Title: ETH_Sem4 / OCII / Named reactions

Front: Simmons-Smith cyclopropanation
Back: - Reacts preferentially with electron-rich multiple bonds
- Adds to same side of heteroatom if there is one close-by

Front: Simmons-Smith cyclopropanation mechanism
Back: 1) Formation of reactive carbenoid
2) Formation of cyclopropane via butterfly-type transition state

Front: Hofmann rearrangement
Back: - Amide converted to amine 1 C shorter through isocyanate intermediate.
- Using Pb(OAc)4 or Hypervalent iodine under mildly acidic conditions, different products can be achieved:
- With first variant: No base-sensitive functional groups! Things like acetals are fine

Front: Hofmann rearrangement mechanism
Back: 1) Deprotonation by base, forming an imine
2) Softer C=N bond attacks the soft Br2, forming an N-substituted Halide
3) Base abstracts another proton
4) Bromine leaves, forming a Nitrene. Nitrene rearranges to isocyanate (not isolated).
5) Solvent or other reagent attacks the electrophilic C, forming a carbamate intermediate. In the case of ROH or RNH2, this is the final step
6) Carbamate loses CO2, forming an amine after workup

Front: Curtius rearrangement
Back: - Similar to Hoffmann. Rearrangement to isocyanate. Isocyanate can be isolated in absence of nucleophilic solvents, otherwise reacts analogously to hofmann rearrangement
- Mechanism only goes via nitrene in photochemical rearrangement with hv

Front: Lossen rearrangement
Back: - Formation of isocyanate from O-Acyl hydroxamic acid
- OH must be activated before rearrangement, by anhydrides (Ac2O), carbodiimides (e.g. CDI) or by a Mitsunobu
- Isocyanate can be isolated and reacted with different nucleophiles to afford amines, carbamates or urea derivatives

Front: Lossen rearrangement mechanism
Back: - Base abstracts H from O-Acyl hydroxamate, forming unstable anion. Good LG (from activated OH) leaves and rearrangement happens, analogously to Hofmann and Curtius

Front: How to convert carboxylic acids to acid chlorides?
Back: - Using catalytic DMF and oxalyl chloride
Or
- Stoichiometric amounts of thionyl chloride. Also works with catalytic DMF.
The last method is especially good for acid labile compounds, since no HCl is produced

Front: Mukaiyama condensation
Back: - Synthesis of amides (and also esters! -> alcohols as nucleophiles instead of amines)
- Carboxylic acid is activated by Mukaiyamas reagent (Nucleophilic, aromatic substitution), (forming a good leaving group with the O), allowing it to be attacked by the amine (or alcohol)

Front: Mukaiyama condensation mechanism
Back: 1) The carboxylate anion attacks the strongly deactivated aromatic in a nucleophilic aromatic substitution, after which a chloride anion leaves.
2) This forms an activated intermediate which can be attacked by an amine or alcohol

Front: Yamaguchi Macrolactonization
Back: - Formation of lactone (ester in ring)
- Done under dilute conditions to minimize byproducts
- Yamaguchi reagent and DMAP used to activate carboxylic acid toward substitution

Front: Yamaguchi Macrolactonization mechanism
Back: 1) Most acidic proton (carboxylic acid) is deprotonated, making the carboxylate (better nucleophile than -OH)
2) Carboxylic acid is activated first using Yamaguchis reagent, forming a good leaving group, and also making the carbonyl more electrophilic
3) The activated mixed anhydride is then attacked by DMAP, a nucleophilic catalyst.
4) The activated acyl-DMAP species can then be attacked by the hydroxy group (intramolecular), forming the lactone
Note: Carboxylic acid cannot be activated only by DMAP -> -O- is not a good LG
Activation by yamaguchi and subsequent activation by DMAP is necessary so that only the original carbonyl is attacked -> if only yamaguchi, OH could attack at both carbonyls, rearranging the ester. Substituting it for DMAP at the least hindered carbonyl gives the correct product

Front: Hunsdiecker reaction
Back: - Formation of one C-shorter alkyl halide from carboxylic acid using silver oxide (or other salts).
- R can be alkyl, aryl (deactivated), alpha-beta unsaturated.
- Activated aromatics or double/triple bonds can undergo addition reactions with the X2
- X = Cl, Br, I
- The more stable the R radical, the faster it will form
- NCS or NBS can be used to replace X2 for alpha-beta unsaturated carbonyls

