Objectives. R/S determination. R/S determination. Epoxidation. Last lecture Chirality

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1 Lst leture hirlity This leture enntiomers distereomers / nottion hirlity jetives optil & iologil properties hirl moleules ontining more thn one hirlity enter. retions tht rete stereoisomers 1 Dr. Ky nderg Whih onfigurtion goes in the lnk: or? (_)-2-hloro-3-methylutn-1-ol l / determintion : l,,, tep 1: nk the 4 toms of the in order of deresing tomi numer. tep 2: Build the model oriented EXATLY s shown on the 2-D pge. 2 Dr. Ky nderg Whih onfigurtion goes in the lnk: or? (_)-2-hloro-3-methylutn-1-ol l / determintion : l,,, tep 1: nk the 4 toms of the in order of deresing tomi numer. tep 2: Build the model oriented EXATLY s shown on the 2-D pge. tep 3: old the yellow (lowest tomi #) so tht the other three re fing your fe. 3 Dr. Ky nderg romohlorofluoromethne etion 7.1 Mirror imge F sees in the mirror ()- or ()- F () l l 4 Dr. Ky nderg xns tht rete stereogeni enter Epoxidtion Epoxidtion 3 2 (peroxyeti id) 3 2 (peroxyeti id) etion (peroxyeti id) (_)-1,2-epoxypropne 3 + hirl 3 (_)-1,2-epoxypropne 5 etion 7.9 xns tht rete stereogeni enter 6 1

2 3 ptilly hirl (_)-1,2-epoxypropne (±)-1,2-epoxypropne hirl Epoxidtion (peroxyeti id) mixture ptilly 3 (_)-1,2-epoxypropne 3 ow do we show remi mixture in JME? tik onds imply this is remi mixture. Epoxidtion 3 2 (peroxyeti id) ()-1,2-epoxypropne = ()-1,2-epoxypropne (±)-1,2-epoxypropne etion 7.9 xns tht rete stereogeni enter 7 etion (_) 50% 3 3 hirl 50% (_) Eletrophili ddition etion hirl optilly prohirl 2 omintion hν, Δ etion 7.9 hirl optilly 50% remi mixture 50% 10 ( +_ ) Alohol to lkyl romide hirl ut remi optilly 2 2 Fumri id hirl optilly intive etion 7.9 ( +_ ) fumrse hirl ut remi optilly ()-( )-mli id hirl 11 optilly emi produt mixture? Viinl hlohydrin E-lkene 3 etion nti-ddition Doule whmmy

3 xns tht rete stereoisomers Viinl hlohydrin (2,3) onfigurtion Z-lkene (2,3) onfigurtion etion xns tht rete stereoisomers E-lkene 3 E vs Z lkene Z-lkene 2 3 etion tereospeifi rxn: nti ddition xns tht rete stereoisomers meso E-lkene 3 3 epresenttion 3 Implies the presene of ll onfigurtions (2,3) (2,3) meso 3 3 etion Z-lkene 2 3 enntiomers xns tht rete stereoisomers E-lkene produt etion xns tht rete stereoisomers Z-lkene produts etion (Z)- 3 rtie 3 A I like to keep the onds of the reting sites in the plne of the pper (E)- 3 nti-ddition etion B D

4 xns tht rete distereomers tereospeifi rxn: syn ddition t ydrogention 3 2 dded from ottom fe etion dded from top fe xns tht rete distereomers etion 7.13 M of hydrogention 3 2 t 2 tereo rxn: syn ddition tereo rxn: preferene for one stereoisomer 20 1,2-dimethylylohexne We re going to fous on how the ethyl groups orienttions hnge s the retion progresses l 2 pprohes top fe of doule ond Viinl rotte hlohydrin 90 o l l ethyls: ngled down, wedge l l 2, 2 Both pprohes hve the sme proility of ourring, therefore produt mixture will e 50% from eh pproh. ethyls: stright out, wedge ethyls: ngled up, wedge l l l l 2 pprohes ottom fe of doule ond 21 l l prtil rotionmore onds L ethyl: stright wter pprohes from wter pushes ethyl nd methyl L ethyl: ngled up T (proton trnsfer) Viinl hlohydrin L ethyl: ngled down wedge l Doule whmmy ethyl: ngled down wedge lens prtilly reking ond l ethyl: ngled down nti-ddition l l Elvis ethyl: ngled down 22 l l Don t forget understood Viinl hlohydrin l l L ethyl: ngled down, wedge wter pushes ethyl nd methyl Viinl hlohydrin wter pprohes from ethyl: ngled up, wedge l T (proton trnsfer) ethyl: ngled up, wedge ethyls: ngled up, wedge l l 23 L ethyl: flttens, wedge I like to keep the onds of the reting speies in the plne of the pper. Now for the pproh from the ottom fe. l l l 24 4

