Remote asymmetric induction by using the 1,3-migration reaction of (diene)iron tricarbonyl complexes

Article abstract of DOI:10.1039/b004671j

Novel strategies for the stereoselective synthesis of molecules with remote stereogenic centers across double bonds have been developed via organoiron methodology allowing highly diastereoselective syntheses of 1,8- and 1,10-diol Fe(CO)₃ comple

Full text of DOI:10.1039/b004671j

Remote asymmetric induction by using the 1,3-migration reaction of
(diene)iron tricarbonyl complexes
Yoshiji Takemoto,* Kiyonori Ishii, Asami Honda, Kazuya Okamoto, Reiko Yanada and Toshiro Ibuka
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. E-mail:
takemoto@pharm.kyoto-u.ac.jp
Received (in Cambridge, UK) 12th June 2000, Accepted 21st June 2000
Novel strategies for the stereoselective synthesis of molecules
with remote stereogenic centers across double bonds have
been developed via organoiron methodology allowing highly
diastereoselective syntheses of 1,8- and 1,10-diol Fe(CO)3
complexes using the stereospecific 1,3- and 1,5-migration of
an Fe(CO)3 group; this strategy could be used for ster-
eoselective functionalization of remote terminal substituents
on acyclic polyene compounds.
One of the more challenging aspects of organic synthesis is the
stereoselective construction of molecules with remote (i.e.
greater than 1,3-related) stereogenic centers with high levels of
diastereo- and enantioselectivity.1 A particularly challenging
goal would be the development of a general strategy for the
control of remote stereogenic centers related across double
bonds of fixed configuration, because this moiety is present in
many natural products, including polyene macrolide antibiotics
such as filipin III.
Scheme 1 Remote stereocontrol based on the 1,3-migration concept of an
Fe(CO)3 group.
The requisite (trienone)- and (tetraenone)Fe(CO)3 complexes
2 and 8 were prepared from the chiral aldehydes 1 and 7
(Scheme 2).3 We first examined the 1,2-reduction of the a,b-
unsaturated ketone 2 via 1,4-asymmetric induction. In contrast
to the reduction of (dienone)Fe(CO)3 complex,4 the reduction of
2 with sodium borohydride in methanol in the presence of
CeCl3·6H2O gave a nearly equimolar ratio of the two diaster-
eomeric trienol complexes.5 To overcome this problem, we next
In the course of our studies on the mobility of the Fe(CO)3
group on polyenes with the aim of constructing several
stereogenic centers using a single chiral auxiliary,2 we have
found that the Fe(CO)3 moiety of (triene)Fe(CO)3 complexes
shifts to the electron-deficient double bond stereospecifically on
treatment with a base such as potassium bis(trimethylsilyl)-
amide (KHMDS) and NaH. By taking advantage of this
1,3-migration of the Fe(CO)3 group, the (polyenone)Fe(CO)3
complexes B could be converted via C into the corresponding
migrated complexes D, where the Fe(CO)3 groups are situated
in the ideal position for controlling several reactions of the
ketone (Scheme 1). We herein report a novel strategy for highly
diastereoselective preparation of polyene- and saturated 1,8-
and 1,10-diols E and F by a combination of the 1,3- or
1,5-migration of the Fe(CO)3 group and subsequent hydride
reduction of the ketone, together with a formal asymmetric
synthesis of epipatulolide C.
Scheme
2 Reagents and conditions: (a) CH3COCH2P(O)(OMe)2,
LiOH·H2O, MeOH (90% for 1, 78% for 7); (b) NaH, THF (81%), (c)
NaBH4, MeOH (91% for 3, 72% for 8); (d) H2O2, 1 M NaOH, MeOH, 0 °C
(83%); (e) H2, PtO2, AcOEt (85%); (f) (EtO)2P(O)CH2CN, NaH, THF, 0 °C
(69%); (g) DIBAL-H, 250 °C (49%); (h) n-Bu3P, CH2Cl2 (71%); (i)
KN(SiMe3)2, THF, 0 °C (70%); (j) H2O2, 1 M NaOH; H2, PtO2 (89%).
DOI: 10.1039/b004671j
Chem. Commun., 2000, 1445–1446
This journal is © The Royal Society of Chemistry 2000
1445