Front: Hunsdiecker reaction mechanism
Back: 1) Deprotonation of carboxylic acid
2) More nucleophilic carboxylate can attack the halogen
3) Rearrangement/decomposition to CO2 and alkyl radical
4) Alkyl radical abstracts halogen, forming alkyl halide

Front: Barton decarboxylation
Back: - Formation of alkanes from carboxylic acids
- via acid chloride and thiohydroxamate ester

Front: Barton decarboxylation mechanism

Front: Acyloin condensation
Back: - Forms acyloin (alpha-hydroxy ketone) from aliphatic ester
- Using molten sodium.
- Can be used to close large rings with two esters

Front: Acyloin condensation mechanism
Back: - Uses molten sodium to reduce esters to a radical anion in a single electron transfer
- After the first reduction, two intermediates dimerize
- The alkoxy groups are eliminated, and the resulting ketones are reduced again. After workup, an enediol results which undergoes keto-enol tautomerism to form the acyloin

Front: Arndt-Eistert Homologation
Back: - Homolog = one CH2 longer
- Converts carboxylic acid into it's homolog in 3 steps
1: Activation
2: Formation of diazo compound
3: Wolff rearrangement
- Ag(I) catalyzes the formation of the carbene, as does hv. This promotes conversion to the ketene
- Goes through ketene: If solvent is alcohol or amine,  homologated ester resp. amide are formed
- 2 eq. of CH2N2 are necessary to trap HCl
- 2 Variants: Activation by acid chloride formation not good for alpha amino acids due to potential epimerization. For alpha amino acids, a mixed anhydride is used to activate the acid
-

Front: Arndt-Eistert Mechanism
Back: 1) Formation of activated carb. acid (acid chloride or mixed anhydride)
2)
- Diazomethane attacks the activated carbonyl
- N2 is eliminated, under hv or Ag(I) catalysis, forming a carbene, which rearranges to a ketene
- Solvent attacks the most electrophilic C (middle one), forming the homologated carboxylic acid after some proton transfers

Front: Wittig reaction
Back: - If R' = Alkyl -> Z olefin
- If R' = EWG (carbonyl, sulfonate) -> E olefin
- Ylides are prepared either before reaction, or in situ
- Water + oxygen sensitive, so ETHER solvents are used
- Reacts fastest with aldehydes, slower with ketones. Doesn't react with carboxylic acid derivatives
- Reaction is driven by stable phosphine oxide

Front: Wittig reaction - Formation of Phosphorus Ylid

Front: Wittig Reaction Mechanism
Back: - Phosphonium Ylid attacks carbonyl C nucleophilically, forming a betaine
- Carbonyl O then attacks the Phosphorus, forming an oxaphosphetane with a very strong P-O bond
- [2+2] retro cycloaddition to yield the product
Selectivity:
- Z Alkene is produced due to steric clash of large PPh3 and Ph. Therefore, betaine where these two are  trans is formed.
- > for EWG groups on the phosphine, the formation of the oxaphosphetane is reversible (as the negative charge can be stabilized), so it equilibrates to the more stable structure (E)

Front: Horner-Wadsworth-Emmons reaction (HWE)
Back: - Wittig modification that leads to E-selective Alpha-Beta unsaturated carbonyls
- More reactive than wittig, so react generally with all ketones and aldehydes
- Generally EWG on alpha C, also on P.
- Bases such as KH, LHDMS, KHDMS, KtBuOH etc are used.
- Generally ethers as solvents

Front: Still-Gennari reaction
Back: - Modification of HWE that leads to (Z) alkenes
- Strongly EWG on P

Front: McMurry reaction
Back: - Coupling of R groups of 2 aldehydes/ ketones
- Low valent Titanium used, and reducing agent to generate Ti(0)
- Aldehydes react much faster than ketones -> chemoselectivity
-  Not much stereoselectivity  due radical intermediates
- Reducing agents usually Zn, Zn-Cu

Front: Tebbe olefination
Back: - Methenylation of carbonyl compounds
-> Methenylates Aldehydes > Ketones > Esters > Amides.
Amides can be selectively methenylated in presence of esters if the amide has an EWG
- Lewis base can be e.g. Pyr (pyridine), DMAP
-> Ex.

