Catalytic asymmetric synthesis of 1,1′-spirobi[indan-3,3′-dione] via a double intramolecular C-H insertion process

Article abstract of DOI:10.1039/b103747c

A highly efficient one-pot construction of optically active 1,1′-spirobi[indan-3,3′-dione] derivative (up to 80% ee) has been achieved by exploiting the double intramolecular C-H insertion reaction of dimethyl 2,2′-methylenebis(α-diazo-β-oxobenzenepropano

Full text of DOI:10.1039/b103747c

Catalytic asymmetric synthesis of 1,1A-spirobi[indan-3,3A-dione] via a
double intramolecular C–H insertion process
Teruki Takahashi, Hideyuki Tsutsui, Masafumi Tamura, Shinji Kitagaki, Makoto Nakajima and
Shunichi Hashimoto*
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
E-mail: hsmt@pharm.hokudai.ac.jp
Received (in Cambridge, UK) 25th April 2001, Accepted 12th July 2001
First published as an Advance Article on the web 9th August 2001
A highly efficient one-pot construction of optically active
1,1A-spirobi[indan-3,3A-dione] derivative (up to 80% ee) has
been achieved by exploiting the double intramolecular C–H
insertion reaction of dimethyl 2,2A-methylenebis(a-diazo-b-
oxobenzenepropanoate) under the influence of dirhodium
(
II) tetrakis[N-phthaloyl-(R or S)-tert-leucinate] as a cata-
lyst.
The development of efficient chiral metal complexes in the field
of asymmetric synthesis has focused mainly on the design and
synthesis of novel chiral ligands. BINAP, BINOL and related
ligands based on the axially chiral 1,1A-binaphthyl skeleton have
achieved significant success in asymmetric catalysis.1 In this
context, certain bifunctional chiral spirans with C2-symmetry
may be regarded as promising ligands, as they contain a totally
rigid spiro backbone which creates an effective asymmetric
environment. Although chiral cis,cis-spiro[4.4]nonane-1,6-diol
has recently shown potential either as a chiral ligand itself2 or as
a precursor to other useful chiral ligands,3 the widespread
application of this class of spiran ligands has received relatively
little attention.4 Clearly, a major obstacle is the difficulty in
obtaining enantiomerically pure spiran molecules, which gen-
erally involves a tedious resolution of racemates via fractional
crystallization5 or chromatography6 of the diastereomeric
mixtures. Thus, the development of a catalytic asymmetric
synthesis of C2-symmetrical chiral spirans would represent
significant improvement over current methodologies for obtain-
ing these ligands.7,8
Recently, Aburel and Undheim reported a new synthetic
approach to generate racemic spiro[4.4]nonane-2,7-dione deriv-
atives from acyclic bis(a-diazoketone) using a Rh2(OAc)4-
catalyzed double intramolecular C–H insertion reaction, though
the product yields are found to be only 27–35%.9 Inspired by
their pioneering work, and taking advantage of our continuing
research in this field,10 we turned our attention to the feasibility
of a high-yielding and enantioselective synthesis of C2-
symmetrical chiral 1,1A-spirobiindan systems. Herein we report
