017ǡ53ǡͻͳͷͻǦͻͳ͸ʹ ‘’›”‹‰Š–̹ʹͲͳ͹‘›ƒŽ‘ ‹‡–›‘ˆŠ‡‹•–”› 

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Acknowledgements

– ™‘—Ž† ‘– Šƒ˜‡ „‡‡ ’‘••‹„Ž‡ –‘ ™”‹–‡ –Š‹• –Š‡•‹• ™‹–Š‘—– –Š‡ Š‡Ž’ ˆ”‘ƒŽ‘–‘ˆ’‡‘’Ž‡ǡ™Š‹ Š†—”‹‰–Š‡•‡›‡ƒ”•Šƒ˜‡•—’’‘”–‡†‡™‹–Š ‘™Ž‡†‰‡ǡ†‹ˆˆ‹ —Ž–“—‡•–‹‘•ǡ ƒ”‡ƒ†Žƒ—‰Š–‡”Ǥ‹–Š–Šƒ–ǡ ™‘—Ž†Ž‹‡ –‘‡š’”‡••›•‹ ‡”‡•–‰”ƒ–‹–—†‡–‘–Š‡ˆ‘ŽŽ‘™‹‰’‡‘’Ž‡ǣ ›•—’‡”˜‹•‘”ǡHansAdolfssonˆ‘”ƒ ‡’–‹‰‡ƒ•ƒŠǤǤ•–—†‡–ǡ‘—” †‹• —••‹‘•ƒ†›‘—” ‘•–ƒ–•—’’‘”–ǤŠƒ›‘—ˆ‘”Ž‹•–‡‹‰–‘ƒŽŽ› ™‘””‹‡•ƒ† ‘ ‡”•†—”‹‰–Š‡•‡›‡ƒ”•Ǩ PherG.Anderssonˆ‘”•Š‘™‹‰‹–‡”‡•–‹–Š‹•–Š‡•‹•Ǥ Š‡ ’”‘‘ˆǦ”‡ƒ†‡”• ‘ˆ –Š‹• –Š‡•‹•Ǣ Hasseǡ Fredrikǡ Pazǡ Alexeyǡ Erikƒ† Markusǡ–Šƒ• ˆ‘” ›‘—” ‘•‹†‡”ƒ–‡ ‘‡–• ™Š‹ Š ‹’”‘˜‡† –Š‹• –Š‡•‹•Ǩ ƒ•–ƒ†’”‡•‡–‡„‡”•‘ˆ–Š‡ Ǧ‰”‘—’ǢDr. Paz Trilloǡ Dr.FredrikTinnisǡ Dr. Helena Lundbergǡ Dr. Alexey Volkovǡ AnǦ dreyShatskiyǡIdaPershagenǡToveKivijärviƒ†GabriellaKerveforsǤ

•’‡ ‹ƒŽ–Šƒ•–‘–Š‡‘ȋȌ͸Ǧ–‡ƒǢFredrikǡAlexeyƒ†PazǨ Fredrikǡ ˆ‘” –Š‡ •—’‡”˜‹•‹‘ †—”‹‰ –Š‡•‡ ›‡ƒ”•Ǩ  ƒ ”‡ƒŽŽ› ˆ‡‡Ž Š‘™ ƒ••‡‡‡’•ƒ‡›‡‘‡Ǩ-Ž•‘ǡ–Šƒ•ˆ‘”ƒŽŽ–Š‡Šƒ’’›Ȁ ”ƒœ›‘Ǧ ‡–•ǡ„‘–Š‹–Š‡Žƒ„ƒ†‘ˆˆ†—–›Ǩ‘—ƒ”‡›’ƒ”–‡”‹ ”‹‡ƒ––Š‡ †‡’ƒ”–‡–ƒ†›Dz•‘—” ‡dz–‘—–”—•–›ˆƒ –•Ǩ Alexeyǡ„‡ˆ‘”‡ •–ƒ”–‡†‹–Š‡‰”‘—’ †‹†‘–‘™–Šƒ–—••‹ƒ• ‘—Ž† „‡•‘•™‡‡–Ǩ Šƒ˜‡Ž‡ƒ”‡†thehardway‘––‘†”‹•Š‘–•™‹–Šƒ—•Ǧ •‹ƒǨŠƒ•ˆ‘”ƒŽŽ†‹• —••‹‘•ƒ†ƒŽŽ–Š‡ˆ—–‹‡•Ǩ- Pazǡ™‹–Š›‘—‹–Š‡Žƒ„‹–‹•ƒŽ™ƒ›•ˆ—ƒ† ƒŽ™ƒ›•‰‡––‘’‹ –Š‡—Ǧ •‹ ǨŠƒ›‘—ˆ‘”›‘—”’ƒ–‹‡ ‡™‹–Š›—•‹ ƒ†–Šƒ›‘—ˆ‘”›‘—” ’‘•‹–‹˜‹–›Ǩ – ™‹ŽŽ †‡ˆ‹‹–‡Ž› Š‡Ž’ ›‘— ™Š‡ ‘–‹—‹‰ –Š‡ ™‘” —’ ‹ ‡¤Ǩ ‘‘†Ž— ƒ†”‡‡„‡”–Šƒ– ƒ‘––Šƒ–ˆƒ”ƒ™ƒ›Ǩ

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Toveƒ†Gabriella™Š‘™‘”‡†ƒƒœ‹‰Ž›™‹–Š‡‘–™‘‘ˆ–Š‡’”‘Ǧ Œ‡ –•Ǥ‘—”‡ˆˆ‘”–•Šƒ˜‡’ƒ‹†‘ˆˆǡ–Š‡’”‘Œ‡ –•ƒ”‡‘™’—„Ž‹•Š‡†ƒ† ƒ •‘Šƒ’’› ‰‘––‘•—’‡”˜‹•‡›‘—„‘–ŠǨ  ŽŽ‡„‡”•‘ˆ–Š‡BeritOlofssonƒ†NicklasSelander‰”‘—’•ˆ‘”‹ ‡ Š‡‹•–”› †‹• —••‹‘• ƒ† ˆ— ”—‹•‡• ‘˜‡” –Š‡ ›‡ƒ”•Ǩ ‡‡„‡” –Š‡ –”ƒ†‹–‹‘ƒŽGrasshopper–‘•‡––Š‡‘‘†ˆ‘”–Š‡ƒˆ–‡”‘‘Ǩ- ƒ•–ƒ†’”‡•‡–‡„‡”•‘ˆ–Š‡Brofficeǡ™‹–Š›‘—ƒ”‘—†™‘”‹•‡˜Ǧ ‡”„‘”‹‰Ǩ Š‡•–ƒˆˆǢJennyǡLouiseǡSigridǡCarinǡKristinaǡOlaƒ†Martinˆ‘” ”‡Ǧ ƒ–‹‰ƒ‹ ‡™‘”‡˜‹”‘‡–Ǥ•’‡ ‹ƒŽ–Šƒ•–‘Carinˆ‘”›‘—”Šƒ”† ™‘”ǨŠƒ•–‘›‘— ‰‘–ƒŽŽ›ƒ••‡•Ǩ- Š‡ girl gang ƒ– –Š‡ †‡’ƒ”–‡– ˆ‘” ƒŽŽ –Š‡ ƒ†˜‡–—”‡• ƒ† ‰‘••‹’‹‰ ƒ„‘—–‡˜‡”›–Š‹‰ǢSaraǡJohannaǡTanjaǡElinǡGabbiƒ†ToveǤ ŽŽˆ”‹‡†•ƒ––Š‡DepartmentofOrganicChemistryǤ Knut & Alice Wallenbergs Stiftelseǡ Ångpanneföreningens ForǦ skningsstiftelseǡ Gålöstiftelsenǡ Stiftelsen Längmanska Kulturfondenǡ HelgeAx:on Johnsons stiftelseǡ Vetenskapsrådetƒ†The Royal Swedish AcademyofScienceˆ‘”ƒ‹‰‹–’‘••‹„Ž‡ˆ‘”‡–‘•Šƒ”‡›”‡•—Ž–•ƒ– ‹–‡”ƒ–‹‘ƒŽ ‘ˆ‡”‡ ‡•Ǥ Toallmyfriendsandrelatives,especiallytheDelzannomob! Moaƒ†Saraǡˆ‘”ƒŽŽ•—’’‘”–ƒ†Žƒ—‰Š–‡”†—”‹‰–Š‡›‡ƒ”•ǡ‹–Šƒ•„‡‡ ”‡ƒŽŽ› ‹ ‡ ‰”‘™‹‰ —’ ‡š– –‘ ›‘—Ǩ †ǡ ›‡•ǡ  ƒ ”‡ƒŽŽ› †‘‡ ™‹–Š • Š‘‘Ž‘™Ǩ ›†‡ƒ”Isabelleǡ‘™™Š‡™‡ƒ”‡‘Ž†‡”‹–ˆ‡‡Ž•Ž‹‡•‘‡‘ˆ–Š‘•‡ƒ™Ǧ ˆ—Ž†ƒ›•™ƒ•‘–ƒ•„ƒ†ƒ• ”‡‡„‡”‡†–Š‡Ǥ –™ƒ•‹ ‡–‘Šƒ˜‡›‘— „››•‹†‡„ƒ –Š‡ƒ†–‘Šƒ˜‡ˆ‘—†›‘—ƒ‰ƒ‹Ǩ ›mumƒ†dadǡ–Šƒ•ˆ‘”ƒŽ™ƒ›•„‡Ž‹‡˜‹‰‹‡‡˜‡™Š‡›‘—†‘ ‘–—†‡”•–ƒ†™Šƒ– ƒƒ –—ƒŽŽ›†‘‹‰Ǥ ƒ‰¡Ž•ƒ”‡”Ǩ ›•‹•–‡”Fridaǡˆ‘”ˆ‹†‹‰–Š‡„‡ƒ—–‹‡•‹Ž‹ˆ‡ƒ†ˆ‘”ƒŽŽ›‘—”‡‡”‰›Ǩ  –Š‹ ƒƒ‰‡†–‘ƒ‡–Š‹•–Š‡•‹•‡˜‡‘”‡„‘”‹‰–Šƒ›Ž‹ ‡–‹Ǧ ƒ–‡ǡ•‘‰‘‘†Ž— Ž‘‘‹‰ƒ––Š‡’‹ –—”‡•Ǩ- Erikǡˆ‘”„‡‹‰›‘—ǡƒŽ™ƒ›•Ǥ  

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References

 ͳ ‘ŽŽ‘™‹‰  •–ƒ†ƒ”† ƒ„„”‡˜‹ƒ–‹‘• ƒ† ƒ ”‘›•ǡ 2017‰—‹†‡Ž‹‡• ˆ‘”ƒ—–Š‘”•ǡ”‰ƒ‹ ‡––‡”•ǣ Š––’ǣȀȀ’—„•Ǥƒ •Ǥ‘”‰Ȁ’ƒ”ƒ‰‘’Ž—•Ȁ•—„‹••‹‘Ȁ‘”Ž‡ˆ͹Ȁ‘”Ž‡ˆ͹̴•–ƒ†ƒ”†̴ƒ „„”‡˜‹ƒ–‹‘•Ǥ’†ˆȋ ‡••‡†ʹͲͳ͹ǦͲ͸ǦʹͳȌ ʹ ǤǤƒ•–ƒ•ǡ ǤǤƒ”‡”ǡGreenChemistry:TheoryandPracticeǡšˆ‘”† ‹˜‡”•‹–›”‡••ǡ1998ǡ’Ǥ͵ͲǤ ͵ Ǥ‹—ǡǤœ‘•–ƒǡChem.Eur.J.ǡ2017ǡ23ǡ͹ͳͷ͹Ǧ͹ͳ͹͵Ǥ Ͷ Ǥ Ǥ‡‹‰ǡAdv.DrugDeliver.RevǤǡ2002ǡ54ǡͳͳͶͷǦͳͳͷͷǤ ͷ ǤǤƒ––ƒ„‹”ƒƒǡ ǤǤ‘†‡ǡNatureǡ2011ǡ480ǡͶ͹ͳǦͶ͹ͻǤ ͸ Ǥ ƒ„‹ ›ǡ The Chemistry of Amidesǡ ‘Š‹Ž‡›Ƭ‘•–†Ǥǡ1970ǡ ’’Ǥʹ͵Ǧ͵ͶǤ ͹ Ǥ Ǥ Žƒ„—‰‹ǡ Stereoelectronic Effects: A Bridge between Structure and Reactivityǡ ‘Š‹Ž‡›ƒ†‘•ǡ2016ǡ’’ǤͳͷʹǦͳ͸͹Ǥ ͺ ƒȌ Ǥ ƒ‹•‡”ǡ Ǥ ƒ—Ž‹†‡ǡ J. Org. ChemǤǡ 2016ǡ 81ǡ ͶͶʹͳǦͶͶʹͺǢ „ȌǤǤ—‹†‡”ǡ Ǥ ƒ—Ž‹†‡, Angew. Chem. Int. EdǤǡ 2015ǡ 54ǡ ͳ͵ͺͷ͸Ǧͳ͵ͺͷͺǢ ȌǤƒ ‡ǡǤ ‘Žœ‡”ǡǤŽ‘ˆ••‘ǡAdv.Synth.CatalǤǡ2014ǡ 356ǡ͵͸ͻ͹Ǧ͵͹͵͸Ǥ ͻ Ǥ —– Š„›ǡǤǤ ‘—Ž†‡ǡǤ Ǥ ƒ††‘™ǡǤǤ Ǥ›Ž‡”ǡ ǤǤŽ‘›†Ǧ ‘‡•ǡ Ǥ Ǥ‘‘‡”Ǧ‹Ž„—”ǡAngew.Chem.Int.EdǤǡ2012ǡ51ǡͷͶͺǦͷͷͳǤ ͳͲ ƒ•ǡǤŠ‘—ǡǤ††‹•ǡǤ–ŠƒŽ‡”ǡǤ —‰‡ǡǤ‡ŽŽ‡”ǡTop.CatalǤǡ2010ǡ 53ǡͻ͹ͻǦͻͺͶǤ ͳͳ ƒȌǤ‘ƒ‹ǡǤ‘ƒ™ƒǡJ.Org.ChemǤǡ1986ǡ51ǡͶͲͲͲǦͶͲͲͷǢ„ȌǤǤƒ†ƒŽǡ ǤǤ ‹”‹ǡǤǤƒ„‡‡ƒǡǤǤƒ”ƒ•Š‹ǡJ. Org. ChemǤǡ 1988ǡ 53ǡ Ͷʹ͵͸ǦͶʹͶͳǢ ȌǤǤƒ†ƒŽǡǤǤ ‹”‹ǡǤǤƒ”ƒ•Š‹ǡSynthesisǡ1987ǡ12ǡ ͳͳʹͺǦͳͳ͵ͲǤ ͳʹ ǤǦǤ•ƒ›ǡ ǤǤ‘„Žǡ ǤǤ ™—ǡJ. Chem. Soc., Perkin TransǤ 1ǡ 1990ǡ ͹ͷ͹Ǧ͹ͷͻǤ ͳ͵ Ǥ‡ŠŽ‘—ŽǡǤ —‹Œƒ””‘ǡǤ—•ǡSynthesisǡ2006ǡ2ǡ͵ͲͻǦ͵ͳͶǤ ͳͶ Ǥ ‘–‘›ƒƒǡ Ǥ ‘‹ǡ Ǥ ƒƒ‘ƒǡ Ǥ ‘–‘ǡ Ǥ ƒ‰ƒ•Š‹ƒǡ Chem. ComǦ munǤǡ2009ǡ12ǡͳͷ͹ͶǦͳͷ͹͸Ǥ ͳͷ Ǥƒ•—ƒ•›ǡǤǤ ‘”ƒŽ•‹ǡǤ‹‰ƒ”ƒǡOrg.ProcessRes.DevǤǡ2006ǡ 10ǡͻͷͻǦͻ͹Ͳƒ†”‡ˆ‡”‡ ‡•–Š‡”‡‹Ǥ ͳ͸ Ǥ Ǥƒ–•‘ǡǤǤ›‡”•ǡǤŠƒŠǡǤ‡•–”—’ǡǤ‡„•–‡”ǡǤ ”‡—†ǡ Ǥ ‘”‰ƒǡ ǤǤƒ”‡›ǡOrg.ProcessRes.Dev.ǡ2003ǡ7ǡͷʹͳǦͷ͵ʹǤ

