Objectives. Configuration. Epoxidation. Epoxidation. Epoxidation. Epoxidation. trans-alkene. trans-ring. O (S)-1,2-epoxypropane

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1 0% % 0% 77% % (2,3)- 3. (2,3)-. (2,3)- 5. (2,3) onfigurtion?-2-hloro-3-fluoroutne LQ #) A) Drw enntiomer. B) Drw distereomer. Lst leture hirlity enntiomers distereomers / nottion This leture hirlity jetives optil & iologil properties hirl moleules ontining more thn one hirlity enter. retions tht rete stereoisomers 2 Dr. Ky nderg xns tht rete stereogeni enter Epoxidtion Epoxidtion 3 2 (peroxyeti id) tereospeifi 3 2 (peroxyeti id) etion 7.9 enntiomers ()-,2-epoxypropne Epoxidtion hirl prohirl enntiotopi (peroxyeti fes id) 3 3 ()-,2-epoxypropne trns-lkene trns-ring 3 etion 7.9 xns tht rete stereogeni enter 3 hirl ptilly intive ()-,2-epoxypropne (±)-,2-epoxypropne hirl Epoxidtion (peroxyeti id) emi mixture ptilly intive 3 ()-,2-epoxypropne 3 ow do we show remi mixture in Mrvin? tik onds imply this is remi mixture. Epoxidtion 3 2 (peroxyeti id) ()-,2-epoxypropne ()-,2-epoxypropne (±)-,2-epoxypropne = etion 7.9 xns tht rete stereogeni enter 5 etion 7.9 6

2 remte () 3 3 hirl () Eletrophili ddition etion hirl optilly intive 3 3 prohirl 2 2 h omintion enntiomers 3 etion 7.9 hirl optilly intive remi mixture 8 ( +_ ) Alohol to lkyl romide hirl ut remi optilly intive 2 2 Fumri id hirl optilly intive etion 7.9 ( +_ ) fumrse (hirl enzyme) hirl ut remi optilly intive ()-( )-mli id hirl optilly tive 9 emi produt mixture? Viinl hlohydrin E-lkene 3 etion nti-ddition Doule whmmy 3 0 xns tht rete stereoisomers Viinl hlohydrin (2,3) onfigurtion Z-lkene (2,3) onfigurtion etion 7.3 Enntiomers remte xns tht rete stereoisomers E-lkene E vs Z lkene etion tereospeifi rxn: nti ddition 2 enntiomers Z-lkene

3 2% 3% 93% % 2% 0% xns tht rete stereoisomers E-lkene 3 3 epresenttion 3 Implies the presene of ll onfigurtions (2,3) (2,3) 3 3 etion enntiomers Z-lkene xns tht rete stereoisomers E-lkene produt etion 7.3 It doesn t mtter whih onds re wedge nd whih re dshed s long s one is nd the other. xns tht rete stereoisomers 3 Z-lkene produts etion 7.3 It doesn t mtter whih onds re wedge nd whih re dshed s long s oth re or oth re. 5. A,B 2. A, 3. A,D. B, 5. B,D 6.,D Whih two from Z-lkene? (Z)- Whih re formed? A 2 3 I like to keep the onds of the reting sites in the plne of the pper (E)- 3 nti-ddition etion B Whih two hve the methyl & ethyl on the sme side of the nti onformtionl plne? D 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 from eh pproh. ethyls: stright out, wedge ethyls: ngled up, wedge l l l l 2 pprohes ottom fe of doule ond l l prtil rotionmore plnr onds L ethyl: stright wter pprohes from ottom wter pushes ethyl nd methyl up 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 nti-ddition l ethyl: ngled down LQ2 elet the onfigurtion ethyl: ngled down l 3

