Alkenes, Alkynes & Variations Beauchamp 1
Organic Reactions Summary Alkenes, alkynes and variations
For Use as a Study Guide
Beauchamp
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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
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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
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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
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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 Ph 3. CH CH=O Normal Wittig 3 Z alkene preferred S 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
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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. LDA, -78oC O 2. workup allylic alcohols, can oxidize to C=O
O 1. LDA, -78oC OH 2. workup allylic alcohols, can oxidize to C=O
allylic alcohols, can oxidize to C=O O o 1. LDA, -78 C OH 2. workup
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Reactions of alkenes, alkynes and conjugated variations a. RBr from alkenes (anti-Markovnikov addition of HBr using free radical chemistry):
mechanism using HBr / ROOR / h for free radical addition to alkane pi bonds (anti-Markovnikov addition = Br adds to less substituted position to form most stable free radical intermediate, and then H adds to more substituted position) HBr H2 overall reaction H C Br C R2O2 (cat.) H C C H C h 3 3 CH2 H2
1. initiation (two steps) R O R O H = 40 kcal/mole O R h O R (cat.)
R BE = +88 kcal/mole BE = -111 kcal/mole O H Br R H Br O reagent H = -23 kcal/mole 2a propagation H H C BE = +63 kcal/mole Br BE = -68 kcal/mole H3C CH2 C Br H3C C H = -5 kcal/mole H2
2b propagation H H2 BE = +88 kcal/mole H = -15 C Br BE = -98 kcal/mole C Br H Br Br H3C C both steps H3C C H2 (2a + 2b) H2 H = -10 kcal/mole
3. termination = combination of two free radicals - relatively rare because free radicals are at low concentrations
H H Br Br C Br C Br H = -68 kcal/mole H3C C H3C C H2 H2 CH3 H H H2 C CH H = -80 kcal/mole C C Br Br Br CH C C CH Br 3 H3C C H2 H2 H2 CH3 very minor products
Example reactions H-Br / h ROOR (cat.) Br achiral
Br2 / h ROOR (cat.) Br achiral
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Br Br2 / h ROOR (cat.) R/S enantiomers
Br Br2 / h ROOR (cat.) cis and trans
b. RBr from alkenes (anti-Markovnikov addition of HBr using borane chemistry):
-- mechanism using 1. BH3 2. Br2 / CH3O for anti-Markovnikov addition of H-Br to alkane pi bonds (concerted, syn addition of H-BH2 to alkene pi bond, followed by complex with Br2 and migration of R group to Br) H2 overall reaction H 1. (BH ) C Br C 3 2 2. Br , CH O H C C H C 2 3 3 3 CH2 H2
step 1 R CH 3 H H3C H B R B R C C H C CH H C C H 2 R 2 syn addition, with H2C CH2 H at more substituted H2C CH2 C position and B at less C H2 substituted position. H2
step 2 R R R H H3C H3C H H C H 3 B R B R B R C C Br C H C C H Br Br H C C Br Br 2 2 H2C C H H H C CH H C CH 2 2 2 2 H2C CH2 Br C C C H H 2 2 H2
H3C O
R R H C H 3 H C H B R 3 B R C CH3 CH3 Br O C O H C C Br 2 H C C H 2 H C CH H 2 2 H C CH C 2 2 H2 C H2
Example reactions 1. (BH ) 3 2 Br achiral 2. Br2, CH3O
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1. (BH3)2 Br 2. Br2, CH3O achiral
Br 1. (BH3)2 2. Br2, CH3O R/S enantiomers
Br 1. (BH3)2 2. Br2, CH3O
() or (dl) enantiomers
c. Alkenes with aqueous sulfuric acid. Alcohol synthesis (Markovnikov addition, rearrangements are possible).
Attack carbocation Acid/base Protonate H H H alkene with water proton H H nucleophile. transfer. pi bond. C H O H H3C C CH3 H C C CH H C C 3 3 slow step 3 H O H H alkene O O H H H H H O H alcohol
H H H H H H H H O H H3C C H3C C slow step C C C C H rearrangement H alkene CH3 H CH3 H o 2 carbocation H O H 3o carbocation
CH3 CH3 CH3 acid catalysis CH H3C C CH2 alkene + water alcohol 3 H3C C C O H2 acid catalysis H3C H alkene + alcohol ether O H alcohol H O
H
Example Reactions OH H2SO4 / H2O hydration + (H3O ) achiral
OH hydration H2SO4 / H2O + (H3O ) enantiomers (R and S)
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OH hydration H2SO4 / H2O + (H3O ) enantiomers (R and S)
OH hydration H2SO4 / H2O (H O+) 3 achiral
OH hydration H2SO4 / H2O (H O+) 3 achiral rearrangement
hydration H2SO4 / H2O + (H3O ) OH diastereomers S S (SR and SS)
d. Alkenes with alcohol + sulfuric acid. Markovnikov addition, ether synthesis (rearrangements are possible).
