Lewis base-catalyzed reactions of cyclopropenones: Novel synthesis of mono- or multi-substituted allenic esters

Article abstract of DOI:10.1039/c3cc46470a

The reactions of cyclopropenones with nucleophiles (H₂O or methanol) could be catalyzed by nitrogen-containing Lewis bases or phosphorus-containing Lewis bases, affording the corresponding mono- or multi-substituted allenic esters in moderate t

Full text of DOI:10.1039/c3cc46470a

ChemComm
View Article Online
View Journal | View Issue
COMMUNICATION
Lewis base-catalyzed reactions of
cyclopropenones: novel synthesis of
mono- or multi-substituted allenic esters†
Cite this: Chem. Commun., 2014,
50, 115
Received 24th August 2013,
Accepted 24th October 2013
Yuan-Liang Yang, Zhen Zhang, Xiao-Nan Zhang, De Wang, Yin Wei* and Min Shi*
DOI: 10.1039/c3cc46470a
www.rsc.org/chemcomm
The reactions of cyclopropenones with nucleophiles (H2O or methanol) Table S in the ESI†) and a nucleophile (H2O or MeOH) as substrates in
could be catalyzed by nitrogen-containing Lewis bases or phosphorus- the presence of DABCO. After initial optimization, DABCO in THF was
containing Lewis bases, affording the corresponding mono- or multi- found to be a suitable system for this reaction (see Table S1 in the ESI†).
substituted allenic esters in moderate to excellent yields.
Furthermore, various Lewis bases and nucleophiles were optimized.
The results are summarized in Table 1 and we found that the
The first reports on synthesis of cyclopropenones were presented by corresponding 2-phenylbuta-2,3-dienoic acid 3a was produced in 50%
Breslow et al.1 and Volpin and co-workers2 in 1959, respectively. yield in the presence of DABCO (20 mol%) and a nucleophile (H2O)
Recent extensive investigations have established the utility of these (1.0 equiv.) (Table 1, entry 1). Under the same reaction conditions, we
molecules as building blocks for the construction of biologically active found that other Lewis bases such as DMAP ( p-N,N-dimethyl-
compounds and important structural motifs in materials science.3 aminopyridine), PPh3, and tris(3,5-bis(trifluoromethyl)phenyl)phos-
Cyclopropenone is an amphiphilic molecule, which reacts readily with phine could not catalyze this reaction (Table 1, entries 2–4). Considering
both nucleophilic and electrophilic reagents; thus, they can be utilized that methanol is more nucleophilic than water, we chose methanol as a
in a wide range of organic reactions.4 Hamada and Takizawa have nucleophile to examine the reaction outcome again. The corresponding
reported the reaction of 2,3-diphenylcycloprop-2-enone 1 with metha- product 3a was obtained in higher yield in the presence of methanol.
nol in the presence of PPh3 to afford (E)-methyl 2,3-diphenylacrylate in
good yield.5 Inspired by Hamada and Takizaka’s work and as a part of
Table 1 Optimization of the reaction conditions
our continuing interest on Lewis bases mediated reactions,6 we are
extremely interested in the Lewis base-mediated/catalyzed chemical
processes of cyclopropenones, since cyclopropenones being all-carbon
1,3-dipolar equivalents can easily react with nitrogen-containing,7 or
Entry
Catalyst
Solvent
NuH (equiv.)
Yielda (%)
phosphorus-containing nucleophiles.8 To our delight, we found a
novel Lewis base-catalyzed reaction for synthesis of allenic esters that
are efficient synthons used widely in organic synthesis.9,10 Although a
variety of methods for preparation of allenes have been developed,11
there are rare reports on the synthesis of allenic esters using Lewis
bases so far. The relevant studies were base-promoted alkyne isomer-
isation reported by Huang and Tan,12 and Lewis base-catalyzed
intramolecular 1,4-addition of conjugated enynes reported by Tang.13
The established method presented here provides another novel way to
access mono- or multi-substituted allenic esters.
