Stereoselective restructuring of 3-arylcyclobutanols into 1-indanols by sequential breaking and formation of carbon-carbon bonds

Article abstract of DOI:10.1002/chem.200902593

On the contrary! A rhodium-catalyzed restructuring reaction of 3-arylcyclobutanols to 1-indanols is reported, in which two chiral quaternary carbon centers are formed in a highly enantioselective fashion by a sequence of two contradictory elementary steps

Full text of DOI:10.1002/chem.200902593

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DOI: 10.1002/chem.200902593
Stereoselective Restructuring of 3-Arylcyclobutanols into 1-Indanols by
Sequential Breaking and Formation of Carbon–Carbon Bonds
Masanori Shigeno, Taiga Yamamoto, and Masahiro Murakami*[a]
Transition-metal catalyzed reactions involving an elemen-
tary step in which a carbon–carbon bond is cleaved provide
access to unique organic transformations that would other-
wise be difficult to achieve.[1,2] Of particular interest is the
desymmetrization of prochiral substrates through the enan-
tioselective cleavage of a carbon–carbon bond, which produ-
ces enantiomerically enriched compounds.[3] We recently de-
scribed a cascade-type reaction of 3-(2-hydroxyphenyl)cyclo-
butanones with electron-deficient olefins giving 5-alkylated
3,4-dihydrocoumarins.[4] Mechanistically, the reaction in-
volves two contradictory elementary steps operating in se-
quence; the first one is breaking of a carbon–carbon bond
of the four-membered carbocycle by b-carbon elimination[5]
and the second one is a carbon–carbon bond formation by
an intermolecular conjugate addition onto the electron-defi-
cient alkene. Such sequences consisting of contradictory ele-
mentary steps are worth pursuing from the synthetic as well
as mechanistic point of view. Herein, we describe the enan-
tio- and diastereoselective synthesis of 1-indanols by restruc-
turing of the carbon framework of 3-arylcyclobutanols.[6] Al-
though construction of chiral quaternary carbon centers re-
mains a significant challenge for synthetic chemists, the pres-
ent reaction gives rise to two chiral quaternary centers in a
highly enantiomerically enriched form in one pot.[7]
Scheme 1. Rhodium-catalyzed reaction of cyclobutanol 1a.
3-Ethyl-1-methyl-3-phenylcyclobutanol (1a), a symmetri-
cal substrate, was heated at 708C in 1,4-dioxane in the pres-
ence of Cs2CO3 (1.5 equiv) and a rhodium(I) catalyst pre-
major cis isomer was 96% ee. Replacement of the BINAP
ligand with (R)-DIFLUORPHOS[9] improved both stereose-
lectivities, such that the cis/trans ratio became 89:11, and im-
portantly, the enantiopurity of the major isomer increased
to 99% ee.[10] A plausible mechanism is shown in Scheme 1;
i) rhodium cyclobutanolate 3 is initially generated by depro-
tonation of the tertiary hydroxyl group of 1a by rhodium
hydroxide (or alkoxide), which acts as a base, ii) the four-
membered ring carbocycle is opened by b-carbon elimina-
tion. The chiral ligand on rhodium induces selective cleav-
age of one of the two enantiotopic carbon–carbon bonds to
generate a chiral quaternary center at the benzylic position,
iii) the resulting alkylrhodium species 4 subsequently under-
goes 1,4-rhodium shift[11] leading to the formation of arylr-
hodium intermediate 5, iv) intramolecular 1,2-addition to
the carbonyl group occurs to stereoselectively form the
pared from [{Rh(OH)ACTHNUTRGNE(UGN cod)}2] (5 mol%) and (R)-BINAP
(11 mol%). Restructuring of the carbon framework oc-
curred to afford 3-ethyl-1,3-dimethylindan-1-ol (2a) as a
mixture of diastereomers (cis/trans=79/21)[8] in 98% com-
bined yield (Scheme 1). The enantiomeric purity of the
[a] M. Shigeno, T. Yamamoto, Prof. Dr. M. Murakami
Department of Synthetic Chemistry and Biological Chemistry
Kyoto University, Katsura, Kyoto 615-8510 (Japan)
Fax : (+81)75-383-2748
E-mail: murakami@sbchem.kyoto-u.ac.jp
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200902593.
Chem. Eur. J. 2009, 15, 12929 – 12931
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
12929