ͺͳ  

 ͳ͹ PrudentPracticesintheLaboratory:HandlingandDisposalofChemicalsǡ ƒ–‹‘ƒŽ ƒ†‡›”‡••ǡ1995ǡ’’Ǥ͵ͶͺǦ͵ͶͻǤ ͳͺ ƒȌ Ǥ ƒŒ‘•ǡ Studies in Organic Chemistry 1: Complex Hydridesǡ Ž•‡˜‹‡”ǡ 1979Ǣ„Ȍ Ǥ‡›†‡Ǧ‡‡ǡReductionsbyAluminoǦandBoroǦhydridesin OrganicSynthesisǡ Ǧ ‡”Žƒ‰ „ Ƭ‘Ǥ ƒǡ1991Ǥ ͳͻ ƒȌǤ‹‘ǡǤ ™ƒ—ƒǡǤ –‘ŠǡTetrahedronLettǤǡ1976ǡ17ǡ͹͸͵Ǧ͹͸͸Ǣ „ȌǤǤƒ‹Ž‡›ǡǤǤ ‘––ǡǤ Ǥƒ†”‡˜ƒŽƒǡJ.Chem.Soc.,PerkinTrans.1ǡ 1980ǡ1ǡͻ͹ǦͳͲͳǢ Ȍ Ǥ Ǥƒ‘ǡǤŠƒ‰ǡǤǤ‘‘ǡSynthesisǡ1986ǡ6ǡ ͶͻͶǦͶͻͻǢ†Ȍ ǤǤ ƒ” Àƒ—ƒ‘ǡǤǤƒ”–À‡œǡ Ǥ Ǥ‘†”À‰—‡œǡǤǤŽ‡Ǧ ˆ‹”‘™‹ œǡ”‡•–ǤŽ‹‡ŽǡJ.Org.Chem.ǡ1992ǡ57ǡͶʹͳͷǦͶʹʹͶǤ ʹͲ Ǥ ƒ˜ƒŽǡ Ǥ ƒ›‘—„ǡ Ǥ ‡ŠŽ‹˜ƒǡ Ǥ ±–ƒ›ǡ Ǥ ƒ˜”‡Ǧ±‰—ŽŽ‹‘ǡ Ǥ‡Ž„”ƒ›‡ŽŽ‡ǡ Ǥ ‹‰ƒ‹ǡ Ǥ ‡ƒ‹”‡ǡ Tetrahedron LettǤǡ 2011ǡ 52ǡ ͶͲ͹ʹǦͶͲ͹ͷǤ ʹͳ Ǥƒ–‘ŠǡǤ—œ—‹ǡǤ—œ—‹ǡǤ‹›ƒŒ‹ǡǤ ƒ‹ǡTetrahedronLettǤǡ1969ǡ 52ǡͶͷͷͷǦͶͷͷͺǤ ʹʹ ǤǤ‘‘ǡǤǤŠŠ‘ǡ ǤǤ‘‘ǡ ǤǤ‹ǡJ.KoreanChem.SocǤǡ1983ǡ27ǡ Ͷ͵ͶǦͶͶͲǤ ʹ͵ ǤǤ”‘™ǡǤ ‡ŽǡJ.Org.ChemǤǡ1973ǡ38ǡͻͳʹǦͻͳ͸Ǥ ʹͶ Ǥ Ǥ‘”‡–ǡǤǤŠ‹‘ǡǤ ǤƒǡJ.Org.ChemǤǡ1968ǡ33ǡ͵͸͵͹Ǧ͵͸͵ͻǤ ʹͷ ƒȌǤǤǤ”ƒ•ƒǡ ǤǤǤƒ–ŠǡǤ‡”‹ƒ•ƒ›ǡTetrahedronǡ 1992ǡ 48ǡ Ͷ͸ʹ͵ǦͶ͸ʹͺǢ „Ȍ Ǥ ‹ƒ‹•ǡ Ǥ ƒ†‘ˆˆǡ Angew. Chem. Int. EdǤǡ 1989ǡ 28ǡ ʹͳͺǦʹʹͲǢ Ȍ Ǥ ƒ„‘”‹ǡ Ǥ ƒƒ‘Šƒ•Š‹ǡ J. Chem. Soc., Perkin Trans. 1ǡ 1991ǡͶ͹ͻǦͶͺʹǢ†ȌǤǤƒǡǤǤŠ‘”•‡ǡǤǤ”‡‡˜‘›ǡJ.Org.ChemǤǡ 1981ǡ46ǡʹͷ͹ͻǦʹͷͺͳǤ ʹ͸ ƒȌ Ǥ‹–‡”ˆ‡Ž†–ǡSynthesisǡ1975ǡ9ǡ͸ͳ͹Ǧ͸͵ͲǢ„ȌǤ‹‡‰Ž‡”ǡǤ Š‡‹†‡”ǡ Ǥ  Š‡‹†‡”ǡ Justus Liebigs Ann. ChemǤǡ 1959ǡ 623ǡ ͻǦͳ͸Ǣ Ȍ ǤǤ ƒ–‡– ͵ǡͳͶ͵ǡͷͶʹ ȋǤ ‹‡‰Ž‡” et alǤǡ 1964ȌǢ †Ȍ ǤǤ ƒ–‡– ’’Ž‹ ƒ–‹‘ ʹͲͲͷȀͲͲʹ͸ͻͺ͵ͳȋˆ‹œ‡”ǡ2005ȌǤ ʹ͹ Ǥ Ǥ Š‘‹ǡ Ǥ Ǥ ‹ǡ Ǥ Ǥ ǡ Bull. Korean Chem. SocǤǡ 2009ǡ 30ǡ ʹͺʹͷǦʹͺʹ͸Ǥ ʹͺ ƒȌ ǤǤ”‘™ǡǤ ǤŠ‘ƒˆǡJ.Am.Chem.Soc.ǡ1964ǡ86ǡͳͲ͹ͻǦͳͲͺͷǢ„Ȍ ǤǤ ”‘™ǡǤǤ ƒ”‰ǡJ.Am.Chem.SocǤǡ1964ǡ86ǡͳͲͺͷǦͳͲͺͻǢ Ȍ ǤǤ”‘™ǡ Ǥ•—ƒ‘–‘ǡJ.Am.Chem.SocǤǡ1964ǡ86ǡͳͲͺͻǦͳͲͻͷǤ ʹͻ ƒŠǡǤǤ‡‹”‡„ǡTetrahedronLettǤǡ1981ǡ22ǡ͵ͺͳͷǦ͵ͺͳͺǤ ͵Ͳ Ǥ”ƒ—‡”ǡ ǤǤ Š™ƒ”œǡǤ Ǥƒ‹•Š‡ˆ•›ǡAngew.Chem.Int.Ed.ǡ1999ǡ 38ǡ͵ͷͶʹǦ͵ͷͶͷǤ ͵ͳ Ǥ‹–ŠǡǤŠ›ƒǡChem.RevǤǡ2014ǡ114ǡͷͶ͹͹ǦͷͷͳͲǤ ͵ʹ Ǥ Ǥ —ŽŽ‘ ǡ Catalysis Without Precious Metalsǡ  Ǧ  ‡”Žƒ‰ „ Ƭ‘Ǥ ƒǡ2010ǡ’’ǤͷͳǦͺͳǤ ͵͵ Ǥ‘Ž‘˜ǡ Ǥ‹‹•ǡǤŽƒ‰„”ƒ†ǡǤ”‹ŽŽ‘ǡ Ǥ†‘Žˆ••‘ǡChem.Soc.RevǤǡ 2016ǡ45ǡ͸͸ͺͷǦ͸͸ͻ͹Ǥ