Front: Bamford-Stevens-Shapiro Olefination
Back: -  Olefination of alpha carbon of aldehydes or kétones.
Uses Tosylhydrazone and base.
- Shapiro: Base = BuLi
- E = H+ mostly

Front: Bamford-Stevens mechanism
Back: - Proton abstraction by base, good LG = Ts leaves.
- Then, N2 is eliminated.
- Under aprotic conditions, neutral carbene is a stable enough intermediate and the reaction proceeds via a [1,2] H-shift.
- Under protic conditions, the carbene binds a proton and forms a carbocation. Under elimination of a proton alpha to it (super acidic), the olefin forms

Front: Shapiro olefination mechanism
Back: - Two deprotonations (very strong base). Leads to rearrangements in which first Ts leavx, then N2. Carbanion intermediate stabilized by Li+.
- Addition of protic solvent then forms the final olefin

Front: Corey-Fuchs reaction
Back: - Aldehyde to terminal alkyne
- Via Wittig like reaction to dibromo olefine, then Strong lithium base to alkyne. Then, work up

Front: Corey-Fuchs Mechanism
Back: 1) Formation of the dibromoylid
i) Phosphine (good nucleophile) attacks Bromine of Tetrabromomethane, and is attacked by the LG again, forming the ylid
2) Reaction with aldehyde
i) Wittig like oxaphosphatane formation, forming the dibromoalkene.
ii) Addition of BuLi deprotonates the alkene (strong base), forming the alkyne.
iii) Second equivalent of BuLi undergoes lithium-halogen exchange to lithiate the alkyne (- charge more stable on sp carbon than sp3)
iv) Aqueous work-up with weak acid yields the terminal alkyne

Front: Seyferth-Gilbert Homologation
Back: - Forms 1 C longer alkynes form ketones and Aldehydes
- Ketones lead to internal alkynes (rearrangement of R groups), while Aldehydes form terminal alkynes
- Uses Ohira-Bestmann reagent and mild, basic conditions

Front: Seyferth-Gilbert Mechanism
Back: - Ohira-Bestmann reagent must first be activated -> Anionic form attacks carbonyl, undergoes wittig like  cycloaddition and then retro [2+2] to form diazoalkane.
- Diazoalkane undergoes elimination of N2.
- Rearrangement of R groups may be concerted with elimination (makes more sense considering we are in protic solvent), or via a carbene (less likelytbh)
R can also be H

Front: Corey-Chaykovsky epoxidation
Back: - Dimethylsulfoxoium methylide and strong Base (NaH) in DMSO in presence of aldehydes or ketones yields epoxides.
- In presence of alpha-beta unsaturated ketones, dimethylsufonium methylide must be used, otherwise cyclopropanation happens
- in iii), more reactive S(Me)3 prefers 1,2 addition to 1,4.

Front: Corey-Chaykovsky cyclopropanation
Back: - DMSOM with alpha-beta unsaturated compounds prefers to undergo 1,4 addition (in contrast to 1,2 of more reactive DMSM, leading to epoxides). This forms a cyclopropane

Front: Corey-Chaykovsky epoxidation mechanism
Back: - Similar to Wittig mechanism, but since S has a lower affinity to oxygen than P, it does not form another S-O bond and just leaves as a leaving group

Front: Corey-Chaykovsky cyclopropanation mechanism
Back: SOMETHING WRONG HERE WITH THE STARTING MATERIAL

Front: Baylis-Hillman reaction
Back: - 1,3 Bifunctional formation
- Reaction of alpha-beta unsaturated amides or esters (or sulphonates, nitriles... see Laszló p. 49) with C electrophiles (carbonyl ketone or aldehyde, imines with EWG groups). Forms carbon bond at alpha C.
- Uses nucleophilic catalyst tertiary amine (mostly DABCO)

Front: Baylis-Hillman mechanism
Back: 1) 1,4 Addition of DABCO catalyst to carboxylic acid derivative. No 1,2 due to steric hinderance, + due to reversibility of attack (DABCO weak base), thermodynamic addition (1,4) will occur. Forms enolate
2) Enolate double bond (softer part) attacks the electrophilic ketone/aldehyde, in an aldol type reaction. 1,3 Hydroxy-carbonyl is deprotonated by DABCO (acidic proton, weak base).
3) After deprotonation, alpha beta unsat. double bond is reformed, kicking out DABCO. Alcohol is protonated and product is formed

Front: Rauhut-Currier reaction
Back: - 1,5 bifunctional version of Baylis-Hillman, using alpha-beta unsaturated electrophile, and catalytic phosphine. Basically Baylis-Hillman but with a Michael acceptor
Same mechanism as Baylis-Hillmann

