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Enantioselective N-Heterocyclic Synthesis of Indenopyrones
Carbene-catalyzed
Kun-Quan Chen,a,b Han-Ming Zhang,b Dong-Ling Wang, a,b De-Qun Sun*,a and Song Ye*,b
The chiral N-heterocyclic carbene-catalyzed [4 + 2] cyclization of -chloroaldehydes and arylidene indanediones was developed, giving the corresponding indenopyrones in good yields with high diastereoselectivities and enantioselectivities. Indenones1 and indeno-fused2 heterocycles are widely presented in many natural and synthetic bioactive and pharmaceutically interesting compounds. Meanwhile, the dihydropyrones are common motifs found in many pharmacological structures, and have been found many bioactivities, such as anticancer,3 anti-inflammatory,3b antiviral,4 cytotoxicity,3b,5 neurotoxicity6 and antifungal activities.5 Thus, combined with those two structural features, indenopyrones would be an interesting target for chemists (Scheme 1). For examples, indenopyrone A displays potent cytotoxicity and topoisomerase I inhibition,2a, 7 while the indenopyrone B had been tested for the uncoupling activity of rat liver mitochondria.8 Indenopyrone C was found to be one of the metabolites of -Lapachone, a new anti-cancer drug.9
a
Marine College, Shangdong University at Weihai, 180 Wenhua West Rd, Weihai 264209, China E-mail: [email protected]
b
Beijing National Laboratory for Molecular Scences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China E-mail: [email protected]
†
Electronic supplementary information (ESI) available. CCDC 1061972. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/
This journal is © The Royal Society of Chemistry 20xx
Scheme 1. Bioactive indenopyrones.
Organic & Biomolecular Chemistry Accepted Manuscript
DOI: 10.1039/C5OB00859J
Several approaches to indenopyrones have been reported.6,9a,10 However, these methods require multi–steps, suffer from critical conditions, and more importantly, the enantioselective synthesis of these compounds remains unexplored. In recent years, N-heterocyclic carbenes (NHCs) have been demonstrated as efficient organocatalysts for various reactions.11 In 2004, Rovis et al. reported the first NHCcatalyzed reaction of α-haloaldehydes.12 In 2006, Bode and coworkers developed the NHC-catalzyed cyclization of chloroaldehydes with oxodienes to give dihydropyrones.13 Since then, the NHC-catalyzed [4 + 2] cyclization reaction of αhaloaldehydes,14 and the related reactions forming dihydropyrones have been well established.15 Recently, we reported the bifunctional NHC-catalyzed [4 + 3] cyclization of enals and aurones.16 Based on the previous works, we are interested in the NHC-catalyzed enantioselective [4 + 2] cyclization of -chloroaldehydes with 1,3-indanediones for the synthesis of indenopyrones. The investigation was initiated by the model reaction of chloroaldehyde 1a and 2-benzylidene-1H-indene-1,3(2H)-dione 2a under NHC catalysis (Table 1). We are encouraged to find that, in the presence of 10 mol% of triazolium precatalyst 4a derived from L-pyroglutamic acid and 2 equiv. of Cs2CO3, the reaction gave the desired indenopyrone 3a in 10% yield with 20:1 dr and 71% ee (entry 1). NHC precursors 4b-4c with a free hydroxyl group resulted in high enantioselectivity (90% and 99% ee) but the yield was still very low (entries 2-3). NHC precursors 5a-5c derived from aminoindanol, developed by Rovis et al. and Bode et al.,17 were then investigated (entries 46). We were happy to find that the yield could be improved to 42% with 92% ee when N-mesityl NHC 5b was employed (entry 5).
J. Name., 2013, 00, 1‐3 | 1
Organic & Biomolecular Chemistry
Journal Name ClC6H4, 2-MeC6H4, 2-MeOC6H4) were tolerated, affording cycloadducts 3e-3j in good to high yields. Both arylidenes with Online 2-naphthyl and with 2-furyl reacted well View toArticle furnish 10.1039/C5OB00859J addition, the reaction cycloadducts 3k and 3l in good yields. InDOI: of chloroadehydes with varied alkyl chains (R = n-C4H9, nC7H15, n-C10H21) went smoothly to give cycloadduct 3m-3q in good yields with high enantioselectivities. It is noteworthy that all the examples gave the products with exclusively cisselectivity.