H H H H H C H O CH H3C C CH3 H C C CH 3 H C C 3 3 slow step 3 H O CH H 3 alkene O O H H3C H H3C H O CH3 ether
H H H H H H CH3 H H C C CH3 H O CH H3C C 3 3 C C slow step C C rearrangement H3C C CH2 H H H CH H alkene CH3 3 O o 2 carbocation H O CH3 H3C H 3o carbocation H3C O
acid catalysis H alkene + water alcohol CH3 CH3 alkene + alcohol acid catalysis ether H3C C C H2 O H C ether 3
Example Reactions OR H2SO4 / ROH hydration + (ROH2 ) achiral
OR hydration H2SO4 / ROH + (ROH2 ) enantiomers (R and S)
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OR hydration H2SO4 / ROH + (ROH2 ) enantiomers (R and S)
OR hydration H2SO4 / ROH + (ROH2 ) achiral
O R hydration H2SO4 / ROH + (ROH2 ) achiral rearrangement
hydration
H2SO4 / ROH (ROH +) OR 2 S diastereomers S (SR and SS) e. Alkenes with 1. HgX2 / H2O 2. NaBH4. Alcohol synthesis with minimal rearrangements (Markovnikov).
mercuric acetate Hg(OAc)2 O O O O Hg O O Hg O O
These d orbital electrons on mercury are available. They ethanoate has a +Hg(OAc) are not usually drawn, but are helpful for understanding common name of electrophile the Hg+ bridge in the cationic intermediate. acetate = OAc
H H O
O O O resonance Hg O Hg O Hg O
The large mercury atom with extra d electron densitiy bridges across the two carbons (like Br+ in the next section) or the protonated epoxide bridge and prevents rearrangement. Nucleophilic attack in the next step occurs from the opposite side to the mercury bridge and H R = H = water nucleophile H occurs at the more + carbon (the more substituted carbon). H forms alcohol product O R O H H R = C = alcohol nucleophile H H O H forms ether product O O proton H transfer
The initial adduct is a stable, organomercury compound, O O but is not usually isolated. It is relatively toxic and need not be isolated. The next step can be run in the same Hg O Hg O reaction pot (reduction of mercury with NaBH4).
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H O The Hg bridge helps to prevent rearrangement. O O H H B H H H O O O H
Hg O
O H H Hg H Hg H H B H H H H Hg metal H
SN2 nucleophilic attack by hydride at the mercury Free radical dissociation of A hydrogen atom is abstracted from the atom displaces acetate as the leaving group. the weak Hg-C bond occurs. mercury by the highly reactive carbon free Acetate can complex at boron taking the place of Other free radical reactions are possible here, but not radical. This forms mercury metal as one of the transferred hydride. This keeps boron with an emphasized in our course. the products. No stereoselectivity is observed octet, which also is negatively charged. here because of the sp2 free radical carbon.
Example Reactions
OH 1. HgX2 / H2O 2. NaBH4 achiral
OH
1. HgX2 / H2O enantiomers 2. NaBH4 R and S
OH
1. HgX2 / H2O 2. NaBH enantiomers 4 R and S
1. HgX2 / H2O 2. NaBH4 achiral OH
OH 1. HgX2 / H2O achiral 2. NaBH4
no rearrangement
1. HgX2 / H2O diastereomers 2. NaBH4 SR and SS CH3 S S OH
y:\files\classes\Organic Chemistry Tool Chest\Reactions Lists\Org rxns summary, alkenes, -ynes, with mechs.doc Alkenes, Alkynes & Variations Beauchamp 16 f. Alkenes with 1. HgX2 / ROH 2. NaBH4. Ether synthesis with minimal rearrangements (Markovnikov).
mercuric acetate Hg(OAc)2 O O O O Hg O O Hg O O
These d orbital electrons on mercury are available. They ethanoate has a +Hg(OAc) are not usually drawn, but are helpful for understanding common name of electrophile the Hg+ bridge in the cationic intermediate. acetate = OAc
H H C 3 O
O O O resonance Hg O Hg O Hg O
The large mercury atom with extra d electron densitiy bridges across the two carbons (like Br+ in the next section) or the protonated epoxide bridge and prevents rearrangement. Nucleophilic attack in the next step occurs from the opposite side to the mercury bridge and H R = H = water nucleophile H occurs at the more + carbon (the more substituted carbon). H C forms alcohol product 3 O R O H H C R = C = alcohol nucleophile H C H3C 3 3 O H forms ether product O O proton H transfer
The initial adduct is a stable, organomercury compound, O O but is not usually isolated. It is relatively toxic and need not be isolated. The next step can be run in the same Hg O Hg O reaction pot (reduction of mercury with NaBH4).
O H3C The Hg bridge helps to prevent rearrangement. O O H3C H B H3C H3C H O O O H
Hg O
O H H Hg H Hg H H B H H H H Hg metal H
SN2 nucleophilic attack by hydride at the mercury Free radical dissociation of A hydrogen atom is abstracted from the atom displaces acetate as the leaving group. the weak Hg-C bond occurs. mercury by the highly reactive carbon free Acetate can complex at boron taking the place of Other free radical reactions are possible here, but not radical. This forms mercury metal as one of the transferred hydride. This keeps boron with an emphasized in our course. the products. No stereoselectivity is observed octet, which also is negatively charged. here because of the sp2 free radical carbon.