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 ͵Ͷ ǤŠ‹ǡǤƒǡ Ǥ‘‰ǡǤ‹‘‰ǡǤƒ‰ǡǤ—‡ǡ Ǥ˜ǡǤ Šƒ‰ǡ Chem.Eur.J.ǡ2017ǡ23ǡͷͶ͸ǦͷͶͺǤ ͵ͷ ǤǦǤ—ƒǡ ǤǦ Ǥ‹‡ǡǤǦǤŠ‘—ǡChemCatChemǡ2016ǡ8ǡ͵Ͳ͵͸Ǧ͵ͲͶͲǤ ͵͸ ƒȌ Ǥ Œ‹ƒǡ The Chemistry of Organic Silicon Compoundsǡ  Ǧ  ‡”Žƒ‰ „  Ƭ ‘Ǥ  ƒǡ 1989Ǣ „Ȍ Ǥƒ” ‹‹‡ ǡ Comprehensive HandǦ bookonHydrosilylationǡ‡”‰ƒ‘ǡ1992Ǣ Ȍ Ǥ”—‡”ǡ Ǥ‹•Š‹›ƒƒǡǤ –‘Šǡ Catalytic Asymmetric Synthesisǡ  Ǧ  ‡”Žƒ‰ „  Ƭ ‘Ǥ  ƒǡ1993ǡ’’Ǥ͵Ͳ͵Ǧ͵ʹʹǢ†Ȍ Ǥ‹•Š‹›ƒƒǡǤ –‘ŠǡCatalyticAsymmetric Synthesisǡ Ǧ ‡”Žƒ‰ „ Ƭ‘Ǥ ƒǡ2000ǡ’’ǤͳͳͳǦͳͶ͵Ǥ ͵͹ Ǥ‡•–‹ǡ ǤǤƒ”•‘ǡOrg.ProcessRes.DevǤǡ2016ǡ20ǡͳͳ͸ͶǦͳͳͺͳǤ ͵ͺ ǤǤ‡ŽŽ•ǡOrg.ProcessRes.DevǤǡ2010ǡ14ǡͶͺͶǦͶͺͶǤ ͵ͻ ƒȌǤ Ǥƒ™”‡ ‡ǡǤǤ”‡™ǡǤǤ—•Š‡ŽŽǡJ.Chem.Soc.,PerkinTrans.1ǡ 1999ǡ ͵͵ͺͳǦ͵͵ͻͳǢ „Ȍ Ǥ ‹‘—ǡ Ǥ Ǥ †‡ ƒ‹– ƒ—‡”ǡ Ǥ ‹ƒ‹‹ǡ Ǥ ‘’‡ŽŽ‹–‹ǡ Ǥ Ž‘”‹ƒ‹ǡ J. Am. Chem. Soc.ǡ 1999ǡ 121ǡ ͸ͳͷͺǦ͸ͳ͸͸Ǣ ȌǤǤ‡ƒ’ƒ–‹ǡSynlettǡ2005ǡ12ǡͳͻ͸ͲǦͳͻ͸ͳǢ†Ȍ ǤǤƒ˜‹•ǡǤǤƒŽ‡ Ǧ œƒǡ Polymethylhydrosiloxane, eǦEROS Encyclopedia of Reagents for OrǦ ganicSynthesis, ‘Š‹Ž‡›Ƭ‘•ǡ–†Ǥǡ2003Ǣ‡ȌǤ‘Žƒ•ǡǤ‘”‹‰ǡSilǦ icones:Preparation,PropertiesandPerformanceǡ‘™‘”‹‰‘”’‘”ƒǦ –‹‘ǡ2005Ǥ ͶͲ ƒȌ Ǥ —™ƒ‘ǡ Ǥ ƒƒŠƒ•Š‹ǡ Ǥ –‘ǡ Tetrahedron LettǤǡ 1998ǡ 39ǡ ͳͲͳ͹ǦͳͲʹͲǢ „Ȍ Ǥ ƒ•ƒ—ƒǡ Ǥ ‘–‘›ƒƒǡ Ǥ ƒ‰ƒ•Š‹ƒǡ Chem. ComǦ mun.ǡ 2007ǡ 46ǡ Ͷͻͳ͸ǦͶͻͳͺǢ Ȍ Ǥ ƒƒ†ƒǡ Ǥ •—–•—‹ǡ Ǥ ‘–‘›ƒƒǡ Ǥƒ‰ƒ•Š‹ƒǡ J. Am. Chem. Soc.ǡ 2009ǡ 131ǡ ͳͷͲ͵ʹǦͳͷͲͶͲǢ †Ȍ Ǥ Š‡‰ǡ Ǥ”‘‘Šƒ”–ǡJ.Am.Chem.Soc.ǡ2012ǡ134ǡͳͳ͵ͲͶǦͳͳ͵Ͳ͹Ǣ‡ȌǤƒ•ǡǤ‹ǡ Ǥ‘”• Š‡‹ǡǤ‹•‹‡™‹ œǡǤ‹‡”• ŠǡǤ‹ ŠƒŽ‹ǡ Ǥ ƒŽŽ‘—ǡ Ǥ —‰‡ǡ Ǥ‡ŽŽ‡”ǡAngew.Chem.Int.EdǤǡ2015ǡ54ǡͳʹ͵ͺͻǦͳʹ͵ͻ͵Ǥ Ͷͳ ƒȌǤ—ƒ†ƒǡ Ǥƒ™ƒƒ‹ǡǤ ƒ‘ƒǡǤ‘–‘›ƒƒǡ Ǥƒ‰ƒ•Š‹ƒǡAnǦ gew.Chem.Int.EdǤǡ2009ǡ48ǡͻͷͳͳǦͻͷͳͶǢ„ȌǤƒ•ǡǤ‡†–ǡǤ­ŽŽ‡”ǡ Ǥ —‰‡ǡǤ‡ŽŽ‡”ǡAngew.Chem.Int.EdǤǡ2012ǡ51ǡͳ͸͸ʹǦͳ͸͸͸Ǣ Ȍ Ǥ•—Ǧ –•—‹ǡǤ—ƒ†ƒǡ Ǥƒ‰ƒ•Š‹ƒǡChem.CommunǤǡ2011ǡ47ǡ͸ͷͺͳǦ͸ͷͺ͵Ǣ †ȌǤ±œ‹‡”ǡ ǤǤ‡ƒƒǡ ǤǦǤ‘”–ƒ‹•ǡǤƒ” ‡ŽǡChemCatChemǡ2011ǡ 3ǡͳ͹Ͷ͹Ǧͳ͹ͷͲǢ‡ȌǤ‘Ž‘˜ǡǤ—‹–”ƒ‰‘ǡ Ǥ†‘Žˆ••‘ǡEur.J.Org.ChemǤǡ 2013ǡʹͲ͸͸ǦʹͲ͹ͲǢˆȌǤŠ‘—ǡǤ —‰‡ǡǤ††‹•ǡǤƒ•ǡǤ‡ŽŽ‡”ǡAngew. Chem.Int.EdǤǡ2009ǡ48ǡͻͷͲ͹ǦͻͷͳͲǢ‰ȌǤŽ‘ǡ ǤƒǡǤ–ŠƒŽ‡”ǡǤ Ǧ ‘—‡ǡ ǤǤ’’‹‰ǡǤ”‹‡••ǡJ.Am.Chem.SocǤǡ2013ǡ135ǡͳͺͳͲͺǦͳͺͳʹͲǢŠȌ ǤŠƒ‰ǡǤŠƒ‰ǡAppl.Organomet.ChemǤǡ2010ǡ24ǡ͹ͷͳǦ͹ͷ͹Ǥ Ͷʹ ƒȌǤƒ•ǡǤ††‹•ǡǤŠ‘—ǡǤ —‰‡ǡǤ‡ŽŽ‡”ǡJ.Am.Chem.SocǤǡ2010ǡ ͳ͵ʹǡ ͳ͹͹ͲǦͳ͹͹ͳǢ „Ȍ Ǥ ƒ•ǡ Ǥ ††‹•ǡ Ǥ —‰‡ǡ Ǥ ‡ŽŽ‡”ǡ Chem. Eur. JǤǡ 2011ǡ 17ǡ ͳʹͳͺ͸ǦͳʹͳͻʹǢ Ȍ Ǥ Ǥ ‘˜ƒŽ‡‘ǡ Ǥ ‘Ž‘˜ǡ Ǥ †‘Žˆ••‘ǡ Org.Lett.ǡ2015ǡ17ǡͶͶ͸ǦͶͶͻǤ Ͷ͵ Ǥ ‹ƒ‹ǡ Ǥ ‘—Œ‹ƒǡ Ǥ ‹–•—†‘‡ǡ Ǥ ‹œ—‰ƒ‹ǡ Ǥ ‹–•—ƒ™ƒǡ Ǥƒ‡†ƒǡChem.Eur.J.ǡ2011ǡ17ǡͳ͹͸ͺǦͳ͹͹ʹǤ

ͺ͵  

 ͶͶ Ǥ ‘„”ƒ›ǡ Ǥ ‡ŽŽ‡—ǡ Ǥ ƒ” ‡Žǡ ǤǦǤ ‘”–ƒ‹•ǡ Adv. Synth. CatalǤǡ 2013ǡ 355ǡ͵͵ͷͺǦ͵͵͸ʹǤ Ͷͷ Ǥƒƒ‹ǡǤƒ‡‘ƒǡǤ—ƒ‹ǡ Ǥ•ƒ‘ǡǤ‘ƒƒŠƒ”ƒǡǤ‰‹™ƒ”ƒǡ TetrahedronLettǤǡ2015ǡ56ǡ͸ͶͶͺǦ͸ͶͷͳǤ Ͷ͸ ǤǤƒ’Žƒ†ǡǤ ‘˜‡›ǡǤ—Š‡”Œ‡‡ǡǤǤƒ†‘™ǡACSCatalǤǡ2015ǡ5ǡ ͶʹͳͻǦͶʹʹ͸Ǥ Ͷ͹ ƒȌǤ‹ǡ ǤǤ‘Ž‹ƒ†‡ƒ‘””‡ǡǤ ”ƒ„‘™ǡǤ‡–”—’ǡǤ —‰‡ǡǤŠ‘—ǡ Ǥ ”ò ‡”ǡ Ǥ ‡ŽŽ‡”ǡ Angew. Chem. Int. Ed.ǡ 2013ǡ 52ǡ ͳͳͷ͹͹ǦͳͳͷͺͲǢ „ȌǤǤŠƒ†™‹ ǡǤƒ”†‡Ž‹•ǡǤ‹ǡǤ†”‘‘˜ǡJ.Org.ChemǤǡ2014ǡ79ǡ ͹͹ʹͺǦ͹͹͵͵Ǣ Ȍ Ǥ Ž‘†‹ƒ—šǡ Ǥ ƒ–ƒ–ǡ Chem. CommunǤǡ 2014ǡ 50ǡ ͻ͵ͶͻǦͻ͵ͷʹǤ Ͷͺ Ǥ ǤŠƒŽǡ Ǥ Ǥ ƒ””‘†ǡJ.Am.Chem.SocǤǡ1965ǡ87ǡͳ͸ǦʹͳǤ Ͷͻ Ǥ‡‹–œǡǤǤ”‹‰Š–‘ǡAngew.Chem.Int.EdǤǡ1988ǡ27ǡʹͺͻǦʹͻͳǤ ͷͲ ƒȌ Ǥ Ǥ — ‡––ǡ Ǥ Ǥ ‡”—–œǡ Organometallicsǡ 1992ǡ 11ǡ ͻͲǦͻͺǢ „ȌǤƒƒ‹ǡ Ǥ —‹‘–‘ǡ Ǥ ——Šƒ”ƒǡ Ǥ —‰‹‘–‘ǡ Ǥ —Œ‹‘–‘ǡ Ǥƒ–•—œƒ‹ǡ Organometallicsǡ 2002ǡ 21ǡ ͵͹ͺͺǦ͵ͺͲʹǢ Ȍ Ǥ Œ‹ƒǡ Ǥ ‹Ǧ Š‘›ƒƒ‰‹ǡǤ‘‰—”‡ǡǤ—ƒ‰ƒ‹ǡǤ ‘”‹— Š‹ǡǤƒƒ–•—‰ƒ™ƒǡǤƒ‰ƒ‹ǡ J.Organomet.ChemǤǡ1975ǡ94ǡͶͶͻǦͶ͸ͳǤ ͷͳ Ǥ‡†Ž‡”ǡǤ‡•–”‡‹ ŠǡModernReductionMethodsǡ Ǧ ‡”Žƒ‰ „ Ƭ‘Ǥ ƒǡ2008ǡ’’Ǥͳͻ͵ǦʹͲ͹Ǥ ͷʹ ƒȌ Ǥ ƒ”ǡ Ǥ ”‘‘Šƒ”–ǡ Organometallicsǡ 2010ǡ 29ǡ ͸Ͳͷ͹Ǧ͸Ͳ͸ͶǢ „ȌǤƒ”ǡǤ”‘‘Šƒ”–ǡJ.Am.Chem.Soc.ǡ2012ǡ134ǡ͸ͶͲǦ͸ͷ͵Ǥ ͷ͵ ǤƒŠƒ”ƒǡǤ‹›ƒ‘–‘ǡǤ‘–‘ǡǤŠ‹‰‡–ƒǡǤ‡ǡǤ—ƒ†ƒǡǤ‘–‘›ƒǦ ƒǡ Ǥƒ‰ƒ•Š‹ƒǡOrganometallicsǡ2015ǡ34ǡͶͺͻͷǦͶͻͲ͹Ǥ ͷͶ Ǥ ƒƒ–ƒ‹ǡ Ǥ Ǥ ƒ•‡‰ƒ™ƒǡ Ǥ —ƒ†ƒǡ Ǥ ƒ‰ƒ•Š‹ƒǡ Dalton TransǤǡ 2015ǡ44ǡͳͻ͵ͶͶǦͳͻ͵ͷ͸Ǥ ͷͷ ƒȌ ǤǤ ”›ǡǤ”ˆƒ‘’‘—Ž‘•ǡǤ Ǥ†Ž‹‰–‘ǡǤǤ‹––ƒǡ ǤǤ‹Ž˜‡”ƒǡ J. Org. ChemǤǡ 1978ǡ 43ǡ ͵͹ͶǦ͵͹ͷǢ „Ȍ Ǥ Ǥ ‘›Ž‡ǡ ǤǤ‡•–ǡǤ Ǥ‘‡ŽŽ›ǡǤǤ •‡”ǡJ.Organomet.ChemǤǡ1976ǡ117ǡ ͳʹͻǦͳͶͲǤ ͷ͸ ƒȌ Ǥ Ǥ ƒ”•ǡ Ǥ Ǥ ‹‡”•ǡ J. Am. Chem. SocǤǡ 1996ǡ 118ǡ ͻͶͶͲǦͻͶͶͳǢ „ȌǤ Ǥƒ”•ǡ Ǥ Ǥ Žƒ ™‡ŽŽǡ Ǥ Ǥ ‹‡”•ǡ J. Org. ChemǤǡ 2000ǡ 65ǡ ͵ͲͻͲǦ͵ͲͻͺǢ ȌǤ‡†Ž‡”ǡǤ‡•–”‡‹ ŠǡAngew.Chem.Int.Ed.ǡ2008ǡ47ǡ ͷͻͻ͹Ǧ͸ͲͲͲǤ ͷ͹ ǤǤ”‘™ǡǤ ‡‹ǡJ.Am.Chem.SocǤǡ1964ǡ86ǡ͵ͷ͸͸Ǧ͵ͷ͸͹Ǥ ͷͺ Ǥ‡”˜‘‹ǡǤǤ”ƒ†ƒŽŽǡǤǤŠƒǡKirkǦOthmerEncyclopediaofChemiǦ cal Technologyǡ  Ǧ  ‡”Žƒ‰ „  Ƭ ‘Ǥ  ƒǡ 1992ǡ ’’Ǥ ʹͲ͹Ǧ ͵ͲͲǤ ͷͻ ǤǤƒ‹•–‡”ǡǤ Ǥ”‘‘‡•ǡ ǤǤ˜ƒ•ǡǤǤƒ–œǡǤǤ›””‡ŽŽǡOrg. ProcessRes.DevǤǡ2000ǡ4ǡͶ͸͹ǦͶ͹ʹǤ ͸Ͳ Ǥƒ”„‡ǡǤǤŠƒ”‡––‡ǡJ.Am.Chem.SocǤǡ2008ǡ130ǡͳͺǦͳͻǤ