Front: Pinacol Coupling
Back: - Formation of a 1,2 diol from a ketone in presence of a reducing metal (generally Mg)
- Aprotic solvent, since proceeds via radical mechanism (similar to acyloin)

Front: Pinacol coupling mechanism
Back: - reducing Mg2+ transfers a single electron to each substrate -> coordinates both, so more likely to react.
- Radicals combine.
- Acidic work-up yields the diol

Front: Benzoin reaction
Back: - Formation of 1,2 benzoin from 2 aldehydes, using a catalyst
- Catalyst can be KCN, or thiamine generated from thiazonium salt, or NHC
Is a form of Umpolung: After deprotonation of the tetrahedral intermediate, it becomes nucleophilic -> previously electrophilic carbonyl becomes a nucleophile

Front: Benzoin mechanism: Cyanide cat.
Back: - CN- catalyst attacks carbonyl, forming a cyanohydrine.
- Presence of EWG CN group increases acidity of alpha proton -> makes proton transfer easier. Formation of carbanion (Umpolung)
- Carbanion nucleophilically attacks the second aldehyde (added in later, can be same, or different. Could prob even be a ketone).
- Proton transfer, then carbonyl reformed, kicking out CN. Benzoin has formed

Front: Benzoin reaction mechanism: Thiamine cat
Back: 1) Activation of thiamine precatalyst by deprotonation, to form an ylid
2) Ylid nucleophilically attacks carbonyl, forming a Breslow intermediate (which is now nucleophilic itself
3) This nucleophilic intermediate then attacks the other carbonyl
4) After H+ transfers, original carbonyl reforms, kicking out catalyst

Front: Stetter Reaction
Back: - Same as benzoin reaction, but with alpha/beta unsaturated carbonyls or nitriles, so forms 1,4 product
Catalyst can be CN-, THC or Thiamines
- Same mechanism as Benzoin

Front: Tischenko reaction
Back: - Coupling of two aldehydes to an ester. Aldehydes do not necessarily need to be the same
- Reaction is catalyzed by Al(OR)3, which coordinates the first aldehyde, allowing for nucleophilic attack by the second aldehydes carbonyl O.
- A common side reaction is the MPV reduction

Front: Tischenko reaction mechanism
Back: 1) Aldehyde coordinates the lewis acid, making it more electrophilic
2) second aldehyde attacks now very electrophilic first aldehyde.
3) Second aldehyde is reduced, first one is oxidized, forming the final product
Lewis acid catalyst is regained

Front: Meerwein-Pondorf-Verley reduction/Oppenauer Oxidation
Back: - Reverse of Oppenauer oxidation
- Side reaction of Tischenko reaction
- very selective for ketones and aldehydes -> other functional groups are unaffected
- Reaction is completely reversible. Equilibrium position can be changed through addition of reagent (isopropanol) or removal of acetone (low b.p.)
- Depending on whether substrate needs to be reduced or oxidized, we add an excess of isopropyl alcohol or acetone, respectively.

Front: MPV reduction mechanism
Back: - Al(OiPr)3 lewis acid coordinates both compounds and induces a transfer hydrogenation reaction
- Note that these are all equilibrium reactions

Front: Cannizzaro reaction
Back: - Disproportionation reaction of 2 aldehydes -> 1 to primary alcohol, the other to carboxylic acid (salt)
- Equilibrium, max 50% yield if both the same aldehyde.
- Using excess of formaldehyde, high yield of alcohol can be obtained
- Aldehydes cannot have alpha protons -> otherwise aldol reaction happens

Front: Cannizzaro mechanism
Back: - Nucleophilic addition of base, then deprotonation.
- Subsequent hydride transfer

Front: Mitsunobu reaction
Back: - Sn2 reaction of primary or secondary alcohol with nucleophile, under inversion of configuration
- Alcohol is activated by DEAD or DIAD and PPh3
- Nucleophile should have a pKa of <13
- Nucleohiles can be Carboxylic acids, imides (to transfer RNH2), DPPA to transfer N3-
- If nucleophile is carboxylic acid, ester can be hydrolyzed to yield alcohol with inversion of config

Front: Mitsunobu mechanism
Back: - DEAD (can also be DIAD) is used to activate the PPh3 and the nucleophile.
- Alcohol attacks activated PPh3, forming strong P-O bond. It is now also a good LG.
- Nucleophile undergoes SN2 reaction with the activated alcohol, under inversion of configuration

