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O
O
O
MeO
OMe
MeO
N
H
N
PIFA
OAc
OAc
HO
OAc
620
621
622
(91%)
O
O
O
O
OMe
OMe
OMe
PIFA
MeO
H
N
N
N
3
O
OH
4
O
Me
OAc
OAc
O
O
624
626
(57%)
623
625
Me
SCHEME 10.100.
Taking advantage of the fact the isomer outcome of hydroxamate oxamidation is
predictable and dependent on alkene geometry, Forslund and Wardrop have suc-
cessfully applied their methodology to the total synthesis of
a
-conhydrine (
629
) and
) (Scheme 10.101).
213
Employing a
one-pot, two-operation procedure, trifluoroacetoxyamidation of
its unnatural diastereomer,
b
-conhydrine (
632
627
lead to the
formation of
, which after concentration but not isolation, was exhaustively
reduced with LiAlH
4
in THF to provide
628
629
in excellent overall yield.
b
-Conhydrine
(
. Importantly, for
applications of this chemistry in more complex targets, it was also found that fission
of the N
632
) was prepared in similar fashion from
Z
-hydroxamate
630
O bonds present in the oxamidation products could be accomplished with a
variety of milder reductive methods, including Mo(CO)
6
.
224
O
PIFA, TFA
LiAlH
4
OMe
H
H
H
N
O
N
CH
2
Cl
2
10 min, 0°C
THF, 13 h, Δ
TFAO
OMe
OH
H
627
628
(not isolated)
(±)−α−Conhydrine (
629
); (93%)
O
PIFA, TFA
LiAlH
4
OMe
H
H
H
N
O
N
CH
2
Cl
2
10 min, 0°C
THF, 13 h, Δ
TFAO
OMe
OH
H
630
631
(not isolated)
(±)−β-Conhydrine (
632
); (92%)
SCHEME 10.101.