ͺͶ  

 ͸ͳ Ǥ‡ŽŽ‡–‹‡”ǡǤǤ‡ Šƒ”ƒǡǤǤŠƒ”‡––‡ǡJ. Am. Chem. SocǤǡ 2010ǡ 132ǡ ͳʹͺͳ͹ǦͳʹͺͳͻǤ ͸ʹ ǤǦǤ —ƒ‰ǡǤǦǤƒ‰ǡǤǦǤƒ‰ǡJ.Org.ChemǤǡ2016ǡ81ǡͶʹ͵ͷǦͶʹͶ͵Ǥ ͸͵ Ǥ Š‡”‡”ǡ ǤǦǤ”‰—Dž †‡ǡ Ǥ†‹™‹†ŒƒŒƒǡǤ Šƒ—ƒǡSynthesisǡ2014ǡ 46ǡʹͷͲ͸ǦʹͷͳͶǤ ͸Ͷ ƒȌ ǤǦǤ —ƒ‰ǡ Ǥ ‡‰ǡ Org. Chem. FrontǤǡ 2015ǡ 2ǡ ͳͷͲǦͳͷͺǢ „Ȍ ǤǦǤ —ƒ‰ǡǤǦ Ǥ‹ƒ‰ǡ Ǥ—ǡ ǤǦǤ—ƒǡSynlettǡ2010ǡͳͺʹͻǦͳͺ͵ʹǤ ͸ͷ Ǥ•—–•—‹ǡǤ—ƒ†ƒǡ Ǥƒ‰ƒ•Š‹ƒǡOrganometallicsǡ2011ǡ30ǡ͸ͺǦ͹͸Ǥ ͸͸ Ǥƒƒ›ƒƒǡǤƒ‡†ƒǡǤ‘–ƒ–•—ǡǤ‡‹›ƒǡǤ Š‹‹ǡǤƒ–‘ǡǤŠ‹†ƒǡ Chem.Eur.J.ǡ2016ǡ22ǡ͵͵ͲͲǦ͵͵Ͳ͵Ǥ ͸͹ Ǥƒ•ǡǤ ‘‹ǡǤ —‰‡ǡǤ‡ŽŽ‡”ǡChem.CommunǤǡ2012ǡ48ǡʹ͸ͺ͵Ǧʹ͸ͺͷǤ ͸ͺ Ǥƒ•ǡǤ‹ǡǤǦǤ—ǡǤ —‰‡ǡǤ‡ŽŽ‡”ǡChem. Eur. JǤǡ 2016ǡ 22ǡ ͹ͲͷͲǦ͹Ͳͷ͵Ǥ ͸ͻ Ǥ‘Ž‘˜ǡ Ǥ‹‹•ǡǤŽƒ‰„”ƒ†ǡ Ǥ‡”•Šƒ‰‡ǡ Ǥ†‘Žˆ••‘ǡ Chem.Commun.ǡ2014ǡ50ǡͳͶͷͲͺǦͳͶͷͳͳǤ ͹Ͳ Ǥ‡‹ƒǡǤ‡”‡œǡJ.Org.Chem.ǡ1987ǡ52ǡʹͷ͹͸ǦʹͷͺͲǤ ͹ͳ ǤŠƒ”†‘ǡǤ‘Š›Ž‹‡ǡǤ‡‰ƒ›ǡǤ‡ƒ‘Ž‹•ǡ Ǥ‘—†‡ǡ ǤŽƒ Š‡–ǡ Chem.Eur.J.ǡ2017ǡ23ǡʹͲͲͷǦʹͲͲͻǤ ͹ʹ Ǥ Ǥ Š‹–‡ǡ Ǥ Ǥ —‘‘”‹ǡ Ǥ Ǥ ‡‘”‰ǡ J. Am. Chem. SocǤǡ 2000ǡ 122ǡ ͳͳͻͻͷǦͳͳͻͻ͸Ǥ ͹͵ ǤǤ’Ž‡–•–‘•‡”ǡ ǤǤŠ‹–‡ǡ Ǥ Ǥ ‡‘”‰ǡTetrahedron LettǤǡ 2004ǡ 45ǡ ʹ͹ͺ͹Ǧʹ͹ͺͻǤ ͹Ͷ ǤǤ’Ž‡–•–‘•‡”ǡ ǤǤŠ‹–‡ǡǤǤ—‘‘”‹ǡ Ǥ Ǥ ‡‘”‰ǡJ.Am.Chem.SocǤǡ 2007ǡ129ǡ͵ͶͲͺǦ͵ͶͳͻǤ ͹ͷ ǤŠƒ‘ǡǤ‹‡ —•ǡOrg.LettǤǡ2014ǡ16ǡ͵ͻͲǦ͵ͻ͵Ǥ ͹͸ Ǥ‘™‡”ǡǤǤ”‡—–œ‡”ǡǤǤ— Š™ƒŽ†ǡAngew.Chem.Int.Ed.ǡ1996ǡ35ǡ ͳͷͳͷǦͳͷͳ͸Ǥ ͹͹ ƒȌǤ‹• ŠŽ‡”ǡ Ǥ ƒ’‹‡”ƒŽ•‹ǡ Ber. Dtsch. Chem. GesǤǡ 1893ǡ 26ǡ ͳͻͲ͵ǦͳͻͲͺǢ „Ȍ Ǥ ‹Ž•‡‹‡”ǡ Ǥ ƒƒ ǡ Ber. Dtsch. Chem. GesǤǡ 1927ǡ 60ǡ ͳͳͻǦͳʹʹǢ Ȍ ǤǤ‘”‰ƒǡǤǤƒŽŽ•ǡJ.Chem.SocǤǡ1931ǡʹͶͶ͹ǦʹͶͷ͸Ǥ ͹ͺ ǤòŠŽ‡ǡAngew.Chem.Int.EdǤǡ1962ǡ1ǡ͸Ͷ͹Ǧ͸ͷʹǤ ͹ͻ Ǥ”‡†‡”‡ ǡǤ ‘’’‡”ǡǤŽ‡ǡ Ǥ‡’ˆ‡”ǡChem.BerǤǡ1959ǡ92ǡ ͺ͵͹ǦͺͶͻǤ ͺͲ Ǥ Ǥ ‹ŽŽǡ Ǥƒ„‹‘™‹–œǡJ.Am.Chem.SocǤǡ1926ǡ48ǡ͹͵ʹǦ͹͵͹Ǥ ͺͳ Ǥ Ǥ ‹ŽŽǡ ǤǤ ‘Š•–‘ǡJ.Am.Chem.SocǤǡ1954ǡ76ǡͻʹͲǦͻʹʹǤ ͺʹ Ǥ ƒœ˜‘†ƒǡǤ‘«‡˜ƒ”ǡǤ‘Žƒ ǡEur.J.Org.ChemǤǡ2013ǡͷ͵ͺͳǦͷ͵ͺ͸Ǥ ͺ͵ Ǥ Ǥ Š‹–‡ǡ Ǥ ‡™ƒŽ†ǡ Ǥ ‘˜ƒ••ƒ‰Š‹ǡ J. Org. ChemǤǡ 2015ǡ 80ǡ ͹ͶͲ͵Ǧ͹ͶͳͳǤ ͺͶ ǤǦǤ ƒŽƒ‰‡ǡ Ǥ • —†‡”‘ǡ Ǥ ƒŽ‡„ǦƒŠ”ƒ‘—‹ǡ Ǥ Š‘•‡œǡ Angew. Chem. Int.EdǤǡ1981ǡ20ǡͺ͹ͻǦͺͺͲǤ ͺͷ ǤǤŠƒ”‡––‡ǡǤ ”‡‘ǡCan.J.Chem.ǡ2001ǡ79ǡͳ͸ͻͶǦͳ͹Ͳ͵Ǥ

ͺͷ  

 ͺ͸ ‘” ”‡˜‹‡™• ‘ –Š‡ •›–Š‡–‹  ƒ’’Ž‹ ƒ–‹‘ ‘ˆ ‡–‡‹‹‹— ‹‘•Ǣ ƒȌǤǤ‹†‡”ǡChem.RevǤǡ1988ǡ88ǡ͹ͻ͵ǦͺͳͳǢ„ȌǤƒ†‡Žƒ‹‡ǡǤƒŽ‡”‹‘ǡ Ǥ ƒ—Ž‹†‡ǡ Chem. Asian J.ǡ 2011ǡ 6ǡ ʹʹʹͶǦʹʹ͵ͻǢ Ȍ Ǥ Ǥ ƒ”ƒœ‡‘ǡ Ǥ Ǥ‡ƒŒ†‡‘ǡǤǤƒŽ‡‘˜ƒǡTetrahedronǡ2000ǡ56ǡ͵Ͳ͹͹Ǧ͵ͳͳͻǤ ͺ͹ ǤǤ‡†Ž‡›ǡǤ‘˜ƒ••ƒ‰Š‹ǡJ.Org.Chem.ǡ2009ǡ74ǡͳ͵ͶͳǦͳ͵ͶͶǤ ͺͺ Ǥ‡‰ǡǤ ‡‡”†‹ǡǤ ƒ”±•ǡǤƒ—Ž‹†‡ǡAngew.Chem.Int.EdǤǡ2014ǡ 53ǡͷͶ͸ʹǦͷͶ͸͸Ǥ ͺͻ šƒ’Ž‡•‘ˆƒŽ›Žƒ–‹‘ǢƒȌǤ‡‰ǡǤ ‡‡”†‹ǡǤƒ—Ž‹†‡ǡJ.Am.Chem. SocǤǡ2013ǡ135ǡͳͶͻ͸ͺǦͳͶͻ͹ͳǢ„ȌǤǤ —ƒ‰ǡǤ Ǥ —ƒ‰ǡǤ Ǥ‹ƒ‘ǡǤ ƒ‰ǡǤǤ‹ƒǡJ.Org.Chem.ǡ2015ǡ80ǡʹͺ͸ͳǦʹͺ͸ͺǤ ͻͲ Ǥ‘ƒǡǤ†‡Žƒ‘””‡ǡǤƒ†ƒƒ„ƒǡǤ—‹†‡”ǡǤ ‘œžŽ‡œǡǤƒ—Ǧ Ž‹†‡ǡJ.Am.Chem.SocǤǡ2016ǡ138ǡͺ͵ͶͺǦͺ͵ͷͳǤ ͻͳ ǤǤ‡ Šƒ”ƒǡ Ǥ‡ŽŽ‡–‹‡”ǡǤǤŠƒ”‡––‡ǡNat.ChemǤǡ2012ǡ4ǡʹʹͺǦʹ͵ͶǤ ͻʹ ǤǦǤ —ƒ‰ǡǤǦ Ǥ —ƒ‰ǡ Ǥ ‡‰ǡ ǤǦǤ‡ǡSci. RepǤǡ 2016ǡ 6ǡ ʹͺͺͲͳǦʹͺͺͳͲǤ ͻ͵ ǤǤ —ƒ‰ǡǤ Ǥ —ƒ‰ǡǤ Ǥ‹ƒ‘ǡJ.Org.ChemǤǡ2016ǡ81ǡͻͲʹͲǦͻͲʹ͹Ǥ ͻͶ Ǥ Ǥ‹ƒ‘ǡ ǤǤ—‘ǡǤǤ‡ǡǤƒ‰ǡǤǤ —ƒ‰ǡAngew.Chem.Int.EdǤǡ 2010ǡ49ǡ͵Ͳ͵͹Ǧ͵ͲͶͲǤ ͻͷ Ǥ Ǥ ‹ƒ‘ǡ Ǥ Ǥ ƒ‰ǡ Ǥ Ǥ —ƒ‰ǡ Angew. Chem. Int. EdǤǡ 2012ǡ 51ǡ ͺ͵ͳͶǦͺ͵ͳ͹Ǥ ͻ͸ Ǥ›”ǡǤ±‰‹‡”ǡǤǤ‡ Šƒ”ƒǡǤǤŠƒ”‡––‡ǡOrg. LettǤǡ 2015ǡ 17ǡ ͵͵ͺ͸Ǧ͵͵ͺͻǤ ͻ͹ Ǥƒ‹•‡”ǡǤ†‡Žƒ‘””‡ǡǤŠƒƒ„ƒǡǤƒ—Ž‹†‡ǡAngew.Chem.Int.EdǤǡ 2017ǡ56ǡͷͻʹͳǦͷͻʹͷǤ ͻͺ Ǥ±‰‹‡”ǡǤǤ‡ Šƒ”ƒǡǤǤŠƒ”‡––‡ǡJ. Org. ChemǤǡ 2016ǡ 81ǡ ͳͲ͵ͶͺǦͳͲ͵ͷ͸Ǥ ͻͻ ǤǦǤ —ƒ‰ǡ Ǥ —ǡ ǤǦ Ǥ ‹ƒ‘ǡ ǤǦǤ ƒ‰ǡ Chem. CommunǤǡ 2014ǡ 50ǡ ͺ͹͸ͳǦͺ͹͸͵Ǥ ͳͲͲ ƒȌ Ǥ Ǥ ‡†Ž‡›ǡ Ǥ ‘˜ƒ••ƒ‰Š‹ǡ Angew. Chem. Int. EdǤǡ 2012ǡ 51ǡ Ͷͷ͹ʹǦͶͷ͹͸Ǣ „Ȍ Ǥ ±Žƒ‰‡”ǡ Ǥ —’—‹•ǡ Ǥ ƒ”‘— Š‡Ǧ ƒ—–Š‹‡”ǡ J.Org.ChemǤǡ 2012ǡ 77ǡ ͵ʹͳͷǦ͵ʹʹͳǢ Ȍ Ǥ ‘—†”‡ƒ—Ž–ǡ Ǥ ±˜‡•“—‡ǡ Ǥ±Žƒ‰‡”ǡJ.Org.ChemǤǡ2016ǡ81ǡͻʹͶ͹Ǧͻʹ͸ͺǤ ͳͲͳ ǤǦǤ —ƒ‰ǡǤǦǤƒ‰ǡǤǦǤ —ǡJ.Org.ChemǤǡ2016ǡ81ǡͳͲʹʹ͹ǦͳͲʹ͵ͷǤ ͳͲʹ ƒȌ Ǥ †ƒǡ Ǥ ƒ–‘ǡ Ǥ Š‹†ƒǡ Org. LettǤǡ 2012ǡ 14ǡ ͻͷͲǦͻͷ͵Ǣ „Ȍ Ǥ ƒ–‘ǡ ǤŠ‹†ƒǡ Org. Biomol. ChemǤǡ 2014ǡ 12ǡ ͵ͳͶ͹Ǧ͵ͳͷͲǢ Ȍ Ǥ ƒƒŒ‹ƒǡ Ǥ†ƒǡ Ǥ ƒ†ƒǡ Ǥ ‹ƒ‹ƒ™ƒǡ Ǥ Š‹”‘ƒ‡ǡ Ǥ ƒ–‘ǡ ǤŠ‹†ƒǡ Chem. Eur.JǤǡ2014ǡ20ǡͳ͹ͷ͸ͷǦͳ͹ͷ͹ͳǤ ͳͲ͵ Ǥ Š‹”‘ƒ‡ǡ Ǥ ƒ†ƒǡ Ǥ ‘”‹ƒ–ƒ–‡ǡ Ǥ ‹ƒ‹ƒ™ƒǡ Ǥ ƒƒ›ƒƒǡ Ǥƒ–‘ǡǤŠ‹†ƒǤAngew.Chem.Int.EdǤǡ2014ǡ53ǡͷͳʹǦͷͳ͸Ǥ ͳͲͶ Ǥ ƒ‘–‘ǡǤƒ‰ƒǡǤ‹•Š‹‘–‘ǡǤƒ•—†ƒǡǤƒ„ƒǡOrg.LettǤǡ2013ǡ15ǡ ͵ͶͷʹǦ͵ͶͷͷǤ