Table 1. Optimization of reaction conditions
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Table 2. The reaction scope.
Entry
Cat
Base
Solvent
Yield (%)[a]
ee (%)[b]
1
4a
Cs2CO3
THF
10
-71[c]
2
4b
Cs2CO3
THF
13
-90[c]
3
4c
Cs2CO3
THF
22
-99[c]
4
5a
Cs2CO3
THF
24
95
5
5b
Cs2CO3
THF
42
92
6
5c
Cs2CO3
THF
35
75
7
5b
NaOAc
THF
42
75
8
5b
Na2CO3
THF
58
80
9
5b
Et3N
THF
51
71
10
5b
DIPEA
THF
77
84
11
5b
DIPEA
dioxane
67
94
12
5b
DIPEA
toluene
42
75
13
5b
DIPEA
DCM
35
90
14
5b
DIPEA
CH3CN
trace
/
15[d]
5b
DIPEA
dioxane
77
94
16[d,e]
5b
DIPEA
dioxane
84
96
[a] Isolated yields. [b] Determined by HPLC using a chiral stationary phase. [c] Enantiomer ent-3a was obtained. [d] The reaction was carried out at 10 oC. [e] The additive of 4Å molecular sieves was added. Mes = 2,4,6-trimethylphenyl, DIPEA = N,N-diisopropylethylamine.
Several bases were then screened with NHC 5b' as the catalyst (entries 7-10). Both inorganic bases and organic bases worked for the reaction, and N,N-diisopropylethylamine was the best, giving the product in 77% yield with 84% ee (entry 10). Screening of solvents revealed that the reaction went better in THF and 1,4-dioxane, than others (entries 10-11 vs 12-14). The yield was further improved when the reaction was carried out at 10 oC (entry 15). Finally, the additive of 4Å molecular sieves was found to benefit both the yield and the enantioselectivity (entry 16). With the optimized reaction condition in hand, the scope of the reaction was then briefly investigated (Table 2). The arylidene indanedione with electron-withdrawing group (Ar = 4-ClC6H4) resulted in some decreased but still good yield (3b) with excellent enantioselectivity. Those with electron-donating groups (Ar = 4-MeC6H4, 4-MeOC6H4) worked very well, giving the desired products 3c-3d in high yields with excellent enantioselectivities. meta-Substituents (Ar = 3-ClC6H4, 3MeC6H4, 3-MeOC6H4) and even ortho-substituents (Ar = 2-
The cis- and absolute configuration of the dihydropyridinone 3e was established by the X-ray analysis of its single crystal (Fig. 1).
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Figure 1. X‐ray structure of indenopyrone 3e. The hydrogens are omitted for clarity.
Figure 2. Proposed catalytic cycle and stereochemical mode
Conclusions
The reaction could be scaled up to 1.0 gram without loss of yield and enantioselectivity (Eq. (1)). In addition, the indenopyrone 3a could be easily transformed into the corresponding indenopyridine 9a,18 derivative 6 in 94% yield with high diastereo- and enantio-purity (Eq. (2)).19
In summary, the NHC-catalyzed [4 + 2] cyclization of chloroaldehyde and arylidene indanediones was developed, giving the corresponding indenopyrones in high yields with exclusive cis-selectivities and excellent enantioselectivities. The reaction worked well for both aromatic and aliphatic choloraldehydes. The indenopyridine derivatives could be obtained by aminolysis of the corresponding indenopyraones. Other related NHC-catalyzed reactions are underway in our laboratory.
The proposed catalytic cycle is depicted in Figure 2. The addition of NHC 5b', generated in situ from the triazolium 5b, to choloraldehyde gives Breslow intermediate I, which is Acknowledgements transformed to the corresponding enolate by elimination of HCl. The [4 + 2] cycloaddition of enolate and arylidene indendione via the endo-transitional state (TS A) affords cycloadduct II Financial support from the National Natural Science Founwith cis-selectivity. The elimination of the NHC catalyst dation of China 21272237, 21425207) is gratefully acknowledged. furnishes the final product 3 and completes the catalytic cycle.
