Organic Synthesis Flashcards
What reactions allow CO bond formation (10)
- Carboxylic ester reduction
- Mitsonobu reaction
- Epoxidation
- Oxymercuration
- Ozonolysis
- Ketones from amides Weinreb
- Dyhydroxilation
- Hydrobroation
- Reduction/oxidation of alcohols, ketones, aldehydes, carboxyl compounds
- Acetal formation and hydrolysis
Swern oxidation, what does it do?
Convert alcohols into aldehydes or ketones
What reagents are needed to allow Swern oxidation? (2) (Not the actual molecules involved)
- DMSO
- Oxalyl chloride
Under what conditions is Swern oxidation carried out?
Basic
Disadvantages of using primary alcohols for CO bond formation?
Possible overoxidation (forming of a carboxilic acid)
Oxidation of primary alcohols leads to …
Aldehydes
Oxidation of secondary alcohols leads to
Ketones
Is it possible for secondary alcohols to overoxidize?
No
Advantage of Swern oxidation? (2)
- Avoids use of toxic metals
- Avoids overoxidation
What is Dess-Martin oxidation for?
CO bond formation from alcohols
What reagent does Dess-Martin oxidation require?
DMP (Dess-Martin Peridonnan)
What advantage offers Dess Martin oxidation?
Avoids overoxidation
What compound is used to reduce carboxylic esters to aldehydes?
DIBAL
What is DIBAL? (2)
- Reducing agent
- Has isobutyl+ Al
What is needed to avoid over reduction to alcohols with DIBAL?
Low temperatures
What is the precursor in Weinreb ketone synthesis?
Weinreb amide
What reagent is needed for Weinreb ketone synthesis?
- Organometallic (like Gignard reagent)
What makes Weinreb amides special? (2)
- OMe group
- CH3 group
(Attached to the N)
What kind of bonds are formed during Weinreb ketone synthesis?
-CC
- CO (reformation)
What kind of hydrocarbon is needed for Ozonolysis?
An alkene
What kind of CO containing compounds can be formed using Ozonolysis? (4)
- Alcohols
- Ketones
- Aldehydes
- Carboxylic acids
What products are obtained with REDUCTIVE work up in Ozonolysis?
(3)
- Alcohols
- Aldehydes
- Ketones
What products is obtained with OXIDATIVE work up in Ozonolysis?
- Carboxylic acids
Why either the formation or hydrolysis of acetals is a CO bond formation? (2)
- Formation: C=O is replaced with 2 C-O bonds
Hydrolysis: the other way around
What is required for acetal formation and hydrolysis?
Acid catalyst
What determines whether an acetal will form or not? (2)
- Water content (excess= hydrolysis, removal = formation)
- Alcohol content (excess = formation)
If acid is both required for acetal formation and hydrolysis, how do you control what you end up with? (2)
Amount of
- Water
- Alcohol
What strategies can be used for CN bond formation? (5)
- Nucleophilic substitution of amines
- Gabriel synthesis
- Reductive amination
- Carboxamide reduction
- Nucleophilic addition-elimination (imines/oximes/hydrazones
How does the nucleophilicity of amines change with the amount of residues?
It is proportional to the number of R’s
What is Gabriel synthesis for?
Primary amines synthesis
What are the reagents needed for Gabriel synthesis? (3)
- Alkyl Hallide
- potassium phtalimide
- hydrazine (for cleavage)
What can you obtain by Reductive amination? (2)
- Imines
- Amines
What condition is needed to perform Reductive amination? (2)
- Acidic (for imines)
- Reducing (for amines)
What are the reagents needed for reductive amination?
- Ketone/aldehyde
-Amine
What is carboxamide reduction?
Reduction of an amide to an amine
What reagent is used for amide reduction?
LiAlH4
From which functional group can be imines, times and hydrazones obtained?
Carbonyl (in ketones and aldehydes)
What is needed for imine formation via reductive amination? Reagents + condition (3)
- ketone/aldehyde
- primary amine
- acidic conditions (mild)
REDUCTIVE AMINATION
What is needed for oxyme formation? Reagents + condition (3)
- ketone/aldehyde
- hydroxylamine
- acidic conditions (mild)
What is needed for hydrazone formation? Reagents + condition (3)
- ketone/aldehyde
- hydrazine
- acidic conditions (mild)
Imine, oxyme and hydrazone formation are… Reactions
Nucleophilic addition-elimination reactions
CS bonds can be formed via… (4)
- Thiolene reaction
- Michael addition
- Lawesson’s reagent
- Thioester oxidation
What are the reagents needed for Thiolene reaction? (3)
- Thiol
- Alkene
- Radical initiator
What is the resulting product of Thiolene reaction?