ͺ͸  

 ͳͲͷ ƒȌ ǤǤ —‡–‡•†‡””‹„ƒǡǤ‡ ‹ǡǤ‘ƒ™ƒ‡ǡǤ ‘”‡”›ǡǤ Ǥ‹š‘ǡ Angew. Chem. Int. Ed.ǡ 2017ǡ 56ǡ ͵͸ͷͷǦ͵͸ͷͻǢ „Ȍ Ǥ ‹š‘ǡ ǤǦ Ǥ ‹‡ǡ Chem.Sci.ǡ2017ǡinpressǡ ǣͳͲǤͳͲ͵ͻȀ ͹• Ͳ͵͸ͳ͵„Ǥ ͳͲ͸ Ǥ Ǥ ƒǡ Ǥ ‡ƒ›ƒ†ǡ Ǥ Ǥ ‹š‘ǡ Angew. Chem. Int. EdǤǡ 2016ǡ 55ǡ ͳ͵Ͷ͵͸Ǧͳ͵ͶͶͲǤ ͳͲ͹ Ǥ Ǥ ”‡‰‘”›ǡ Ǥ Šƒ„‡”•ǡ Ǥ ƒ™‹•ǡ Ǥ ƒ—„‡ ǡ Ǥ Ǥ ‹š‘ǡ Chem.Eur.J.,2015ǡ21ǡͳͳͳǦͳͳͶǤ ͳͲͺ ǤǦǤ —ƒ‰ǡǤ—ǡ Ǥ ƒǡChem.CommunǤǡ2016ǡ52ǡͳͳͻ͸͹Ǧͳͳͻ͹ͲǤ ͳͲͻ ǤƒƒŒ‹ƒǡǤƒ–‘ǡǤŠ‹†ƒǡOrg.LettǤǡ2015ǡ17ǡͳ͸ͻ͸Ǧͳ͸ͻͻǤ ͳͳͲ Ǥƒ–ƒŠƒ”ƒǡǤ‘„ƒ›ƒ•Š‹ǡǤ —Œ‹–ƒǡǤƒ–•—‘–‘ǡǤƒ–‘ǡǤŠ‹†ƒ,J.Am. Chem.SocǤǡ2016ǡ138ǡͷʹͶ͸ǦͷʹͶͻǤ

ͳͳͳ ”‡Ǧƒ –‹˜ƒ–‹‘ ‘ˆ ‘ȋȌ͸ ‹   ˆ‘” ͳͲ ‹ ƒ– ͺͲ ι „‡ˆ‘”‡ ƒ††‹‰ ™‡”‡”‡“—‹”‡†ˆ‘””‡ƒ –‹‘•’‡”ˆ‘”‡†ƒ–͸Ͳ郐†„‡Ž‘™Ǥ ͳͳʹ Ǥ”‹ƒ•Ǧ‰ƒ”–‡ǡ ǤǤŠƒ”ƒǡǤǤ‘””‹•ǡǤ Ǥƒ‡ŽŽǡJ.Am.Chem.Soc.ǡ 2012ǡ134ǡͺͶͺǦͺͷͳǤ ͳͳ͵ Ǥ ††‹•ǡ Ǥ ƒ•ǡ Ǥ —‰‡ǡ Ǥ ‡ŽŽ‡”ǡ Angew. Chem. Int. Ed., 2011ǡ 50ǡ ͸ͲͲͶǦ͸ͲͳͳǤ ͳͳͶ Ǥ ƒƒ†ƒǡ Ǥ ‘–‘›ƒƒǡ Ǥ ƒ‰ƒ•Š‹ƒǡ Eur. J. Org. Chem.ǡ 2008ǡ ͶͲͻ͹ǦͶͳͲͲǤ ͳͳͷ Ǥ Ǥ› ‘ ǡOrg.ProcessRes.Dev.,2007ǡ11ǡͳͷ͸ǦͳͷͻǤ ͳͳ͸ Ǥ ‡Ž†ƒǡ Ǥ ƒ—–Š‹‡”ǡ Ǥ ‡ ‡”ǡ Ǥ ‡ŽŽƒ•ǡ Ǥ ‹”ǡ Ǥ ƒ•–‡›ǡ Ǥ—„„‹ƒŠǡJ.Am.Geriatr.Soc.ǡ2003ǡ51ǡ͹͵͹Ǧ͹ͶͶǤ ͳͳ͹ ƒȌ Ǥ –‘”ǡ Ǥ ‡””‡ŽŽǡ Ǥ œ—•œ‘˜‹ œǡ J. Am. Chem. Soc.ǡ 1954ǡ 76ǡ ʹͲʹͻǦʹͲ͵ͲǢ „Ȍ Ǥ –‘”ǡ Ǥ Ǥ ƒ†‡•ƒǡ J. Am. Chem. Soc.ǡ 1956ǡ 78ǡ ͷͳʹͺǦͷͳʹͻǢ Ȍ Ǥ–‘”ǡǤ”‹œœ‘Žƒ”ƒǡ Ǥƒ†‡•ƒǡ Ǥœ—•œ‘˜‹ œǡǤ ‡””‡ŽŽǡ J.Am.Chem. Soc.ǡ 1963ǡ 85ǡ ʹͲ͹ǦʹʹʹǢ †Ȍ Ǥ Ǥ ‘‘ǡ Enamines; Synthesis, Structure and Reactionsǡ ƒ” ‡Ž ‡‡”ǡ  Ǥǡ 1998Ǣ ‡ȌǤ—Š‡”Œ‡‡ǡ ǤǤƒ‰ǡǤ ‘ˆˆƒǡǤ‹•–ǡChem.Rev.ǡ2007ǡ107ǡ ͷͶ͹ͳǦͷͷ͸ͻǤ ͳͳͺ ǤǦ Ǥ —‘ǡ ǤǦ Ǥ ‹‡ǡ ǤǦǤ ƒǡ ǤǦǤ Š‘—ǡ J. Am. Chem. Soc.ǡ 2008ǡ 131ǡ ͳ͵͸͸Ǧͳ͵͸͹Ǥ ͳͳͻ Ǥƒ‹ Šǡ Ǥƒ˜‹†•‡ǡBer.Dtsch.Chem.Ges.ǡ1936ǡ69ǡʹͳͲ͸ǦʹͳͳʹǤ ͳʹͲ Ǥ ‡Žƒ‰‡”ǡ Ǥ ‘”‡ǡ Ǥ ‡ƒ”†ǡ Ǥ ƒ”•‹‰›ǡ J. Org. Chem.ǡ 2006ǡ 71ǡ ͹ͶͺͳǦ͹ͶͺͶǤ ͳʹͳ ƒȌ Ǥ ƒ”Ž—‡‰ƒǡ Ǥ Ǥ ‡”ƒ†‡œǡ Ǥ œƒ”ǡ Ǥ ƒŽ†‡•ǡ Eur. J. Org. Chem.ǡ 2004ǡ 10ǡ ͶͻͶǦͷͲ͹Ǣ „Ȍ Ǥ Ǥ ‡ƒ– ‡††›ǡ Ǥ ”‰ƒ‘ƒ”ǡ Ǥ Ǥ ‡”ƒ†‡ǡ Org. Lett.ǡ 2005ǡ 7ǡ ͶͶʹ͹ǦͶͶ͵ͲǢ Ȍ Ǥ Ǥ ‡ŠŽ‹ǡ Ǥ ‡‰”‘•ǡ Ǥ ‘Žǡ Chem.Commun.ǡ 2005ǡ 8ǡ ͻ͹͵Ǧͻͺ͸Ǣ †Ȍ Ǥ ƒǡ Ǥ Š‡ǡ Ǥ Š‘—ǡ Ǥ ‹ǡ Org.Lett.ǡ2012ǡ14ǡͶ͹ͷͲǦͶ͹ͷ͵Ǥ ͳʹʹ Ǥ Š‡†ǡ Ǥ Ǥ ‡ƒ›ƒ†ǡ Ǥ ƒ •–‡ŽŽǡ Ǥ ‡ŽŽ‡”ǡ Angew. Chem. Int. Ed.ǡ 2003ǡ42ǡͷ͸ͳͷǦͷ͸ͳͻǤ ͳʹ͵ Ǥ‘Ž‘˜ǡ Ǥ‹‹•ǡ Ǥ†‘Žˆ••‘ǡOrg.Lett.ǡ2014ǡ16ǡ͸ͺͲǦ͸ͺ͵Ǥ