Front: Appel reaction
Back: Conversion of alcohol to halide
- Can also be used with CCl4, Cl2, Br2, CI4, I2, MeI etc.
- Can be used on carboxylic acids to form oxazolines etc

Front: Appel mechanism

Front: Corey-Winter olefination
Back: Formation of alkene from cis-diol or cis- dithiol
-  Activates diol through two addition eliminations of a thiocarnonyldiimidazole
- Elimination then occurs at high temperatures

Front: Corey-Winter mechanism
Back: 1) Formation of thionocarbonate through 2 consecutive addition-elimination reactions
2) Phosphite attacks thiocarbonyl, forming bond and eliminating it to form a carbenoid
3) Carbenoid and second equivalent of phosphite form a bond, and under heat, are eliminated to form the alkene, CO2 and regaining the phosphite

Front: Barton-McCombie deoxygenation
Back: - Replacement of hydroxy group with an H.
- Works with primary, secondary and tertiary alcohols

Front: Barton-McCombie mechanism
Back: 1) Strong base deprotonates alcohol
2) Alcohol attacks, forming thioxoester. Cl- LG, Na+ from before as counterion
3) Thioxoester is attacked by SnBu3nradical, forming a primary, secondary or tertiary radical on the carbon
4) Carbon radical attacks another equivalent of HSnBu3, binding an H and forming another eq. of radical that enters the cycle

Front: Payne rearrangement
Back: - Rearrangement of 2,3 epoxy alcohol to more stable epoxide.
- Base catalyzed
MISSING OH IN PRODUCT`
- SN2 reaction
- Since SN2, Hydroxy group must be in a position to undergo a backside attack. E.g.:

Front: Birch reduction - EDG
Back: EDG give 1,4 double bond reduction patterns

Front: Birch reduction: EWG
Back: For EWG, 2,5 pattern

Front: Pinacol rearrangement
Back: - Rearrangement of diol to form ketone or aldehyde
- Involves migration of R groups

Front: Pinacol rearrangement mechanism
Back: - Acid catalyzed elimination of H2O.
- If R groups have large enough migratory aptitude, will migrate to carbocation. Generally more substituted R
- Not very good reaction. Can lead to varying stereochemistry, eliminations, lack of regioselectivity.
- Semipinacol rearrangement is used more due to this

Front: Semipinacol rearrangement
Back: - Pinacol rearrangement, but carbocation generated through different leaving group -> regioselectivity problem no longer as bad

Front: Favorskii rearrangement
Back: - Ring contraction with alpha-halide ketone

Front: Favorskii rearrangement mechanism
Back: 1) Alpha-halo ketone is deprotonated at the C for which the reaction is productive. H at Cl is more acidic, but nothing happens, so enolate equilibristes to more productive one.
2) Enolate attacks Cl-C, forming a cyclopropane intermediate.
3) Carbonyl can be attacked by nucleophile, and carbonyl can then close down, rearranging the ring such that the more stable carbanion is made.
4) protonation

Front: Wolff rearrangement
Back: - Formation of ketenes from alpha-diazo ketenes
- Rearrangement is induced by adding light, heat or transition metal compounds (anything that promotes formation of carbene). E.g. Ag2O

Front: Wolff rearrangement mechanism
Back: 1) hv, heat or Ag2O induce nitrogen elimination, forming carbene.
- Requires aprotic solvent!
2) Carbene rearranges to ketene

Front: Beckmann rearrangement
Back: - Rearrangement of oxime to substituted amide.
- H never migrates
- R group anti to LG migrates
- Requires strong acid in aqueous solution

Front: Beckmann rearrangement mechanism
Back: 1) Oxime is protonated on OH
2) [1,2] alkyl shift (basicslly an SN2) from R1 that is anti to LG onto N
3) Carbocation formed, is attacked by solvent (water).
4) loss of proton forms hydroxy imine
5) Tautomerisation to more stable amide

Front: Benzil rearrangement
Back: - Rearrangement of alpha-diketones under basic conditions to alpha-hydroxy carboxylic acids

Front: Benzil rearrangement mechanism
Back: 1) OH- attacks the reactive diketone.
2) -O- closes down, "forcing" the R group to move to the carbonyl.
3) acid has formed, proton transfer occurs (acid more acidic than alcohol)
4) after workup, alpha-hydroxy acid

