Chemistry Reference
In-Depth Information
of vinylcyclopropane
114
under the conditions of the homo-Pauson-Khand reaction gave
enone
115
in 86% yield with high diastereoselectivity. The structure of
115
was confirmed
by X-ray analysis of the 2,4-dinitrophenylhydrazone derivative. The further steps provided
(
-agarofuran
116
to complete the total synthesis and validate the first synthetically
practical homo-Pauson-Khand [(3
±
)-
α
1]cycloaddition employing vinylcyclopropane in-
termediates. This is an important advance in Pauson-Khand reaction.
Mukai and co-workers completed the first total syntheses of two tricyclic sesquiterpenes
represented by
120
via a Rh(I)-catalyzed Pauson-Khand-related reaction.
62
As shown in
Scheme 8.17, acetal
117
, derived from dimethyl D-tartrate, was converted into the appro-
priate ene-allenene
118
. The initial reaction conditions chosen, which employed 5 mol%
[RhCl(CO)
2
]
2,
5 atm CO in refluxing toluene did not provide the expected enone
118
.
Several other catalysts and conditions failed to provide the desired results. Success was
achieved by the reaction of allene
118
with a cationic rhodium catalyst under an atmosphere
of carbon monoxide in refluxing toluene to provide the key bicycle[4.30]nonene
119
in
74% yield. The stereochemistry was confirmed by NOE experiments and rationalized by
the formation of the expected rhodacycle in which the intermediate adopts the more stable
chair conformation. Completion of the total synthesis relied upon the successful conversion
of enone
119
into the stereoselective isopropylcyclopropane ring to provide both tricyclic
sesquiterpenes represented by
120
.
+
2)
+
Me
O
1
atm
CO,
toluene
TBSO
Me
Me
OMe
5
mol%
[RhCO(dppp)
2
]Cl
O
MOMO
reflux, 1 hour
74%
OH
CO
2
Me
118
117
TBSO
OR
Me
Me
MOMO
RO
H
O
Me
H
H
CO
2
Me
Me
119
120
:
R
=
H,
Ac
Scheme 8.17
The total synthesis of sesquiterpenes via an allenyl Pauson-Khand-type
reaction.
Isocarbacyclin
124
is an analog of the vasodilator prostacyclin and has been previ-
ously prepared via an enantioselective total synthesis described by Saito.
63
Because of the
recognition of the bicyclic core present in isocarbacyclin, a synthetic Pauson-Khand ap-
proach outlined in Scheme 8.18 was developed. L-Ascorbic acid
121
was converted via
a series of steps to enyne
122
on multi-gram scale. The reaction of
122
was then studied
under both stoichiometric and catalytic Pauson-Khand conditions.
Choice of the stoichiometric conditions by which alkyne
122
reacted with dicobalt
octacarbonyl in CH
2
Cl
2
(followed by heating to 65
◦
C in acetonitrile) furnished enone