4, which, without purification, was transformed by demethox-
ycarbonylation to give spirobiindanone 1. As might be expected
from the results of Undheim,9 a product yield of only 29% was
12
found. The use of Rh2(O2CC7H15)4, Rh2(O2CCPh3)4 or
Rh2(O2CC3F7)4 also resulted in low yields.‡ Thus, we were
gratified to find that the reaction proceeded smoothly at 0 °C
with the aid of chiral dirhodium(II) carboxylates, Rh2(S-
PTPA)4, Rh2(S-PTA)4, Rh2(S-PTV)4, Rh2(S-PTPG)4, and
Rh2(S-PTTL)4, derived from N-phthaloyl-(S)-phenylalanine,
-alanine, -valine, -phenylglycine, and -tert-leucine, respec-
tively,10 to give synthetically useful product yields (Table 1).
Although no explanation for the striking contrast between the
achiral and chiral dirhodium(II) carboxylates can be offered at
present, the advantage of our catalysts extends beyond stereo-
control in this system.§ While the formation of (R)-1,1A-
spirobi[indan-3,3A-dione] (R)-1 was favored in all cases, Rh2(S-
PTTL)4 characterized by an exceptionally bulky tert-butyl
group proved to be the catalyst of choice for displaying a
reasonable degree of enantioselectivity (68% ee, entry 5).¶
Further screening of solvents confirmed that the use of toluene
was the superior choice for allowing smooth insertion at 210 °C
to provide (R)-1 in 78% yield with 80% ee (entry 6), which,
upon a single recrystallization from ethanol, produced the
25
optically pure sample, mp 212–213 °C, [a]D 2237.0 (c 0.69,
CHCl3) [lit.,5b [a]D24 +238.7 (c 0.64, CHCl3) for (S)-1], in 67%
yield. The use of Rh2(R-PTTL)4 also generated (S)-1 with 79%
ee (entry 7). Thus, both enantiomers of 1 are equally available.
The use of DCM provided (R)-1 with 60% ee (entry 8),
however, 0 °C was found to be the temperature limit for
allowing smooth cyclization. It is of particular interest that the
use of benzotrifluoride (a,a,a-trifluorotoluene)14 greatly ac-
celerated the insertion rate, though the largest ee was found to
be 72% at 223 °C (entry 9).
a facile path to optically pure 1,1A-spirobi[indan-3,3A-dione] 1,5b
a potential intermediate in the synthesis of the hitherto unknown
cis,cis-1,1A-spirobi[indan-2,2A-diol], via an enantioselective
double intramolecular C–H insertion process with up to 80%
ee.
At the outset of this work, we explored the double cyclization
of bis(a-diazo-b-keto ester) 2 in the presence of 2 mol % of
Rh2(OAc)4.† While the use of DCM as solvent gave a complex
mixture of products, the catalysis of 2 in toluene was found to
proceed sluggishly at rt to produce spirobiindanone derivative
The stereochemical outcome observed here suggests that the
chiral rhodium(II) carbene intermediate generated via Rh2(S-
PTTL)4-catalyzed decomposition of 2 preferentially inserts into
a methylene C–Hs bond to give (3S)-indan-1-one derivative 3,
which undergoes a second C–H insertion at the methine C–H
bond with well-established retention of configuration15 to
1604
Chem. Commun., 2001, 1604–1605
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b103747c