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Example Reactions
O 1. HgX / CH OH 2 3 achiral 2. NaBH4
O 1. HgX / CH OH 2 3 enantiomers 2. NaBH4 R and S
O
1. HgX2 / CH3OH enantiomers 2. NaBH4 R and S
1. HgX / CH OH 2 3 achiral 2. NaBH4 O
O
1. HgX2 / CH3OH achiral 2. NaBH4 no rearrangement
diastereomers 1. HgX2 / CH3OH SR and SS 2. NaBH4 CH3 S S O
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g. Electrophilic addition of HCl, HBr, HI to alkenes = Markovnikov addition, synthesis of RX compounds with possibile rearrangements H H Cl C Cl a H a not this primary carbocation not observed way (less stable) b H Cl H Cl Cl Which carbon atom b reacts first, ...second? C add a H2 nucleophile tertiary carbocation only product (more stable) Forms pi bonds. lose beta proton Starts rearrange over. There are two carbon choices for an electrophile to react with. Which carbon gives up the electrons and becomes a carbocation is based on the most stable carbocation that can form (leading to a regioselective reaction). Such a reaction is generally not stereoselective because the flat carbocation allows attack of the nucleophile to both faces. We expect three possible reactions from the carbocation, add a nucleophile, lose a beta proton or rearrange.
c. b achiral Cl rearrangement H Cl
O b a Cl O OH a Cl 40% (solvent) OH achiral
40% Cl O O O (dl mixture) OH resonance O O 20% H
Example Reactions Br
H-Br
only shows regioselectivity Markovnikov additioni
I I
D-I D D only shows stereoselectivity (dl) enantiomers (dl) enantiomers
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I I
D-I D D only shows stereoselectivity (dl) enantiomers (dl) enantiomers
H-Br CH3 Br Br CH3 shows regioselectivity but not stereoselectivity diastereomers (if no rearrangement)
H-Br
shows possible rearrangements Br
h. Electrophilic addition of HCl, HBr, HI to alkynes = Markovnikov addition, synthesis of RX compounds, can use 1 equivalent or 2 equivalents H H CH C C 2 C C H H Cl C H C H C 3 3 H C Cl Cl 3 1 eq. HCl
CH2 CH3 CH3 Cl C H Cl C C Cl H C Cl 3 H C Cl H3C 2 eqs. HCl 3 Cl
Br
H-Br
shows regioselectivity Markovnikov additioni
Br Br
H-Br E/Z diastereomers
Br Br
H-Br Ph Ph shows regioselectivity E/Z diastereomers
H Cl
O O
OH Cl 50% / 50% shows regioselectivity (solvent) O
y:\files\classes\Organic Chemistry Tool Chest\Reactions Lists\Org rxns summary, alkenes, -ynes, with mechs.doc Alkenes, Alkynes & Variations Beauchamp 20 i. Electrophilic addition of HCl, HBr, HI to conjugated diene or triene = Markovnikov addition, synthesis of RX compounds, can use 1 equivalent or 2 equivalents
H + A 1,2-addition 1,4-addition C CH2 H C C 3 H H Br C CH2 Br H H C C resonance Br Br 2 H H Temp = -80oC 80% 20% B (a kinetic choice) C CH2 Temp = +40oC 20% 80% H3C C H (a thermodynamic choice when more energy is available)
a b Br 3o carbocation Br H is best resonance 2 4 1 3 a b Br Br
kinetic product thermodynamic product larger + in intermediate more stable alkene
a b c Br Br H resonance resonance 2 4 6 3 5 1 a H H b Br H c Br Br
1,2 addition - This looks second 1,4 addition 1,6 addition - This looks best because the alkenes are conjugated. least favorable because because the alkenes are more it breaks conjugation substituted and conjugated.
y:\files\classes\Organic Chemistry Tool Chest\Reactions Lists\Org rxns summary, alkenes, -ynes, with mechs.doc Alkenes, Alkynes & Variations Beauchamp 21 j. Alkenes with Br2 or Cl2. Synthesis of vicinal dihalide (anti addition).
Br
Br Br CCl4 Br 85% Br Br
bromine is a red orange liquid (dl) mixture dissolved in the solvent, the color disappears as it is added
Cl Cl Cl Cl CHCl3 81% Cl Cl meso (achiral)
chlorine is a green gas, dissolved in the solvent
Br a b Br Br HC CH Br 2 CH2 Br HC HC CH
CH CH2 H C HC CH a 2 H2C Br 2 HC Br 88% 12% HC b 1,2-addition is the kinetic CH2 Br 1,4-addition is the CH thermodynamic product product because bromine 2 attack is faster at the more a because the double bond is more substituted (E or positive seconday carbon Z is possible) atom.
Br bromination Br Br (or Cl2) Br enantiomers R and S
Br bromination Br Br (or Cl ) 2 meso, RS
Br
Br bromination Br Br Br (or Cl ) 2 enantiomers RR and SS
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Br Br Br bromination (or Cl ) 2 enantiomers Br RR and SS
bromination Br Br Br (or Cl2) Br achiral
Br bromination Br Br (or Cl2) Br diastereomers S SRR and SSS
Br
Br Br Br 3% 21% Br
4 o Br2 / CHCl3 / 0 C 2 3 Br Br Br 1 5% 71%
k. Alkenes with Br2/H2O or Cl2/H2O. Synthesis of bromohydrin or chlorohydrin (anti + Markovnikov addition).
