CHEM 252 Finals Flashcards

Alkenes to alcohols (org 1)

H2O addition (M/no/C+), oxymercuration-demercuration (M/no/triangle), hydroboration-oxidation (anti-M/syn/square)

Alkenes to diols (org 2)

OsO4 oxidative cleavage (diol), KMnO4 oxidative addition (cold, diol)

Linear ethers to alcohols

HA addition to linear ethers (aq/high T, SN2 for 1° & SN1 for 2°/3°)

Alkenes/alkynes to 2 ketones

Ozonolysis with reductive workup (Me2S/PPh3/Et3N, cold)

Alkynes to carbonyls/tautomers

Alkyne hydrolysis (H2SO4/HgSO4, M)

Alkenes/alkynes to 2 carboxyls

Ozonolysis with oxidative workup (H2O2/cold), KMnO4 oxidative cleavage (hot)

Benzyl alkene oxidation

KMnO4 (hot)

Full oxidation of alcohols

KMnO4 (no T), H2CrO4

1 step oxidation of alcohols

PCC/Swern

Imine hydrolysis

HX/aq (ketone)

Ester/amine/nitrile hydrolysis

HX or NaOH (aq/hot, carboxyl/ate)

Acid chloride/anhydride hydrolysis

H2O (carboxyl)

Acid deriv/nitrile to aldehyde reduction (topic 5)

LiAlH(OtBu)3 (cold/quench), DIBAL-H reduction (cold/hydrolysis)

Nitrile to ketone/CO2 to carboxyl reductions (topic 5)

Grignard reagents (ether/quench)

AnCO ketone reducing agents

LiAlH4 (quench), NaBH4 (EtOH/quench)

AnCO nitrile reducing agents

NaBH3CN (pH 4-5)

R- reagents in AnCO: ketone to alcohol

Grignard (RMgX/quench), Alkylithium (RLi/quench)

AnCO ketone to hydrate/diol

NaOH (quench)

AnCO ketone to hemiacetal

NaOR (quench)

Ylide synthesis

Ph3P + R2X to Ph3PR2 (+ base-X)

Wittig reactions

Ketone + Ph3PR2 to alkene + Ph3P=O via square

Unstabilised Ylides

Unstabilised ylide: EDG, both aldehydes/ketones, Z alkene

Stabilised Ylides

Stabilised ylide: EWG, aldehydes only, E alkene

Horner-Wadsworth-Emmons

Ketone + phosphonate ester ([(EtO)2P(O)R2]Na) to alkene + [(EtO)2PO2]Na

Weak, neutral Nu addition ketones to hydrates/acetals/thioacetals

Water/alcohols/thiols (acidic, 2x)

Weak, neutral Nu addition ketones to imines

Amine (acidic)

Weak, neutral Nu addition ketones to cyanohydrin

HCN (acidic)

Silyl ether alcohol proctecting groups

SN2 Si-Cl substitution w/ NR3, SN2 Si-O substitution w/ Bu4NF + quench

tert-butyl ether alcohol protecting groups

Alkene addition in acid, acidic ether cleavage w/ H2O

C=O protecting groups

Acidic 2x alcohol addition, aqueous acid acetal hydrolysis

C=O to alkanes

Desulfurisation (thioacetal then H2, Raney Ni), Wolff-Kishner reduction (H2N-NH2 in H+/NaOH then NaOH(aq), heat)

Cyanohydrins to carboxylic acids

Nitrile hydrolysis with HCl(aq), heat (alpha-hydroxy carboxylic acid) or conc. H2SO4, heat (alpha,beta-unsat carboxylic acid)

Carbonyls to substituted amines

Reductive amination (NH3 in pH 5 then NaBH3CN in pH 5)

Acid halide synthesis from carboxylic acid

Acid bromide (PBr3 or PBr5), acid chloride (SOCl2)

SnCO 1 step reducing agents (topic 7)

LiAlH(OtBu)3 (cold, acid chlorides), DIBAL-H (cold, esters/nitriles)

SnCO full reducing agents (topic 7)

LiAlH4 (all)

Primary alcohol to aldehyde (topic 7)

PCC or Swern conditions

Primary alcohol or aldehyde to carboxylic acid (topic 7)

KMnO4/NaOH or H2CrO4

Acid derivative to aldehyde (topic 7)