Thioeter
Examples of radical initiatiors (2)
- DPAP
- VA044
Are thiols soft or hard nucleophiles?
Soft nucleophiles
What does Michael addition with thiols and vinil containing carbonyl compounds give?
Thioeters
Requirements for CS Michael addition (2)
- Thiol
- Vynil + carbonyl compound
What is a Michael addition?
Reaction between
- Michael donor (nucleophiles, enolates)
- Michael acceptor (unsaturated carbonyl compound)
What’s an enolate?
Organic anion derived from deprotonation of C=O compounds
What’s Lawesson’s reagent?
- Thiation reagent
- Has S, P (form a square) and metoxyphenyl
What does Lawesson’s reagent do?
Converts carbonyl into thiocarbonyl compound
What can you obtain from thioether oxidation (2)?
- Sulfoxides
- Sulfones (further oxidation)
Can be sulfoxides chiral?
Yes! If substituents (R’s) are different
Sulfide is the same as
Thioether
What kind of radical initiators are used for Thiolene reaction?
Photoinitiators
Mention the main types of ways to get CC bonds (3)
- From carbonyl compounds (5)
- From olefins and alkynes formation (3)
- From coupling reactions (4)
What kind of bond is formed by Grignard reactions
C-C bonds
Aldol reaction, what kind of bonds does it allow to form?
CC bond
What are the general steps for aldol reaction? (2)
- addition step (aldol addition)
- elimination step (aldol condensation)
What are the starting compounds for aldol reaction? (2)
- alpha hydrogen containing ketone/aldehyde
- other (or the same) ketone/aldehyde
What condition is needed for aldol reaction?
Basic
What functional groups does an aldol have?
- Alcohol
- Aldehyde/ketone
What’s the resulting product of an aldol reaction?
- Unsaturated carbonyl compound (at alpha -beta position)
What CC bond forming reactions need enolizable compounds? (3)
-Aldol reaction
-Mannich reaction
- Michael addition
What reaction forms both CN and CC bonds?
Mannich reaction
What compounds are needed for the Mannich reaction? (3)
- Aldehyde
-Enolizable aldehyde or ketone - Amine (primary or secondary)
What is the resulting product of Mannich reaction?
- Mannich base (beta amino carbonyl compound)
What conditions are required for Mannich reaction?
Acidic
What are the general steps in a Mannich reaction? (3)
- Imine formation
- Enolate formation
- Nucleophilic addition
What reaction can be used for CC and CS bond formation?
Michael addition
What compounds are required for Michael addition?
- a,b unsaturated carbonyl (double or triple bond) compound (electrophile)
- nucleophile
What condition is required for Michael addition?
Basic
What is the general mechanism for Michael addition? (2)
- Nucleophile formation (deprotonation by a base)
- Nucleophilic attack
Are soft or hard nucleophiles needed for Michael addition?
Soft
What should be kept in mind when synthesizing alkenes?
Their resulting configuration (cis or trans)
Synonym for olefin
Alkene
How can olefins be synthesized? (3)
- Wittig reaction
- Wittig- Horner reaction
- Olefin methatesis
What kind of bond is made by Wittig reaction?
CC bond (insaturation)
What are the compounds needed for Wittig reaction? (2)
-Aldehyde or ketone (electrophile)
- Phosphonium ylide (nucleophile)
What kind of stereo selectivity does Wittig reaction have?
Both E and Z
What determines the stereoselectivity of the Wittig reaction? (2)
- Stable ylides give E therefore Unstable ylides give Z
- Salt absence gives E, presence gives Z
What determines the stability of an ylide?
Stability= presence of electron withdrawing groups
How is an ylide formed, using what compounds? (3)
- alkyl Halide
- phosphorus containing molecule (tryphenilphosphine usually)
- Strong base
How is the intermediate in Wittig reaction called? What is special about it
- Betaine
- Four member cycle
What kind of bonds are synthesized with the Wittig Horner reaction?
CC bonds (unsaturation)
What kind of reagent does Wittig Horner es depends on?
Phosphate esters
What kind of condition is needed for Wittig Horner reaction?
Basic (strong)
What’s the main product of the Wittig Horner reaction?
E Olefin with one ester residue
How is the selectivity of the Wittig Horner reaction achieved?
By steric hindrance
What are the compounds needed for Wittig Horner reaction? (3)
- aldehyde or ketone
- phosphate ester
- base
What is an ylide?
Molecule where there is positive (usually N or P) and negative charge (usually O or C) in adjacent atoms
What kind of intermediate is formed in Wittig Horner reaction?