Br
Br Br Br H H Br O H H O H H O H O O
Br H H (dl) mixture
Cl Cl H H Cl Cl Cl O O H H H H O H O O
H (dl) mixture H Cl
OH anti + Markovnikov Br2 / H2O addition (or Cl / H O) 2 2 Br enantiomers R and S
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OH anti + Markovnikov addition Br2 / H2O (or Cl2 / H2O) enantiomers RS and SR Br
OH anti + Markovnikov addition
Br2 / H2O Br (or Cl2 / H2O) enantiomers RR and SS
OH anti + Markovnikov addition Br2 / H2O (or Cl2 / H2O) enantiomers RR and SS Br
OH Br2 / H2O anti + Markovnikov addition (or Cl2 / H2O)
Br achiral no rearrangement
Br Br2 / H2O anti + Markovnikov (or Cl2 / H2O) addition OH S S diastereomers SRR and SSS
l. Alkenes with Br2/ROH or Cl2/ROH. Synthesis of bromo or chloro “ethers”.
Br
Br Br Br H H Br O H CH O H CH 3 3 O H O O
Br H C (dl) mixture 3 H3C
Cl Cl H H Cl Cl Cl O O H CH3 H CH3 O H O O
H3C (dl) mixture H C Cl 3
OR anti + Markovnikov Br2 / ROH addition (or Cl / ROH) 2 Br enantiomers R and S
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OR anti + Markovnikov addition Br2 / ROH (or Cl2 / ROH) enantiomers RS and SR Br
OR anti + Markovnikov addition Br2 / ROH Br (or Cl2 / ROH) enantiomers RR and SS
OR anti + Markovnikov Br2 / ROH addition (or Cl2 / ROH) enantiomers Br RR and SS
anti + Markovnikov Br2 / ROH OR addition (or Cl / ROH) 2 Br achiral
Br Br / ROH anti + Markovnikov 2 addition (or Cl2 / ROH) OR diastereomers S S SRR and SSS
-- m. Alkenes with 1. BH3 2. H2O2/HO . Hydroboration/oxidation = anti-Markovnikov alcohols.
The mechanism for this reaction is given at the beginning of this document.
1. BH3 1. syn addition 2. H2O2 / HO OH 2. oxidation achiral
OH 1. syn addition 1. BH3 2. oxidation 2. H2O2 / HO enantiomers R and S
OH 1. syn addition 1. BH3 2. oxidation 2. H2O2 / HO enantiomers R and S
1. syn addition 1. BH3 2. oxidation 2. H2O2 / HO OH achiral
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1. BH 1. syn addition 3 2. oxidation 2. H2O2 / HO
OH achiral
OH 1. syn addition 1. BH3 2. oxidation 2. H2O2 / HO CH3 diastereomers S S SRR and SSS H
-- n. Alkenes with 1. BH3 2. Br2/CH3O . Hydroboration/bromination = anti-Markovnikov R-Br.
alkyl migration, with CH2CH2R bromide leaving R CH2CH2R RH2CH2C CH2CH2R group, reacts 2x more B but not shown. R B RH2CH2C B 3 Br Br CH CH R Br 2 2 CH2CH2R Br strong Lewis base Lewis acid Br trivalent boron (trigonal planar) tetravalent H3C O trivalent boron boron Lewis acid/base reaction Br Br R R R R B B Br H2C R B(OCH ) H2C R C 3 4 C CH3 O CH2CH2R H2 H2 O anti-Markovnikov product similar reactions, H3C 3x total A weaker -Br-Br bond is broken and a stronger (two more times) tetravalent C-Br bond is formed. Bromide is a good boron leaving group in the strongly basic solution.
1. BH3 1. syn addition 2. bromination 2. Br2 / CH3O Br achiral
Br 1. syn addition 1. BH3 2. bromination 2. Br2 / CH3O enantiomers R and S
1. BH3 1. syn addition 2. bromination 2. Br2 / CH3O
Br achiral
Br 1. syn addition 1. BH3 2. bromination 2. Br2 / CH3O
achiral
Br 1. syn addition 1. BH3 2. bromination 2. Br2 / CH3O CH3 S diastereomers S SRR and SSS H
y:\files\classes\Organic Chemistry Tool Chest\Reactions Lists\Org rxns summary, alkenes, -ynes, with mechs.doc Alkenes, Alkynes & Variations Beauchamp 26
-- o. Alkynes with 1. HBR2 2. H2O2/HO . Hydroboration/oxidation = anti-Markovnikov aldehydes.
