Chemistry Reference
In-Depth Information
Me
Me
MeO
2
C
MeO
2
C
MeO
2
C
MeO
2
C
(Ph
3
P)
3
RhCl
1
.
1
1
1
4
Scheme 11.48
1. [Ru(CO)
2
Cl]
2
2. HCl, EtOH
Me
+
Me
CO
2
Me
O
TBSO
MeO
2
C
11.143
11.145
11.144
Scheme 11.49
(Scheme 11.48).
69
The reaction, employing Wilkinson's catalyst, (Ph
3
P)
3
RhCl, is made more rapid by the
addition of silver(I) ions. These halophilic ions abstract chloride from the catalyst to generate a more reactive
cationic rhodium complex. Use of chiral ligands can give excellent enantioselectivity.
70
A ruthenium catalyst,
[Ru(CO)
2
Cl]
2
, is more effective for hindered substrates; the reaction can be intermolecular in special cases,
using alkoxy cyclopropanes (Scheme 11.49).
71
The [5
2] cycloaddition was used in a synthesis of core structure of the cyathane diterpenes
11.146
,
tricyclic compounds that promote nerve growth factor (Scheme 11.50).
72
The synthetic strategy revolved
around using the cycloaddition of vinyl cyclopropane
11.147
to create the six- and seven-membered rings in
a single step.
The chosen starting material was limonene
11.148
, which could be cut down to a five-membered ring
11.149
by a sequence involving an intramolecular aldol reaction (Scheme 11.51). The side chain for the
alkynyl arm could then be partly installed by a stereoselective Claisen rearrangement, placing an alde-
hyde group
trans
to the
iso
-propyl group. The vinyl cyclopropyl moiety could be attached with acetylene
chemistry, prior to the completion of the alkynyl arm. The ketonic substrate
11.147
underwent smooth
and selective cycloaddition on treatment with a rhodium catalyst; in contrast the alcohol
11.154
gave a
complex mixture.
The mechanism proposed involves formation of a metallacyclopentene
11.156
, followed by strain-driven
ring opening of the cyclopropane to form a metallacyclooctadiene
11.157
(Scheme 11.52). This ring expansion
is then followed by reductive elimination.
+
O
O
HO
H
HO
11.146
11.147
Scheme 11.50