4 3% 6% 8% 83% l l Don t forget understood Viinl hlohydrin l l L ethyl: ngled down, wedge wter pushes ethyl nd methyl down Viinl hlohydrin wter pprohes from top l ethyl: ngled up, wedge T (proton trnsfer) ethyl: ngled up, wedge ethyls: ngled up, wedge l l L ethyl: flttens, wedge I like to keep the onds of the reting speies in the plne of the pper. ow for the pproh from the ottom fe. l l l lenge l 2, 2 l l l l X l l X A B D 2-hloro--methylylohexnol In WeAssign nd erlier in the text, we llowed you to show just one of the enntiomers, ut e wre tht the produt mixture tully ontins oth. y ttention to instrutions involving stereospeifi retions. 2 xns tht rete distereomers tereospeifi rxn: syn ddition t ydrogention 3 2 dded from ottom fe etion dded from top fe Distereomers elet the true sttement regrding the produts. t. oth re hirl 2. oth re hirl 3. only is is hirl. only trns is hirl hirl? is 3 2 dded from ottom fe trns dded from top fe xns tht rete distereomers 3 2 M of hydrogention syn ddition 2 t Less hindered fe tereoseletive rxn: preferene for one stereoisomer tereospeifi rxn: 3 2 etion 7.3,2-dimethylylohexne 3 2 LQ #3 A) M B) mop ) stereoisomer not formed D) desription of M & mop. 2

5 mino group etion Distereomers (2,3)-3-minoutn-2-ol ( 2,3 )-3-minoutn-2-ol liquid olid, mp 9 o esolution of enntiomers eprtion of remi mixture into its enntiomeri omponents esolution of enntiomers etion 7. We n use the different melting points to seprte them But how do we seprte enntiomers whih hve the sme melting points, oiling points, et.? 25, slt distereomers, slt 26 Mximum # of stereoisomers = 2 n When stereogeni enters re equivlently sustituted (possile ugrs forms), the # is less thn 2 n. ldohexose (sugr) llose (2,3,,5)- (2,3,,5)- (2,3,,5)- (2,3,,5)- (2,3,,5)- ltrose (2,3,,5)- (2,3,,5)- (2,3,,5)- et. gluose etion totl. 27 2,3,,5,6-penthydroxyhexnl 3 holi id 3 holi 3 id # of hirlity enters? (ile) etion 7.2 LQ A) ow mny enntiomers of holi id re there? B) ow mny distereomers of holi id re there? # of stereoisomers? 2 = 208 Any possiility of -forms? 28 The mrine orgnism new highly potent nlogue utilizes hirl enzymes of ryosttin to tlyze only one of the stereoisomers yosttin yosttin synthesis Bugul neritin, orl-like ritter lled ryozon tht is the soure of the promising ner drug ryosttin. The urrent reipe lls for 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 0 to 5 used to mke most ommerilly vile drugs steps nd 2% yield 29 ws produed in >3% yield nd only 7 steps

6 . 2. yosttin synthesis symmetri enter is synonymous with hirl enter Dniel omins: ew 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--pyridones," ure nd Applied hem., 997, 69, 77. 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 997, 53, Dniel L. omins, Xinghi hen nd Lwrene A. Morgn, "Enntiopure - Ayldihydropyridones s yntheti Intermedites: Asymmetri ynthesis of (-)-eptiine nd (-)-Tylophorine," J. rg. hem., 997, 62, 735. Jeffrey T. Kuethe nd Dniel L. omins, "Asymmetri Totl ynthesis of (+)-nnistivine," J. rg. hem., 200, 69, tereogeni enters other thn ron i: four tetrhedrlly distriuted sustituents i & etion 7.6 sp 3 hyridized toms with 3 different sustituents nd lone pir 33 tereogeni enters other thn ron very fst o resolution euse of immedite remiztion due to rpid inversion (smll energy rrier) etion tereogeni enters other thn ron slow etion 7.6 sp 3 hyridized toms with 3 different sustituents nd lone pir ine the inversion is slow, enntiomers n e resolved (seprted) (lrger energy rrier for inversion from to.) 35 tereogeni enters other thn ron onfigurtion + etion 7.6 sp 3 hyridized toms with 3 different sustituents nd lone pir Given tht the lone pir is the lowest rnking, selet the onfigurtion. 2 Inversion from to does not our redily euse of the lrge energy rrier of inversion. 3 (_)-utyl methyl sulfoxide 0 % 90 % 36 6