5 3 (2_,3_)- 3-penten-2-ol E/Z Enntiomers & / di di di 1 etion esolution of enntiomers eprtion of remi mixture into its enntiomeri omponents esolution of enntiomers N etion N N 2 3 enntiomers etion 7.12 Mximum # of stereoisomers = When stereogeni enters re equivlently sustituted (possile ugrs meso forms), the # is less thn 3 holi 3 id 3 etion 7.12 ldohexose (sugr) llose (2,3,4,5)- (2,3,4,5)- (2,3,4,5)- (2,3,4,5)- (2,3,4,5)- ltrose (2,3,4,5)- (2,3,4,5)- (2,3,4,5)- et. gluose totl. 27 2,3,4,5,6-penthydroxyhexnl holi id (ile) # of hirlity enters? ow mny enntiomers of holi id re there? ow mny distereomers? of holi id re there? # of stereoisomers? Any possiility of meso-forms? 28 The mrine orgnism new highly potent nlogue utilizes hirl enzymes of ryosttin 1 to tlyze only one of the stereoisomers yosttin 1 yosttin synthesis 19 steps nd 2% yield Bugul neritin, orl-like ritter lled ryozon tht is the soure of the promising ner drug ryosttin. The urrent reipe lls for 14 tons of hrvested Bugul to produe out hlf n oune of ryosttin. ientists hve sueeded t mking ext replis of ryosttin from hemils tht n e ought in ny l tlog, ut their proesses n tke up to 70 expensive steps, ompred to the 10 to 15 used to mke most ommerilly vile drugs. 14 ws produed in >3% yield nd only 17 steps

6 yosttin synthesis symmetri enter is synonymous with hirl enter Dniel omins: New syntheti methodologies, strtegies for symmetri synthesis, direted metlltion retions, stereoseletive redutions, tlyti symmetri synthesis, new hirl uxiliries, nd the totl synthesis of nturl produts nd iologilly tive ompounds Dniel L. omins, jn. Joseph, o ong, im. Al-wr, hristopher J. Foti, Yue-mei Zhng, Xinghi hen, Donld. LMunyon nd Mri Guerr-Weltzien, "Asymmetri ynthesis nd yntheti Utility of 2,3- Dihydro-4-pyridones," ure nd Applied hem., 1997, 69, 477. Dn omins work Dniel L. omins, resh M. Thkker, Mtthew F. Bevsky, nd Mohmmed M. Bdwi, "hirl Auxiliry Medited itet-pengler etions: Asymmetri yntheses of (-)-Ludnosine, (+)-Gluine nd (-)-Xylopinine," Tetrhedron 1997, 53, Dniel L. omins, Xinghi hen nd Lwrene A. Morgn, "Enntiopure N - Ayldihydropyridones s yntheti Intermedites: Asymmetri ynthesis of (-)-eptiine nd (-)-Tylophorine," J. rg. hem., 1997, 62, Jeffrey T. Kuethe nd Dniel L. omins, "Asymmetri Totl ynthesis of (+)-nnistivine," J. rg. hem., 2004, 69, tereogeni enters other thn ron i: four tetrhedrlly distriuted sustituents i & etion 7.16 sp 3 hyridized toms with 3 different sustituents nd lone pir 33 tereogeni enters other thn ron N N very fst No resolution euse of immedite remiztion due to rpid inversion (smll energy rrier) etion 7.16 N 34 tereogeni enters other thn ron etion 7.16 sp 3 hyridized toms with 3 different sustituents nd lone pir tereogeni enters other thn ron etion sp 3 hyridized toms with + 3 different sustituents nd lone pir slow ine the inversion is slow, enntiomers n e resolved (seprted) (lrger energy rrier for inversion from to.) Inversion from to does not our redily euse of the lrge energy rrier of inversion (_)-utyl methyl sulfoxide 6