ͺ͹  

 ͳʹͶ Ǥ ‘„ƒ›ƒ•Š‹ǡ Ǥ ƒ•ƒ‘ǡ Ǥ ƒ‘Šǡ Ǥ ™‘ǡ Ǥ ™ƒ„— Š‹ǡ Eur. J. Org. Chem.ǡ2016ǡʹ͹ͲǦʹ͹͵Ǥ ͳʹͷ Š‡ ‘—’Ž‹‰ ‘•–ƒ–‹ͳ ˆ‘”–Š‡—•ƒ–—”ƒ–‹‘™ƒ•εͳͲ œ™Š‹ Š ‹•ƒ‹†‹ ƒ–‹‘‘ˆ–Šƒ––Š‡‡ƒ‹‡‹•–Š‡trans‹•‘‡”Ǥ ‘””‡ˆ‡”‡ ‡•‡‡ ǤǤ”— ‡ǡǤǤ ‘”„ƒ–›ǡJ.Org.Chem.ǡ1970ǡ35ǡʹͳͳ͵Ǧʹͳͳ͹Ǥ ͳʹ͸ ƒȌ Ǥ Žˆ‘•‹ǡ Ǥ ‘Ž„‡”‰ǡ Ǥ Ǥ —ǡ Ǥ ‡˜‹‰ǡ Ǥ ‡‹‰•ǡǤǤ ‘Š•‘ǡ ǤǤŽ‡‹‡ǡǤ‹‰Š–ǡǤǤƒ‰›ǡǤǤ‡””›ǡǤ–‡ˆƒ‹ƒǡGreenChem.ǡ 2008ǡ10ǡ͵ͳǦ͵͸Ǣ„ȌǤ”ƒ–ǡǤ‡ŽŽ•ǡ Ǥ ƒ›Ž‡”ǡ Ǥ‡††‘ǡǤǤ Ž”‘›ǡ Ǥ„‘—ǦŠ‡Šƒ†ƒǡǤ Ǥ—ǡGreenChem.ǡ2016ǡ18ǡʹͺͺǦʹͻ͸Ǥ ͳʹ͹ ǤǤ‹ǡǤǤ ”ƒ ŽǡJ.Phys.Chem.ǡ1987ǡ91ǡʹ͹ͳ͸Ǧʹ͹ʹͳǤ ͳʹͺ Ǥƒƒ•ǡǤ Ǥ ƒ••‡ǡǤ Ǥ–ƒŠ—‹•ǡ Ǥ›„‡”‰ǡJ.Org.Chem.ǡ1967ǡ32ǡ ͳͳͳͳǦͳͳͳͷǤ ͳʹͻ ƒȌ Ǥ Ǥ Ǥ Š‘™ǡ ǤǤǤŠ‹—ǡ Ǥ Ǥ ƒƒ‹ǡ Ǥ Ǥ ƒ†ƒ„ƒǡ Pharm. Res.ǡ 1996ǡ 13ǡ ͳ͹ͻǦͳͺʹǢ „ȌǤǤƒ†ƒ„ƒǡ Ǥ Ǥ –‡˜‡•‘ǡ Ǥ Ǧƒ‡ǡ Ǥ Ǥ ƒƒ‹ǡBiorg.Med.Chem.ǡ1996ǡ4ǡͳ͸ͷǦͳ͹ͺǢ ȌǤǤƒ†ƒ„ƒǡCurr.Med. Chem.ǡ2003ǡ10ǡʹͲͺͳǦʹͳͲͺǤ ͳ͵Ͳ ”‹ƒœ‘Ž‡ • ƒˆˆ‘Ž†• ™‹–Š ‡†‹ ‹ƒŽ •‹‰‹ˆ‹ ƒ ‡Ǣ Ǥ ƒ‹†‡”ǡ Ǥ Ǥ Žƒǡ Ǥ ƒ‹†ǡInflammCellSignalǡ2014ǡ1:e95Ǥ ͳ͵ͳ ƒȌǤò”ò•–ǡ Ǥƒ”ƒ—çǡǤƒ‹•‡”ǡǤƒ•†‡‹”ǡEur.J.Med.Chem.ǡ2012ǡ 48ǡʹͻ͸Ǧ͵ͲͶǢ„ȌǤ‹‡ǡǤŠƒ‰ǡǤƒ•–”ڏǡǤƒǡChem.SciǤǡ2016ǡ7ǡ ͹ͳ͵Ǧ͹ͳͺǢ ȌǤ†‡‘‡”ƒǡǤ–‘’‹ǡǤǤ ƒ” ‹ƒǦ ƒ”‹„ƒ›ǡJ.Am.Chem.SocǤǡ 2013ǡ135ǡ͸͸ʹ͸Ǧ͸͸͵ʹǢ†ȌǤǤƒ†ƒ„ƒǡǤ–ƒ‘˜‹ǡǤ‹æŽ‡”ǡAdv.HetǦ erocycl.Chem.ǡ1984ǡ37ǡʹͳ͹Ǧ͵ͶͻǢ‡ȌǤƒ†™ƒǡ1,3ǦDipolarCycloaddition Chemistryǡ ‘Š‹Ž‡›ƒ†‘•ǡ1984Ǥ ͳ͵ʹ ƒȌǤ‡Ž†ƒŽǡǤǤ‘”‘‡ǡChem.RevǤǡ2008ǡ108ǡʹͻͷʹǦ͵Ͳͳͷƒ†”‡ˆ‡”Ǧ ‡ ‡•–Š‡”‡‹Ǣ„Ȍ ǤǤ ‡‹ǡ ǤǤ”‹’’ǡǤǤ”ƒ•‘˜ƒǡǤǤ Šƒ”’Ž‡••ǡ ǤǤ ‘‹ǡAngew.Chem.Int.Ed.ǡ2009ǡ48ǡͺͲͳͺǦͺͲʹͳǢ ȌǤǤ‘””‡ŽŽǡ ǤǤŽŽ‡”›ǡǤǤ ‘‹ǡAngew.Chem.Int.Ed.ǡ2013ǡ52ǡͳ͵Ͳ͵͹Ǧͳ͵ͲͶͳǤ ͳ͵͵ Ž–Š‘—‰Š™‡‡˜‡”‡š’‡”‹‡ ‡†ƒ›‹••—‡•—•‹‰ƒœ‹†‡•ǡ‹–‹•‹’‘”–ƒ– –‘ƒŽ™ƒ›•„‡ƒ™ƒ”‡‘ˆ–Š‡‡š’Ž‘•‹‘”‹••ƒ••‘ ‹ƒ–‡†™‹–Š–Š‡•›–Š‡•‹• ƒ†—•‡‘ˆ‘”‰ƒ‹ ƒœ‹†‡•ǢǤ”¡•‡ǡǤ ‹ŽǡǤ‡’’‡”ǡǤ‹‡”ƒǡ Angew.Chem.Int.Ed.ǡ2005ǡ44ǡͷͳͺͺǦͷʹͶͲǤ ͳ͵Ͷ Ǥ‘ŽˆˆǡJustusLiebigsAnn.Chem.ǡ1912ǡ394ǡͷͻǦ͸ͺǤ ͳ͵ͷ ƒȌ Ǥ —‹•‰‡ǡ Ǥ œ‡‹‹‡•ǡ Ǥ ڄ‹—•ǡ Chem. Ber.ǡ 1966ǡ 99ǡ Ͷ͹ͷǦͶͻͲǢ „ȌǤ”‘‡ šǡǤ˜‡”„‡”‰ŠǡǤƒ›ǡ Ǥ‡–•ǡ Ǥ̵„„±ǡTetrahedronǡ 1971ǡ27ǡ͵ͷʹ͹Ǧ͵ͷ͵ͶǤ ͳ͵͸ Ǥ Ǥ †‡”•‘ǡ Ǥ Ǥ ‡”›ǡ Ǥ Ǥ ‡‹”‡„ǡ J. Org. Chem.ǡ 1991ǡ 53ǡ ͸ͻͶ͸Ǧ͸ͻͶͺǤ ͳ͵͹ ƒȌ Ǥ Ǥ —ǡ Ǥ Ǥ ‹ǡ J. Am. Chem. Soc.ǡ 1964ǡ 86ǡ ʹʹͳ͵Ǧʹʹͳ͹Ǣ „ȌǤǤ‡‹ŽƒŠǡ Ǥ ‘šǡ Ǥ Ǥ —ǡ J. Org. ChemǤǡ 1975ǡ 40ǡ ͺͳͻǦͺʹͶǢ ȌǤǤ‘’‡œǡǤǤ—ǡǤǤ ‘—ǡJ.Org.Chem.ǡ2013ǡ78ǡͳͷ͹͸ǦͳͷͺʹǢ †Ȍ Ǥ ‘—”ƒǡ Ǥ ƒ‡—‰Š‹ǡ Ǥ ‘‘†ƒǡ Ǥ Ǥ –‘ǡ Bull. Chem. Soc. JpnǤǡ

ͺͺ  

 1981ǡ54ǡʹ͸ͳǦʹ͸͸Ǣ‡Ȍ Ǥǯƒ„„±ǡChem.Rev.ǡ1969ǡ69ǡ͵ͶͷǦ͵͸͵ƒ†”‡ˆǦ ‡”‡ ‡•–Š‡”‡‹Ǥ ͳ͵ͺ Ǥ‹ƒ Š‡––‹ǡǤ‘ ƒ”ǡǤǤ”‘ ‡ǡǤ–”ƒ†‹ǡGazz.Chim.ItalǤǡ1967ǡ97ǡ ͵ͲͶǦ͵ʹͲǤ ͳ͵ͻ Ǥ–”ƒ†‹ǡǤ‘ ƒ”ǡGazz.Chim.Ital.ǡ1969ǡ99ǡͳͳ͵ͳǦͳͳ͵͹Ǥ ͳͶͲ ƒȌ Ǥ Š‘ƒ•ǡ Ǥ ƒƒǡ Ǥ ‘Šǡ Ǥ ‹‡‡•ǡ Ǥ ‡Šƒ‡ǡ Chem. CommunǤǡ 2016ǡ52ǡʹͺͺͷǦʹͺͺͺǢ„ȌǤŠ‘—ǡǤ—ǡǤ‹—ǡ Ǥ ƒ‘ǡǤƒ‰ǡǤ‹ǡ Eur. J. Org. Chem.ǡ 2016ǡ 10ǡ ͳͺͺ͸ǦͳͺͻͲǢ Ȍ Ǥ Ǥ ƒƒ Šƒ”›ǡ ǤǤŠƒ•ŠƒǡChem.Eur.J.ǡ2013ǡ19ǡͳ͵ͳ͹ͷǦͳ͵ͳͺͳǢ†ȌǤ ǤǤƒ‡ ‡ǡ Ǥ ƒ‘ǡ Ǥ ‹ǡ Ǥ —ƒ‰ǡ Ǥ ƒ‰ǡ Chem. Eur. J.ǡ 2011ǡ 17ǡ ͵ͷͺͶǦ͵ͷͺ͹Ǣ ‡ȌǤ‡ŽŠ‡‹”ƒǡǤŽ„‡†ǡ ǤǦǤ‘•ǡǤ”‡••›ǡChem.Eur.J.ǡ2011ǡ17ǡ ͳʹͻͳ͹ǦͳʹͻʹͳǢˆȌǤ‡Šƒ‡ǡ ǤŠ‘ƒ•ǡǤ’•‘‡”ǡSynthesisǡ2017ǡ49ǡ ͶͳͻͳǦͶͳͻͺǤ ͳͶͳ ƒȌ Ǥ Šƒƒ†ǡ Ǥ ƒ–ǡ Ǥ ‘Šƒƒǡ Org. Lett.ǡ 2016ǡ 18ǡ ʹͺͲǦʹͺ͵Ǣ „ȌǤ—œ‡–•‘˜ǡǤǤ —Ž‡˜‹ ŠǡǤ Ǥ‹ǡǤ ‡˜‘”‰›ƒǡAngew. Chem. Int. Ed.ǡ 2014ǡ 53ǡ ͻͲʹͳǦͻͲʹͷǢ Ȍ Ǥ ƒ”–‹ǡ Ǥ ‡ä‹ƒǡ Ǥ ƒ•‹ƒǡ Tetrahedron Lett.ǡ 2004ǡ 45ǡ ͹͵ͲͳǦ͹͵ͲʹǢ †Ȍ Ǥ Ǥ ƒ†ƒ„ƒǡ Tetrahedronǡ 1969ǡ 25ǡ ͵Ͳͷ͵Ǧ͵Ͳ͸͸Ǣ ‡Ȍ Ǥ Ǥ ƒ†ƒ„ƒǡ Tetrahedronǡ 1966ǡ 22ǡ ʹͶͷ͵Ǧ ʹͶ͸ͲǤ ͳͶʹ ƒȌǤ‡’ˆǡǤ ƒ’‡ŽǡǤǤˆ‹ƒŽǡ Ǥƒ›”ǡChem.Eur.J.ǡ2003ǡ9ǡʹʹͲͻǦ ʹʹͳͺǢ„ȌǤǤ ‹ ‘––ǡTetrahedronǡ1982ǡ38ǡ͵͵͸͵Ǧ͵ͶͶ͸Ǥ ͳͶ͵ ƒȌ ǤǤ ”‡‡Š‹ŽŽǡǤ—‡ǡProg.Med.Chem.ǡ1993ǡ30ǡʹͲ͵Ǧ͵ʹ͸Ǣ„ȌǤ”›ƒǡ Ǥ —ƒ”ǡ Ǥ ‘›ǡ Ǥ Ǥ ‘†Š‹ǡ Eur. J. Med. Chem.ǡ 2013ǡ 59ǡ ͹ǦͳͶǢ ȌǤǤ —‹Ž‡ǡ Ǥ Ž ƒ”ƒœǡ Ǥ Ǥ ‹”‹•Šƒ™ǡ Ǥ Ǥ ‘™‡”ǡ Ǥ Ǥ „†‡ǡ Ǥ —”„‡”ǡǤ Ǥ–‘ •ǡJ.Med.Chem.ǡ2009ǡ52ǡ͵ͳʹ͵Ǧ͵ͳͶͳǤ ͳͶͶ ƒȌ ǤǦǤ ƒ‹ǡ Ǥ Ǥ –‡’ƒǡ Ǥ Ǥ Ž—‡”ǡ ǤǦ Ǥ Šƒ‰ǡ ǤǦǤ —ǡ J.Am.Chem.Soc.ǡ2011ǡ133ǡ͹ʹʹʹǦ͹ʹʹͺǢ„ȌǤǤ‡‡ǡǤ Ǥ‹ǡ Ǥ‹ǡ Ǥ Ǥ ‹ǡ Ǥ Ǥ ‹ǡ Ǥ Ǥ ‡‘‰ǡ Ǥ Šƒ‰ǡ Ǥ Ǥ ‹ǡ ǤǦǤ Šƒ‰ǡ Bioorg.Med. Chem. Lett.ǡ 2010ǡ 20ǡ ͷͶͳǦͷͶͷǢ Ȍ Ǥ —ƒ”ǡ ǤŠƒ†ƒǡ Ǥ‹‡Ž•‡ǡ Ǥ Ǥ Šƒ”ƒǡ Bioorg. Med. Chem.ǡ 2012ǡ 20ǡ ͵ͺͶ͵Ǧ͵ͺͶͻǢ †ȌǤ ‘—„‡–ǡ Ǥ Šƒ”†‘ǡ Ǥ —ƒ”ǡ Ǥ Ǥ Šƒ”ƒǡ ǤǤ‡‡†—ǡ Bioorg. Med.Chem. Lett.ǡ 2013ǡ 23ǡ ͹͸ͳǦ͹͸͵Ǣ ‡Ȍ ǤǦǤ Šƒ‰ǡ Ǥ Ǥ ƒ‡ǡ ǤǤ‡‡ǡ ǤǦ Ǥ ƒ‡ǡ ǤŠƒ‰ǡ Ǥ Ǥ ‹ǡ Bioorg. Med. Chem. Lett.ǡ 2011ǡ 21ǡ ͹ʹ͹Ǧ͹ʹͻǢ ˆȌ ǤǦ Ǥƒ‰ǡ ǤǦǤ ‹—ǡ ǤǦǤ Šƒ‰ǡ ǤǦǤ ƒ‰ǡ ǤǦǤŠƒ‘ǡ ǤǦǤŠƒ‘ǡ Ǥ ‹ƒǡ Ǥ ƒǡ Ǥ ƒ‰ǡ ǤǦǤ ƒ‰ǡ ǤǦǤ —‰ǡ ǤǦǤƒ‰ǡ ǤǦ Ǥ—‘ǡǤ ‘–‘ǡǤǤ‘””‹•Ǧƒ–• Š‡ǡǤǦǤƒǡǤǦǤ‡‰ǡǤǦǤ—‘ǡ ǤǦǤ—ǡǤǦǤ—ǡǤǦ Ǥ‡‡,J.Med.Chem.ǡ2014ǡ57ǡ͸ͲͲͺǦ͸ͲͳͺǤ ͳͶͷ ƒȌ Ǥ ƒ”‡”ǡ Ǥ ‹Ž‡”ǡ Coord. Chem. Rev.ǡ 1994ǡ 133ǡ ʹͳͻǦ͵ͲͲǢ „ȌǤ‘”ƒ Š‹ƒǡ Ǥ Ǥ ‡ŽŽ‹ ƒ‹ǡ Ǥ Ǥ –‹‹ǡ Ǥ ƒ ‹ˆ‹ ‘ǡ Ǥ ƒ–‹Ž‡ǡ Inorg.Chem.ǡ 2009ǡ 48ǡ ͳͲͺͲͲǦͳͲͺͳͲǢ Ȍ Ǥ –ŠƒŽ‡”ǡ Ǥ  Š”Ú†‡”ǡ Ǥ ‘—‡ǡǤ Šƒ”†–ǡǤ —‰‡ǡǤ‡ŽŽ‡”ǡǤ”‹‡éǡEur. J. Org. Chem.ǡ 2010ǡ Ͷͺͻ͵ǦͶͻͲͳǢ †Ȍ Ǥ ƒƒƒǡ  ƒ•Š‹ƒǡ Dalton Trans.ǡ 2013ǡ 42ǡ