Step 1 H H
BO BO H H H H reactive form of borane THF = tetrahydrofurane borane/THF complex (a good Lewis acid) R R R H C H H C 2 H C H B 2 2 H H H CH2 H CH2 CH2 CH H B R 2 H B R CH2 H B R H concerted C C reaction H CC C C C C H C C R H similar reaction R H similar reaction R H H H H H a second time H H a third time H H alkene + borane monoaklylborane diaklylborane triaklylborane There are no more hydrides to transfer. The transfer of two electron pairs is concerted. The boron and hydrogen atom add from the same face (syn), so this reaction is stereoselective. The boron adds at the less substituted carbon so this reaction is also regioselective. In subsequent reactions the boron can be converted to another group in exactly the same position, so whereever the boron ends up will indicate the position of the actual group introduced (OH or Br for us). Step 2 H H O O O H O O H O H H weak strongstrong weak There is a strong electron pair donor on each side of the equilibrium equation that can complex with trivalenet boron, but only the peroxide anion reacts further. All of these are present.
alkyl migration, CH CH R with hydroxide H CH CH R RH CH C 2 2 CH2CH2R 2 2 2 2 CH CH R leaving group B 2 2 RH CH C B O O RH2CH2C B 2 2 OCH CH R CH2CH2R O 2 2 strong Lewis base Lewis acid H O tetravalent trivalent (trigonal planar) boron H O boron trivalent boron Lewis acid/base reaction CH2CH2R CH CH R CH CH R OCH CH R RH CH C 2 2 O O 2 2 RH CH CO 2 2 2 2 OCH CH R 2 2 OCH CH R B 2 2 B 2 2 RH2CH2CO B O ligand O H trivalent similar reactions, O dissociation (two more times) H boron H tetravalent O H H boron proton tetravalent transfer boron
H2 C OH similar reactions, H O R C (two more times) H A weaker -O-O- bond is broken and a stronger C-O 2 bond is formed. Hydroxide, HO is an acceptable Anti-Markovnikov alcohol is leaving group in the strongly basic solution formed in a regioselective (compatible with the reaction conditions). and stereoselective manner.
y:\files\classes\Organic Chemistry Tool Chest\Reactions Lists\Org rxns summary, alkenes, -ynes, with mechs.doc Alkenes, Alkynes & Variations Beauchamp 27
O anti-Markovnikov 1. HBR2 addition 2. H2O2 / HO H aldehyde
O anti-Markovnikov 1. HBR2 addition 2. H O / HO 2 2 aldehyde H
O 1. HBR2 2. H2O2 / HO ketone
O O 1. HBR2 2. H2O2 / HO
2 ketones
-- -- p. Alkenes with CHCl3 / RO or CHBr3 / RO . Carbene synthesis of dihalocyclopropanes.
Cl Cl Cl Cl Cl CH O R Cl C Cl C = C
Cl Cl Cl Cl chloroform alkoxide singlet carbene (trichloromethane) strong base pKa 25 A different type of elimination reaction.
Cl Cl electron C electron donation acceptance stereoselective reaction Cl Cl
concerted reaction C R R (occurs in one step) CC CC R R H H H H "cis" alkenes form "cis" cyclopropane rings
"trans" alkenes form "trans" cyclopropane rings
y:\files\classes\Organic Chemistry Tool Chest\Reactions Lists\Org rxns summary, alkenes, -ynes, with mechs.doc Alkenes, Alkynes & Variations Beauchamp 28
q. Alkenes with CH2I2 / Zn (Simmons-Smith Rxn). Carbenoid synthesis of cyclopropanes. Example Reactions syn addition CBr2 CHBr3 / NaOH enantiomers R and S
CBr 2 syn addition CHBr3 / NaOH enantiomers RR and SS
CBr2 syn addition CHBr3 / KOC(CH3)3 meso RS and SR
syn addition CCl2 CHCl3 / NaOH meso RS and SR
CCl2 syn addition
CHCl3 / NaOH achiral
syn addition CHCl3 / KOC(CH3)3 CCl2
S S diastereomers CH3 SSR and SRS
The first pair of dots represents Simmons-Smith reaction easily lost 4s electrons on zinc, I that reduce a C-I bond.
I +2 +2 I Zn I Zn I H C I Zn H C H C
H H H carbenoid complex The second pair of dots represents The stabilization by the metal makes the complex more 3d electrons on zinc that are stable, and less reactive. This makes the carbenoid invoked in the metal complex. complex more selective for the desired reaction.
H H electron C electron donation acceptance H2 concerted reaction C (occurs in one step) R R CC R R CC "cis" alkenes form "cis" cyclopropane rings H H H H "trans" alkenes form "trans" cyclopropane rings
y:\files\classes\Organic Chemistry Tool Chest\Reactions Lists\Org rxns summary, alkenes, -ynes, with mechs.doc Alkenes, Alkynes & Variations Beauchamp 29
Example Reactions (Simmons-Smith reaction) syn addition CH2 CH2I2 / Zn(Cu) enantiomers R and S
CH 2 syn addition CH2I2 / Zn(Cu) enantiomers RR and SS
CH2 syn addition CH2I2 / Zn(Cu) meso RS and SR
syn addition CH CH2I / Zn(Cu) 2 2 meso RS and SR
CH2 syn addition
CH2I / Zn(Cu) 2 achiral
syn addition CH2 CH2I2 / Zn(Cu) S S diastereomers CH3 SSR and SRS
r. Alkenes with meta chloroperbenzoic acid (mCPBA). Synthesis of epoxides.