Front: Ozonolysis
Back: - For tetrasubstituted alkenes: Oxidative workup yields ketones, reductive with SMe2 also. For NaBH4, yields secondary alcohols

Front: Ozonolysis mechanism
Back: 1) 1,3 dipolar cycloaddition of ozone onto alkene, forming very unstable primary ozonide
2) Primary ozonide undergoes cycloreversion, forming an aldehyde and a carbonyl oxide (1,3 dipole), which undergo regioselective 1,3 cycloaddition to form the slightly more stable secondary ozonide

Front: Luche reduction
Back: - Reduction of carbonyl in alpha-beta unsaturated ketones
- Prevents 1,4 addition by having CeCl3 coordinate to most lewis basic group (carbonyl O)
- Reduces most lewis basic carbonyl in presence of less lewis basic carbonyl (e.g. reduces ketones in presence of aldehydes)

Front: Hydroboration
Back: - Antimarkovnikov (adds to less substituted C), syn addition
- Does triple addition
- Oxidation by NaOH yields alcohol

Front: Hydroboration mechanism
Back: 3 times.
Then:

Front: Clemmensen reduction
Back: - Reduction of aldehyde or ketone to alkane
- Acid sensitive FG not tolerated

Front: Wolff-Kishner reduction
Back: - Aldehyde or ketone to alkane
- base sensitive FG not tolerated.
- N2 driving force

Front: Wolff-Kishner mechanism

Front: Mozingo reduction
Back: - Aldehyde or Ketone to alkane
- Milder
- via thioacetal

Front: Reductive amination
Back: - Best way to make amines. Through iminium
- Slightly acidic solution, + weak reducing agent,

Front: Wharton reaction
Back: - Reaction of alpha, beta epoxy ketones to allylic alcohols using hydrazine (wolff-Kishner conditions)

Front: SeO2 oxidation mechanism

Front: Ley oxidation
Back: - TPAP (cat.) and NMO
- Alcohol to aldehydes/ketones
- Water removing conditions

Front: Ley oxidation mechanism
Back: - Forms water, so Molecular sieves are required

Front: TEMPO oxidation mechanism
Back: - Generation of active oxidizing agent
- TEMPO is catalytic, regenerated by NaOCl

Front: TEMPO oxidation
Back: - Only 1° alcohols
- NCS can also be used to regenerate TEMPO

Front: DMP oxidation mechanism

Front: DMP oxidation

Front: Swern oxidation

Front: Swern mechanism

Front: Moffatt oxidation
Back: - Better for base-labile groups I guess

Front: Corey-Kim Oxidation
Back: - Allows higher temperatures than Swern

Front: Corey-Kim mechanism

Front: Moffat oxidation mechanism

Front: Pinnick oxidation
Back: - Oxidation of aldehydes to carboxylic acids in aqueous solution
- Requires alkene as a scavenger to remove HOCl, which consumes NaClO2

Front: Pinnick oxidation mechanism

Front: Upjohn dihydroxylation
Back: Cis dihydroxylation using OsO4 in catalytic amounts and NMO to regenerate OsO4

Front: Claisen condensation
Back: - Condensation of 2 esters to form Beta-kEtoesters
- Use non-nucleophilic base, such as LDA or NaH, or base with same OR group as ester (to prevent transesterification)

Front: Claisen rearrangement
Back: - [3,3] sigmatropic rearrangement of allyl vinyl ethers or allyl-phenyl ethers to form gamma,delta unsaturated carbonyls or ortho/para allylphenols

Front: Claisen rearrangement of substituted allyl phenyl ether

Front: Claisen-Ireland rearrangement
Back: - [3,3] sigmatropic rearrangement of O-TMSketene acetals to gamma,delta unsaturated acids
- Workup then yields carboxylic acid
- TMS Ketene is synthesized from allylic esters

Front: Cope-elimination
Back: - Elimination of trialkylamine-N-oxides with Beta hydrogens to form double bonds

Front: Cope rearrangement
Back: - 1,5 diene rearranges to form more stable 1,5, diene

Front: Balz-Schiemann reaction
Back: - Substitution of NH2 on Aryl with F

Front: Baeyer-Villiger oxidation/rearrangement
Back: - Oxidation of ketones to esters
[1,2] shift.
- R group that forms more stable cation migrates (H+ > 3° > 2° etc)
- Competes with epoxidation if double bonds are present!

