Chemistry Reference
In-Depth Information
TBSO
TBSO
1. K
2
OsO
4
, NMO,
citric acid
2. PhI(OAc)
2
Pd(OAc)
2
,
BBEDA
O
O
N
Ns
N
O
O
Ns
11.220
11.221
R
HO
TBSO
TBSO
O
1. K
2
CO
3
2. NaBH(OAc)
3
H
2
CO, HCO
2
H
O
O
N
H
O
O
Ns
11.222
11.223
HCO
2
HO
HCO
2
HO
O
O
NH
3
, MeOH
N
N
O
O
1
1
2
1
.
2
BBEDA =
PhHC
N
N
CHPh
Scheme 11.75
Me) had to be used to block this pathway.
101
Selective cleavage of the
exo
-cyclic alkene of
11.221
allowed removal of the
N
-protecting group by an elimination-reduction sequence, which also reduced
the ketone. Pictet-Spengler ring closure was accompanied by conversion of both the alcohol and the TBS
ether to formate esters; cleavage of the formate esters then yielded the natural product
11.225
.
An alternative mechanism involves the use of metal hydrides (Scheme 11.76). Palladium(0) complexes
can oxidatively add to acetic acid to generate such a hydride. Rather than an oxidative cyclization occurring,
a sequence of insertion into the palladium-hydrogen bond, followed by insertion into the palladium-carbon
bond forms the new bicyclic complex
11.230
.
=
alkyne (R
-Hydride elimination then releases the product
11.227
and
regenerates the acetoxypalladium hydride.
102
The alkyl palladium(II) species
11.230
, which has no counterpart in the Pd(II)/Pd(IV) mechanism of
Scheme 11.71, is particularly interesting. As with such species in the Heck reaction (Section 5.1.10), if it does
not have a
-hydrogen available, it can be intercepted in other ways resulting in tandem processes. Multiple
cyclizations are possible, for instance via a long sequence of neopentyl intermediates (Scheme 11.77).
103
Intermolecular reactions are possible, although, strictly, they should not be referred to as cycloisomeriza-
tion reactions, as they involve the coupling of two components. Without the discipline provided by being
intramolecular, these reactions can suffer from the issue of regioselectivity. While this is not a problem with
symmetrical alkynes, as in the synthesis of diene
11.233
(Scheme 11.78),
104
little or no selectivity is observed
with many simple substrates. One solution is to employ a propargyl alcohol as the substrate.
105
Coordination
of the hydroxy group to ruthenium then provides the required regiocontrol. This concept has been employed in
a synthesis of ancepsenolide
11.237
by reaction of a chiral propargylic alcohol
11.235
with 1,11-dodecadiene