1
2
3
DABCO
DMAP
PPh3
P(3,5-(F3C)2CeH3)3
DABCO
DABCO
DABCO
DABCO
DBU
Et3N
DMAP
—
DABCO
PPh3
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
H2O (1.0)
H2O (1.0)
H2O (1.0)
H2O (1.0)
3a0 (50)
N.R
N.R
4
N.R
5b
MeOH (1.0)
MeOH (2.0)
MeOH (5.0)
MeOH (10.0)
MeOH (10.0)
MeOH (10.0)
MeOH (10.0)
MeOH (10.0)
MeOH (10.0)
MeOH (10.0)
MeOH (10.0)
MeOH (10.0)
3a (78)
3a (86)
3a (89)
3a (95)
N.R
N.R
N.D
6b
7b
8b
9b
10b
11b
12b
13b,c
14b
15b,d
16b,d
N.R
3a (89)
3a (82)
N.D
Initial examination was carried out by using (3-oxo-2-
phenylcycloprop-1-enyl)methyl acetate 2a (for the preparation of 2, see
K2CO3
CH3ONa
N.D
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032,
P. R. China. E-mail: weiyin@sioc.ac.cn, mshi@sioc.ac.cn; Fax: +86-21-64166128
† Electronic supplementary information (ESI) available: Experimental procedures,
characterization data of new compounds. CCDC 917097. For ESI and crystallographic
data in CIF or other electronic format see DOI: 10.1039/c3cc46470a
a
Isolated yield. Unless otherwise specified, to
a
mixture of 2a
(0.10 mmol) and catalyst (0.02 mmol) in THF (1.0 mL) under an Ar
atmosphere at 0 1C NuH was added, then the resulting mixture was
stirred at room temperature for 3 days. The reaction was conducted at
room temperature for 5 hours and 4 Å MS was added. The catalyst
b
c
d
loading was 10 mol%. 0.1 mmol of inorganic base was used.
This journal is ©The Royal Society of Chemistry 2014
Chem. Commun., 2014, 50, 115--117 | 115

View Article Online
Communication
ChemComm
We further identified that 10.0 equiv. of MeOH relative to 2a was the
We continued to examine the substrate generality of the reaction
best ratio, affording 3a in 95% yield (Table 1, entries 5–8). Other using various mono- or disubstituted cyclopropenone derivatives 2 with
nitrogen-containing Lewis bases (DBU, Et3N, DMAP) could not promote MeOH. Unfortunately, DABCO could not catalyze these reactions due to
this reaction (Table 1, entries 9–11). In the absence of DABCO, the its lower nucleophilicity. Thus, we switched to more nucleophilic
reaction did not occur. The phosphorus-containing Lewis base PPh3 phosphorus-containing Lewis bases (PPh3 or PBu3). To our delight,
could also catalyze this reaction, giving 3a in 82% yield (Table 1, entry the reactions proceeded smoothly, giving the desired products in good
14). Decreasing the catalyst loading to 10 mol% slightly reduced the yields, and the results are presented in Table 3. The corresponding
yield of 3a (Table 1, entry 13). Inorganic bases (K2CO3 and CH3ONa) did products 4 were obtained in moderate to high yields (57–92%). When
not catalyze this reaction under the standard conditions (Table 1, R1 = Ph and R3 = H, R2 having no substituent on the benzene ring or
entries 15 and 16). Thus, finally, we established the optimal reaction having electron-donating or -withdrawing groups as substituents on the
conditions: 20 mol% of DABCO as the catalyst in THF at room 2-, 3-, 4-positions of the benzene ring, the reactions could proceed
temperature, for the synthesis of compound 3a.
smoothly, giving the corresponding products 4a–4b and 4f–4h in high
Having identified the optimal reaction conditions, we next set out to yields (Table 3, entries 1 and 2, and 6–8). When R2 was a naphthyl or
examine the scope and limitations with various cyclopropenone deri- more sterically hindered phenanthryl group, the reactions also pro-
vatives 2 and MeOH. The results are summarized in Table 2. A variety ceeded well (Table 3, entries 3–5). When 2x was used as the substrate
of cyclopropenone derivatives 2 having either electron-donating or (R1 = 4-ClC6H4, R2 = Me and R3 = H), the reaction also proceeded
-withdrawing groups as substituents on the 2-, 3-, 4-positions of a smoothly, affording 4i in 90% yield (Table 3, entry 9). When R1 = C6H5
benzene ring underwent the reactions smoothly, affording the corres- and R2, R3 = (CH2)5, the reaction was conducted at room temperature
ponding products 3 in moderate to high yields (54–96%) (Table 2, for 3 days in the presence of 20 mol% PBu3, providing 4j in 79% yield
entries 1–11). If R1 was 2-CO2MeC6H4, the reaction did not take place at (Table 3, entry 10). Finally, as for substrate 2z (R1 = C6H5 and R2 = CH3,
room temperature, and was carried out at 50 1C for 30 minutes, R3 = 4-ClC6H4), the reaction was catalyzed by 20 mol% PPh3, furnishing
furnishing the corresponding product 3k in 54% yield (Table 2, the corresponding product 4i in 57% yield. We observed that, in
entry 10). When R1 was a 2-naphthyl group, the reaction also proceeded general, if R3 was not a hydrogen atom, the reaction would proceed
efficiently to give the corresponding product 3m in 78% yield (Table 2, slowly, presumably due to the steric effect (Table 3, entries 1–9 vs.
