Lesson 1

How does nucleophilicity change?

1. More nucleophilic when more negatively charged

2. Increases as size increases (as you go down)

3. Increases as electronegativity decreases (as you go left)

What are nucleophiles?

Lewis bases (donate electrons to form covalent bonds)

Donate electrons

Ex: OH-, halogens, H2O, ROH, RNH2, etc.

What are electrophiles?

Lewis acids (gain electrons through covalent bonds)

Receive electrons

They are electron deficient

Ex: carbocations, carbonyl compounds, alkyl halides; O and halogens create partial charges

What are leaving groups?

When the electrophile receives electrons, it will kick off something else it is attached to (leaving group)

What makes a good leaving group? Bad?

Good: stable in solution (resonance, weak base (increases with size), neutral)

Bad: unstable in solution (strong bases. hydrogens, most carbons)

How do you make a bad leaving group a good one?

Protonate it (aka acid catalysis)

What is TsO-?

Tosylate

Good leaving group

What is MsO-?

Mesylate

Good leaving group

What is AcO-?

Acetate

Good leaving group

What are constitutional isomers?

Same formula, different connections

Different chemical and physical properties

What are conformational isomers?

Same formula, same connections, different rotation around a sigma bond

Same physical and chemical properties

Cannot be isolated

Eclipsed or staggered

What are stereoisomers?

Same formula, same connectivity, different spatial arrangement

Ex: enantiomers, diastereomers, epimers

What are chiral molecules?

Do not have symmetry about the atom

No plane of symmetry

Not superimposable

How to determine R and S?

Locate priority

If lowest priority is back (dashed lines), then R is clockwise and S is counterclockwise

If lowest priority is not back switch directions of R and S

What are enantiomers?

Non-superimposable mirror images

Same physical characteristics

Have opposite configuration of all chiral centers

Same magnitude of rotation, but opposite sign

Separate them via resolution

What are diastereomers?

Non-superimposable non-mirror images

Different characteristics

Opposite configuration for at least one, but not all, chiral centers

Unrelated optical activities

Can be physically separated

What are epimers?

Diastereomers that differ at one single chiral carbon

All epimers are diastereomers, but not the inverse

What are anomers?

Molecules that can be cyclic (AKA sugars)

C1 is thus an anomeric center (two configurations)

What are meso compounds?

With an internal plant of symmetry in a molecule with > 1 chiral centers

Symmetrical chiral centers have opposite configurations

Optically inactive

What are geometric isomers?

Restricted rotation about a double bond or ring

Do not require chiral centers

All physical and chemical properties are different

Type of diastereomer

Cis vs trans

E vs Z

How to calculate degrees of unsaturation?

2n + 2 H’s expected if the hydrocarbon is saturated

[(2n + 2) - #H]/2 = DOU

Treat halogens as hydrogen, ignore oxygens, subtract the number of nitrogens from the number of Hs

What is the relationship between stability and reactivity?

Strong inverse

What does ring strain do?

Destabilizes the ring

Weakens C-C bonds

Increases reactivity

What is induction?

Electrons in a sigma bond will shift towards the more electronegative atom

Electronegative substituents withdraw electron density, while electropositive ones do the opposite (donate)

What are electron withdrawing groups?

Halogens, oxygen

What are electron donating groups?

Alkyl groups (C_xH_y)

What is the stability of carbocations from most to least?

Given R carbocations are attached to R groups at a carbon

Most: tertiary (three groups to push electrons towards the carbocation) > secondary > primary >

Least: methyl (no groups to push electrons towards the carbocation)

What is the stability of carbanions from most to least?

Most: methyl > primary > secondary > tertiary

Alkyl R groups donate electrons —> more negative things towards a negative charge —> unstable

What is resonance stabilization?

Stabilization due to delocalization of electrons

- or + charge or lone electron pair next to a pi bond causes it

What are rules of resonance?

1. More resonance structures = more stable

2. Delocalization is only though p-orbitals (cannot be sp hybridized)(must have a double/triple bond of some sort)

3. Lowest energy structures contribute the most to the hybrid

When is a resonance structure low in energy?

Octet rule satisfied (most important)

Lowest formal charge

Negative charges on more electronegative atoms

How is the strength of an acid determined?

Relative stability of conjugate base

Acids donate protons more easily when the conjugate base is stable (therefore are more acidic)

What makes a conjugate base stable?

1. Negative charge on a more electronegative atom

2. Resonance increases stability of anion

3. Induction: proximity of electronegative atom to an electron withdrawing group (halogens, O)

   1. Also how many electron withdrawing groups are present

What is staggered conformation?

Substituents do not overlap in a plane

What is eclipsed conformation?

Substituents overlap in a plane

What is the anti conformation?

Two largest substituents 180 degrees from one another

What is the gauche conformation?

Two largest substituents are next to one another, but not eclipsed

What is syn conformation?

Two largest substituents on top of each other and eclipsed

What are the conformational isomers (newman projections) ranked in stability? Energy?

Most stable: anti > gauche > syn

Most energy: syn > gauche > anti

What is the chair cyclohexane?

See image

What is the boat cyclohexane?

See image

What is the axial position? Equatorial?

Axial: in boat/chair, when substituents point up or down

Equatorial: in boat/chair, when substituents point diagonal

What does a ring flip do?

See image

Axial → equatorial

Equatorial → axial

Is axial or equatorial more stable?

Equatorial

Axial has more steric strain

What ring conformation is most stable?

Boat, with most substituents in equatorial positions

What are characteristics of a chiral center?

AKA: stereocenter, stereogenic center, asymmetric center

sp³ hybridized

Tetrahedral geometry

Four different substituents

How do you know how many isomers a molecule has?

2^n

n = # of chiral centers

What does it mean to be optically active?

Chiral molecule that rotates plane-polarized light

Cannot be predicted based on structure

Must measure via polarimeter experimentally

What is dextrorotary? Levorotary?

Dextrorotary (d): + optical activity, clockwise rotation

Levorotary (l): - optical activity, counterclockwise rotation

How are substituents prioritized?

1. Atom with highest atomic number has highest priority

2. Heavier isotopes have higher priority

3. If two atoms are identical, move to the first point of difference → use above rules

4. Atoms with double bonds count as two of them

How do you assign R and S?

1. Lowest priority should face the back (dashed wedge)

2. Trace circle from 1-4 priority

3. Clockwise is R, counterclockwise is S

4. If you had to move things to make the lowest priority be back, switch R and S

How to do hand trick for R and S?

1. Put thumb in position of lowest priority

2. Curl hand to follow path of 1-3 priorities

3. If right hand curls correctly, it is R; if left hand works, it is S

How do you decide R or S for fischer projections?

1. Groups on the horizontal are towards you, groups on the vertical are away

2. Put rest of fingers towards 1

3. Curl fingers to 2

4. If right hand works = R; left hand = S

When do you use E vs Z?

When there is a double bond

E: trans

Z: cis