second chiral quaternary center as the rhodium tertiary alco-
holate,[12] v) the rhodium alcoholate acts as a base to deprot-
onate another molecule of the cyclobutanol 1a to release
the tertiary indanol 2a.
The generality of the method is illustrated with cyclobuta-
nols 1b–g having various substituents at the 1- and 3-posi-
tions (Scheme 2). Butyl-, isopropyl-, and phenyl-substituted
Scheme 3. Comparison between the stereoselectivities of the restructur-
ing reactions of trans-1h and cis-1h.
mining steps are involved in the overall transformation. In
the first stereo-determining step, carbon–carbon bond a is
cleaved in preference to bond b by b-carbon elimination ir-
respective of the 3-substituent under the influence of the di-
phosphane ligand having (R)-axially chirality. As a result, R
configuration arises at the benzylic carbon starting from
trans-1h, and S configuration from cis-1h. In the second
stereo-determining step, the Re-face of the carbonyl group
is selectively attacked by the arylrhodium intermediate irre-
spective of the stereochemistry of the benzylic quaternary
carbon center. In both stereo-determining steps, the axis
chirality of the ligand on rhodium governs the stereochemi-
cal course of the reaction.
We carried out the reaction using 1-butyl-3-methyl-3-phe-
nylcyclobutanol (1i) having a methyl group at the 3-position
to confirm that the stereoselection made in the second
stereo-determining step is controlled by the chiral ligand
(Scheme 4). Thus, 1-indanol 2i possessing only one chiral
center was produced from the methyl-substituted cyclobuta-
nol 1i. The enantioselection in the carbonyl addition step
can be ascribed only to the chiral ligand. The enantioselec-
Scheme 2. Diastereo- and enantioselective synthesis of 1-indanols 2b–g.
a) Major isomer designated. b) The reaction was carried out at 608C. c)
The reaction was carried out with 10 mol% [{Rh(OH)ACTHNUGTRENUNG(cod)}2] and
22 mol% (R)-DIFLUORPHOS. d) The reaction was carried out at 508C.
cyclobutanols 1b–d gave the corresponding 1-indanols 2b–
2d in good yields with high diastereoselectivities and excel-
lent enantioselectivities. The restructuring reaction of 1e
bearing a sterically demanding tert-butyl group required a
higher catalyst loading, but still proceeded with high enan-
tioselectivity. Methoxy- and chloro substituents were tolerat-
ed on the phenyl ring and the corresponding 1-indanols 2 f
and 2g were formed in good yields with high levels of enan-
tiomeric excess.
Both trans and cis isomers of cyclobutanol 1h were sub-
jected to the restructuring reaction to test its stereospecific-
ity (Scheme 3). The reaction of trans-1h afforded cis-2h se-
lectively (cis/trans=91:9, 94% combined yield) and the
enantioselectivity observed with the major isomer was 99%
ee. On the other hand, the reaction of cis-1h produced
trans-2h selectively (trans/cis=94:6), again with an excellent
enantioselectivity of 99% ee for the major trans isomer.[13]
Thus, a reasonable level of stereospecificity was observed
between 1h and the product of restructuring (2h). Compari-
son with authentic samples of the enantiomerically enriched
1-indanol 2h prepared separately[14] revealed their absolute
configurations to be (1S, 3R) for cis-2h and (1S, 3S) for
trans-2h. These results led us to the following mechanistic
interpretation, as depicted in Scheme 3. Two stereo-deter-
Scheme 4. Rhodium-catalyzed synthesis of 1-indanol 2i possessing only
one chiral center.
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Restructuring of 3-Arylcyclobutanols into 1-Indanols
COMMUNICATION
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the chiral ligand is the major factor in determining the ste-
reochemical course of the carbonyl addition step with 1a–
1h.
In summary, we have developed a rhodium-catalyzed re-
structuring reaction of 3-arylcyclobutanols to 1-indanols pos-
sessing two chiral quaternary carbon centers with high dia-
stereo- and enantioselectivities through a sequence of two
contradictory elementary steps, that is, carbon–carbon bond
cleavage and carbon–carbon bond formation, both occurring
with high enantioselectivity.
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[14] See the Supporting Information for details.
Acknowledgements
This work was supported by Grants-in-Aid for Scientific Research (Nos.
17750087 and 19205013) from the Ministry of Education, Culture, Sports,
Science and Technology, Japan and the Asahi Glass Foundation. M.S.
thanks the Japan Society for the Promotion of Science for a fellowship
support.
À
C C
Keywords: 1,2-addition
·
asymmetric synthesis
·
activation · indanols · rhodium
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Received: August 24, 2009
Published online: November 2, 2009
Chem. Eur. J. 2009, 15, 12929 – 12931
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
12931