Rh(I)-catalyzed cyclocarbonylation of enynes with glyceraldehyde: An available carbonyl source derived from sugar alcohols

Article abstract of DOI:10.1055/s-0031-1290311

Catalytic cyclocarbonylation reactions using a glyceraldehyde derivative as a carbonyl source are described. The rhodium(I)-catalyzed reaction of enynes with glyceraldehyde acetonide gave bicyclic cyclopentenones as the products. This presents an interesting use of a sugar alcohol derived carbon resource as well as a convenient procedure for the cyclocarbonylation of enynes. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0031-1290311

LETTER
393
Rh(I)-Catalyzed Cyclocarbonylation of Enynes with Glyceraldehyde:
An Available Carbonyl Source Derived from Sugar Alcohols
Rh(I)-Catalyzed
C
e
yclocarbon
i
ylation
i
of Eny
c
nes hi Ikeda, Tsumoru Morimoto,* Takayuki Tsumagari, Hiroki Tanimoto, Yasuhiro Nishiyama, Kiyomi Kakiuchi
Graduate School of Materials Science, Nara Institute of Science and Technology (NAIST), Takayama, Ikoma, Nara 630-0192, Japan
Fax +81(743)726081; E-mail: morimoto@ms.naist.jp
Received 20 October 2011
of dppp [1,3-bis(diphenylphosphino)propane], the reac-
tion of 2a with two equivalents of rac-1 in toluene at re-
flux resulted in the complete consumption of 2a in two
hours to give the desired product 3a in 82% yield
Abstract: Catalytic cyclocarbonylation reactions using a glyceral-
dehyde derivative as a carbonyl source are described. The rhodi-
um(I)-catalyzed reaction of enynes with glyceraldehyde acetonide
gave bicyclic cyclopentenones as the products. This presents an in-
teresting use of a sugar alcohol derived carbon resource as well as a (Scheme 1). Chiral (R)-1 also reacted smoothly to afford
convenient procedure for the cyclocarbonylation of enynes.
the racemic product in high yield, however, the chirality
of (R)-1 appeared to have no effect on the enantioselectiv-
ity during the synthesis of 3a. As a result, it was found that
the multifunctionalized aldehyde 1, which is derived from
a sugar alcohol, such as glycerol and D-mannitol, also can
be utilized as an effective carbonyl source in the cyclocar-
bonylation of enynes.10
Key words: rhodium, cyclocarbonylation, enyne, glyceraldehyde,
sugar alcohol
The transition-metal-catalyzed cyclocarbonylation of
enynes is an attractive research area, in that it provides
easy access to the construction of bicyclic cyclopentenone
frameworks from open-chain compounds.1 Because of its
synthetic usefulness, considerable efforts have been fo-
cused on identifying an easy-to-handle carbonyl source
that can be substituted for carbon monoxide in such reac-
tions. Recent studies by us and others have demonstrated
that formyl compounds, such as aldehydes2 and a for-
mate,3 could be utilized as a carbonyl source using a strat-
egy based on the catalytic decarbonylation of the formyl
group. Quite recently, it was found that readily available
carbon resources, including aldoses, can be used as a car-
bonyl source in such reactions. Chung et al. reported on
rhodium(I)-catalyzed reactions of an enyne with D-glu-
cose as a carbonyl source.4 Independently, we reported on
the use of aldose derivatives as a carbonyl source in cyclo-
carbonylation reactions.5 We next targeted on the use of
sugar alcohols or their derivatives as a new carbonyl
source in the transformation. Sugar alcohols as well as
carbohydrates represent readily available carbon resourc-
es that occur widely in nature. Chung’s report revealed
that xylitol is also applicable as a carbonyl source through
a dehydrogenation–decarbonylation sequence of the alco-
hol moiety in the presence of a catalyst.4 Herein we report
on the highly efficient cyclocarbonylation of enynes using
glyceraldehyde acetonide, which is simply prepared from
glycerol6 and D-mannitol, as a carbonyl source.7
Ph
O
Ph
+
[RhCl(cod)]2 (cat.)