mCPBA (peroxyacid) has two electron buffered solution poor oxygen atoms in the peroxide bond, prevents acid from and the meta-Cl makes them even more reacting with epoxide electron poor by its inductive effect. O O Cl 5 atoms Cl H
O O View this complicated group H of arrows as two different O one step O groupings in the transition 3 atoms concerted state, one of five atoms and reaction CC one of three atoms. It might R R R R be easier to think about this way. H H CC The reaction can occur from either the top face or the bottom face. The alkene is electron rich. H H
costs (bond energy in kcal/mole) gains (bond energy in kcal/mole) changes C=O (even trade) = -176 C=O (even trade) = +176 in energy O-H (even trade) = + 110 O-H (even trade) = - 110 O-O (very weak) = +45 C-O (very weak) = -90 C=C (weak pi bond) = +64 C-O (very weak) = -90 Total = - 466 ring strain of an epoxide H = -44 kcal/mole is also a cost = + 27 exothermic, even with ring strain Total = + 422 Example Reactions (mCPBA) y:\files\classes\Organic Chemistry Tool Chest\Reactions Lists\Org rxns summary, alkenes, -ynes, with mechs.doc Alkenes, Alkynes & Variations Beauchamp 30
O
Ar H O syn addition (mCPBA) enantiomers O O R and S
O O syn addition Ar H
(mCPBA) O O enantiomers RR and SS
O O syn addition Ar H meso (mCPBA) O O RS and SR
O syn addition Ar H O meso (mCPBA) O O RS and SR
O O syn addition Ar H
(mCPBA) O O achiral
O syn addition Ar H O (mCPBA) O O diastereomers S S SSR and SRS
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s. Alkenes with OsO4 or KMnO4. “Syn” synthesis of vicinal diols.
KMnO4 and OsO4 change in oxidation state...? are electron poor each carbon goes from -1 to 0 (2 electrons lost) manganese goes from +7 to +5 (2 electrons gained) O O K Mn O O O O O O O H O O Mn Mn O Mn H H O O O O O O R R KMnO4 H CC CC CC H2O R CC R R R R R HO H H H H H H H H The stereochemistry is The alkene is electron rich Use analogies with hydroxide set at this point as "syn" hydrolysis of esters and imides addition presented earlier.
O O O H O O H O H H H H Mn O O Mn O O O H O O H CC CC R R R R CC H H R H H R OsO4 has a similar mechanism. H H
Very expensive OsO4 can be continually reoxidized with an inexpensive amine oxide (like morpholine N- oxide) O O O O resonance O N O N Os + O Os O O Os O O O O O osmium tetroxide amine oxide reduced OsO morpholine 3 (Os = +8) (N = -1) (Os = +6) (N = -3)
Example Reactions
y:\files\classes\Organic Chemistry Tool Chest\Reactions Lists\Org rxns summary, alkenes, -ynes, with mechs.doc Alkenes, Alkynes & Variations Beauchamp 32
OsO4 or OH syn addition
KMnO4 OH achiral
OH OsO4 or syn addition KMnO 4 CH3 S S diastereomers OH SSR and SRS
o t. Alkenes with 1. O3 / -78 C 2. CH3SCH3 or Zn. Synthesis of aldehydes or ketones.
Ozone is an electron poor oxidzing reagent. O O O O O O O O O o C -78 C -78oC C 2 C1 C2 1 H R R R R R R R Cyclic five atom R H Peroxide transition state bond rotate C1 C2 with six electron ruptures resonance 180o movement. Molozonide is highly o (shown). R H unstable, even at -78 C O and rearranges to a more H R Simple alkenes are electron rich. O stable ozonide with only C2 one peroxide bond. C1 R R O Rejoins with only one peroxide bond (use polarities). O O O O S resonance H C CH OO 3 3 R S S C1 C2 R R R C C H3C CH3 H3C CH3 H R 1 2 O H dimethylsulfoxide ketone aldehyde R (DMSO) ozonide The C=C is completely cleaved at -78oC. The second step decides what will happen to the ozonide. In this example, it is reduced by DMS to two carbonyl compounds, (an aldehyde and a ketone).
Example Reactions O o 1. O3 / -78 C O 2. CH3SCH3 CH H2C H3C
O o 1. O3 / -78 C CH3 2. CH3SCH3 CH HC H3C O
O o CH3 1. O3 / -78 C CH HC 2. CH3SCH3 H3C O
y:\files\classes\Organic Chemistry Tool Chest\Reactions Lists\Org rxns summary, alkenes, -ynes, with mechs.doc Alkenes, Alkynes & Variations Beauchamp 33
O 1. O / -78oC C 3 H 2. CH3SCH3 H C O
o 1. O3 / -78 C 2. CH SCH 3 3 O O H2C
O 1. O / -78oC C 3 H 2. CH3SCH3 CH3 S S O
o u. Alkenes with 1. O3 / -78 C 2. NaBH4. Synthesis of alcohols. O O O BH3 H BH ketone OO 3 aldehyde R O -78oC b. NaBH workup O R R R 4 C1 C2 H BH -- is electron C1 C C C several R O 4 2 1 2 steps rich, the ozonide R R H R ozonide R H is electron poor H BH 3 H BH3 H H O O H O H O O R C R H C R H R C R H C R H H final workup The ketone becomes The aldehyde becomes (neutralization) H H a secondary alcohol. a primary alcohol.