-Four cycle intermediate (Betane)
Mechanism of Wittig Horner reaction (3)
- Deprotonation of the phosphonate ester (formation of an ylide)
- Nucleophilic attack
- Elimination of the intermediate
What is meant by methatesis?
Exchange of chemical bonds between two molecules
What kind of methatesis can happen to olefins? (3)
- Cross methatesis
- Ring closing
- Ring opening
What’s needed for olefin methatesis? (2)
-alkene
- Metal carbene complex (catalyst)
What metals are commonly used for Olefin methatesis? (3)
- Ruthenium
- Tungsten
- Molybdenum
What is a common olefin methatesis catalyst?
Grubbs series
What is the olefin methatesis general mechanism? (2)
- Formation of an intermediate (4 membered ring)
- Rearrangement of electrons in the cycle and liberation of the catalyst and product
What’s the product of olefin methatesis?
Olefin with different R’s respect.to the original olefin
What stereoselectivity does Olefin methatesis have?
E (sometimes preferred) and Z
What is a coupling reaction?
Joining of two molecules by a covalent bond, results in a molecule with higher complexity
What kind of CC coupling did we learn? (4)
- Sonogashira
- Suzuki-Miyaura
- Heck reaction
- Negishi reaction
What metal is commonly used in coupling reactions?
Pd (Palladium)
What molecules are joined via Sonogashira coupling? (2)
- Alkyne
- Vynil or aryl halide
What is the generic mechanism for coupling reactions? (3)
- Oxidative addition
- Transmetallation
- Reductive elimination
What condition is needed for Sonogashira coupling?
Basic
What kind of catalyst is used in coupling reactions?
Metal catalyst
What does a Sonogashira reaction do?
CC bond formation via coupling
What does a Suzuki -Miyaura reaction do?
CC bond formation via coupling
What does a Heck reaction do?
CC bond formation via coupling
What does a Negishi reaction do?
CC bond formation via coupling
What are the compounds needed for Suzuki -Miyaura coupling? (2)
- Halo alkene (vynil group) or halo aryl
- Boronic acid
What condition is required for Suzuki-Miyaura coupling?
Basic
What are the compounds involved in a Heck reaction? (2)
- aryl or vynil halide
- alkene
Is there selectivity in Heck coupling?
Yes, for the syn product
What kind of metals are used for Negishi coupling catalyst? (2)
- Palladium
- Nickel
What metal in the catalyst is used for Sonogashira coupling?
Pd
What compounds are used in Negishi coupling? (2)
- organic halide
- organo- Zinc- halide reagent
In Negishi coupling, what happens before the Reductive elimination step?
Isomerization
One advantage of Negishi coupling is…
High functional group tolerance
What is meant by total synthesis?
Synthesis of a complex molecule from simple commercially available precursors
What does a Mitsonobu reaction perform?
Converts an alcohol to a different functional group (like ester)
What kind of bonds can Mitsonobu reaction make? (3)
C-O, C-S, C-N
What reagents are needed to perform Mitsonobu reaction?(2)
- DEAD
- Triphenylphosphine (PPh3)
What does an oxymercuration reaction do?
Converts an alkene to an alcohol or an eter
What special reagents are needed for oxymercuration? (2)
- Mercuric acetate Hg(OAc)2
- Reducing agent (NaBH4)
What does a hydroboration reaction do?
Converts an alkene into an alcohol
What kind of alcohol product is obtained from hydroboration?
Anti-Markovnikov
What kind of product results from oxymercuration
Markovnikov product
What special reagents are needed for hydroboration reaction?
- Borane or Borane containing molecule
What compounds are used for the oxidation step in hydroboration? (2)
- Peroxide
- NaOH
What compound can be used for aldehyde reduction?
Borohydride
What compound can be used to reduce an ester?
Aluminium hydride
What does a Corey- Bakshi- Shibata reaction do?
Prochiral ketone reduction to chiral alcohols (non racemic mixture)
What special reagents are needed to perform Corey-Bakshi-Shibata (CBS) reaction? (2)
- Borohydride
- CBS catalyst (oxazaborolidine catalyst)
What does a dihydroxilation reaction do?
Converts an alkene to an vicinal diol
What catalyst is used for dihydroxilation?
Osmium tetroxide
What oxidant is commonly used for dihydroxilation?
NMO
What does epoxidation do?
Converts an alkene and a peroxy compound into an epoxide and a carboxylic acid
What is special about Sharpless dihydroxilation?
It uses a chiral catalyst to obtain enantioslectivity of the diols
What is special about Sharpless epoxidation?
It converts allyl alcohols to epoxides in a stereo selective manner
What catalyst is needed for Sharpless epoxidation?
- A chiral titanium complex with a tartrate ligand