ͺͻ  

 ʹͺ͵ͳǦʹͺͶͲǢ ‡Ȍ Ǥ Ǥ ƒ•‡ǡ Ǥ Ǥ ‡†”‘ǡ Ǥ Ǥ ‘–ƒŽǡ Ǥ Ǥ ‘™‡”ǡ ǤǤ‡Ž•‘ǡ Ǥ ƒ”‘ǡ Ǥ Ǥ ‡‹šǡ Nat. Chem.ǡ 2016ǡ 8ǡ ͳͳʹ͸Ǧͳͳ͵ͲǢ ˆȌǤ Ǥƒ•–‹‡ǡ Ǥ Ǥ ”‹„‘˜ǡ Ǥ ƒ‡•ǡ J. Am. Chem. Soc.ǡ 2006ǡ 128ǡ ͳͶʹʹͲǦͳͶʹʹͳǢ ‰Ȍ Ǥ ‹ ‡–ǡ Ǥ ‘•ǡ Ǥ ‡„‡ƒ—ǡ Ǥ ‹‘•‘™•‹ǡ TetrahedronLettǤǡ1997ǡ38ǡ͹ͷʹ͹Ǧ͹ͷ͵ͲǤ ͳͶ͸ ƒȌǤǤŽŽƒǡǤǤ—ƒ”ǡǤƒ†Š—ǡǤ—‹›ƒ—”–Š›ǡ Org.LettǤǡ2013ǡ 15ǡͳ͵͵ͶǦͳ͵͵͹Ǣ„ȌǤŠ—ǡǤ‹ǡ ǤŠƒ‰ǡǤŠ‡ǡǤ—ǡǤƒǡǤƒ‰ǡ Ǥ‹ǡǤ‹—ǡ Ǥ‹ǡOrg. Lett.ǡ 2015ǡ 17ǡ ͵ͺ͹ʹǦ͵ͺ͹ͷǢ Ȍ ǤǦǤ ‹ǡ ǤǦ ǤŠƒ‰ǡǤǦǤ‘‰ǡOrg.Lett.ǡ2014ǡ16ǡʹͺʹʹǦʹͺʹͷǢ†Ȍ Ǥ‹ǡǤƒ‰ǡ Ǥƒ‰ǡǤŠƒ‰ǡǤŠƒ‰ǡǤ ‡”ƒǡOrg. Lett.ǡ 2016ǡ 18ǡ ʹ͹ͶʹǦʹ͹ͶͷǢ ‡Ȍ Ǥ ‡Œ‡†‘”ǡ Ǥ ג‡œǦ‘• ‘ǡ Ǥ Ǥ ƒ” ÀƒǦ‡ŽŽƒ†‘ǡ J.Org.Chem.ǡ 2013ǡ 78ǡ ͵Ͷͷ͹Ǧ͵Ͷ͸͵Ǣ ˆȌ Ǥ ƒ†‹ǡ Ǥ  Š‡‘‡ǡ Ǥ ‘––ƒǡ Org.Biomol.Chem.,2009ǡ7ǡʹͺͶͳǦʹͺͶ͹Ǣ‰ȌǤ‡‹„ŽǡǤ‡–ǡǤ‡’‡ǡ J.Am.Chem.Soc.ǡ2015ǡ137ǡͳʹͺͲͶǦͳʹͺͲ͹Ǥ ͳͶ͹ ǤǤŠƒ”‡––‡ǡǤ ”‡‘ǡTetrahedronLett.ǡ2000ǡ41ǡͳ͸͹͹Ǧͳ͸ͺͲǤ ͳͶͺ Ǥ‡Žƒ˜ƒǡǤ—ƒ–Š‹ǡǤǤƒŽƒ•—„”ƒƒ‹ƒǡ Eur.J.Org.Chem.ǡ2014ǡ ͷͺͲ͸ǦͷͺͳͷǤ ͳͶͻ Ǥ ŠƒŠ‘†‡‡ǡ Ǥ ƒ‰‰ƒ‡ǡ Ǥ ‹”‹›ƒǡ Ǥ ƒ––ƒ”ƒ™ƒ”ƒ’ƒǡ TetraheǦ dronLett.ǡ2016ǡ57ǡͷ͵ͷͳǦͷ͵ͷͶǤ ͳͷͲ Ǥ Šƒ†ƒǡ Ǥ Šƒ†ƒǡ Ǥ —ƒ”ǡ Ǥ Ǥ ƒ’‘‘”ǡ Ǥ Ǥ Šƒ”ƒǡ GreenChemǤǡ2013ǡ15ǡʹʹͻͶǦʹ͵ͲͳǤ ͳͷͳ ƒȌ Ǥ ƒ‘ǡ Ǥ Ǥ Šƒ‘ǡ Ǥ ‡‰ǡ Ǥ Ǥ ‹ǡ Ǥ Ǥ Š‡ǡ Synlettǡ 2011ǡ 9ǡ ͳʹͺͳǦͳʹͺͶǢ „Ȍ Ǥ ‘ ƒ”ǡ Ǥ Ǥ ‘••‹ǡ Ǥ ”‹ƒ” ‘ǡ J. Heterocycl. Chem.ǡ 1979ǡ16ǡͻʹͷǦͻʹ͹Ǥ ͳͷʹ Ǥ—ƒ‰ƒ‹ǡǤƒ–•—ƒ‰ƒǡǤŠ‹„ƒ•ƒ‹ǡAngew.Chem.Int.EdǤǡ2004ǡ43ǡ Ͷ͹ͺǦͶͺʹǤ ͳͷ͵ ƒȌǤ —• ‘ǡ Ǥ‹ƒ Š‡––‹ǡǤ‘ ƒ”ǡǤ‰‘ǡChem.BerǤǡ1963ǡ96ǡͺͲʹǦͺͳʹǢ „Ȍˆ‹‘˜ǡǤƒ—Ž‡˜ǡǤ‡Ž‹ƒ‡˜ǡǤ‡”›‘œ‹ƒǡǤ‹’’• Š‹Ž†ǡ Ǥ‡„ƒǡ Ǥ Š‹Ǧ ‹ǡ Ǥ Ž–•‘˜ǡ Ǥ Ž‡’—Š‹ǡ Ǥ œŠ‹‘˜ƒǡ Ǥ ‡Šƒ‡ǡ Eur.J.OrgChem.ǡ2014ǡ͵͸ͺͶǦ͵͸ͺͻǤ ͳͷͶ Ǥ ‹‡ǡ Ǥ Ǥ ‘’‡œǡ Ǥ ƒ•–”ڏǡ Ǥ ƒǡ Ǥ Ǥ ‘—ǡ J. Am. Chem. SocǤǡ 2015ǡ137ǡʹͻͷͺǦʹͻ͸͸Ǥ ͳͷͷ Ǥ —ǡ Ǥ ‹ǡ Ǥ ƒǡ Ǥ ‡ǡ Ǥ ‡‰ǡ J. Am. Chem. SocǤǡ 2008ǡ 130ǡ ͳͶͲͶͺǦͳͶͲͶͻǤ ͳͷ͸ ƒȌǤ‹—ǡǤǦǤƒ‰ǡǤŠ‡ǡǤ ‡ǡEur.J.Org.ChemǤǡ2009ǡʹͲͷͻǦʹͲ͸ʹǢ „ȌǤ—ǡǤ ‡ǡǤŠ‡‰ǡǤƒǡǤ—ǡǤŠƒ‰ǡǤƒ‘ǡǤ‹ǡOrg.LettǤǡ 2010ǡ12ǡͺͻ͹ǦͺͻͻǤ ͳͷ͹ ƒ”„‘š›Ž‹ ƒ ‹†•ƒ”‡‘™–‘”‡ƒ –™‹–Š†‹ƒœ‘ ‘’‘—†•–‘›‹‡Ž†‡•Ǧ –‡”•ǢƒȌǤǤ —””‘™ǡǤ Ǥ›‡”•ǡJ. Am. Chem. Soc.ǡ 2004ǡ 126ǡ ͳʹʹʹʹǦͳʹʹʹ͵Ǣ„ȌǤǤ“—‹–‹‡”‹ǡ ǤǤŠ‡ƒ”Ǧƒ ‡ǡ ǤǤ ‡‹ǡ ǤǤŠƒ™ǡ J.Org.Chem.ǡ2016ǡ81ǡͷʹ͹ͺǦͷʹͺͶǤ