Example Reactions OH o 1. O3 /-78C OH 2. NaBH4 H3C
OH o 1. O3 / -78 C 2. NaBH4
OH
y:\files\classes\Organic Chemistry Tool Chest\Reactions Lists\Org rxns summary, alkenes, -ynes, with mechs.doc Alkenes, Alkynes & Variations Beauchamp 34
OH o 1. O3 / -78 C 2. NaBH4
OH
o 1. O3 / -78 C 2. NaBH 4 OH OH H3C
OH o diastereomers 1. O3 / -78 C (SR and SS) 2. NaBH4 CH3 S S OH
o -- v. Alkenes with 1. O3 / -78 C 2. H2O2 / HO . Synthesis of carboxylic acids or ketones. O O O OH ketone OO peroxide intermediate R O -78oC b. NaBH workup OH R R R 4 O O C1 C2 -- C several O H BH4 is electron 1 C C1 C2 R R R 2 steps rich, the ozonide R H ozonide is electron poor R H rearrangement of peroxide (hydride shift)
OH O OH H O H O H basic O conditions C2 H H C C R O 2 H 2 R O final workup R O (neutralization) carboxylic acid
Example Reactions O HO O o 1. O3 / -78 C C 2. H2O2 / HO C H3C OH OH
O o 1. O3 / -78 C 2. H2O2 / HO C H3C OH
O 1. O / -78oC 3 C 2. H2O2 / HO H3C OH
y:\files\classes\Organic Chemistry Tool Chest\Reactions Lists\Org rxns summary, alkenes, -ynes, with mechs.doc Alkenes, Alkynes & Variations Beauchamp 35
CO H o 2 1. O3 / -78 C 2. H2O2 / HO CO2H
HO O 1. O / -78oC 3 O C 2. H2O2 / HO OH
CO2H o 1. O3 / -78 C 2. H2O2 / HO CH3 S S O
w. Alkenes with Pd / H2. Synthesis of “alkane” from “alkene” (hydrogenation). Simplistic mechanism:
Hydride transfer also bonds carbon H H to the metal atom. H H C C M M M M C H C C C H H H metal HOMO metal hydride metal HOMO metal hydride H LUMO sigma bond complex 2 bond LUMO pi bond complex Hydride transfer releases an alkane and regenerates the metal catalyst. H C H M C adds H . 2 Neutral metal atom can begin Syn (cis) addition of two hydrogens the process over = catalytic. to the pi bond. Generally H2 adds from the less sterically hindered face (i.e. the H2 adds to the more open face). Example reactions
syn addition Pd / H2 achiral
syn addition Pd / H2 achiral
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syn addition
Pd / H2 achiral
syn addition Pd / H2 achiral
syn addition Pd / H2 achiral
syn addition Pd / H2 diastereomers SR and SS S S
x. Alkenes with Pd / D2. Same hydrogenation reactions with deuterium from “alkene” (hydrogenation w/”D” = deuterium). * = chiral center D syn addition S Pd / D2 D * R / S
D syn addition R Pd / D 2 * * R RR and SS (enantiomers) D D syn addition R Pd / D D 2 * * S RS and SR (meso,achiral)
R D syn addition Pd / D2 * * RS and SR (meso,achiral) S D
D D syn addition Pd / D2
achiral
y:\files\classes\Organic Chemistry Tool Chest\Reactions Lists\Org rxns summary, alkenes, -ynes, with mechs.doc Alkenes, Alkynes & Variations Beauchamp 37
R D syn addition Pd / D * 2 D S * * diastereomers S S SSR and SRS
y. Alkynes with aqueous sulfuric acid (plus some Hg+2 catalyst). Synthesis via enols (Markovnikov addition).
O H2SO4 / H2O + +2 Markovnikov addition = H3O (Hg ) (enol tautomerization to keto)
O H2SO4 / H2O Markovnikov addition = H O+ (Hg+2) (enol tautomerization 3 to keto)
H2SO4 / H2O O + +2 = H3O (Hg ) O
O
H2SO4 / H2O + +2 = H3O (Hg ) Markovnikov addition (enol tautomerization to keto)
y. HX addition to alkynes. Markovnikov addition.
H Br Br (or HCl or HI) Markovnikov addition
Br H Br Markovnikov (or HCl or HI) addition
H Br Br (or HCl or HI) Br
Br
H Br (or HCl or HI) Markovnikov addition
y:\files\classes\Organic Chemistry Tool Chest\Reactions Lists\Org rxns summary, alkenes, -ynes, with mechs.doc Alkenes, Alkynes & Variations Beauchamp 38
z. Bromination (or chlorination) of alkynes. Bridging bromonium ion.
Br2 Br or anti addition Cl2
Br Br Br2 or anti addition
Cl2 Br Br Br2 or anti addition
Cl2 Br Br
Br2 or anti addition Cl2 Br
aa. 1. Hydroboration 2. oxidation of alkynes (anti-Markovnikov addition makes aldehydes or ketones via enolate).
O 1. HBR2 2. H2O2 / HO anti Markovnikov addition H
O 1. HBR2 anti Markovnikov 2. H2O2 / HO addition
O 1. HBR2 2. H2O2 / HO O
1. HBR2 2. H2O2 / HO anti Markovnikov O addition
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bb. Catalytic hydrogenation reduces triple bond to “alkane”.
Pd / H2
Pd / H2
Pd / H2
Pd / H2
cc. Catalytic hydrogenation with quinoline “poison” of Pd catalyst reduces triple bond to Z alkene (syn addition).
Pd / H2 quinoline (Lindlar's Cat.)
Pd / H2 quinoline (Lindlar's Cat.)
Pd / H2 quinoline (Lindlar's Cat.)
Pd / H2 quinoline (Lindlar's Cat.)
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dd. Sodium metal + liquid ammonia reduction of triple bond to E alkenes.
Na / NH3 (liq - =33oC)
Na / NH3 (liq - =33oC)
Na / NH3 (liq - =33oC)
Na / NH3 (liq - =33oC)
ee. Zipper reaction moves triple bond to terminal position where it can be removed to form sp carbanion nucleophile.
1. NaNR2 2. WK
Zipper reaction
1. NaNR2 2. WK
Zipper reaction
1. NaNR2 2. WK
Zipper reaction
1. NaNR2 2. WK
Zipper reaction
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ff. Formation of conjugate base + addition of aldehyde electrophile forms propargyl alcohol.
OH 1. NaNR2 2. O
H
1. NaNR2 OH 2. O
H
OH 1. NaNR2 2. O
H
1. NaNR2 2. O
H OH
gg. Formation of conjugate base + addition of ketone electrophile forms propargyl alcohol.
1. NaNR2 2. O OH
1. NaNR2 2. O OH
1. NaNR2 2. O OH
1. NaNR2 2. OH O
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hh. Formation of conjugate base + addition of methyl or primary RX electrophile forms a longer alkyne.
1. NaNR2 2.
Br
1. NaNR2 2.
Br
1. NaNR2 2.
Br
1. NaNR2 2.
Br
ii. Formation of conjugate base + addition of secondary electrophile reacts in a nonproductive E2 reaction.
1. NaNR2 2. Br
E2 reaction
1. NaNR2 2. Br
E2 reaction
1. NaNR2 2. Br
E2 reaction
1. NaNR2 2. Br
E2 reaction
y:\files\classes\Organic Chemistry Tool Chest\Reactions Lists\Org rxns summary, alkenes, -ynes, with mechs.doc Alkenes, Alkynes & Variations Beauchamp 43 jj. Use zipper reaction to move alkyne through a linear chain to the end position. Work up 4 ways: a. with mild acid to generate the terminal alkyne, b. with an MeX or primary RCH2X to make a longer alkyne, c. with an aldehyde or ketone compound (C=O) or d. with an epoxide.
1. excess NaNR2 2. workup
1. excess NaNR2 2. Br Ph Ph Ph = phenyl
1. excess NaNR2 2. OH H2CO 3. workup
1. excess NaNR2 2. O OH
Ph Ph Ph = phenyl 3. workup
kk. Formation of conjugate base + addition of epoxide electrophile forms an alkynyl alcohol via SN2 reaction.
1. NaNR2 2. O R
R OH
1. NaNR2 OH 2. O
1. NaNR2 OH 2. O
1. NaNR2 2. O
R OH R
y:\files\classes\Organic Chemistry Tool Chest\Reactions Lists\Org rxns summary, alkenes, -ynes, with mechs.doc Alkenes, Alkynes & Variations Beauchamp 44 ll. Epoxides with terminal acetylides (followed by workup = neutralization).
Na HO O R achiral
2. WK R
O Na HO R R chiral R 2. WK R
R O Na OH R achiral 2. WK R R Na S O R and SRR S S 2. WK S diastereomers S OH mm. Epoxides with lithium diisopropyl amide (LDA, followed by workup = neutralization).
1. Li R OH R N R R O lithium diisopropylamide (LDA) 2. WK S S enantiomers 1. Li O N R R achiral lithium diisopropylamide (LDA) OH R 2. WK
1. Li O N OH R R lithium diisopropylamide (LDA) achiral 2. WK
not stereoismers R OH R 1. Li N O R R lithium diisopropylamide (LDA) S S S 2. WK S S OH
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nn. Aldehydes and ketones with terminal acetylides.
OH O Na 1. R 2. WK H enantiomers (R and S) R O Na enantiomers (R and S) R 1. R HO 2. WK
OH O Na R 1. R 2. WK achiral diastereomers
OH O Na 1. R R 2. WK enantiomers (R and S)
oo. Aldehydes and ketones with secondary amines (enamine synthesis, alkylation, hydrolysis).
H
TsOH (-H2O) O N N 2o amines E & Z possible H H H O TsOH (-H2O) N N E & Z possible 2o amines
H O TsOH (-H2O) N N
2o amines achiral S R also possible H
O TsOH (-H2O) N N
2o amines
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