Organic Hall

Question 1

Question 2

Phosphorus as a nucleophile vs N , Why is it a goof nucleophile?

Answer 2

It has Larger orbitals, e rich and is less electronegative. Can donate e easier.

Question 3

Why does P like to be oxidised ?

Answer 3

P-O and P=O bonds are very strong.

Oxidising Phosphine is favoured as it gives P 5 bonds which is its resting state.

Question 3

Why does P like to be oxidised ?

Answer 3

P-O and P=O bonds are very strong.

Oxidising Phosphine is favoured as it gives P 5 bonds which is its resting state.

Question 4

P acts as an electrophile in Sn2

Answer 4

Phosphates are a good LG, low Pka

Question 5

Question 6

Carboxylic acid to acid chloride, with POCl3, What solvent ?

What bond is made and what is broken?

Answer 6

DCM

Question 7

Appel Reaction

Answer 7

Conversion of ROH to RCl

Question 8

Phosphine as Reducing Agent

Answer 8

Ph3P to reduce N-oxides, acts as nucleophile and attacks electrophilic O-

Question 9

Question 10

What is the Wittig reaction?

Answer 10

Phosphorus ylide addition to carbonyls gives new alkene bonds between two molecules

Question 11

What is a Ylide?

How is it formed ?

Answer 11

a species which carries both a positive and a negative charge on adjacent atoms

commonly formed by the deprotonation of phosphonium salts, themselves formed by nucleophilic addition of trialkyl or triaryl phosphines to alkyl halides

Question 12

Phosphorus ylides react with aldehydes and some ketones to give alkenes, what is the driving force for the reaction?

Answer 12

Thermodynamic driving force for reaction often described as formation of a strong P=O bond and C=C bond.

Question 13

Answer 13

Question 14

Wittig Reaction: cis = (Z), trans = (E)

Answer 14

Question 15

Answer 15

Question 16

What is the Horner-Wadsworth-Emmons Reaction?

What does it require?

Answer 16

Reaction of a phosphonate stabilised carbanion with a carbonyl (aldehyde or ketone)
Requires a Electron Withdrawing Group (CO2R, C≡N, C=O etc.) alphato the carbanion for good yields

E SELECTIVE !

Question 17

Answer 17

Question 18

The pKa’s of phosphonatesin HWE reaction are …….. then the corresponding ylides
Therefore 1.
2.

Answer 18

Much higher

1. need strong base for deprotonation (BuLi)
2. once deprotonated much more nucleophilic

Question 19

What is the advantage of using Horner-Wadworth-Emmons in the Lab instead of Wittig?

Answer 19

Remove phosphate by washing with aq. base (in Wittig, Ph3P=O difficult to remove

Question 20

Why is HWE selective for E-alkenes only? (trans)

Answer 20

There is no steric hinderance, big groups away from eachother, proved by drawing cirlce thing.
Z big groups are too crowded

Question 21

Answer 21

Question 22

What does the Mitsunobu Reaction allow?

What is required for the reaction?

Answer 22

allows the inversion of stereochemistry of an alcohol, via an SN2 process.
The Mitsunobu reaction activates the OH group to be a good leaving group (via reaction with the PPh3).

We also require the reagent DEAD and a NUCLEOPHILE with an acidic proton (eg. RCO2H, ROH, RSH, etc).

Question 23

What are the problems with using DEAD reagent?

Alternatives?

Answer 23

Thermodynamically unstable, likely to explode as can be turned into many gases.

DIAD
ADDP

Question 24

What is the Staudinger Reaction?

Answer 24

The Staudinger Reaction is the reduction of azides by Ph3P, controlled by sterically bulky R groups
This is a mild alternative to the reduction of azide by hydrogenation

Question 25

Answer 25

Question 26

Answer 26

Question 27

Answer 27

Question 28

Differences in reactions with Organosilicons and Carbon containing compounds?