dppp
O
O
O
O
O
H
toluene, reflux
2 h
2a
3a 82%
rac-1 (2 equiv)
O
O
H
3a 87% (0%ee)
O
(R)-1 (2 equiv)
Scheme 1 Use of glyceraldehyde as a carbonyl source in cyclocar-
bonylation of enyne
Using (R)-1 as a carbonyl source, we examined the reac-
tions of various enynes, which were different with respect
to the substituents on the alkyne terminus and the alkene
moiety, and the atom linking the two (Table 1).11 All the
reactions of enynes were conducted in the presence of 2.5
mol% of [RhCl(cod)]2 and 5 mol% of dppp, in refluxing
toluene (conditions A). In the case of reactions that did not
proceed smoothly under these conditions, conditions B, 5
mol% of [RhCl(cod)]2, 10 mol% of dppp, and xylene at
130 °C were used. Alkyl-substituted O-linking enynes 2b
and 2c also reacted with aldehyde (R)-1 to furnish the cor-
responding carbonyl compounds (Table 1, entries 2 and
3). Reactions involving enynes 2d–f containing 1,1-di-
substituted and 1,2-disubstituted alkene moieties proceed-
ed smoothly to give the corresponding products 3d–f in
moderate to high yields (Table 1, entries 4–6). Enynes
2g–i, linked by tosylamide underwent cyclocarbonylation
in excellent yields (Table 1, entries 7–9). In most cases of
C-linked enynes 2j–n, more severe conditions (B) were
required to achieve the maximum yield (Table 1, entries
Racemic and chiral glyceraldehyde acetonide, rac- and
(R)-1, were synthesized in two steps from glycerol8 and D-
mannitol,9 respectively. We first examined the cyclocar-
bonylation of enyne 2a with rac-1. Under catalytic condi-
tions consisting of 2.5 mol% of [RhCl(cod)]2 and 5 mol%
SYNLETT 2012, 23, 393–396
x
x.
x
x.
2
0
1
2
Advanced online publication: 19.01.2012
DOI: 10.1055/s-0031-1290311; Art ID: U57611ST
© Georg Thieme Verlag Stuttgart · New York

394
K. Ikeda et al.
LETTER
10–14). Although the 1,7-enynes 2o and 2p were applica- the alkyne and alkene units, were positioned on contigu-
ble to this transformation, the yields were low (Table 1, ous carbons of a ring system, the cyclocarbonylation pro-
entries 15 and 16). For substrates 2q–s where two groups, ceeded diastereoselectively, resulting in the formation of
Table 1 Rh(I)-Catalyzed Cyclocarbonylation Reactions of Various Enynes Using (R)-1 as a Carbonyl Source
Entry Enyne
1
Conditionsa Time (h) Product
Yield (%)b
2a
2b
2c
R = Ph
R = Bu
R = t-Bu
A
A
B
2
5
30
3a
3b
3c
87
82
73
R
R
R
R
2
3
O
O
O
O
O
4
5
2d
2e
R = Ph
R = Bu
A
B
6
30
3d
3e
87
61
O
6
2f
B
22
3f
74
Ph
R
(single diastereomer)c
O
O
O
H
(E/Z = 93:7)
7
8
9
2g
2h
2i
R = Ph
R = Bu
R = Me
A
B
A
5
2
4
3g
3h
3i
98
77
90
R
R
TsN
TsN
O
R
10
11
12
13
2j
2k
2l
R = Ph
R = Bu
R = Me
R = H
B
B
B
B
40
36
17
4
3j
3k
3l
87
93
93
69
R
EtO2C
EtO2C
EtO2C
EtO2C
O
2m
3m
14
15
16
17
2n
2o
2p
2q
B
B
B
B
24
22
50
22
3n
3o
3p
3q
69
O
O
Bu
Bu
O
O
O
44 (33)d
Bu
Ph
Bu
Ph
N
O
O
TsN
O
Ts
26
O
76
Bu
Bu
(cis/trans = 97:3)c
O
H
OTBS
OTBS
Ph
18
19
2r
2s
B
B
6
3r
3s
58
Ph
(single diastereomer)c
O
O
O
48
37
O
Ph
Ph
(single diastereomer)c
O
O
a Conditions A: enyne (0.5 mmol), (R)-1 (1 mmol), [RhCl(cod)]2 (0.0125 mmol), and dppp (0.025 mmol) in toluene (1 mL) at reflux under N2;
conditions B: enyne (0.5 mmol), (R)-1 (1 mmol), [RhCl(cod)]2 (0.025 mmol), and dppp (0.05 mmol) in xylene (1 mL) at 130 °C under N2.
b Isolated yield.
c Diastereomeric ratios were determined by GC analysis.
d The value in parentheses is the yield of the recovered enyne.