Notes and references
1 (a) A. A. Nagel, D. R. Liston, S. Jung, M. Mahar, L. A. Vincent, D. Chapin, Y. L. Chen, S. Hubbard and J. L. Ives, J. Med. Chem., 1995, 38, 1084; (b) J.-M. Contreras, I. Parrot, W. Sippl, Y. M. Rival and C. G. Wermuth, J. Med. Chem., 2001, 44, 2707; (c) J. R. Dimmock, G. A. Zello, E. O. Oloo, J. W. Quail, H.-B. Kraatz, P. Perjési, F. Aradi, K. Takács-Novák, T. M. Allen, C. L. Santos, J. Balzarini, E. De Clercq and J. P. Stables, J. Med. Chem., 2002, 45, 3103; (d) M. A. Ali, M. S. Yar, M. Z. Hasan, M. J. Ahsan and S. Pandian, Bioorg. Med. Chem. Lett., 2009, 19, 5075. 2 (a) D. Strumberg, Y. Pommier, K. Paull, M. Jayaraman, P. Nagafuji and M. Cushman, J. Med. Chem., 1999, 42, 446; (b) T. Ito, T. Tanaka, M. Iinuma, K.-i. Nakaya, Y. Takahashi, R. Sawa, J. Murata and D. Darnaedi, J. Nat. Prod., 2004, 67, 932; (c) X. Xiao, Z.-H. Miao, S. Antony, Y. Pommier and M. Cushman, Bioorg. Med. Chem. Lett., 2005, 15, 2795; (d) B. Insuasty, F.
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Orozco, C. Lizarazo, J. Quiroga, R. Abonia, M. Hursthouse, M. Nogueras and J. Cobo, Biorg. Med. Chem., 2008, 16, 8492. 3 (a) C. Gerald, M. W. Walker, L. Criscione, E. L. Gustafson, C. BatzlHartmann, K. E. Smith, P. Vaysse, M. M. Durkin, T. M. Laz, D. L. Linemeyer, A. O. Schaffhauser, S. Whitebread, K. G. Hofbauer, R. I. Taber, T. A. Branchek and R. L. Weinshank, Nature, 1996, 382, 168; (b) O. Benavente-García and J. Castillo, J. Agric. Food. Chem., 2008, 56, 6185. 4 (a) S. E. Hagen, J. Domagala, C. Gajda, M. Lovdahl, B. D. Tait, E. Wise, T. Holler, D. Hupe, C. Nouhan, A. Urumov, G. Zeikus, E. Zeikus, E. A. Lunney, A. Pavlovsky, S. J. Gracheck, J. Saunders, S. VanderRoest and J. Brodfuehrer, J. Med. Chem., 2001, 44, 2319; (b) H. Li, J. Tatlock, A. Linton, J. Gonzalez, A. Borchardt, P. Dragovich, T. Jewell, T. Prins, R. Zhou, J. Blazel, H. Parge, R. Love, M. Hickey, C. Doan, S. Shi, R. Duggal, C. Lewis and S. Fuhrman, Bioorg. Med. Chem. Lett., 2006, 16, 4834. 5 K. Koyama, K. Ominato, S. Natori, T. Tashiro and T. Tsuruo, J Pharmacobiodyn, 1988, 11, 630. 6 M. R. Mahmoud, M. M. El-Shahawi, E. A. A. El-Bordany and F. S. M. A. El-Azm, Synth. Commun., 2010, 40, 666. 7 A. Morrell, S. Antony, G. Kohlhagen, Y. Pommier and M. Cushman, Bioorg. Med. Chem. Lett., 2006, 16, 1846. 8 M. W. Whitehouse and J. E. Leader, Biochem. Pharmacol., 1967, 16, 537. 9 (a) R.-Y. Yang, D. Kizer, H. Wu, E. Volckova, X.-S. Miao, S. M. Ali, M. Tandon, R. E. Savage, T. C. K. Chan and M. A. Ashwell, Biorg. Med. Chem., 2008, 16, 5635; (b) X.-S. Miao, P. Song, R. E. Savage, C. Zhong, R.-Y. Yang, D. Kizer, H. Wu, E. Volckova, M. A. Ashwell and J. G. Supko, Drug Metab. Dispos., 2008, 36, 641. 10 (a) J. Bloxham and C. P. Dell, J. Chem. Soc., Perkin Trans. 1, 1993, 3055; (b) N. Thasana and S. Ruchirawat, Tetrahedron Lett., 2002, 43, 4515; (c) S. B. Ferreira, C. R. Kaiser and V. F. Ferreira, Synlett, 2008, 2008, 2625; (d) S. R. De, S. K. Ghorai and D. Mal, J. Org. Chem., 2009, 74, 1598; (e) N. Wu, A. Messinis, A. S. Batsanov, Z. Yang, A. Whiting and T. B. Marder, Chem. Commun., 2012, 48, 9986; (f) N. G. Khaligh, Tetrahedron Lett., 2012, 53, 1637; (g) A. M. Akondi, M. L. Kantam, R. Trivedi, B. Sreedhar, S. K. Buddana, R. S. Prakasham and S. Bhargava, J. Mol. Catal. A: Chem., 2014, 386, 49. 