Answer 28

1. silicons ability to stabilise α-anionsand β-cations,
2. the ability to become 5-coordinate (occasionally even 6)
3. the strength of the Si-O and Si-F bonds

Question 29

Silicon chemistry is dominated by its ability to form….

Answer 29

very strong bonds to electronegative elements particularly oxygen (Si-O 368 kJmol-1) and fluorine (Si-F 582 kJmol-1).

Question 30

Why are Si-C bonds relatively stable?

Do you often see Si-Si bonds?

Answer 30

Silicon does however make strong enough bonds to carbon (Si-C 290 kJmol-1), this combined with the poor leaving group ability of carbon anions makes Si-C bonds reasonably stable.

not often as forms very weak bonds

Question 31

silicon can stabilise ……. by accepting electrondensityinto the ……

organo-silicons can also stabilise a …… by overlap with the …..

Answer 31

silicon can stabilise an α-carbanion by accepting electrondensityinto the σ* of the Si-C bond.

Also in organosilicon chemistry, organo-silicons can stabilise a β-cation by overlap with the C-Si bond.

Question 32

What it SN2@Si reaction?

Answer 32

A very common reaction of silicon involves an “SN2” type displacement of a Cl-by an HO-(forming a strong Si-O bond). This is not a true SN2 reaction as the 2nd row nature of silicon allows the formation of a pentacoordinate intermediate.

One of the biggest uses of silicon in organic synthesis is as a “protecting group” for the hydroxyl functionality.

Question 33

Answer 33

An alternative to strong bases is the use of imidazole as a nucleophilic catalyst (and base)

Question 34

What is a soluble lab reagent for a sources of F-, to remove Si protecting group ?

Answer 34

TBAF which is soluble in organic solvents. used in DCM

Question 35

What affcts the rate of reaction when removing Silicon protecting groups?

Answer 35

The size of the R group, larger R groups give more steric hinderance and slow the reaction .

Question 36

Question 37

Why can reactions involving the C-Li bond be regarded as the reaction of C- and Li+?

Answer 37

The C-Li sigma bond is much closer in energy to the C sp3 bond so thus the Carbon sp3 orbital contributes most to the C-Li bond.

Question 38

Organometallics can act as a sources of ….

Answer 38

Nucleophilic R-, useful in making c-c bonds.

Question 39

Grignard reagents are normally formed by…

Answer 39

reacting magnesium metal with alkyl or aryl halides in ether solvents (normally Et2O or THF)

Doesn’t work with sp hybridised carbons

Question 40

RMgHal by Oxidative Insertion, what is oxidative insertion?

Answer 40

Mg is inserted into bond and oxidised

Question 41

Grynyard reagenst are ,
1.
2.
Solvent choice?

Answer 41

Nucleophilic
basic

THF or Et2O,

Question 42

Why does oxidative insertion of Li require 2 moleclues of Li?

Answer 42

Li can only become 1+ so oxidative insertion requires two atoms of Li.

Question 43

What is Orthometalation?

Answer 43

Deprotonation at the Ortho position and adding Li

As you go from sp3 to sp2 etc more s character increases stability of anion.

Question 44

Organolithiums can also be formed through a process called halogen/lithium exchange (or more generally halogen/metalexchange).

Answer 44

Effectively the halogen and the metal simply swap places, the key to this process is pKa. For all halogen metal exchanges the stable product is the most stable anion

BuLi pKa ca. 50, PhLi pKa 43

Question 45

Question 46

Organolithiums are very “hard” nucleophiles, so will mainly add 1,2-

Answer 46

organocoppers are very “soft” nucleophiles and will add mainly 1,4-.

Question 47

Alkene geometry depends on the outcome of the attack of the sulfonyl anion on the aldehyde
In polar solvents the anti-product is formed and thus the (E)-alkene

Answer 47

Question 48

Sulfur ylides react to give trans-epoxides selectively.

Question 49

Unstabilised sulphur ylide –1,2 addition

Stabilised sulphur ylide –1,4 addition