Synlett 2012, 23, 393–396
© Thieme Stuttgart · New York

LETTER
Rh(I)-Catalyzed Cyclocarbonylation of Enynes
395
tricyclic cyclopentenones 3q–s (Table 1, entries 17–19). We next examined the use of the sugar alcohol based al-
In general, reactions with aldehyde (R)-1 produced the de- dehyde (R)-1 in the asymmetric cyclocarbonylation. As
sired carbonylated compounds not only in higher yields shown in Scheme 1, the use of chiral (R)-1 did not result
than those with acetylated aldose derivatives as a carbonyl in an enantioselective transformation. The reaction of 2a
source,5 but in yields comparable to those with simple al- with (R)-1 using (S)- and (R)-BINAP as a ligand, instead
dehydes.2
of dppp, was then carried out to give the carbonylated
product 3a in lower yield and lower enantioselectivity:
46% yield [50% ee (S)] and 54% yield [46% ee (R)], re-
spectively. From the results of screening various ligands
and solvents, the use of (S)-tolBINAP as a ligand in the
solvent-free system afforded the best results from the
viewpoints of chemical yield and enantioselectivity.2b,c
The results are summarized in Table 2. The asymmetric
conditions led to the formation of high yields of the carbo-
nylated products with moderate to high enantioselectivi-
ties. When enyne 2a (0.5 mmol) was reacted with (R)-1
(1.0 mmol) in the presence of [RhCl(cod)]2 (0.0125
mmol) and (S)-tolBINAP (0.025 mmol) at 130 °C, 2a was
completely consumed within two hours to give the carbo-
nylated product 3a in 65% with 80% ee (S; Table 2, entry
1).13 The use of rac-1 instead of (R)-1 afforded similar re-
sults: 70% yield and 79% ee. The reaction of enyne 2b in
which the phenyl group in 2a is replaced with a butyl
group also resulted in the formation of the carbonylated
product 3b in higher yield and ee (Table 2, entry 2). Sim-
ilar tendencies were observed in the reactions of other
enynes 2g,h,j,k, which are linked by nitrogen and carbon
atoms (Table 2, entries 3–6).
In the next series of experiments, the efficiency of the car-
bonyl transfer from the decarbonylation process to the cy-
clocarbonylation process was examined. The reaction of
2a with cyclohexylidene analogue 412 under similar cata-
lytic conditions in xylene at 130 °C gave the carbonylated
product 3a in 82% yield, along with 135% of 5
(Scheme 2). Based on the amount of the decarbonylated
residue 5, the abstracted carbonyl moiety from aldehyde 4
was partially consumed in the cyclocarbonylation step.
Thus, the decarbonylation of 4 proceeded catalytically,
and independent of the cyclocarbonylation process, re-
sulting in a partial release of free carbon monoxide.2a
O
[RhCl(cod)]2 (cat.)
Ph
dppp
O
O
+
H
xylene, 130 °C
1 h
O
2a (0.250 mmol)
4 (0.50 mmol)
Ph
O
O
O
+
O
Finally, we investigated the effect of the chirality of
tolBINAP on the efficiency of the reaction under the
above asymmetric catalytic conditions using (R)-1. There
was no difference in isolated chemical yields and ee val-
ues between the reactions using (S)- or (R)-tolBINAP
(65% yield, 80%ee; Scheme 3). At an early stage of each
reaction, at which point the carbonylation is linearly de-
pendent on the reaction time, the rate of formation of the
product 3a is slightly, but clearly, different: the turnover
frequency (TOF) is 5.20·10–1 h–1 for (S)-tolBINAP com-
pared with 3.23·10–1 h–1 for (R)-tolBINAP (Figure 1).
Thus, these results would issue from the diastereotopic
combination of the chirality of (R)-1 with that of the
ligand, S or R, thus implying that the rate-determining step
of the reaction is involved in the decarbonylation process
of the aldehyde.
