Becauseawidearrayofnitrogen-??containingcompoundsexhibitbioactivity,thedevelopmentofnew methodsfortheformationofC?Nbondsisacentralchallengeinorganicchemistry.Furthermore, becausethetwomirror-??imageisomers(?enantiomers?)ofamoleculegenerallyhavedifferentbiological activityduetothe?handedness?ofthemoleculesoflife(e.g.,peptides,DNA,RNA,andcarbohydrates), thereisaneedinthebiomedicalcommunitytoefficientlygeneratecompoundsinstereoisomericallypure form.Finally,thedevelopmentofcatalyzedreactionsisdesirable,sincetheyoftenofferadvantagesfrom thestandpointsofefficiency/economy. Thisproposalisdirectedataddressingallthreeofthesechallenges,specifically,thediscoveryofnew methodsforthecatalyticandenantioselectivesynthesisofnitrogen-??containingcompounds.Inparticular, theresearchplandescribesthedevelopmentofthefirstphotoinduced,copper-??catalyzedmethodsforthe constructionofC?Nbonds.Thecouplingreactionsareanticipatedtoproceedunderunusuallymild conditions,tohavebroadapplicabilityforthegenerationofdiversefamiliesofnitrogen-??containing compounds,andtoproceedwithgoodstereoselectivity(whenapplicable).Furthermore,theresearch plandescribesmechanisticstudies(e.g.,stereochemical,massspectrometry,fluorometry,andelectron paramagneticresonancespectroscopy)thatwillprovideinsightintotheunusualreactionpathwayof thesephotoinduced,copper-??catalyzedC?Nbond-??formingreactions,whichlikelyproceedthrougha radicalintermediate.
/RELEVANCE Thedevelopmentofefficientnewchemicalprocesseshasanimpactonawidearrayofdisciplinesthat requirethesynthesisoforganiccompounds(e.g.,biologicalchemistry,pharmaceuticalchemistry,and biology).Nitrogen-??containingcompoundshaveahighpropensitytobebioactive(e.g.,AbilifyTM, CrestorTM,CymbaltaTM,LipitorTM,NexiumTM,andPlavixTM);consequently,thediscoveryofnovel approachestothesynthesisofnitrogen-??containingcompounds,whichisthefocusofthisproposal,isan importantendeavorforthebiomedicalcommunity.