entry 12). However, if R1 was a benzyl group, the reaction could not take entries 10 and 11).
place, presumably due to the electronic effect (Table 2, entry 13). We
We have screened various chiral monophosines or bifunctional
also investigated the reaction of substrate 2ab with an Ms protecting phosphines as well as chiral multifunctional phosphines, such as
group, and the reaction also proceeded very well to provide 3a in 57% phosphine-amide type catalysts, phosphine-thiourea/urea type cata-
yield. During these investigations, we also found that the electronic lysts, for their asymmetric variant. The preliminary results show that
effect of substituents on the benzene ring had an impact on the the chiral multifunctional phosphine-thiourea catalyst LB1 was fairly
reaction rate. If R1 was bearing an electron-donating group, the reaction effective in the reaction of cyclopropenone 2q with MeOH in toluene
rate was slower than that of those bearing an electron-withdrawing at room temperature, giving the corresponding product (S)-4c in 80%
group (Table 2, entries 1, 8, 11 vs. entries 2–7, 9, 10). The structure of 3 isolated yield with 57% ee (Scheme 1, eqn (1)). Employing the
has been unambiguously determined by X-ray diffraction of the substrate 2r containing a naphthyl group improved the ee value to
analogue 3j. The ORTEP drawing and its CIF data are provided in 71% in 70% isolated yield (Scheme 1, eqn (2)). The exploration of
the ESI.†14
more effective chiral phosphines and further tests for determining
the substrate generality are underway.
Table 2 DABCO catalyzed reactions of cyclopropenone derivatives 2
with methanol
Table 3 PPh3 catalyzed reactions of single or disubstituted cycloprope-
none derivatives 2 with methanol
Entry
R1/R2
Time
Yielda (%)
1
2
3
4
5
6
7
8
4-MeOC6H4/Ac (2b)
4-NO2C6H4/Ac (2c)
4-tBuC6H4/Ac (2d)
4-ClC6H4/Ac (2e)
4-BrC6H4/Ac (2f)
3-FC6H4/Ac (2g)
3-BrC6H4/Ac (2h)
3-MeC6H4/Ac (2i)
2-CNC6H4/Ac (2j)
2-CO2MeC6H4/Ac (2k)
2-MeOC6H4/Ac (2l)
1-Naphthyl/Ac (2m)
Bn/Ac (2n)
8 h
3b (93)
3c (94)
3d (91)
3e (96)
3f (83)
3g (90)
3h (89)
3i (90)
3j (90)
3k (54)
3l (93)
3m (78)
N.D
Entry
R1/R2/R3
Time
Yielda (%)
5 min
36 h
2.5 h
2 h
3 h
1 h
1
2
3
4
5
6
7
8
C6H5/C6H5/H (2p)
30 min
30 min
60 min
2 h
60 min
45 min
30 min
15 min
30 min
3 d
4a (92)
4b (93)
4c (87)
4d (80)
4e (95)
4f (87)
4g (91)
4h (83)
4i (90)
4j (79)
4k (57)
C6H5/4-ClC6H4/H (2q)
C6H5/2-naphthyl/H (2r)
C6H5/1-naphthyl/H (2s)
C6H5/9-phenanthryl/H (2t)
C6H5/3-MeC6H4/H (2u)
C6H5/2-BrC6H4/H (2v)
C6H5/2,4-Cl2C6H3/H (2w)
4-ClC6H4/Me/H (2x)
7 h
9
30 min
30 min
24 h
24 h
48 h
72 h
10b
11
12
13
14
9
10b
11c
C6H5/(CH2)5 (2y)
C6H5/CH3/4-ClC6H4 (2z)
3 d
C6H5/Ms (2ab)
3a (57)
a
b
c
Isolated yield. The reaction was catalyzed by 20 mol% PBu3. The
catalyst loading was 20 mol%.
a
b
Isolated yield. The reaction was carried out at 50 1C.
