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1.3 The Intramolecular Pauson-Khand Reaction
The establishment of the intramolecular variant of the PK reaction by Schore in 1981
provided a crucial advance associated with this methodology, which has allowed this
metal-mediated cyclisation technique to grow considerably in importance and utility within
preparative organic chemistry. 18 As illustrated in Scheme 1.10, it was shown within the
original landmark publication that both hept-6-en-1-ynes and oct-7-en-1-ynes perform in
the intramolecular PK process to deliver the bicyclic enones shown. In addition to this and
by extension, others went on to show that similar oxygen- and nitrogen-tethered enynes
could also take part in similar cyclisations to deliver the equivalent bicyclopentenone
products. 19
Co 2 (CO) 8
O
Isooctane, 95 °C, 4 d
31%
Co 2 (CO) 8
O
Isooctane, 95 °C, 4 d
35%
Scheme 1.10
A short period after Schore's initial publications in this area, Magnus further enhanced
the efficacy of this method by showing that appreciable stereoselectivity could be embedded
within intramolecular processes, a feature that was to prove key to the application of the
PK reaction in natural product synthesis. As illustrated in Scheme 1.11, substituents at
the propargylic (C3) and allylic (C5) positions have a preference to become situated on
the exo -face of the resulting bicyclic PK products, and syn to the ring fusion hydrogen. 20
Furthermore, the level of stereoselectivity achieved is enhanced by bulky substitution at
the terminal alkyne carbon. With the stereochemical reaction outcomes established for a
number of substrate substitution patterns, Magnus and co-workers went on to utilise these
methods within the synthesis of precursors to the linearly-fused triquinane natural products,
coriolin and hirsutic acid. 20a,c
In addition, the employment of a similar stereoselective
TBSO
TMS
TBSO
TMS
OTBS
Co 2 (CO) 6
CO, heptane,
110 °C (sealed tube), 20 h
+
O
O
TMS
79%
3%
H
H
TMS
OMOM
Co 2 (CO) 6
CO, heptane,
90 °C (sealed tube), 36 h
O
TMS
68%
H
MOMO
Scheme 1.11
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