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Table 1 Enantioselective double C–H insertion reaction of 2 catalyzed by chiral dirhodium(II) complexesa
Yield of
1 (%)b
Ee of
1 (%)c
Entry
Catalyst
Solvent
Temp./°C
Time/h
1
2
3
4
5
6
7
8
9
Rh2(S-PTPA)4
Rh2(S-PTA)4
Rh2(S-PTV)4
Rh2(S-PTPG)4
Rh2(S-PTTL)4
Rh2(S-PTTL)4
Rh2(R-PTTL)4
Rh2(S-PTTL)4
Rh2(S-PTTL)4
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
CH2Cl2
CF3C6H5
0
0
0
0
0
0.5
1
0.5
1
0.5
1
1
71
68
66
67
83
78
76
72
66
25
23
24
21
68
80
279d
60
210
210
0
1
1
223
72
a Reactions were carried out as follows: 2 mol % of catalyst was added to a stirred solution of diazo compound 2 (0.20 mmol) in the indicated solvent (2 ml)
at the indicated temperature under argon. After the reaction proceeded to completion, the solvent was evaporated in vacuo and the residue was treated with
90% aqueous DMSO (1.5 ml) at 120 °C for 1 h. Standard workup followed by chromatography provided (R)-1. b Overall isolated yield. c Determined by
HPLC (column, Daicel chiralcel OD; 4.6 3 250 mm 3 2; eluent, 15% propan-2-ol in hexane; flow rate, 1.0 ml min21; retention time, 31.2 min [(R)-1] and
35.1 min [(S)-1]). d (S)-1 was preferentially formed.
2 N. Srivastava, A. Mital and A. Kumar, J. Chem. Soc., Chem. Commun.,
provide (R)-1 after demethoxycarbonylation. Thus, the sense
1992, 493.
and magnitude of enantioselection indicates the level of
differentiation between methylene C–H bonds during the first
3 A. S. C. Chan, W. Hu, C.-C. Pai, C.-P. Lau, Y. Jiang, A. Mi, M. Yan, J.
Sun, R. Lou and J. Deng, J. Am. Chem. Soc., 1997, 119, 9570; W. Hu,
C–H insertion. In accordance with the order of reactivity of the
M. Yan, C.-P. Lau, S. M. Yang, A. S. C. Chan, Y. Jiang and A. Mi,
target C–H bond (methine C–H > methylene C–H),16 we could
Tetrahedron Lett., 1999, 40, 973.
4 Y. Jiang, S. Xue, K. Yu, Z. Li, J. Deng, A. Mi and A. S. C. Chan,
J. Organomet. Chem., 1999, 586, 159; M. A. Arai, T. Arai and H. Sasai,
Org. Lett., 1999, 1, 1795.
not observe the first insertion product 3,9 which makes it
possible to conduct this one-pot reaction under the constant
conditions.
In summary, we have achieved the first catalytic, enantio-
selective synthesis of 1,1A-spirobi[indan-3,3A-dione] (1) of up to
80% ee, in which the use of Rh2(R or S-PTTL)4 as a catalyst is
crucial to the success of the double C–H insertion process. The
present protocol has the advantages of operational simplicity as
well as a facile entry to optically pure 1 via a single
recrystallization, thus providing great potential for large-scale
preparation. Elaboration of (R)- or (S)-1 to hitherto unexplored
chiral ligands such as 1,1A-spirobi[indan-2,2A-diol] for metal
catalyzed enantioselective reactions is currently in progress.
This research was supported in part by a Grant-in-Aid
(No.11470465) from the Ministry of Education, Science, Sports
and Culture, Japan. We thank Ms S. Oka of the Center for
Instrumental Analysis at Hokkaido University, for mass
measurements.
5 (a) S. Hagishita, K. Kuriyama, M. Hayashi, Y. Nakano, K. Shingu and
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7 For asymmetric synthesis of 4,9-dimethylspiro[4.4]nonane-2,7-dione
using Rh(I)-catalyzed hydroacylation twice, see: M. Takahashi, M.
Tanaka, E. Sakamoto, M. Imai, A. Matsui, K. Funakoshi, K. Sakai and
H. Suemune, Tetrahedron Lett., 2000, 41, 7879.
8 For synthesis of enantiomerically pure trans,trans-spiro[4.4]nonane-
1,6-diol by asymmetric reduction of racemic spirodiketone, see: C.-W.
Lin, C.-C. Lin, Y.-M. Li and A. S. C. Chan, Tetrahedron Lett., 2000, 41,
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Notes and references
† Bis(a-diazo-b-keto ester) 2 was prepared from diphenylmethane-2,2A-
dicarboxylic acid11 in 70% yield by the following three-step sequence: i,
SOCl2, toluene, reflux; ii, LiCH2CO2Me, THF, 278 °C; iii, MsN3, Et3N,
MeCN.
‡ Overall isolated yield: Rh2(O2CC7H15)4, 28%; Rh2(O2CCPh3)4, 13%;
Rh2(O2CC3F7)4, 17%.
§ While reaction of the corresponding bis(a-diazoketone) with Rh2(OAc)4
in CH2Cl2 provided 52% yield of 1, Rh2(S-PTTL)4 gave a complex mixture
of products under the same conditions.
¶ Rh2(S-DOSP)4 developed by Davies13 was found to be less reactive than
our catalysts; catalysis of 2 with 2 mol % of Rh2(S-DOSP)4 in toluene
proceeded at rt sluggishly to afford, after demethoxycarbonylation, (S)-1 in
48% yield with 8.3% ee.
15 D. F. Taber, E. H. Petty and K. Raman, J. Am. Chem. Soc., 1985, 107,
196.
16 D. F. Taber and R. E. Ruckle, Jr., J. Am. Chem. Soc., 1986, 108,
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1 R. Noyori, Asymmetric Catalysis in Organic Synthesis, Wiley, New
York, 1994; Catalytic Asymmetric Synthesis, ed. I. Ojima, Wiley-VCH,
New York, 2000.
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