5 (0.335 mmol)
3a (0.204 mmol)
61%
135%
82%
Scheme 2 Efficiency of carbonyl-transfer from aldehyde 4 to 2a
Table 2 Asymmetric Cyclocarbonylation Reactions Using (R)-1 as
a Carbonyl Sourcea
O
[RhCl(cod)]2 (5 mol%)
(S)-tolBINAP (10 mol%)
O
O
X
O
H
X
130 °C
+
H
(R)-1
Entry
Enyne 2
2a
Time (h) Product 3 Yield (%)b ee (%)c
1
2
3
4
5
6
2
18
3
3a
3b
3g
3h
3j
65
87
90
95
88
75
80 (S)
88 (S)
61 (S)
74 (S)
47 (R)
70 (R)
2b
2g
Ph
Ph
[RhCl(cod)]2 (5 mol%)
tolBINAP (10 mol%)
2h
4
O
(R)-1
+
O
O
130 °C
2j
22
24
H
2a
3a
2k
3k
65% [80% ee (S)]
65% [80% ee (R)]
(S)-tolBINAP 14 h
a The reaction was carried out with enyne (0.5 mmol), (R)-1 (1 mmol),
[RhCl(cod)]2 (0.025 mmol), and dppp (0.05 mmol) at 130 °C under
N2.
18 h
(R)-tolBINAP
Scheme 3 Asymmetric reaction of 2a using (S)- and (R)-tolBINAP
b Isolated yield.
c The ee and the absolute configuration were determined by HPLC
using chiral stationary columns and specific optical rotation using a
polarimeter, respectively.
In conclusion, we report here on the use of a sugar alcohol
derived aldehyde as a carbonyl source in the cyclocarbo-
nylation of enynes. The racemic and chiral sugar alcohol
© Thieme Stuttgart · New York
Synlett 2012, 23, 393–396

396
K. Ikeda et al.
LETTER
Synth. Catal. 2005, 347, 1750. (h) Kwong, F. Y.; Li, Y. M.;
Lam, W. H.; Qiu, L.; Lee, H. W.; Yeung, C. H.; Chan, K. S.;
Chan, A. S. C. Chem. Eur. J. 2005, 11, 3872. (i) Shibata,
T.; Toshida, N.; Yamasaki, M.; Maekawa, S.; Takagi, K.
Tetrahedron 2005, 61, 9974. (j) Kwong, F. Y.; Lee, H. W.;
Lam, W. H.; Qiu, L.; Chan, A. S. C. Tetrahedron:
Asymmetry 2006, 17, 1238.
(3) Lee, H. W.; Chan, A. S. C.; Kwong, F. Y. Chem. Commun.
2007, 2633.
(4) Park, J. H.; Cho, Y.; Chung, Y. K. Angew. Chem. Int. Ed.
2010, 49, 5138.
(5) Ikeda, K.; Morimoto, T.; Kakiuchi, K. J. Org. Chem. 2010,
75, 6279.
(6) For reviews on the synthetic transformation of glycerol, see:
(a) Pagliaro, M.; Ciriminna, R.; Kimura, H.; Rossi, M.; Pina,
C. D. Angew. Chem. Int. Ed. 2007, 46, 4434. (b) Zheng, Y.;
Chen, X.; Shen, Y. Chem. Rev. 2008, 108, 5253. (c) Zhou,
C.-H.; Beltramini, J. N.; Fan, Y.-X.; Lu, G. Q. Chem. Soc.
Rev. 2008, 37, 527. (d) Jérôme, F.; Pouilloux, Y.; Barrault,
J. ChemSusChem 2008, 1, 586.
(7) For a review on the synthetic transformation of D-mannitol,
see: de Olivaira, P. S. M.; Ferreira, V. F.; de Souza, M. V. N.
Quim. Nova 2009, 32, 441.
Figure 1 Profile of asymmetric reaction of 2a with (R)-1
(8) (a) Newman, M. S.; Renoll, M. J. Am. Chem. Soc. 1945, 67,
1621. (b) Hong, J. H.; Oh, C. H.; Cho, J. H. Tetrahedron
2003, 59, 6103.
(9) (a) Schmid, C. R.; Bryant, J. D.; Dowlatzedah, M.; Philips,
J. L.; Prather, D. E.; Schantz, R. D.; Sear, N. L.; Vianco, C.
S. J. Org. Chem. 1991, 56, 4056. (b) Schmid, C. R.; Bryant,
J. D. Org. Synth., Coll. Vol. IX 1998, 450.
(10) Under identical reaction conditions, the use of glycerol itself
as a carbonyl source gave 3a only in 11% yield, along with
13% of the hydrogen adduct of 2a and 30% of a mixture of
dimers of 2a.