Front: Baeyer-Villiger mechanism

Front: Darzens reaction
Back: - Formation of aloha-beta epxôxy ester from aldehydes and ketones with alpha-halo esters.
- Alpha-haloester must be deprotonated -> therefore, must be most acidic species in solution!
- Base is often NaOEt
- Also works with alpha-halo nitriles, ketones, etc. (any EWG group)
- Can be used to form homologated aldehyde by decarboxylating after rxn

Front: Darzens mechanism

Front: Dieckmann condensation
Back: - Intramolecular claisen condensation
- Forms 5,6,7 and 8 membered rings in good yield (but for 7,8 -33 membered Thorpe.Ziegler is better)

Front: Eschenmoser Claisen Rearrangement
Back: Allylic or benzyllic alcohols undergo rearrangement in presence of N,N dimethyl acetamide dimethyl acetals to form gamma,delta unsaturated amides

Front: Mislow evans rearrangement
Back: [2,3] sigmatropic rearrangement of allyl sulfoxides to form allylic alcohols in presence of phosphites

Front: Wittig rearrangement
Back: - [2,3] sigmatropic rearrangement to form homoallylic alcohols from allyl ether.
- Base induced and at low temperatures
- Carbanion can also be formed through transmetallation of stannanes by BuLi

Front: Johnson-Claisen reaerrangement
Back: - [3,3] sigmatropic rearrangement of allylic alcohols to form gamma,delta unsatuturated esters

Front: Oxy-cope rearrangement
Back: - Rearrangement of 3-Hydroxy-1,5-diene to form delta,epsioln unsaturated aldehyde/ketone
- Base induced -> driving force is to delocalize the negative charge on the O

Front: Knoevenagel condensation
Back: - Base catalyzed aldol-type reaction

Front: Knoevenagel mechanism with tertiary amines

Front: Knoevenagel mechanism with primary/secondary amines

Front: Henry reaction
Back: - Alpha-nitro alkane most acidic component, + not electrophilic -> always acts as donor!
- Often, dehydration happens, esp. if e.g. aromatic aldehydes. Can be suppressed through properly chosen conditions!

Front: Hofmann elimination

Front: Mannich reaction
Back: - Formation of beta-amino carbonyl (mannich base) from enolizable carbonyl and iminium

Front: Pictet-Spengler reaction
Back: - Formation of tetrahydroisoquinoline derivatives via "Mannich-type" reaction
- Via iminium, then electrophilic aromatic substitution

Front: Reformatsky reaction
Back: - Condensation of alpha-halo ester and aldehyde/ketone to form a beta-hydroxyester in presence of Zn-dust

Front: Reformatsky mechanism
Back: - Zn transmetalates into C-Br bond, and allows enolization of ester, even if aldehyde is enolizable!

Front: Thorpe-Ziegler reaction
Back: - Condensation of dinitrile to form a ring. Good for larger rings also!
- Uses strong, non-nucleophilic base!
- Under Acidic conditions, imine (tautomerized from enamine) forms carbonyl, and nitrile can be hydrolyzed to carboxylic acid, then decarboxylated to form carbonyl on ring

Front: Thorpe-Ziegler mechanism
Back: - Most acidic proton is alpha to nitrile, pKa =25. Requires strong, non-nucleophilic base to abstract!
- Forms 5 ring, incl. enamine amine tautomerism.
- Under strongly acidic conditions, imine is hydrolyzed to carbonyl and nitrile to carboxylic acid, which under heat is then decarboxylated

Front: Perkin reaction
Back: - Formation of alpha-beta unsaturated carboxylic acid from carboxylic acid anhydrides and aldehydes or ketones under weakly basic conditions

Front: Perkin mechanism

Front: Prilezhaev reaction
Back: - Epoxidation of more electron-rich double bond selectively! E.g. disubstituted epoxidized selectively in presence of terminal one
- Coordinating substituents direct peroxyacid, so epoxidation will occur on same side as e.g. heteroatom.
- Side-reactions: Amines are oxidized, Ketones can do Baeyer-Villiger
- Alpha-beta unsaturated esters are epoxidized, but alpha.beta unsat. ketones are not!
- Alkynes are not epoxidized in presence of alkenes

Front: Riley selenium dioxide oxidation
Back: Ketones and aldehydes with alpha protons form diketones
Alkenes form allylic alcohols

Front: Riley Selenium dioxide mechanism

Front: Robinson annelation
Back: - Tandem Michael-Aldol reaction
-> first, michael addition to acceptor, then aldol reaction from acceptor to donor carbonyl, then dehydration

Front: Robinson annelation mechanism

Front: Kumada coupling
Back: - Coupling of sp2 with good LG and Grignard
- Grignard strong base and nucleophilic! -> no base sensitive groups or carbonyls allowed!

