chapter 33 — stereoselective reactions of cyclic compounds...
TRANSCRIPT
Chapter 33 — Stereoselective reactions of cyclic compounds: Part A
Reading guide: Ch. 18 Read only pages 457–474 Ch. 33 Skip section on unsaturated 6-membered rings (858–861)
- Stereoselective reactions for acyclic and cyclic compounds (25 picoseconds in the life of a ketone)
- 4-membered rings - 5-membered rings, and stereoselectivity in epoxidations - Enantiomers, diastereomers, and reaction selectivity - Saturated 6-membered rings: chair conformations, A-values - Equatorial vs. axial selectivity for small and large reagents …
Cyclic vs. Acyclic
O
Me Me Me+
OH OH
LiAlH4
attack from rear attack from front
OMe Me MeOH OHLiAlH4
+
50 50
10 90
Stereoselectivity in flexible acyclic compounds is possible, but much harder to understand… we’ll handle cyclic compounds in this chapter
4-membered rings
MeMe
Me
O
O
OO
LDAO
OLi
O
OLi
Saturated 4-membered rings:
puckered squares
Unsaturated 4-membered rings:
essentially flat
Reactions of unsaturated (flat) 4-membered rings
Attack of Nucleophile or Electrophile from least hindered face
O
O LDA
O
OLi
O
OBnBnBrMe Me
Me
O
O LDA
O
OLi
O
OMeMeI
Saturated 5-membered rings: envelopes
OH
Me≤ 20 conformations
Me
OH
Me
OH
Me
OH
Unsaturated 5-membered rings — basically flat
O
O
MeO
OMe
H
O
O
Me
O
O
MeBu
O
O
MeBu
+
MinorMajor
(±) (±)
Bu2CuLi
Enantiomers, Diastereomers, and Stereoselectivity 1.
Racemic starting materials give racemic products
O
O
Me
O
O
Me
O
O
Me
+
Bu2CuLi
O
O
Me
O
O
MeBu Bu
O
O
MeBu
O
O
MeBu
+ +
MajorMinor MinorMajor
Marking a racemic product with (±) is used to avoid having to draw every enantiomer of a molecule with ≥ 2 stereocenters. For molecules with a single stereocenter, don’t specify the stereochemistry or use a wiggly line
Enantiomers, Diastereomers, and Stereoselectivity 2.
Enantiopure starting materials can give enantiopure products
O
OMe2CuLi O
O
Me
O
O O
PhO
O OLi
PhO
O O
Ph
LDA Br
O
O O
Ph
Major Minor
Enantiomers, Diastereomers, and Stereoselectivity 3.
Achiral starting materials give racemic products
OCuLi
Br
1)
2)
O
(±)
O 1) Me2CuLi2) H2O
O
Saturated 6-membered rings (Good-old chair)
R
R ∆G
MeEti-Prt-BuOMe
COOHCOOEtPh
CNCCH
1.81.82.1
> 4.50.6
1.41.22.9
0.20.5
A-value(–∆G, kcal/mol)R
Conformational control is measured by the energy of the ring flip equilibrium, also called “A-value.”
H
R
H
H
H
H H
HR
H
H
H
H
H H
H
“Locked” cyclohexane rings (won’t ring flip)
H
MeMe
MeMe
H
H
RR H
H H
H
Trans-decalins are locked, but cis-decalins can ring flip!
H
H H
H
HH
H
H
H
HHH H
H
trans-decalin
cis-decalin
Reactions, orbitals, and axial vs. equatorial attack
Carbonyl attack: π*
Large nucleophiles attack equatorially
O
HH
HH
Nu
Nu
Small nucleophiles attack axially