328
Chemistry Letters Vol.36, No.2 (2007)
Two Isolable Conformers of Dihydropentahelicenediol Derivatives:
Stereochemical Property and Its Utility for Asymmetric Reactions
Ken Ohmori, Sanae Furuya, Shigeo Yamanoi, and Keisuke Suzukiꢀ
Department of Chemistry, Tokyo Institute of Technology, SORST-JST Agency, O-okayama, Meguro-ku, Tokyo 152-8551
(Received November 28, 2006; CL-061406; E-mail: ksuzuki@chem.titech.ac.jp)
Conformation of dihydropentahelicenediol 2 and the related
OH
compounds was studied. Two isolable conformers, i.e. the di-
equatorial and the diaxial forms, interconvert only at elevated
temperatures, where the equilibrium ratio depends on bulkiness
of the substituents attached to the hydroxy groups. The palladi-
um-catalyzed asymmetric allylic substitution was used to test the
potential utility of phosphine derivatives, 6eq and 6ax, as chiral
ligands.
SmI2
CHO
CHO
THF
0 °C, 5 min
quant.
OH
1
2
only isomer
obtained
kinetically
OH
H
toluene,
H
OH
H
HO
OH
reflux, 1 h
H
During the synthetic studies on some natural products
(Figure 1),1 we became interested in the phenanthrenediol motif
embedded as a partial structure in these molecules. Among two
conformers associated with the rotation around the biaryl axis,
the diequatorial conformer is stabilized in aprotic solvents by
the hydrogen bonding between two hydroxy groups, while the
diaxial counterpart is preferred in protic solvents due to the steric
repulsion of the solvated hydroxy groups.2 Although this confor-
mational issue most likely has biological relevance, these natural
products are undergoing fairly rapid conformational change.
We reasoned that, if these conformers could be separated,
they might be useful for biological studies, and also find use in
selective organic synthesis. In this relation, we reported the syn-
thesis of enantiopure trans-diol 2 via the SmI2-mediated pinacol
cyclization of (R)-2,20-binaphthyldicarbaldehyde (1).1a Al-
though the kinetic product was only composed of the diequato-
rial form 2eq, we became interested in obtaining its diaxial coun-
terpart 2ax, differing from 2eq in the helicity and the relative
orientation of two hydroxy groups. We expected that these con-
formers would be isolable and handled as separated entities, be-
cause of the pentahelicene-like structure. In this communication,
we wish to describe the study along these lines.
3 : 97
2ax
2eq
Scheme 1. Preparation and conformational behavior of penta-
helicene derivative 2.
the same ratio was reached by heating of 2ax for 1.5 h or 2eq
for 8 h in toluene (reflux), respectively.3 This great preference
of the diequatorial conformer 2eq could be ascribed to the intra-
molecular hydrogen bonding between two hydroxy groups.
A notable point is that these conformers were easily separa-
ble by silica-gel column chromatography [Rf values on TLC
(silica gel 60, hexane/EtOAc = 1/1): 2eq = 0.28, 2ax =
0.20], and remained stable at room temperature. The barrier
for the conformational change was assessed by studying the
time course of the isomerization from 2ax (thermodynamically
unfavorable conformer) into 2eq by HPLC to show that
ꢀGz
in toluene at 25 ꢁC is 28 kcal/mol,4 high enough
2ax!2eq
to allow the handling as a stable conformer at ambient temper-
ature.
In order to enhance the availability of 2ax, we sought to
break the hydrogen bonding, which was achieved by masking
two hydroxy groups in 2. For example, acetylation of 2eq
(Ac2O, pyridine, 25 ꢁC, 1 h) smoothly gave the corresponding
bis-acetate 3eq as its diequatorial form unchanged. However,
heating in toluene (reflux, 20 h) gave a mixture (3eq/3ax =
45/55). Installation of silyl groups made the equilibrium more
favorable of the diaxial conformers. Although treatment of 2eq
with t-BuMe2SiCl [imidazole, DMF, 25 ꢁC, 12 h] gave only
the mono-silyl ether as its diequatorial form in 88% yield, a
longer reaction at higher temperature (100 ꢁC, 20 h) led to a
clean formation of bis-silyl ether 4 in 98% yield. At this stage,
the conformer ratio (4eq/4ax) was 32/68, suggesting that the
gauche repulsion of two vicinal substituents, destabilized the
diequatorial conformer.5
Simple heating of 2eq in toluene (reflux, 1 h) led to a
conformer equilibration, giving the diaxial conformer 2ax, albeit
1
in a very minor amount (3% assessed by H NMR). This was
proven to be the equilibrium ratio (2eq/2ax = 97/3), because
CO2H
O
NH
HO
HO
HO
O
OH
O
O
MeO
OH
OH
MeO
O
OH
HO
HO
PD-116740
aglycon of pradimicins
H
Double installation of more bulky silyl group (TBDPS) was
also achieved at high temperature (100 ꢁC, 20 h) to give 93%
yield of bis-silyl ether 5, which, delightedly, was only composed
of the diaxial form 5ax. Even after heating of 5ax in toluene for
8 h, no trace of the diequatorial isomer 5eq was observed.
The conformer 5ax could be deprotected to give the free
diaxial conformer 2ax (eq 1); treatment of 5ax with n-Bu4NF
HO
H
H
HO
OH
OH
H
diequatorial
diaxial
Figure 1.
Copyright Ó 2007 The Chemical Society of Japan