investigated the 1,2-reduction of the 1,3-migrated complex 3,
which was easily accessible from 2 by the stereospecific
1,3-migration of the Fe(CO)3 group. According to the reported
procedure,2 2 was treated with 1.5 equiv. of NaH in THF at 0 °C
to give the desired product 3 in 81% yield along with the
recovered starting material (2%). The stereochemistry of 3 was
deduced from the previous result, namely, that the 1,3-migra-
tion of the Fe(CO)3 group proceeded with inversion of
configuration. In contrast to 2, the reduction of the migrated
product 3 with NaBH4 provided the alcohol 4 as the single
isomer in 91% yield. The desired 3,5,7-triene-2,9-diol 5 was
easily synthesized by reaction of 4 with 30% hydrogen peroxide
in the presence of 1 M NaOH solution. Furthermore, subsequent
hydrogenation of 5 on platinum oxide in AcOEt gave the
1,8-anti-diol 6 in 85% yield. To confirm the absolute ster-
eochemistry, the diastereomerically pure alcohol 6 was con-
verted into the corresponding (R)- and (S)-MTPA esters,
respectively. As expected, the absolute stereochemistry of the
C2 position was revealed to be (R)-configuration by comparing
their 1H NMR spectra.6
To extend the applicability of this method, we next examined
the reduction of the (tetraenone)Fe(CO)3 complex 8, which was
prepared stereoselectively from 7 in 4 steps. The key reaction in
this case would be a double 1,3-migration reaction of the
Fe(CO)3 group (i.e., 1,5-migration). Then we investigated the
migration reaction of 8 with several bases. Although we could
not obtain the migration product by treatment of 8 with NaH, the
reaction of 8 with 0.3 equiv. of KHMDS in THF at 0 °C
provided the 1,5-migration product 9 in 70% yield along with
the recovered starting material (7%). In the latter case, the
1,3-migration product of the Fe(CO)3 group, an intermediate of
the 1,5-migration reaction, could not be observed in the crude
reaction mixture. Similarly, the reduction of 9 with NaBH4 in
methanol gave rise to the alcohol 10 in 72% yield as a single
isomer. The transformation of 10 into 11 was performed by the
same reaction sequence as that of 4 to give the 1,10-syn-diol 11
in 89% yield. The absolute stereochemistry was also determined
by the MTPA-ester method.6 The result revealed that the
1,5-migration of the Fe(CO)3 group should occur with retention
of configuration as a result of a double inversion mechanism.
Finally, we applied this method to a formal asymmetric
synthesis of epipatulolide C (Scheme 3).7 By a similar 5-step
sequence, the chiral aldehyde 12 was transformed into the
(2S,9R)-triol derivative 13 as a single isomer. After protection
and deprotection of the hydroxy groups of 13, the resulting
alcohol was oxidized, and Wittig condensation of the aldehyde
so obtained and subsequent removal of the TBS group gave the
unsaturated ester 14, which had been converted into racemic
epipatulolide C in three steps.
Scheme 3 Reagents and conditions: (a) PMBOCH2COCH2P(O)(OEt)2, t-
BuOH, toluene (54%); (b) KHMDS (0.1 eq.), THF, 0 °C (62%); (c) NaBH4,
MeOH (83%); (d) H2O2, NaOH; (e) H2, PtO2 (89%); (f) TBDPSCI,
imidazole (64%), (g) DDQ (72%); (h) Swern oxidation; Ph3PNCHCO2Me
(69%); (i) AcOH, THF, H2O (74%).
Sciences Foundation, Suzuken Memorial Foundation and
Grant-in-Aid for Scientific Research (C) from the Ministry of
Education, Science, Sports, and Culture, Japan.
Notes and references
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This work shows how a combination of the mobility and the
stereodirecting ability of the Fe(CO)3 group can be used to
prepare stereoselectively compounds with remote stereogenic
centers. Further applications to the construction of more remote
stereogenic centers across double bonds are underway in these
laboratories.
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This article is dedicated to the memory of Professor Toshiro
Ibuka. This work was supported in part by The Japan Health
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