LiAlH(OtBu)3 or DIBAL-H

Aldehyde to primary alcohol (topic 7)

NaBH4, LiAlH4, LiAlH(OtBu)3, DIBAL-H

Acid derivative or carboxylic acid to primary alcohol (topic 7)

LiAlH4 (or NaBH4 for acid chloride only)

Nitro group or azide to amine (topic 7)

LiAlH4 or H2/Pd

Nitrile to amine (topic 7)

LiAlH4

Amide to amine (topic 7)

LiAlH4

Imine to amine (topic 7)

NaBH3CN, NaBH4, LiAlH4, LiAlH(OtBu)3, DIBAL-H

Nitrile to aldehyde (topic 7)

DIBAL-H or LiAlH(OtBu)3

Hardest to reduce & oxidise: oxygen compounds

Acid derivatives & primary alcohols

Hardest to reduce: nitrogen compounds

Nitro groups

R- reagents for SnCO (topic 7): nitriles

Basic/aprotic, to ketones

SnCO R- reagents (topic 7): CO2

Basic/aprotic, to carboylic acids

SnCO R- reagents (topic 7): acid chlorides/esters

Basic/aprotic, 2 eqs, to alcohols

SnCO hydro/alkoxides for acid derivs

Hydrolysis to carboxylic acids (basic/protic, 2 eqs OH-)

SnCO hydro/alkoxides for nitriles

Hydrolysis to carboxylic acids (basic/protic, 3 eqs OH-, heat)

SnCO hydro/alkoxides for acid chlorides

Alcoholysis to esters (basic/protic)

Weak, neutral Nu AnCO (topic 7): acid chloride/anhydride to carboxylic acid

Neutral hydrolysis

Weak, neutral Nu AnCO (topic 7): acid deriv/nitrile to carboxylic acid

Acidic hydrolysis (heat, eql)

Weak, neutral Nu AnCO (topic 7): acid chloride/anhydride to ester

Neutral alcoholysis

Weak, neutral Nu AnCO (topic 7): carboxylic acid to ester

Acidic hydrolysis (heat, eql)

Weak, neutral Nu AnCO (topic 7): acid chloride/anhydride to 2° amine

Aminolysis (acidic/neutral, 2 eq)

Weak, neutral Nu AnCO (topic 7): carboxylic acid to 2° amine

Aminolysis (acidic/neutral, DCC)

Amine protecting groups: t-butyloxy-carboxyl

Boc anhydride addition w/ base, acidic carbamate hydrolysis w/ H3O+

Amine protecting groups: carboxybenzyl

Cbz chloride addition w/ base, hydrogenation of carbamate w/ H2, Pd/C

Enolate halogenation

Basic/acidic, X2, thermo

Simple enolate alkylation

Basic, RX, thermo/kinetic dep on base

Enolate beta-keto ester alkylation

1. NaOet, 2. RX, 3. NaOH(aq), 4. H+, heat (ketone + alcohol + CO2)

Acetoacetic ester to ketone

Acetoacetic ester alkylation at alpha-carbon by enolate SN2 alkylation (1. NaOR, 2. RX) then ester hydrolysis & decarboxylation (1. NaOH(aq), 2. H+, heat)

Beta-keto acid to ketone

SnCO ester hydrolysis & decarboxylation (low heat to enol + CO2 then tautomerisation to keto)

Claisen condensation

Basic, NaOR (matching) + ester enolate + 2nd ester = beta-ketoester by SnCO Claisen condensation then alpha-carbon deprotonated by NaOR

Acidic Aldol condensation

H3O+(aq) + C=O enol + 2nd C=O = alcohol by AnCO Aldol addition then alkene by E2 Aldol condensation

Basic Aldol condensation

NaOH(aq) + thermo C=O enolate + 2nd C=O = alcohol by AnCO Aldol addition then alkene by E1cB Aldol condensation w/ NaOH(aq) & heat

Crossed Aldol: non-enolisable aldehyde + enolisable ketone

Aldehyde E+ & ketone Nu in NaOH, H2O forms OH from E+ C=O

Crossed Aldol: any C=O + quantitative aldehyde enolate

Aldehyde/ketone E+ enolate in LDA, then 1. quantiative aldehyde enolate Nu, 2. quench forms OH from Nu C=O

