Alkenes, Alkynes & Variations Beauchamp 1 Organic Reactions Summary Alkenes, alkynes and variations For Use as a Study Guide Beauchamp y:\files\classes\Organic Chemistry Tool Chest\Reactions Lists\Org rxns summary, alkenes, -ynes, with mechs.doc Alkenes, Alkynes & Variations Beauchamp 2 Making alkenes and alkynes o o o a. mechanism using potassium t-butoxide, KOC(CH3)3, SN2 at and E2 at 1 , 2 and 3 RBr, H C H H C H 3 O SN2 3 C C Br O C H C Br 3 H H CH3 H H D H H E2 D C Br C C D H C 3 O H R Z E C CH3 H C C Br Ha C b H3C H3C CH 3 Ha CH3 Hb H H C 3 O C Br C H C E2 (-CH2-H) H3C H2 E2 Br CH CH3 3 Ha C E2 (-CHb-H) Hb E2 (-CHa-H) Example reactions E2 > SN2 KOC(CH3)3 anti Br elimination Br KOC(CH3)3 E2 R E2 KOC(CH3)3 Br R Br KOC(CH3)3 E2 S S H3C CH3 Br C S 2 KOC(CH3)3 O CH3 N no other option y:\files\classes\Organic Chemistry Tool Chest\Reactions Lists\Org rxns summary, alkenes, -ynes, with mechs.doc Alkenes, Alkynes & Variations Beauchamp 3 b. Double elimination from dibromoalkanes to form alkynes and terminal acetylides used in many additional reactions (SN2 with RBr, C=O addition to aldehyses and ketones, and reaction with epoxides) Br Br Br H 2 eqs. Br2 Na h H Na N N H R R N R R H rd R R 3 equivalent H most stable a anion in mixture O H a H H Na 2. workup b 2. H2 C H2 Na C b X R R H S 2 O c N O H c CH H2OH 2. b R CH C Na R O R b d d HO 2. H OH O 2 O Na The zipper reaction moves a triple bond in an unbranched linear chain to the end and allows all of the above reactions. H2 C CH CH2 Na 2 C H N C C C R R C C R R R H N R R R R H N H H Na H C C C C C C R R C H C C C R R C C H H H Na N H H H N R R R R R R N H C 2. workup C R H H C O C C H H H H R C H2 y:\files\classes\Organic Chemistry Tool Chest\Reactions Lists\Org rxns summary, alkenes, -ynes, with mechs.doc Alkenes, Alkynes & Variations Beauchamp 4 o o o c. mechanism using NaCC-R to make a bigger alkyne, SN2 at methyl, 1 and 2 RBr and only E2 at 3 RBr, H H SN2 C C Br R C C C Br C H R H H H D D SN2 C C Br R C C C Br R C H H R CH2 H2C H3C CH3 H H C H C C Br 3 Br C H C O C R H2 E2 > SN2 H CH3 C H C Ha E2 (-CH2-H) E2 (-CHa-H) 2 E2 (-CHb-H) CH SN2 3 Hb Example reactions SN2 NaCC-R inversion of Br R configuration Br NaCC-R R E2 > SN2 NaCC-R E2 Br R Br NaCC-R E2 > SN2 S S achiral Br C NaCC-R C R SN2 y:\files\classes\Organic Chemistry Tool Chest\Reactions Lists\Org rxns summary, alkenes, -ynes, with mechs.doc Alkenes, Alkynes & Variations Beauchamp 5 o o d. mechanism using triphenylphosphine to make triphenylphosphonium salt, SN2 at methyl, 1 and 2 RBr and only E2 at 3o RBr, used to make a triphenylphosphonium ylid to make Z and E alkenes with aldehydes and ketones. Br Ph H H Ph O Br S 2 Ph N CH Ph Ph P C 2 1. n-BuLi CH3 Ph P C P 2. H2C=O C Ph H CH Ph C 3 CH3 Li H CH3 Ph H H betaine Ph = phenyl ylid salt H Ph O Ph O Ph Ph Ph C H H H CH P C P C Ph P O C 3 Ph C CH3 Ph C CH3 Ph Z alkenes CH H H 3 CH3 CH3 oxaphosphatane Br Ph H3C O H H Ph Br S 2 Ph Ph P N CH Ph C 2 1. n-BuLi CH2 C Ph P C P 2. H2C=O Ph C H CH3 Ph H3C CH2 CH2 Li Ph CH CH3 3 H C CH betaine Ph = phenyl 3 ylid salt 3 H Ph O Ph O Ph Ph Ph C H H H C CH P C P C Ph P O 3 C 3 Ph C CH3 Ph C CH3 Ph Z alkenes CH H3C H C 2 CH2 3 CH2 H3C H3C oxaphosphatane H3C Schlosser Modification of the Wittig reaction to make E alkenes H OH2 H H H H O C O C Ph3P O C acid/base Ph3P