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DOI: 10.1055/s-0036-1590880
Synthesis of 3,3-Disubstituted 2-Oxindoles by Deacylative Alkylation of 3-Acetyl-2-oxindoles
We gratefully acknowledge financial support from the Spanish Ministerio de Ciencia e Innovación (MICINN) (projects CTQ2010-20387 and Consolider Ingenio 2010, CSD2007-00006), the Spanish Ministerio de Economía y Competitividad (MINECO) (projects CTQ2013-43446-P and CTQ2014-51912-REDC), the Spanish Ministerio de Economía, Industria y Competitividad, Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER, EU) (projects CTQ2016-76782-P and CTQ2016-81797-REDC), the Generalitat Valenciana (PROMETEO2009/039 and PROMETEOII/ 2014/017) and the University of Alicante. A.O.-M. thanks MINECO for a predoctoral fellowship.Publikationsverlauf
Received: 09. Juni 2017
Accepted after revision: 22. Juli 2017
Publikationsdatum:
22. August 2017 (online)
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Abstract
An innovative and efficient monoalkylation and nonsymmetrical 3,3-dialkylation of oxindoles has been achieved. First, the monoalkylation of 3-acetyl-2-oxindoles can be performed in good yields under mild reaction conditions using alkyl halides and benzyltrimethylammonium hydroxide (Triton B) as base at room temperature. This methodology is applied to construct the synthetically challenging compound 1,3-dimethyl-2-oxindole. Subsequent deacylative alkylation (DaA) of the alkylated 3-acetyl-2-oxindoles with alkyl halides takes place efficiently using LiOEt or by conjugate addition with electron-deficient alkenes in the presence of Triton B at room temperature under argon, affording the corresponding unsymmetrically 3,3-disubstituted 2-oxindoles. This simple methodology has been applied to the synthesis of precursors of horsfiline, esermethole, physostigmine, and phenserine alkaloids.
Supporting Information
- Copies of 1H and 13C NMR spectra of new products.Supporting information for this article is available online at https://doi.org/10.1055/s-0036-1590880.
- Supporting Information
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References
- 1a Cao Z.-Y. Wang Y.-H. Zeng Y.-P. Zhou J. Tetrahedron Lett. 2014; 55: 2571
- 1b Shen K. Liu X. Feng X. Chem. Sci. 2012; 3: 327
- 1c Singh GS. Desta ZY. Chem. Rev. 2012; 112: 6104
- 1d Dalpozzo R. Bartoli G. Bencivenni G. Chem. Soc. Rev. 2012; 41: 7247
- 1e Zhou F. Liu Y.-L. Zhou J. Adv. Synth. Catal. 2010; 352: 1381
- 1f Galliford CV. Scheidt KA. Angew. Chem. Int. Ed. 2007; 46: 8748
- 2a Ashimori A. Matsuura T. Overman LE. Poon DJ. J. Org. Chem. 1993; 58: 6949
- 2b Matsuura T. Overman LE. Poon DJ. J. Am. Chem. Soc. 1998; 120: 6500
- 3a Shaughnessy KH. Hamann BC. Hartwig JF. J. Org. Chem. 1998; 63: 6546
- 3b Kundig EP. Seidel TM. Jia Y.-X. Bernardinelli G. Angew. Chem. Int. Ed. 2007; 46: 8484
- 3c Marsden SP. Watsonand EL. Raw SA. Org. Lett. 2008; 10: 2905
- 3d Altman RA. Hyde AM. Huang X. Buchwald SL. J. Am. Chem. Soc. 2008; 130: 9613
- 3e Ruck TR. Huffman MA. Kim MM. Shevlin M. Kandur WV. Davies IW. Angew. Chem. Int. Ed. 2008; 47: 4711
- 4a Jia Y.-X. Kündig EP. Angew. Chem. Int. Ed. 2009; 48: 1636
- 4b Perry A. Taylor RJ. K. Chem. Commun. 2009; 3249
- 4c Ghosh S. De S. Kakde BN. Bhunia S. Adhikary A. Bisai A. Org. Lett. 2012; 14: 5864
- 5a Tian X. Jiang K. Peng J. Du W. Chen Y.-C. Org. Lett. 2008; 10: 3583
