?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.relation=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F9843%2F&rft.title=CATALYTIC%2C+ASYMMETRIC+ACYL+HALIDE-ALDEHYDE+CYCLOCONDENSATIONS+IN+COMPLEX+MOLECULE+SYNTHESIS+AND+APPLICATION+TO+THE+INSTALLATION+OF+QUATERNARY+CARBON+STEREOCENTERS&rft.creator=Kassick%2C+Andrew+Jonathan&rft.description=The+synthetic+utility+of+recently+developed+catalytic%2C+asymmetric+acyl+halide-aldehyde+cyclocondensation+(AAC)+reactions+has+been+successfully+demonstrated+in+complex+molecule+total+synthesis.+Extensive+use+of+the+enantiomerically+enriched+beta-lactone+products+of+AAC+methodology+has+led+to+the+enantioselective+total+synthesis+of+the+potent+microtubule-stabilizing+agent%2C+(-)-laulimalide+(1).+Additional+highlights+of+the+synthesis+include+a+diastereoselective+aldol+reaction+that+united+major+fragments+85+and+86+and+a+remarkably+high-yielding+modified+Yamaguchi+macrolactonization.+Novel+methodology+was+also+developed+to+effect+both+the+one-pot+interconversion+of+beta-lactones+to+dihydropyranones+and+the+Lewis+acid-mediated+addition+of+allenylstannane+reagents+to+glycal+acetates.+Asymmetric+AAC+reactions+have+also+been+instrumental+in+recent+studies+toward+the+total+synthesis+of+the+cytotoxic+marine+natural+product%2C+amphidinolide+B1+(133).+By+exploiting+AAC+methodology%2C+several+key+stereochemical+relationships+present+in+major+fragments+171+and+172+were+established.+A+highly+enantioselective+installation+of+the+C16+tertiary+carbinol+stereocenter+was+acheived+through+the+application+of+Mukaiyama's+Sn(IV)-allylation+protocol%2C+and+a+rapid+synthesis+of+sulfone+subunit+174+was+realized+from+commercially+available+gamma-butyrolactone.+Regioselective+beta-lactone+ring+opening+by+phosphonate+anions+was+also+documented.+The+enantiomerically+enriched+beta-lactone+products+of+AAC+methodology+have+also+been+demonstrated+to+serve+as+useful+templates+for+the+installation+of+asymmetric+quaternary+carbon+stereocenters.+Treatment+of+beta-lactones+with+NaHMDS+in+the+presence+of+an+in+situ+electrophile+at+low+temperature+resulted+in+enolization+and+subsequent+alkylation+to+afford+to+afford+trans-3%2C4-disubstituted+lactones+in+moderate+to+good+yield+with+good+levels+of+diastereoselectivity.+Resubjecting+the+monoalkylated+products+to+the+reaction+conditions+and+a+different+electrophile+resulted+in+the+efficient+production+of+3%2C3-disubstituted-beta-lactones+in+high+yield+with+high+trans-diastereoselectivity.+A+more+efficient+route+to+3%2C3-disubstituted+beta-lactones+was+realized+starting+from+the+cis-3%2C4-disubstituted+beta-lactones+products+of+the+recently+developed+second+generation+AAC+reaction.+Asymmetric+quaternary+carbon+formation+was+accomplished+in+two+steps+affording+the+desired+3%2C3-disubstituted-beta-lactones+in+high+yield+with+excellent+diastereoselectivity.&rft.date=2005-01-31&rft.type=University+of+Pittsburgh+ETD&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.language=en&rft.identifier=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F9843%2F1%2Fkassickaj_etd.pdf&rft.identifier=++Kassick%2C+Andrew+Jonathan++(2005)+CATALYTIC%2C+ASYMMETRIC+ACYL+HALIDE-ALDEHYDE+CYCLOCONDENSATIONS+IN+COMPLEX+MOLECULE+SYNTHESIS+AND+APPLICATION+TO+THE+INSTALLATION+OF+QUATERNARY+CARBON+STEREOCENTERS.++Doctoral+Dissertation%2C+University+of+Pittsburgh.++++(Unpublished)++