ͻͲ  

 ͳͷͺ ƒȌ Ǥ ›”ƒ’’ƒǡ Ǥ Ǥ ƒŒǡ Ǥ —‰›ƒŽǡ Ǥ Ǥ —†˜ƒǡ Ǥ Ǥ ƒŽ‹ƒ–Šǡ ǤǤǤƒ‹ǡEur.J.Med.Chem.ǡ2017ǡ126ǡʹͳͺǦʹʹͶǢ„ȌǤ •ƒ‹ŽǡǤŠƒˆ‹ǡ Ǥ‹‰ŠǡǤ‹†‹“ǡǤŠƒŒ—”‹ƒǡǤ‘—ˆǡǤƒ†ƒ˜ǡǤƒ‹ƒǡǤǤ‹‰Šǡ ǤǤŽƒǡǤ •ŽƒǡǤŠƒ”ƒǡ ǤǤǤ—ƒ”ǡEur.J.Med.Chem.ǡ2016ǡ 123ǡ ͻͲǦͳͲͶǢ Ȍ Ǥ ƒ‘ǡ Ǥ Ǥ Žƒǡ Ǥ ƒ˜‡†ǡ Ǥ —†‡Œƒǡ Ǥ Ǥ ƒ•ǡ ǤŠ—Žƒ’ǡ Eur. J. Med. Chem.ǡ 2015ǡ 95ǡ ͻ͸ǦͳͲ͵Ǣ †Ȍ Ǥ ƒ—”ǡ Ǥ —ƒ”ǡ ǤǤ Šƒ”ƒǡ Ǥ Ǥ —’–ƒǡ Eur. J. Med. Chem.ǡ 2014ǡ 77ǡ ͳʹͳǦͳ͵͵Ǣ ‡Ȍƒ‡•ŠǡǤ—ǡǤǤ‡‡ǡǤǤƒ‰ƒŽŽƒ’ƒŽŽ›ǡǤǤ‡‡ǡEur. J. Med. Chem.ǡ 2009ǡ44ǡ Ͷ͸ͲǦͶ͹ʹǢ ˆȌ Ǥ ƒ”–Š‹‡›ƒǡ Ǥ Ǥ‡‡Žƒǡ Ǥ Ǥ ƒŽ‹–Šƒǡ ǤǤ ‡”—ƒŽǡ Bioorg. Med. Chem. Lett.ǡ 2009ǡ 19ǡ ͵͵͹ͲǦ͵͵͹͵Ǣ ‰ȌǤǤƒ‰ƒŽŽƒ’ƒŽŽ›ǡǤ—ǡƒ‡•ŠǡǤ—†ŠƒǡǤǤǤ‡‡ǡǤ ǤǤ‡Ǧ ƒ‡”–•ǡ Ǥ ‡‹„‘Šǡ Ǥ Ǥ ‡‡ǡ Bioorg. Med. Chem. Lett., 2007ǡ 17ǡ ͸͸͵ͺǦ͸͸ͶʹǢ ŠȌ Ǥ Ǥ ”ƒ•ƒ†ǡ Ǥ Ǥ —ƒ”ǡ Ǥ ƒ‡•Šǡ Int. J. Chem. Sci.ǡ 2007ǡ5ǡͷͶʹǦͷͶͺǢ‹ȌǤǤ ƒ‘ƒ”ǡǤǤ‘ƒƒ–Šƒƒ‹ǡǤ”ƒ„Š—•™ƒ›ǡ Med. Chem. Res.ǡ 2007ǡ 15ǡ ͶͲ͹ǦͶͳ͹Ǣ ŒȌ ƒ•ƒ’’ƒǡ Ǥ Ǥ ƒ†ƒ•Š‹˜ƒǡ Ǥƒ–‡Ž‹‰—ǡǤǤ™ƒ›ǡǤǤƒ‰ƒ’’ƒǡBioorg.Med.Chem.ǡ2003ǡ11ǡ Ͷͷ͵ͻǦͶͷͶͶǤ ͳͷͻ Ǥ Ǥ Ǥ ƒ„‘‘–Š‹”‹ǡ Ǥ ƒ•–‘‰‹ǡ ‘’Ǥ ‡–‡”‘ › ŽǤ Š‡Ǥǡ Synthesis of HeterocyclesviaCycloadditionsIǡ’”‹‰‡”Ǧ‡”Žƒ‰ǡ2008ǡ’’ǤͳǦͶͶǤ ͳ͸Ͳ Ǥ • Š™ƒ†‡ǡ Ǥ ˜§”Þǡ Ǥ Ǥ ‡‹••‡”ǡ Ǥ Ž‡‹„‡ ǡ ǤǤ ƒ””‡‹”ƒǡ Org.Lett.ǡ2005ǡ7ǡͷ͹ͶͳǦͷ͹ͶʹǤ ͳ͸ͳ ƒȌǤ ‹ƒ‰ǡǤŠ‡ǡJ.Org.ChemǤǡ2008ǡ73ǡͻͳͺͳǦͻͳͺ͵Ǣ„Ȍ ǤǤ‘†‡ǡǤ Ǥƒ””‡‹”ƒǡOrg.LettǤǡ2001ǡ3ǡͳͷͺ͹ǦͳͷͻͲǤ ͳ͸ʹ ǤǤ —ŽŽ‡”ǡǤŠ‡ǡǤǤ‹–‡”ǡǤǤƒ’’ǡJ.Am.Chem.SocǤǡ2005ǡ127ǡ ͷ͵͹͸Ǧͷ͵ͺ͵Ǥ ͳ͸͵ ǤǤǤ‘’‡•ǡǤǤ—‡•ǡǤǤǤǤ‹Š‘‡‡Ž‘ǡTetrahedronǡ2010ǡ 66ǡ͸Ͳ͹ͺǦ͸ͲͺͶǤ ͳ͸Ͷ ƒȌ Ǥ ƒ›‘ǡ Ǥ ‡„Ž‡†•ǡ Ǥ ‹ ‘—Ž‡ƒ—ǡ Ǥ ƒƒ–›ǡ Ǥ˜ƒ †‡” ‡‡ǡ Ǥ ”ƒ ‡ǡ ǤǦǤƒ’ƒ‰‡ǡJ.Org.Chem.ǡ2010ǡ75ǡ͸ͲͷͲǦ͸Ͳͷ͵Ǣ„ȌǤ •Š‹Ǧ ƒ™ƒǡǤ—†‘Šǡ Ǥ‘•Š‹†ƒǡǤƒ•—Šƒ”ƒǡǤƒƒ„‡ǡǤƒ‹–‘ǡOrg. Lett.ǡ 2002ǡ4ǡͳͻͲ͹ǦͳͻͳͲǤ ͳ͸ͷ Ǥ Ǥ —ƒ”ǡ Ǥ ‘˜‹†ƒ”ƒŒ—ǡ Ǥ ‡—ƒǡ Ǥ ƒ•ƒ–Š —ƒ”ǡ J. Chem. Pharm.Res.ǡ2015ǡ7ǡʹͷͲǦʹͷ͹Ǥ ͳ͸͸ ƒȌǤ—‹Ž‹ ‘ǡ ǤǤǯƒŽ ‘–”‡•ǡǤ ”òƒ‰‡”ǡNatureǡ1950ǡ166ǡʹʹ͸Ǧʹʹ͹Ǣ „Ȍ Ǥ —ƒ‹›ƒƒǡ Ǥ ‘•Š‹‘ǡ J. Am. Chem. Soc.ǡ 1960ǡ 82ǡ ͷ͵͵ͻǦͷ͵ͶʹǢ ȌǤ Ǥ—”–ŠǡǤǤŠŽ„‡”‰ƒ†ƒŽŽǡǤƒ‡‘— Š‹ǡJ.Org.Chem.ǡ1996ǡ 61ǡͺ͹ͷͷǦͺ͹͸ͳǢ†Ȍ ǤǦ Ǥ ‹ǡǤ‹ƒ‰ǡǤ Ǥ Š‹ƒœ‹ǡǤŠƒ‘ǡJ.Org.Chem.ǡ 1997ǡ62ǡͺͺǦͻʹǢ‡ȌǤǤ ±†‘—ǡǤ Ǥƒ”•‘•ǡǤǤǤ‹•‡—šǡǤ ǤŠ‹––Ž‡ǡ Org.Lett.ǡ2005ǡ7ǡ͵ͳ͹ͻǦ͵ͳͺʹǢˆȌǤ —–•‹‡†ŽǡǤ ƒœ‹‘ǡǤƒ”‡ŽŽǡChem. Eur. J.ǡ 2010ǡ 16ǡ ͸ͺ͹͹Ǧ͸ͺͺ͵Ǣ ‰Ȍ Ǥ ƒƒƒǡ Ǥ –‘ǡ Ǥ ‹•Š‹ƒ™ƒǡ Ǥ‘Š‘–‘ǡ Ǥ ƒƒ‘–‘ǡ Nippon Kagaku Kaishiǡ 2002ǡ 3ǡ Ͷ͹ͳǦͶ͹͵Ǣ ŠȌǤǤ‡†‡Ž•‘ŠǡǤ‡‡ǡǤ‹ǡ Ǥ‡›••‹‡”ǡǤǤ—ŽƒŠǡ

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 ǤǤ‹—ˆ‘Ž‹‹ǡ Org. Lett.ǡ 2009ǡ 11ǡ ͳͷ͵ͻǦͳͷͶʹǢ ‹Ȍ Ǥ ‹‹ƒ–ƒǡ Ǥ——”ƒǡ Ǥƒ‰ƒƒ Š‹ǡ Ǥ ƒ‡†ƒǡ Org. Lett.ǡ 2011ǡ 13ǡ ʹͻ͸͸Ǧʹͻ͸ͻǢ ŒȌǤ‘•Š‹—”ƒǡǤǤ‹††Ž‡–‘ǡǤǤ‘†‘”ƒǡǤ Ǥƒ•–‡”ǡǤǤ‘•‹ǡ ǤǤƒ•ƒ‡˜ǡǤǤŠ†ƒ‹ǡOrg.Lett.ǡ2013ǡ15ǡͶͲͳͲǦͶͲͳ͵ǢȌǤ ƒǡ ǤŠƒ‰ǡǤ‹ƒ‰ǡ ǤƒǡSynthesisǡ2014ǡ46ǡͷͲ͵ǦͷͲͻǤ ͳ͸͹ ǤǤ—‡Š‡ǡǤ Ǥ‡ƒ˜‡”ǡǤ ”ƒœǡJ.Org.Chem.ǡ1964ǡ29ǡͳͷͺʹǦͳͷͺ͸Ǥ ͳ͸ͺ ƒȌ Ǥ ƒ•ƒ‹ǡ Ǥ ‘•Š‹‘ƒǡ Bull. Chem. Soc. Jpn.ǡ 1968ǡ 41ǡ ʹʹͳʹǦʹʹͳͷǢ „ȌǤ‘ ƒ”ǡǤǤ‘••‹ǡǤ”‹ƒ” ‘ǡǤƒ‰‘ǡJ.Heterocycl.ChemǤǡ1980ǡ 17ǡͺͺͳǦͺͺͷǤ ͳ͸ͻ Ǥ Ǥ Ž„‹‹ǡ Ǥ Ž„‹‹ǡ Ǥ ƒ†‹‡”ƒǡ Ǥ ƒ”ƒ‡ŽŽƒǡ J. Chem. Research (S)ǡ 1984ǡ͵͸Ǧ͵͹Ǥ ͳ͹Ͳ ǤǦ Ǥ ‹ƒǡ Ǥ Ǥ Ǥ ‡Œƒ‹ǡ Ǥ —ƒ‰ǡ Ǥ —ǡ Ǥ Š‡‰ǡ ǤŠƒ‰ǡ Ǥ Ǥ‘‡›ǡ Ǥƒ‰ǡSynlettǡ2013ǡ24ǡ͹ͻǦͺͶǤ ͳ͹ͳ Ǥ Ǥ ‡††›ǡ Ǥ ‘˜‡”†Šƒǡ Ǥ ƒ’ƒ–Šǡ Ǥ —ƒ–‹ǡ Ǥ Ǥ ‡††›ǡ Ǥƒ†‹ ŠŠ‘”ǡSynth.CommunǤǡ2012ǡ42ǡ͸͵ͻǦ͸ͶͻǤ ͳ͹ʹ ǤǤƒ‰—•‘ǡ Ǥ”ƒƒ–ƒǡJ.Comput.Chem.ǡ1998ǡ19ǡͳ͹ͻͷǦͳͺͲͶǤ ͳ͹͵ Ǥ —ǡǤœ‘•–ƒǡAdv.Synth.Catal.ǡ2015ǡ357ǡʹͷͺ͵Ǧʹ͸ͳͶǤ ͳ͹Ͷ Ǥƒ‡†ƒǡǤ‘Œ‹ƒǡJ.Chem.Soc.,PerkinTrans.1ǡ1977ǡ3ǡʹ͵ͻǦʹͶ͹Ǥ ͳ͹ͷ ƒȌ Ǥ Ǥ ƒ‹ǡ Ǥ Ǥ Š‹–”‡ǡ Ǥ Ǥ ‹‹›ƒ”ǡ Ǥ Ǥ ƒ–Š‹”ƒ˜ƒǡǤǤ‡†”‡ǡ ǤǤ‡‡”ǡ Ǥ Ǥ ŠƒŠƒ‡ǡ Ǥ Ǥ Š‹•‘‘ǡ Curr. Sci.ǡ 2006ǡ 90ǡ ͹ͻ͵ǦͺͲ͵Ǣ „ȌǤƒÏƒ•œǡǤ‹‡ĂǡEur.J.Med.Chem.ǡ2015ǡ97ǡͷͺʹǦ͸ͳͳǢ ȌǤǤƒ•”ǡ ǤǤ ‹‡‹ƒŠǡArch.Pharm.Pharm.Med.Chem.ǡ2002ǡ6ǡʹͺͻǦʹͻͷǤ ͳ͹͸ ǤǤƒ‘ǡJ.Hetercyclic.Chem.ǡ1969ǡ6ǡʹ͸ͳǦʹ͸ͶǤ ͳ͹͹ Ǥ ƒ’—ƒ‘ǡ Ǥ —••Ž‡”ǡ Ǥ Ǥ ‹”ǡ Ann. Univ. Sarav., Math. Naturwiss.FakǤǡ1981ǡ16ǡ͹ǦͳͺǤ ͳ͹ͺ Ǥ Ǥ ƒŒƒ’ƒ•Šƒǡ Ǥ Ǥ Ž•ƒǡ Ǥ Ǥ ‹––ƒǡ J. Org. ChemǤǡ 2017ǡ 82ǡ ͷ͸͹ͺǦͷ͸ͺͺǤ ͳ͹ͻ Ǥ ‹‡„• Š‡”ǡ Ǥ „‡‰ƒœǡ Ǥ ‘ŽŽǡ Phosphorus and Sulfur Relat. Elem.ǡ 1988ǡ35ǡͷǦ͵ͶǤ ͳͺͲ ƒȌ Ǥ ‹‡„• Š‡”ǡ Ǥ ‘ŽŽǡ Ǥ „‡‰ƒœǡ Z. ChemǤǡ 1987ǡ 27ǡ ͺǦͳͷǢ „ȌǤǤ”‰‹Žƒ‰‘•ǡ Ǥ Ǥƒ„”‡”ƒǡ Ǥ Ǥ Ǥ ”‹‹Ó‘ǡ Ǥ Ǥ ƒ•–”‘ǡ Synth. Commun.ǡ1996ǡ26ǡͳͳͺ͹Ǧͳͳͻ͹Ǥ ͳͺͳ Ǥ ƒ”–ƒǡǤ ‡›†‡ǡ Ǥ—‰ǡSynthesisǡ2000ǡ6ǡͺͲͷǦͺͲͺǤ ͳͺʹ Ǥ‡”‡ŽƒǡǤǤ‹œ•ƒǡJ.Am.Chem.SocǤǡ1962ǡ84ǡͶͻͺͺǦͶͻͺͻǤ ͳͺ͵ Ǥ Ž‡‹’‡–‡”ǡ Ǥ  Š—Ž‡„—”‰ǡ Ǥ —‰ǡ Ǥ ƒ”–ƒǡ J.Org. ChemǤǡ 2005ǡ 70ǡ͸ͷͻʹǦ͸͸ͲʹǤ ͳͺͶ Ǥ ƒ ‡ǡ Ǥ ƒ•–‘Ž†‹ǡ Ǥ ‘–‹ ‡ŽŽ‹ǡ Ǥ ƒˆ”ƒ‡ǡ Ǥ ‘ŽŽ‡”ǡ Ǥ ƒ‰‡”ǡ Ǥ ‘Žœ‡”ǡChem.Eur.J.ǡ2015ǡ21ǡͳͺͻ͸͸Ǧͳͺͻ͹ͲǤ

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