Front: Negishi coupling
Back: - Sp3 C coupling to sp2 with LG
- organozinc less reactive, tolerates more functional groups
- Prepared by transmetallation of grignards or organoltithiums

Front: Kumada mechanism

Front: Negishi mechanism

Front: Stille Cross-Coupling
Back: - Uses stannanes
- Butyl ligands do not transmetallate very quickly, so only the R group is transferred

Front: Stille cross-coupling mechanism

Front: Stille Carbonylate cross-coupling

Front: Stille carbonylative cross coupling mechanism

Front: Stille cross coupling with acid chlorides

Front: Suzuki-Miyaura cross coupling

Front: Suzuki mechanism
Back: - Boronate needs to be activated with base

Front: Hiyama Cross-coupling

Front: Hiyama mechanism

Front: Sonogashira coupling
Back: - Coupling of sp2 w/ LG to terminal alkyne using Pd and Cu(I) catalysts, and base

Front: Sonogashira mechanism
Back: - Cu+ cycle to activate Alkyne towards transmetallation
1) Cu+ coordinates alkyne, making it more acidic
2) Base abstracts proton, Alkyne coordinates head on with Cu+
At same time, regular Oxidative addition of R-X to Pd0
3) Transmetallation, adding alkyne to Pd2
4) Reductive elimination

Front: Buchwald-Hartwig cross-Coupling
Back: - Forms C-N, C-O and C-S bonds from Aryls with LG (Cl, Tf etc) and amides, alcohols or thiols resp.
- Uses strong base

Front: Buchwald-Hartwig mechanism
Back: - 2 possibilities for Substitution/ Transmetallation: Either NR2 adds directly, or first base adds and is then substituted by NR2
- C-N RE is much faster than C-O RE, which is why the amine is added instead of the alcohol. If only alcohol is around, the slower one will happen -> Alcohol is added

Front: Ullmann biaryl ether and amine synthesis
Back: - Copper mediated synthesis of biaryl ethers or amines

Front: Ulmann Biaryl mechanism

Front: Birch reduction mechanism
Back: - Protonation takes place at more stable anion: Meta position for EDG, 1 pos. for EWG

Front: Heck reaction
Back: - Coupling of R-LG to alkene/alkyne using Pd catalysts and base

Front: Miyaura Arylboronic ester synthesis + Mechanism
Back: - Like Suzuki, but Nucleophile contains B-B bonds

Front: Olefin metathesis mechanism
Back: Basically a [2+2] cycloaddition and then a [2+2] cycloreversion

Front: Enyne metathesis
Back: - Converts alkene and alkyne into 1,3 diene

Front: Enyne metathesis mechanism

Front: Reppe carbonylation
Back: - Coupling of unsaturated hydrocarbon to carbon monoxide and nucleophiles to form carboxylic acid derivatives

Front: Reppe carbonylation mechanism

Front: Wacker oxidation
Back: - Aldehyde/Ketone from alkene
- Uses Pd(II) and Cu(II) and an oxidant

Front: Tsuji-Wacker oxidation
Back: - Like Wacker but terminal alkenes turned into methyl ketones in presence of water as a nucelophile and an oxidant to regenerate Pd(0)

Front: Tsuji-Wacker mechanism

Front: Corey-Gilman-Ganem reaction
Back: - Oxidation of alpha-beta unsaturated or benzyllic aldehydes to esters
- Uses MnO2 and catalytic KCN
- Also works when starting with allylic alcohols

Front: Corey-Gilman-Ganem mechanism

Q: Buchner ring expansion
A: Ring expansion using carbenoids, cyclopropanation and subsequent electrocyclisation

Q: Buchner ring expansion mechanism
A: - Carbenoid is electrophile, is attacked by aromatic ring -> then cyclopropanation
- After this, electrocyclisation to product

Q: Chichibabin amination reaction
A: - Nucleophilic aromatic substitution of electron-deficient aromatics

Chichibabin amination mechanism

Q: Dakin oxidation
A: - oxidation of electron rich aromatic aldehydes or ketones to phenol derivatives
- If Aromatic not electron rich, oxidation goes to carboxylic acid

Q: Dakin oxidation mechanism
A: - Similar to Baeyer-Villiger