Advanced Organic Synthesis Design
Advanced Organic Synthesis Design CHE 686
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This 6 page Class Notes was uploaded by Dr. Alana Bauch on Wednesday October 21, 2015. The Class Notes belongs to CHE 686 at Syracuse University taught by Nancy Totah in Fall. Since its upload, it has received 88 views. For similar materials see /class/225658/che-686-syracuse-university in Chemistry at Syracuse University.
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Date Created: 10/21/15
You should be familiar with at least the following Oxidations oxidation of alcohols Cr03 HZSO4 PCC PDC PDCDMF Mn02 COCI2 DMSO Et3N 803pyridine Jones Reagent Swern oxidation DessMartin periodinane TPAP NMO Ag2C03 celite NaCIOZ Fetizon39s reagent epoxidation mCPBA H202 NaOH tBuOH VOacac2 dihydroxylation OsO4 NMO oxidative cleavage KMnO4 RuO4 NaIO4 03 DMS oxidation of ketones mCPBA or CF3CO3H LDA TMSCI mCPBA LDA TMSCI PdOAc2 Baeyer Villager rxn Rubottom oxidation Saegusa oxidation Reductions reduction of double amp triple bonds H2 PhP3RhCI Brown39s catalyst Wilkenson39s catalyst Crabtree39s catalyst HZPdBaSO4 Lindla r39s catalyst Ph2PCH24PPh2Rhnbd BF4 Cy3PrCODpy PFB ROH 9 c02H ROH 9 COZH allylic OH only 9 CH0 diol acto 9 lactone CH0 9 COZH does not oxidize alcohols epoxidation of e rich olefins can be OH directed epoxidation of enones epoxidation of allylic alcohols only always OH directed gives syn addition cleaves double bonds diols dicarbonyls 9 COZH or ketone ketone 9 lactone O inserts at more highly subst site ketone 9 a hydroxy ketone ketone 9 a5unsaturated ketone reduction of CC least hindered first reduction of CC OH directed reduction of CC OH directed reduction of CEO 9 cis olefin reduction of carbonyl derivatives LiAlH4 NaBH4 NaBH4CeCI3 LisBu3BH KsBu3BH LiAlOtBu3H BH3 ZnBH42 BEt3 NaBH4 NH4BHOAc3 epoxide opening LiEthH REDAL DIBAL Luche reduction L selectride K selectride Super Hydride con39ugate reduction Et3iH PhP3RhCI Mg LiNH3 deoxygenation thioacetal RaNi H2NNHTs NaCNBH3 HZNNHZ KOH Wolff Kishner Protecting Groups alcohols TBS BPS MOM THP AC 32 Bn acetonide benzylidene acetal aldehydes amp ketones acetals thioacetals 12rdn of enones enones give l4reduction selective rdn of COZH over COZR will reduce CHOketones good for chelation controlled reduction 5hydroxy ketone 9 13syn diol 5hydroxy ketone 9 13anti diol must bond to OH first best reagent for ring opening of epoxides amprdn of C X epoxy OH 9 13diol epoxy OH 9 12diol COZR 9 CH0 l4rdn on enone to give silyl enol ether l4rdn on enone l4rdn on enone can trap intermediate enolate a5unsataturated carbonyls give db migration for 12 and 13diols for 12 and 13diols regioselective cleavage possible THE DIELSALDER REACTION The DielsAlder reaction occurs with high levels of stereoselectivity The reaction proceeds via a syn addition and as such the relative stereochemistry of substituents contained on the diene and the dienophile is maintained over the course of the reaction Thus reaction of butadiene with a cis substituted dienophile leads to the cis product whereas reaction of butadiene with a transsubstituted dienophile leads to the trans product By the same token dienes in which the substituents at the 1 and 4 positions occupy the same orientation in the scis configuration both groups either Routside or Rinside will give the cis product whereas those having substituents that occupy different orientations one substituent Routside and one substituent Rinside will give the corresponding trans product Stereochemistry of the dienophile is maintained 6 ECO2Me A acone I gt cisproduct 002Me 002Me cis 002M e 002 M e K J Agt U trans product MeOzc quot39c02M e trans Stereochemistry of the diene is maintained Rout R Rin A or gt clsproduct Rin R Rout symmetrical orientation Rout R Rin gt trans product u unsymmetrical orientation The same principles hold true when looking at a DielsAlder reaction in which both the diene and the dienophile bear substituents Thus for the reaction below note that the stereochemistry of the diene is maintained symmetrical orientation of groups leads to cis relative stereochemistry in the product as is that of the dienophile cis dienophile leads to cis relative stereochemistry in the product CH3 9H3 coch3 coch3 E A O cis relationship in product coch3 CO2CH3 CH3 6H3 symmetrical orientation CH3 CH3 COzCH3 C02CH3 I L cis relationship in product 002043 quot 00ch3 CH3 CH3 cus When looking at the relative stereochemistry of substituents on the diene vs those on the dienophile consider that the dienophile can approach the diene in either of two orientations a the dienophile approaches the diene such that its electron withdrawing substituents are oriented away from the diene 7 system the exo orientation CH3 9H3 39 CO2CH3 H amp CE CH H3 CO2CH3 coch3 CO CH 39 2 3 CH3 exo transition state exo product minor b the dienophile approaches the diene such that its electron withdrawing substituents are oriented toward the diene 7 system the endo orientation E COzCHs CH OH H 3 3 H CH3 39 COch3 heat H E gt CHs H CH 7H E 3CO2CH3 5 CO2CH3 H C020H3 CH3 endo transition state endo product major In most cases formation of the endo product is favored Relative Reactivity in Normal 9 dienes reactivity of diene increased by e donating groups planarity of p systems ability to adopt scis conformation relative reactivity with maleic anhydride Electron Demand DielsAlder Reactions ph NEt2 OEt O gt gt gt gt gt Ph 1400 110 12 O H NJK Ph MeO gt gt I gt I I 9 5 COgH Ph gt gt gt I I 3 2 1 R CI CI CI CI CI gtgtgt R R CI CI 01 With small R 000016 completely unreactive CI CI tBu 9 dienophiles reactivity of dienophile increased by e withdrawing groups weak 7 bond relative reactivity with cyclopentadiene very reactive dienophiles o Nl NO ON COCI l N Ph gt gt gt gt NO ON CIOC NO ON 0 4x107 5x105 4x104 0 0 ON ON Io gt gt t gt r gt 0 CN 0 o 6000 900 90 1 001 mono activated dienophiles COCI CHO COR 002R CN CO2R gtgt i gt i gt i gt i E III J 20 10 5 1 reactive unactivated dienophiles DE IO
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