Intramolecular Aldol

Weak base (NaOH/aq) + thermo enolate aldehyde w/ 2nd attached C=O ketone forms 5/6 membered ring w/ OH from aldehyde E+ & attached ketone

Intramolecular Claisen

Weak base (NaOR + quench) + enolate ester w/ 2nd attached ester forms 5/6 membered ring w/ C=O from E+ C=O & attached ester

Aldol & Claisen synthesis motif: beta-hydroxycarbonyl

Aldol addition

Aldol & Claisen synthesis motif: beta-ketoester

Claisen condensation

Aldol & Claisen synthesis motif: alpha,beta-unsaturated carbonyl

Aldol condensation

Aldol-Claisen: quantitative carbonyl + ester

Quantiative carbonyl enolate in LDA with ester E+ + quench forms beta-diketone

Quantiative ester enolate in NaH with carbonyl aldehyde E+ + quench forms beta-hydroxyester

Aldol-Claisen: quantitative carbonyl + ester

Intramolecular Aldol-Claisen

Weak base (NaOR) C=O aldehyde enolate formation in presence of attached ester forms 5/6 membered ring w/ E+ C=O & attached aldehyde + negative charge on alpha-carbon

Aldol-Claisen reaction motifs

beta-hydroxyester = Aldol-Claisen addition w/ aldehyde E+ & ester Nu, alpha,beta-unsatured ester = Aldol-Claisen condensation w/ aldehyde E+ & ester Nu, beta-keto = Aldol-Claisen condensation with ester E+ & aldehyde Nu

Unsaturated carbonyl addition reactions

Simple (1,2) addition w/ strong Nu (reducing agents, Grignards) forming kinetic addition product w/ C=C

Conjugate (1,4) addition w/ weak/bulky Nu (neutral Nu, Gilmans, enolates) formign thermo addition product W/ C=O

Michael addition reactions

Conjugate addition with enolate Nu (1. NaH, 2. quench)

Robinson annulation reactions

Michael addition w/ NaOR, HOR, heat then intramolecular aldol w/ enolate Nu, NaOR, HOR, heat

Michael & Robinson motifs

delta-diketo = Michael addition w/ alpha,beta-unsaturated ketone E+ & ketone Nu, cyclic alpha,beta-unsaturated C=O = Aldol condensation w/ attached ketone E+ & Nu

Phenyl halogenation

X2, FeX3, forms Ph-X w/ HX & FeX3

Phenyl nitration

HNO3, H2SO4, forms Ph-NO2 w/ HSO4- & H3O+

Phenyl sulfonation

SO3, H2SO4, forms Ph-SO3H w/ H2SO4

Post-EArS modification to amines

Ph-NO2 w/ H2/Pd or Fe, HCl to form Ph-NH2

Phenyl desulfonation

Ph-SO3H w/ H2SO4 & heat (eql) to destabilise ring (+ charge on ortho C) then H2O & heat (eql) to form Ph + H3SO4+

Diazonium formation

NaNO2 + HX(aq) to NO+ + H2O + salts, then Ph-NH2 w/ H2N+=O to form diazonium cation

Azo dye formation

Ph-OH w/ diazonium cation

Friedel-Crafts

Alkylation (RCl, AlCl3 to form Ph-R w/ HCl & AlCl3) or acylation (ROCl, AlCl3 to form Ph-COR w/ HCl & AlCl3)

Aryl alkyl ketone reduction

Ph-COR w/ Zn(Hg), HCl (Clemmensen) or H2/Pd

SnAr of aryl halides with o/p EWG substituents

1. NaOH, 2. quench to replace Cl with OH

Aryl diazonium salt substitutions

CuX for Ph-X, KI for Ph-I, H3PO2 for Ph-H, 1. HBF4, 2. heat for Ph-F, H2SO4(aq), heat for Ph-OH

Phenyl side-chain oxidation

Side-chains with benzyl C-H or pi bond (alkane, alkene, alkyne, ketone) w/ 1. KMnO4, NaOH, heating, 2. H3O+ (quench) to form Ph-COOH

Phenyl side-chain halogenations

Br2, light to brominate via radical, HCl to chlorinate via C+

Epoxide opening

Acidic (SN1-like), basic (SN2-like + quench)