O C Ph3P Ph3P R at -78oC neutralize R C H R R C H C C R R The stereochemistry R R H betaine H C of the alkene is 2 flat sp2 carbon determined in this step. Li can react from extra equivalent of n-BuLi either side H H O O C Ph3P C R Ph3P R C R phosphine C R oxide H H E alkene y:\files\classes\Organic Chemistry Tool Chest\Reactions Lists\Org rxns summary, alkenes, -ynes, with mechs.doc Alkenes, Alkynes & Variations Beauchamp 6 Example reactions 1. Br P 2. n-BuLi Ph Ph 3. CH3CH=O Normal Wittig Ph Z alkene preferred 1. Br P R Ph Ph 2. n-BuLi Ph 3. CH CH=O Normal Wittig 3 Z alkene preferred 1. P Br Ph Ph 2. n-BuLi Ph 3. CH3CH=O E2 1. R Br P S Ph Ph 2. n-BuLi Normal Wittig Ph 3. CH3CH=O S Z alkene preferred 1. Br P Ph Ph Ph 2. n-BuLi Normal Wittig 3. CH3CH=O Z alkene preferred 1. Br 2. n-BuLi P 3. CH3CH=O o Schlosser modification Ph Ph 4. -78 C, n-BuLi 5. HCl, warm of the Wittig Ph E alkenes preferred e. Ohira-Bestmann modification of the Seyferth-Gilbert reaction (makes terminal alkynes from aldehydes and a special ‘Wittig’ reagent). Overall reaction from aldehyde to the terminal alkyne – simplified Ohira-Bestmann reaction O O O O H O O K P R OMe K N R P R H OMe R N O O OMe N OMe given terminal N alkynes y:\files\classes\Organic Chemistry Tool Chest\Reactions Lists\Org rxns summary, alkenes, -ynes, with mechs.doc Alkenes, Alkynes & Variations Beauchamp 7 Possible mechanism – with mechanism details O O O O O O O P P P R OMe R O OMe R OMe OMe OMe O OMe N N N N O given N N R H R H R H H C C O O C O O C C C R P R O R P OMe N N OMe resonance H OMe O P H OMe N N OMe N N N OMe N rearrangement = N2 leaves, N and H migrates across N Example reactions 1. RO Na O O O P 2. OMe H difficult to make OMe alkyne at branch point N2 1. RO Na O O 2. O P OMe difficult to make OMe H alkyne at branch point N2 1. RO Na O O O 2. P OMe H difficult to make OMe alkyne at branch point N2 y:\files\classes\Organic Chemistry Tool Chest\Reactions Lists\Org rxns summary, alkenes, -ynes, with mechs.doc Alkenes, Alkynes & Variations Beauchamp 8 f. ROH with sulfuric acid / heat. Synthesis of alkenes (our only useful E1 reaction. Rearrangement is possible). H H H O SO3H OSO3H H O H O H H (heat) H O O E1 H H O SO3H H slow step H OSO3H pK = -10 water is a good a H o secondary alcohol leaving group bp = +83 C bp = +161oC alcohol alkene distills out o Tbp = 78 C H H H H O CH (heat) H H H 3 O CH3 O H H H O SO3H H3C C H3C C C C C C H rearrangement H slow step H pKa = -5 CH3 CH3 H o o alcohol 2 carbocation 3 carbocation H3C H H3C C HO3S O H O H C CH3 alkene (E1 mechanism) CH3 Example reactions OH H2SO4 / probably E2 OH H SO / 2 4 E1 H SO / 2 4 E1 OH OH H2SO4 / E1 OH E1 H2SO4 / rearrangement y:\files\classes\Organic Chemistry Tool Chest\Reactions Lists\Org rxns summary, alkenes, -ynes, with mechs.doc Alkenes, Alkynes & Variations Beauchamp 9 g. Making Allylic Alcohols from Epoxides using LDA (E2 reaction using LDA + epoxides) a H O Li H O Li O C C H O H H N H H H C C H CH2 H CC E2-like H C H H 2 2. workup H C H H reaction 2 proton LDA, lithium diisopropyl amide transfer (always a base in our course) b H O Li H Li O O O CC CH3 H CH3 N H H CH3 CC H CH2 H C C E2-like H C H H 2 2. workup H C H H reaction 2 proton LDA, lithium diisopropyl amide transfer (always a base in our course) Example reactions OH 1.