Chemistry of Cyclohexanes

Question 1

What is a big factor which affects the rate of Sₙ² substitution of cyclohexyl (pseudo)halides
i.e. the reaction seen below

Answer 1

The rate of Sₙ² substitution of cyclohexyl (pseudo) halides is effected by steric hindrance to approach of the nucleophile

Question 2

What is the mechanism for the following reaction?

Answer 2

• Attack of the Nu at the δ⁺ carbon
• Breaking of the C-X bond

Question 3

tBu is so large it…

Answer 3

… always occupies the equatorial region

Question 4

What is most stable chair conformer of the following anti isomer?

Answer 4

tBu must always be in equatorial

Question 5

What is the most stable chair conformer of the following syn isomer

Answer 5

tBu must always be in equatorial

Question 6

What is the difference between the direction of Nu attack for a Sₙ² substitution for the anti vs syn isomer

Answer 6

• Nu attacks from the bottom for the anti isomer (C-X bond in the equatorial plane)
• Nu attacks from the top for the syn isomer (C-X bond in the axial plane)
• Because of this, the C-Nu bond is in the axial plane for the product of the anti isomer
• and the C-Nu bond is in the syn plane for the product of the syn-isomer

Question 7

What is the difference between the speed of the Nu attack for a Sₙ² substitution for the anti vs syn isomer

Answer 7

The anti isomer will react so much slower because the sigma orbital which the Nu attack is within the ring of the cyclohexane

Question 8

What is a 1,2-addition of cyclohexanone?

Answer 8

• Attack of the δ⁺ carbon by the Nu
• Nu: H⁻ e.g. NaBH₄, LiAlH₄

Question 9

6 membered rings with one sp² centre can adopt a chair conformation, and can therefore undergo attack…

Answer 9

From the axial or equatorial positions

Question 10

How does the type of nucleophile affect the diastereoselectivity of addition

Answer 10

• Depends on the side of the nucleophile
• Small (→ axial attack): LiAlH₄ (“small” H⁻ sources)
• Large (→ equatorial attack): K[sBu₃B-H] (“large” H⁻ source)

Question 11

What will be the product if the Nu attack from the axial position for the following reaction
i.e. the way a small Nu would attack

Answer 11

• Nu is in axial position

Question 12

What will be the product if the Nu attacks from the equatorial position for the following reaction
i.e. the way a large Nu would attack

Answer 12

Nu is in equatorial position

Question 13

6 membered rings with two sp² centres adopt a half-chair conformation
Their reactions occur via….

Answer 13

… a lower-E chair-like transition state, rather than the higher-E twist boat transition state

Question 14

What would happen to the sterochemistry of the transition state and final product if the Electrophile was attacked from the top of the ring

Answer 14

• Starts off as a ‘half-chair’
• Forms a ‘twist-boat’ intermediate
• Electrophile points forward into the plane

Question 15

What would happen to the sterochemistry of the transition state and final product if the electrophile was attacked from the bottom of the ring?

Answer 15

• Starts off as a ‘half-chair’
• Forms a chair intermediate
• Electrophile points back into the plane
• This is the major product because the chair intermediate is more stable