116 | Chem. Commun., 2014, 50, 115--117
This journal is ©The Royal Society of Chemistry 2014

View Article Online
ChemComm
Communication
mechanism has also been proposed. Further studies on the
mechanistic details of this catalytic system along with the
reaction properties of the other cyclopropenones are currently
underway in our laboratory.
We thank the Shanghai Municipal Committee of Science and
Technology (11JC1402600), the National Basic Research Program
of China (973)-2009CB825300, and the National Natural Science
Foundation of China for financial support (21072206, 20472096,
21102166, 21372241, 21302203, 21372250, 20672127, 21121062
and 20732008).
Notes and references
1 R. Breslow, R. R. Haynie and J. Mirra, J. Am. Chem. Soc., 1959, 81, 247.
2 D. N. Kursanov, M. E. Volpin and Y. D. Koreshkov, Izv. Akad. Nauk
SSSR, Ser. Khim., 1959, 560.
Scheme 1 Asymmetric reaction of cyclopropenone with MeOH cata-
lyzed by chiral phosphine catalyst LB1.
3 (a) H. Tokuyama, M. Isaka, E. Nakamura and Y. Morinaka, J. Antibiot.,
1992, 45, 1148; (b) R. Ando and Y. Morinaka, J. Am. Chem. Soc., 1993,
115, 1174; (c) R. Ando, T. Sakaki, Y. Morinaka, C. Takahashi,
Y. Tamao, N. Yoshii, S. Katayama, K.-I. Saito, H. Tokuyama,
M. Isaka and E. Nakamura, Bioorg. Med. Chem., 1999, 7, 571.
4 For reviews: (a) K. T. Potts and J. S Baum, Chem. Rev., 1974, 74, 189;
(b) T. Eicher and J. L. Weber, Top. Curr. Chem., 1975, 57, 1;
(c) K. Komatsu and T. Kitagawa, Chem. Rev., 2003, 103, 1371.
5 A. Hamada and T. Takizawa, Chem. Pharm. Bull., 1975, 23, 2933.
6 (a) Y. Wei and M. Shi, Chem. Rev., 2013, 113, 6659; (b) Y. Wei and
M. Shi, Acc. Chem. Res., 2010, 43, 1005.
7 (a) A. Kascheres and D. Marchi, J. Org. Chem., 1975, 40, 2985;
(b) Y. Tamura, H. Matsushima and M. Ikeda, Tetrahedron, 1975,
32, 431; (c) K. N. Hemming, M. V. R. Khan, V. Kondakal, A. Pitard,
M. I. R. Qamar and C. Rice, Org. Lett., 2012, 14, 126.
8 (a) A. Hamada and T. Takizawa, Chem. Pharm. Bull., 1975, 23, 2933;
´
´
´
´
´
(b) M. Alajarvın, C. Lopez-Leonardo, A. Alvarez-Garcıa, P. Llamas-
´
´
Lorente, P. Sanchez-Andrada, J. Berna, A. Pastor, D. G. Baustista and
P. Jones, Chem.–Eur. J., 2010, 16, 3728.
9 For selected reviews about allene chemistry, see: (a) S. Patai, The
Chemistry of Ketenes, Allenes and Related Compounds, Wiley, New York,
1980; (b) S. R. Landor, The Chemistry of the Allenes, Academic Press,
London, 1982; (c) R. W. Bates and V. Satcharoen, Chem. Soc. Rev., 2002,
31, 12; (d) R. Zimmer, C. U. Dinesh, E. Nandanan and F. A. Khan, Chem.
Rev., 2000, 100, 3067; (e) Modern Allene Chemistry, ed. N. Krause and
A. S. K. Hashmi, Wiley-VCH, Weinheim, Germany, 2004; ( f ) A. Barbero
and F. J. Pulido, Synthesis, 2004, 779; (g) S. Ma, Chem. Rev., 2005,
105, 2829; (h) S. Yu and S. Ma, Angew. Chem., Int. Ed., 2012, 51, 3074.
