Asymmetric Synthesis

Question 1

When using (S)-CBS, in the correct orientation, which side does the hydride add from?

Answer 1

The hydride adds from the front

Question 2

When using (R)-CBS, in the correct orientation, which side does the hydride add from?

Answer 2

The hydride adds from the back

Question 3

What conditions are needed for the asymmetric reduction of a carbonyl?

Answer 3

(S/R)-CBS

BH₃

Question 4

What is the correct orientation for the predictive mnemonic to reduce ketones?

Answer 4

The carbonyl must be pointing upwards, with the large group on left and the small group on the right.

Question 5

What are the reaction conditions for the key asymmetric step in the alpha-Alkylation of Enolates using Oxazolidinones?

Answer 5

1) LDA @ -78 degrees

2) The electrophilic alkyl halide adding on to the alpha position.

Question 6

What are the reaction conditions for the key asymmetric step in the syn-Aldol reaction using Oxazolidinones?

Answer 6

1) (Bu)₂BOTf, Et₃N

2) Carbonyl containing compound that will be attacked by the enolate

3) H⁺

Question 7

When using (S)-proline, on which side does the OH add and which side does the R group add?

Answer 7

OH adds to the bottom face (dashed bond)

R group adds to the top face (wedged bond)

Question 8

When using (R)-proline, on which side does the OH add and which side does the R group add?

Answer 8

OH adds to the top face (wedged bond)

R group adds to the bottom face (dashed bond)

Question 9

What are the relative positions of the carbonyl and OH of the anti-aldol product for the predictive mnemonic when using Proline?

Answer 9

The carbonyl in the product must be on the right hand side facing upwards

The OH must be on the left-hand side facing upwards

Question 10

What are the conditions for AD mix alpha?

Answer 10

K₂OsO₂(OH)₄
K₃Fe(CN)₆
(DHQ)₂PHAL

Question 11

What are the conditions for AD mix beta?

Answer 11

K₂OsO₂(OH)₄
K₃Fe(CN)₆
(DHQD)₂PHAL

Question 12

What must the relative orientation of the alkene be to complete the asymmetric hydroxylation of an alkene?

Answer 12

The alkene must be pointing down from left to right

Question 13

On which face does AD mix alpha add to?

Answer 13

The bottom face (wedged bonds)

Question 14

On which face does AD mix beta add to?

Answer 14

The top face (dashed bonds)

Question 15

What are the key features of the CBS reduction TS?

Answer 15

1) Conformation fix; this comes from the chair conformation of the six-membered ring TS

2) Steric factors; the largest ketone substituent prefers to be in the equatorial position on the chair conformation

Question 16

What are the key features of the asymmetric alpha-Alylation of Enolates using Oxazolidinones?

Answer 16

1) Enolate geometry has the oxygen and larger group cis

2) Conformational fix: chelation of the lithium enolate to the C=O of the oxazolidinone fixes the conformation

3) Steric hindrance: enolate attacks the electrophile opposite to the sterically bulky ⁱPr group on the chiral auxiliary.

Question 17

What are the key features of the Zimmerman-Traxler TS model?

Answer 17

1) The cis-boron enolate leads to the syn-aldol

2) Conformational fix; dipole minimisation

3) Steric hindrance; bulky R group of carbonyl favours the equatorial position

4) The aldehyde coordinates on the opposite side to the ⁱPr group of the chiral auxiliary

Question 18

What are the key features of the Zimmerman-Traxler chair transition state for the asymmetric anti-Aldol reaction using Proline?

Answer 18

1) Trans-enamine is formed and this leads to the anti-adol product

2) Conformational fix; this comes from two H-Bonds (intramolecular H-bond to amine, and intermolecular H-Bond to oxygen of the aldehyde), and a chair conformation

3) Steric hindrance; the bulky ⁱPr group sits in the equatorial position