Chemistry Reference
In-Depth Information
Although the synthesis of
15
is quite effi cient compared with other reported syntheses
[10 - 12] , only moderate
anti
-
anti
diastereoselectivity (4/1 up to 6/1) was achieved in the
ZACA reactions, which resulted in modest yields (45-60%) of desired stereochemically
pure products. The results disclose a limitation of the current ZACA process, which is
1,3 -
syn
-selective for 1-alkenes with a methyl or alkyl group at the C4 position [13-15].
It has been shown that the ZACA reaction of 1,4-pentadiene
16
gave a racemic
alcohol
19
after oxidation with oxygen (Scheme 8C.6) [16,17]. It was proposed that the
racemization would occur through cyclocarboalumination of the initially formed mono-
carboalumination product
17
to cyclobutane
18
, followed by ring opening in the other
direction to form the enantiomer of
17
, that is,
ent
- 17
. The proposed mechanism was
supported by the deuterium labeling experiment illustrated in Scheme 8C.6.
Me
3
Al
(-)-(NMI)
2
ZrCl
2
(cat.)
O
2
*H
H*
H*
H*
OH
(
R
)
(
R
)
AlMe
2
16
17
(
R
)-
19
H*
H* = H or D
O
2
H*
H*
AlMe
2
OH
(
S
)
(
S
)
18
Me
2
Al
H*
(
S
)-
19
ent
-17
Scheme 8C.6.
However, the introduction of substituents to one of the two olefi n moieties of
16
was
found to block this racemization to occur, and thus the resulting substituted dienes
20
serve as viable substrates for the ZACA reaction. The ZACA reaction of
20
catalyzed
by (NMI)ZrCl
2
afforded the corresponding alkenols
21
in good yields with good to
excellent enantioselectivity (Scheme 8C.7 ). Results are summarized in Table 8C.2 .
R
1
1) R
3
Al
(NMI)
2
ZrCl
2
(5 mol %)
R
1
R
R
2
R
2
OH
2) O
2
R
3
R
3
20
21
Scheme 8C.7.
8C.2.2. ZACA Reaction of Activated Alkenes
A tandem Claisen rearrangement-ZACA reaction of allyl aryl ethers
22
affords the
corresponding 3 - hydroxy - 2 - methylpropoylphenols
23
with good enantiopurity in good
yields (Scheme 8C.8) [18]. This tandem process creates two new C-C bonds and one
new C-O bond to provide polyfunctionalized chiral building blocks
23
for organic syn-
theses. Various ally aryl ethers
22
bearing an electron-donating or electron-withdrawing
group in the aryl moiety are tolerated in this tandem process (Table 8C.3). Interestingly,
