Page 1117 - Advanced Organic Chemistry Part B - Reactions & Synthesis

For example, the unhindered exocyclic double bond in 4-t-butylmethylenecyclohexane 1093
gives both stereoisomeric products. 77
SECTION 12.2
Addition of Oxygen at
O CH 2 Carbon-Carbon Double
CH 2 MCPBA O Bonds
(CH ) C CH Cl (CH ) 3 C CH 2 + (CH 3 3
) C
3 3
3
2
2
31%
69%
Hydroxy groups exert a directive effect on epoxidation and favor approach from
78
the side of the double bond closest to the hydroxy group. Hydrogen bonding between
the hydroxy group and the reagent evidently stabilizes the TS.

OH HO
H H
peroxybenzoic
O
acid
H

This is a strong directing effect that can exert stereochemical control even when steric
effects are opposed. Entries 4 and 5 in Scheme 12.11 illustrate the hydroxy-directing
effect. Other substituents capable of hydrogen bonding, in particular amides, also can
exert a syn-directing effect. 79
The hydroxy-directing effect has been studied computationally, as the hydrogen
80
bond can have several possible orientations. Studies on 2-propen-1-ol show the same
preference for the spiro TS as for unfunctionalized alkenes. There is a small preference
for hydrogen bonding to a peroxy oxygen, as opposed to the carbonyl oxygen. The
TSs for conformations of 2-propen-1-ol that are not hydrogen-bonded are 2–3 kcal/mol
higher in energy than the best of the hydrogen-bonded structures. For substituted allylic
alcohols, A 1 2 and A 1 3 strain comes into play. Figure 12.9 shows the structures and
relative energies of the four possible TSs for prop-2-en-1-ol. The syn,exo structure
with hydrogen-bonding to the transferring oxygen is preferred to the endo structure,
in which the hydrogen-bonding is to the carbonyl oxygen.
Torsional effects are important in cyclic systems. A PM3 study of the high
stereoselectivity of compounds 4a-d found torsional effects to be the major difference
81
between the diastereomeric TSs. The computed TSs for 4a are shown in Figure 12.10.
The structures all show similar stereoselectivity, regardless of the presence and nature
of a 3-substituent.

77
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79
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81
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