(11) Typical Procedure for the Rhodium-Catalyzed
Cyclocarbonylation Reaction of Enyne 2a with
Glyceraldehyde Acetonide (R)-1 (Conditions A)
To a suspension of [RhCl(cod)]2 (6.16 mg, 0.0125 mmol),
dppp (10.63 mg, 0.025 mmol), and (R)-1 (131.0 mg, 1.0
mmol) in anhyd toluene (1 mL) was added enyne 2a (86.1
mg, 0.5 mmol) under N2. After degassing the mixture
through three freeze–pump–thaw cycles, the solution was
stirred at reflux for an appropriate time. The reaction mixture
was evaporated under reduced pressure. The residue was
purified by column chromatography on silica gel with
hexane–EtOAc (v/v = 2:1) as the eluent.
derived aldehydes used in this study are readily prepared
in two steps from glycerol and D-mannitol, respectively.
Various enynes can be carbonylated using these deriva-
tives. The present study provides a demonstration show-
ing that such carbonyl sources can be conveniently used in
the cyclocarbonylation of enynes.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
Acknowledgment
This work was financially supported, in part, by a Grant-in-Aid for
Scientific Research on Innovative Area ‘Molecular Activation
Directed toward Straightforward Synthesis’ from MEXT. T.M. ac-
knowledges the grant for Mitsui Chemicals Inc. Award in Synthetic
Organic Chemistry to the Society of Synthetic Organic Chemistry,
Japan. We also thank Ms. Mika Yamamura and Ms. Yuriko
Nishiyama for assistance in obtaining HRMS.
Compound 3a
Yield: 87%; colorless oil; Rf = 0.31 (hexane–EtOAc, 2:1).
1H NMR (500 MHz, CDCl3): d = 2.31 (dd, J = 17.5, 2.4 Hz,
1 H), 2.82 (dd, J = 17.5, 6.4 Hz, 1 H), 3.27–3.32 (m, 1 H),
3.19–3.23 (m, 1 H), 4.35 (t, J = 7.6 Hz, 1 H), 4.56 (d,
J = 16.2 Hz, 1 H), 4.91 (d, J = 16.2 Hz, 1 H), 7.33–7.38 (m,
3 H), 7.49 (d, J = 6.7 Hz, 2 H). 13C NMR (125 MHz, CDCl3):
d = 40.3, 43.2, 66.2, 71.3, 128.0, 128.5, 128.6, 130.5, 134.6,
177.4, 206.8.2a
References and Notes
(1) For recent reviews of the Pauson–Khand reaction, see:
(a) Gibson, S. E.; Stevenazzi, A. Angew. Chem. Int. Ed.
2003, 42, 1800. (b) Shibata, T. Adv. Synth. Catal. 2006, 348,
2328. (c) Lee, H. W.; Kwong, F. Y. Eur. J. Org. Chem.
2010, 789.
(2) (a) Morimoto, T.; Fuji, K.; Tsutsumi, K.; Kakiuchi, K. J. Am.
Chem. Soc. 2002, 124, 3806. (b) Shibata, T.; Toshida, N.;
Takagi, K. Org. Lett. 2002, 4, 1619. (c) Shibata, T.;
Toshida, N.; Takagi, K. J. Org. Chem. 2002, 67, 7446.
(d) Fuji, K.; Morimoto, T.; Tsutsumi, K.; Kakiuchi, K.
Angew. Chem. Int. Ed. 2003, 42, 2409. (e) Jeong, N.; Kim,
D. H.; Choi, J. H. Chem. Commun. 2004, 40, 1134. (f) Fuji,
K.; Morimoto, T.; Tsutsumi, K.; Kakiuchi, K. Tetrahedron
Lett. 2004, 45, 9163. (g) Kwong, F. Y.; Lee, H. W.; Qiu, L.;
Lam, W. H.; Li, Y. M.; Kwong, H. L.; Chan, A. S. C. Adv.
(12) (a) Yin, H.; Franck, R. W.; Chen, S. L.; Quigley, G. J.;
Todarot, L. J. Org. Chem. 1995, 57, 644.
(b) Chattopadhyay, A.; Mamdapur, V. R. J. Org. Chem.
1995, 60, 585.
(13) Using a combination of [IrCl(cod)]2 and (S)-tolBINAP, the
reaction of 2a with (R)-1 in 1,4-dioxane at 120 °C resulted in
the more enantioselective formation of (S)-3a (89% ee),
although the chemical yield was much lower (31%).
Synlett 2012, 23, 393–396
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