10 (a) D. W. C. MacMillan, J. Am. Chem. Soc., 2002, 124, 13646; (b) S. Ma,
H. Ren and Q. Wei, J. Am. Chem. Soc., 2003, 125, 4817; (c) J. E. Wilson and
G. C. Fu, Angew. Chem., Int. Ed., 2006, 45, 1426; (d) S. Ma and Z. Gu, J. Am.
Chem. Soc., 2006, 128, 4942; (e) Y. S. Tran and O. Kwon, J. Am. Chem. Soc.,
2007, 129, 12632; ( f ) C. E. Henry and O. Kwon, Org. Lett., 2007, 9, 3069;
(g) Y. Li, H. Zou, J. Gong, J. Xiang, T. Luo, J. Quan, G. Wang and Z. Yang,
Org. Lett., 2007, 9, 4057; (h) C. Zhou, C. Fu and S. Ma, Angew. Chem., Int.
Ed., 2007, 46, 4379; (i) Z. Lu, S. Zheng, X. Zhang and X. Lu, Org. Lett., 2008,
10, 3267; ( j) B. J. Cowen, L. B. Saun-ders and S. J. Miller, J. Am. Chem. Soc.,
2009, 131, 6105; (k) X. Guan, Y. Wei and M. Shi, J. Org. Chem., 2009,
74, 6343; (l) Q.-M. Zhang, L. Yang and X.-F. Tong, J. Am. Chem. Soc., 2010,
132, 2550; (m) G. Chai, S. Wu, C. Fu and S. Ma, J. Am. Chem. Soc., 2011,
133, 3740; (n) X.-N. Zhang, H.-P. Deng, L. Huang, Y. Wei and M. Shi,
Chem. Commun., 2012, 48, 8664.
Scheme 2 Plausible reaction mechanism.
A plausible mechanism for this reaction is outlined in
Scheme 2. The transformation is believed to proceed via con-
jugate addition of Lewis base (LB) to cyclopropenone, affording
zwitterionic intermediate A.15 Subsequently, methanol is depro-
tonated to give intermediate B. Then the three-membered ring is
opened and the acetate anion is released, leading to intermedi-
ate C. The acetate anion grabs a proton of intermediate C to give
intermediate D, which upon loss of the Lewis base catalyst gives
rise to the final product 3. Alternatively, the conjugate addition
of LB to cyclopropenone produces a cyclopropene enolate A0,
which undergoes ring opening to give a ketene intermediate B0.
Subsequently, the ketene intermediate E reacts with methanol to
afford the final product. A more detailed investigation on the
reaction mechanism will be reported in due course.
11 For recent reviews on the syntheses of allenes, see (a) K. M. Brummond
and J. E. DeForrest, Synthesis, 2007, 795; (b) S. Yu and S. Ma, Chem.
Commun., 2011, 47, 5384.
In summary, we have investigated novel and interesting reactions
of cyclopropenones with alcoholic nucleophiles catalyzed by different 12 H. Lu, D. Leow, K.-W. Huang and C.-H. Tan, J. Am. Chem. Soc., 2009,
131, 7212.
Lewis bases, affording the corresponding allenic esters in moderate to
high yields under mild conditions. This is the first example on the
13 (a) W. Zhang, H. Xu, H. Xu and W. Tang, J. Am. Chem. Soc., 2009,
131, 3832; (b) W. Zhang, S. Zheng, N. Liu, J. B. Werness, I. A. Guzei
Lewis base-catalyzed formation of allenic esters from cyclopropenones.
Based on this unprecedented method, axially chiral allenic esters
have also been furnished in moderate yield and ee in the presence
of multifunctional chiral phosphine LB1. A plausible reaction
and W. Tang, J. Am. Chem. Soc., 2010, 132, 3664.
14 The crystal data of compound 3j have been deposited in CCDC with
number 917097.
15 For theoretical investigations on the relative stabilities of other
possible zwitterionic intermediates, see ESI†.
This journal is ©The Royal Society of Chemistry 2014
Chem. Commun., 2014, 50, 115--117 | 117