11 (a) D. Enders, O. Niemeier and A. Henseler, Chem. Rev., 2007, 107, 5606; (b) M. N. Hopkinson, C. Richter, M. Schedler and F. Glorius, Nature, 2014, 510, 485. 12 N. T. Reynolds, J. Read de Alaniz and T. Rovis, J. Am. Chem. Soc., 2004, 126, 9518. 13 M. He, G. J. Uc and J. W. Bode, J. Am. Chem. Soc., 2006, 128, 15088. 14 (a) T.-Y. Jian, L.-H. Sun and S. Ye, Chem. Commun., 2012, 48, 10907; (b) L. Yang, F. Wang, P. J. Chua, Y. Lv, L.-J. Zhong and G. Zhong, Org. Lett., 2012, 14, 2894; (c) H.-M. Zhang, H. Lv and S. Ye, Org. Biomol. Chem., 2013, 11, 6255; (d) L. Yang, F. Wang, R. Lee, Y. Lv, K.-W. Huang and G. Zhong, Org. Lett., 2014, 16, 3872. 15 (a) M. He, B. J. Beahm and J. W. Bode, Org. Lett., 2008, 10, 3817; (b) E. M. Phillips, M. Wadamoto, H. S. Roth, A. W. Ott and K. A. Scheidt, Org. Lett., 2009, 11, 105; (c) S. De Sarkar and A. Studer, Angew. Chem., Int. Ed., 2010, 49, 9266; (d) X. Zhao, K. E. Ruhl and T. Rovis, Angew. Chem., Int. Ed., 2012, 51, 12330. 16 Z.-Q. Liang, Z.-H. Gao, W.-Q. Jia and S. Ye, Chem. Eur. J., 2015, 21, 1868. 17 (a) M. S. Kerr, J. Read de Alaniz and T. Rovis, J. Org. Chem., 2005, 70, 5725; (b) J. Mahatthananchai and J. W. Bode, Chem. Sci., 2012, 3, 192. 18 For the bioactive of indenopyridines, see: (a) M. Jayaraman, B. M. Fox, M. Hollingshead, G. Kohlhagen, Y. Pommier and M. Cushman, J. Med. Chem., 2001, 45, 242; (b) D. Mueller, R. A. Davis, S. Duffy, V. M. Avery, D. Camp and R. J. Quinn, J. Nat. Prod., 2009, 72, 1538; (c) M. CondaSheridan, P. V. N. Reddy, A. Morrell, B. T. Cobb, C. Marchand, K. Agama, A. Chergui, A. Renaud, A. G. Stephen, L. K. Bindu, Y. Pommier and M. Cushman, J. Med. Chem., 2012, 56, 182. 19 T. R. Kelly, C. T. Jagoe and Q. Li, J. Am. Chem. Soc., 1989, 111, 4522.
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This article can be cited before page numbers have been issued, to do this please use: K. Chen, H. Zhang, D. Wang, D. Sun and S. Ye, Org. Biomol. Chem., 2015, DOI: 10.1039/C5OB00859J.
This is an Accepted Manuscript, which has been through the Royal Society of Chemistry peer review process and has been accepted for publication. Accepted Manuscripts are published online shortly after acceptance, before technical editing, formatting and proof reading. Using this free service, authors can make their results available to the community, in citable form, before we publish the edited article. We will replace this Accepted Manuscript with the edited and formatted Advance Article as soon as it is available. You can find more information about Accepted Manuscripts in the Information for Authors. Please note that technical editing may introduce minor changes to the text and/or graphics, which may alter content. The journal’s standard Terms & Conditions and the Ethical guidelines still apply. In no event shall the Royal Society of Chemistry be held responsible for any errors or omissions in this Accepted Manuscript or any consequences arising from the use of any information it contains.
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Received 00th January 20 xx, Accepted 00th January 20 xx
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DOI: 10.1039/x0xx00000x www.rsc.org/
Enantioselective N-Heterocyclic Synthesis of Indenopyrones
Carbene-catalyzed
Kun-Quan Chen,a,b Han-Ming Zhang,b Dong-Ling Wang, a,b De-Qun Sun*,a and Song Ye*,b
The chiral N-heterocyclic carbene-catalyzed [4 + 2] cyclization of -chloroaldehydes and arylidene indanediones was developed, giving the corresponding indenopyrones in good yields with high diastereoselectivities and enantioselectivities. Indenones1 and indeno-fused2 heterocycles are widely presented in many natural and synthetic bioactive and pharmaceutically interesting compounds. Meanwhile, the dihydropyrones are common motifs found in many pharmacological structures, and have been found many bioactivities, such as anticancer,3 anti-inflammatory,3b antiviral,4 cytotoxicity,3b,5 neurotoxicity6 and antifungal activities.5 Thus, combined with those two structural features, indenopyrones would be an interesting target for chemists (Scheme 1). For examples, indenopyrone A displays potent cytotoxicity and topoisomerase I inhibition,2a, 7 while the indenopyrone B had been tested for the uncoupling activity of rat liver mitochondria.8 Indenopyrone C was found to be one of the metabolites of -Lapachone, a new anti-cancer drug.9
a
Marine College, Shangdong University at Weihai, 180 Wenhua West Rd, Weihai 264209, China E-mail: [email protected]
b
Beijing National Laboratory for Molecular Scences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China E-mail: [email protected]
†
Electronic supplementary information (ESI) available. CCDC 1061972. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/
This journal is © The Royal Society of Chemistry 20xx
Scheme 1. Bioactive indenopyrones.
Organic & Biomolecular Chemistry Accepted Manuscript
DOI: 10.1039/C5OB00859J
Several approaches to indenopyrones have been reported.6,9a,10 However, these methods require multi–steps, suffer from critical conditions, and more importantly, the enantioselective synthesis of these compounds remains unexplored. In recent years, N-heterocyclic carbenes (NHCs) have been demonstrated as efficient organocatalysts for various reactions.11 In 2004, Rovis et al. reported the first NHCcatalyzed reaction of α-haloaldehydes.12 In 2006, Bode and coworkers developed the NHC-catalzyed cyclization of chloroaldehydes with oxodienes to give dihydropyrones.13 Since then, the NHC-catalyzed [4 + 2] cyclization reaction of αhaloaldehydes,14 and the related reactions forming dihydropyrones have been well established.15 Recently, we reported the bifunctional NHC-catalyzed [4 + 3] cyclization of enals and aurones.16 Based on the previous works, we are interested in the NHC-catalyzed enantioselective [4 + 2] cyclization of -chloroaldehydes with 1,3-indanediones for the synthesis of indenopyrones. The investigation was initiated by the model reaction of chloroaldehyde 1a and 2-benzylidene-1H-indene-1,3(2H)-dione 2a under NHC catalysis (Table 1). We are encouraged to find that, in the presence of 10 mol% of triazolium precatalyst 4a derived from L-pyroglutamic acid and 2 equiv. of Cs2CO3, the reaction gave the desired indenopyrone 3a in 10% yield with 20:1 dr and 71% ee (entry 1). NHC precursors 4b-4c with a free hydroxyl group resulted in high enantioselectivity (90% and 99% ee) but the yield was still very low (entries 2-3). NHC precursors 5a-5c derived from aminoindanol, developed by Rovis et al. and Bode et al.,17 were then investigated (entries 46). We were happy to find that the yield could be improved to 42% with 92% ee when N-mesityl NHC 5b was employed (entry 5).
J. Name., 2013, 00, 1‐3 | 1
Organic & Biomolecular Chemistry
Journal Name ClC6H4, 2-MeC6H4, 2-MeOC6H4) were tolerated, affording cycloadducts 3e-3j in good to high yields. Both arylidenes with Online 2-naphthyl and with 2-furyl reacted well View toArticle furnish 10.1039/C5OB00859J addition, the reaction cycloadducts 3k and 3l in good yields. InDOI: of chloroadehydes with varied alkyl chains (R = n-C4H9, nC7H15, n-C10H21) went smoothly to give cycloadduct 3m-3q in good yields with high enantioselectivities. It is noteworthy that all the examples gave the products with exclusively cisselectivity.
Table 1. Optimization of reaction conditions
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Table 2. The reaction scope.
Entry
Cat
Base
Solvent
Yield (%)[a]
ee (%)[b]
1
4a
Cs2CO3
THF
10
-71[c]
2
4b
Cs2CO3
THF
13
-90[c]
3
4c
Cs2CO3
THF
22
-99[c]
4
5a
Cs2CO3
THF
24
95
5
5b
Cs2CO3
THF
42
92
6
5c
Cs2CO3
THF
35
75
7
5b
NaOAc
THF
42
75
8
5b
Na2CO3
THF
58
80
9
5b
Et3N
THF
51
71
10
5b
DIPEA
THF
77
84
11
5b
DIPEA
dioxane
67
94
12
5b
DIPEA
toluene
42
75
13
5b
DIPEA
DCM
35
90
14
5b
DIPEA
CH3CN
trace
/
15[d]
5b
DIPEA
dioxane
77
94
16[d,e]
5b
DIPEA
dioxane
84
96
[a] Isolated yields. [b] Determined by HPLC using a chiral stationary phase. [c] Enantiomer ent-3a was obtained. [d] The reaction was carried out at 10 oC. [e] The additive of 4Å molecular sieves was added. Mes = 2,4,6-trimethylphenyl, DIPEA = N,N-diisopropylethylamine.
Several bases were then screened with NHC 5b' as the catalyst (entries 7-10). Both inorganic bases and organic bases worked for the reaction, and N,N-diisopropylethylamine was the best, giving the product in 77% yield with 84% ee (entry 10). Screening of solvents revealed that the reaction went better in THF and 1,4-dioxane, than others (entries 10-11 vs 12-14). The yield was further improved when the reaction was carried out at 10 oC (entry 15). Finally, the additive of 4Å molecular sieves was found to benefit both the yield and the enantioselectivity (entry 16). With the optimized reaction condition in hand, the scope of the reaction was then briefly investigated (Table 2). The arylidene indanedione with electron-withdrawing group (Ar = 4-ClC6H4) resulted in some decreased but still good yield (3b) with excellent enantioselectivity. Those with electron-donating groups (Ar = 4-MeC6H4, 4-MeOC6H4) worked very well, giving the desired products 3c-3d in high yields with excellent enantioselectivities. meta-Substituents (Ar = 3-ClC6H4, 3MeC6H4, 3-MeOC6H4) and even ortho-substituents (Ar = 2-
The cis- and absolute configuration of the dihydropyridinone 3e was established by the X-ray analysis of its single crystal (Fig. 1).
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Figure 1. X‐ray structure of indenopyrone 3e. The hydrogens are omitted for clarity.
Figure 2. Proposed catalytic cycle and stereochemical mode
Conclusions
The reaction could be scaled up to 1.0 gram without loss of yield and enantioselectivity (Eq. (1)). In addition, the indenopyrone 3a could be easily transformed into the corresponding indenopyridine 9a,18 derivative 6 in 94% yield with high diastereo- and enantio-purity (Eq. (2)).19
In summary, the NHC-catalyzed [4 + 2] cyclization of chloroaldehyde and arylidene indanediones was developed, giving the corresponding indenopyrones in high yields with exclusive cis-selectivities and excellent enantioselectivities. The reaction worked well for both aromatic and aliphatic choloraldehydes. The indenopyridine derivatives could be obtained by aminolysis of the corresponding indenopyraones. Other related NHC-catalyzed reactions are underway in our laboratory.
The proposed catalytic cycle is depicted in Figure 2. The addition of NHC 5b', generated in situ from the triazolium 5b, to choloraldehyde gives Breslow intermediate I, which is Acknowledgements transformed to the corresponding enolate by elimination of HCl. The [4 + 2] cycloaddition of enolate and arylidene indendione via the endo-transitional state (TS A) affords cycloadduct II Financial support from the National Natural Science Founwith cis-selectivity. The elimination of the NHC catalyst dation of China 21272237, 21425207) is gratefully acknowledged. furnishes the final product 3 and completes the catalytic cycle.
Notes and references
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