1
2
3
4
base
trans-12
kinetic
cis-12
thermodynamic
base
O
O
O M +
M +
s-cis
s-trans
TS-A
TS-B
OH O
R
O
R
2
3
4
R O
O
R
O
R
O
1
2
3
4
acid
trans-12
cis-12
thermodynamic
O
O
OH
TS-C
TS-D
OH O
R
O
R
2
3
4
R O
OH
R
OH
R
OH
+
kinetically
favored
H
11
11
‡
‡
‡
‡
(eq 1)
(eq 2)
X
X
X
X
X
X
X
X
X
X
Scheme 2 Stereochemical consequences of reaction conditions in conjugate additions
O
R
OH
R
O
X
O
X
X = OR', H, R"
1,4 Conjugate
Addition
1
2
O
R'
R
OH R'
R
X = Ms, Ts, Tf
Nucleophilic
Substitution
3
4
OX
O
R
OH
R
X
M = Hg, Pd
Oxymetalation
7
8
ML n
O
R'
R
OH R'
R
Dehydration
9
1 0
O
O
OH
R
OH
R
Nucleophilic
Ring Opening
5
6
O
1 2
3
4
1 2
3
4
1 2
3
4
1 2
3
4
1 2
3
4
1 2
3
4
1 2
3
4
1 2
3
4
1 2
3
4
1 2
3
4
(eq 1)
(eq 2)
(eq 3)
(eq 4)
(eq 5)
Scheme 1 General approaches to O1–C2 bond formation
Synthesis of Saturated Tetrahydropyrans
47