- 5b He R. Ding C. Maruoka K. Angew. Chem. Int. Ed. 2009; 48: 4559
- 5c Cheng L. Liu L. Jia H. Wang D. Chen Y.-J. J. Org. Chem. 2009; 74: 4650
- 5d Wu X. Liu Q. Liu Y. Wang Q. Zhang Y. Chen J. Cao W. Zhao G. Adv. Synth. Catal. 2013; 355: 2701
- 5e Wei Y. Wen S. Liu Z. Wu X. Zheng B. Ye J. Org. Lett. 2015; 17: 2732
- 5f Mechler M. Peters R. Angew. Chem. Int. Ed. 2015; 54: 10303
- 5g Müller JM. Stark CB. W. Angew. Chem. Int. Ed. 2016; 55: 4798
- 5h Ohmatsu K. Kikoyama M. Ooi T. J. Am. Chem. Soc. 2011; 133: 1307
- 5i Zhu Q. Lu Y. Angew. Chem. Int. Ed. 2010; 49: 7753
- 5j Peng J. Huang X. Cui H.-L. Chen Y.-C. Org. Lett. 2010; 12: 4260
- 5k Bui T. Syed S. Barbas CF. III. J. Am. Chem. Soc. 2009; 131: 8758
- 5l Jiang K. Peng J. Cui H.-L. Chen Y.-C. Chem. Commun. 2009; 3955
- 5m Li X. Xi Z.-G. Luo S. Cheng J.-P. Org. Biomol. Chem. 2010; 8: 77
- 5n Wang L.-L. Peng L. Bai J.-F. Huang Q.-C. Xu X.-Y. Wang L.-X. Chem. Commun. 2010; 46: 8064
- 5o Trost BM. Czabaniuk LC. J. Am. Chem. Soc. 2010; 132: 15534
- 5p Trost BM. Frederiksen MU. Angew. Chem. Int. Ed. 2005; 44: 308
- 6 For a recent review, see: Weaver JD. Recio AIII. Grenning AJ. Tunge JA. Chem. Rev. 2011; 111: 1846
- 7 Linton EC. Kozlowski MC. J. Am. Chem. Soc. 2008; 130: 16162
- 8 Kumar N. Das MK. Ghosh S. Bisai A. Chem. Commun. 2017; 53: 2170
- 9a Grenning AJ. Tunge JA. Angew. Chem. Int. Ed. 2011; 50: 1688
- 9b Grenning AJ. Tunge JA. J. Am. Chem. Soc. 2011; 133: 14785
- 10 For a review, see: Mei H. Xie C. Aceña JL. Soloshonok VA. Röschenthaler G.-V. Han J. Eur. J. Org. Chem. 2015; 6401
- 11a Xie C. Zhang L. Sha W. Soloshonok VA. Han J. Pan Y. Org. Lett. 2016; 18: 3270
- 11b A very similar reaction principle was employed but using harsher conditions, see: Reisch J. Muller M. Labitzke H. Arch. Pharm. 1984; 317: 639
- 12 Jha M. Chou T.-Y. Blunt B. Tetrahedron Lett. 2011; 67: 982
- 13 Zhang QB. Jia WL. Ban YL. Zheng Y. Liu Q. Wu LZ. Chem. Eur. J. 2016; 22: 2595
- 14 Shelke AM. Suryavanshi G. Org. Biomol. Chem. 2015; 13: 8669
- 15 Sampson PB. Liu Y. Patel NK. Feher M. Forrest B. Li S. Edwards L. Laufer R. Lang Y. Ban F. Awrey DE. Mao G. Plotnikova O. Leung G. Hodgson R. Mason J. Wei X. Kiarash R. Green E. Qiu W. Chirgadze NY. Mak TW. Pan G. Pauls HW. J. Med. Chem. 2015; 58: 147
- 16 Trost BM. Brennan MK. Org. Lett. 2006; 8: 2027
- 17 Trost BM. Zhang Y. J. Am. Chem. Soc. 2006; 128: 4590
- 18 Huang A. Kodanko JJ. Overman LE. J. Am. Chem. Soc. 2004; 126: 14043
- 19 Pinto A. Jia Y. Neuville L. Zhu J. Chem. Eur. J. 2007; 13: 961
- 20 Xia XD. Lu LQ. Liu WQ. Chen DZ. Zheng YH. Wu LZ. Xiao WJ. Chem. Eur. J. 2016; 22: 8432
- 21 Hugel HM. Greenwood RJ. Mackayb MF. Aust. J. Chem. 1992; 45: 1953
- 22 Ju X. Liang Y. Jia P. Li W. Yu W. Org. Biomol. Chem. 2012; 10: 498
- 23 Kikue N. Takahashi T. Nishino H. Heterocycles 2015; 90: 540
- 24 Zhou Y. Zhao Y. Dai X. Liu J. Li L. Zhang H. Org. Biomol. Chem. 2011; 9: 4091
- 25 Zhou B. Hou W. Yang Y. Feng H. Li Y. Org. Lett. 2014; 16: 1322
- 26 Trost BM. Zhang Y. Chem. Eur. J. 2011; 17: 2916
- 27 Yasui Y. Kamisaki H. Takemoto Y. Org. Lett. 2008; 10: 3303
- 28 Wang S. Huang X. Li B. Ge Z. Wang X. Li R. Tetrahedron Lett. 2015; 71: 1869
- 29 Zhao Y. Sharma N. Sharma UK. Li Z. Song G. Van der Eycken EV. Chem. Eur. J. 2016; 22: 5878
- 30 Liu F. Li P. J. Org. Chem. 2016; 81: 6972
For recent reviews, see: