Base-Promoted 1,6-Aza-Michael Addition of Azauracils to para-Quinone Methides

Rupashri Dash; Sudhir Kumar Hota; Sandip Murarka

doi:10.1055/a-2104-5943

Synthesis, Table of Contents

Synthesis 2024; 56(04): 677-685
DOI: 10.1055/a-2104-5943

special topic

Synthetic Development of Key Intermediates and Active Pharmaceutical Ingredients (APIs)

Base-Promoted 1,6-Aza-Michael Addition of Azauracils to para-Quinone Methides

Rupashri Dash‡

,

Sudhir Kumar Hota‡

,

Sandip Murarka ∗

Abstract

All articles of this category

Abstract

We report an efficient higher order conjugate addition of azauracils to substituted para-quinone methides (p-QMs) mediated by triethylamine to furnish hitherto unknown diarylmethane scaffolds through construction of a C–N bond. The protocol features mild conditions, high atom economy, and broad scope, and enables convenient access to biologically relevant new chemical entities (NCEs) comprised of p-QM and azauracil hybrids in good to excellent yields.

Key words

azauracil - para-quinone methides - 1,6-addition - aza-Michael - metal-free

Full Text

References

References

1a Weiner B, Szymański W, Janssen DB, Minnaard AJ, Feringa BL. Chem. Soc. Rev. 2010; 39: 1656
1b Bariwal J, Van der Eycken E. Chem. Soc. Rev. 2013; 42: 9283
1c Sánchez-Roselló M, Aceña JL, Simón-Fuentes A, Del Pozo C. Chem. Soc. Rev. 2014; 43: 7430
1d Ruiz-Castillo P, Buchwald SL. Chem. Rev. 2016; 116: 12564

2a Wang J.-Y, Hao W.-J, Tu S.-J, Jiang B. Org. Chem. Front. 2020; 7: 1743
2b Parra A, Tortosa M. ChemCatChem 2015; 7: 1524
2c Lima CG. S, Pauli FP, Costa DC. S, de Souza AS, Forezi LS. M, Ferreira VF, de Carvalho da Silva F. Eur. J. Org. Chem. 2020; 2650

3a Chu W.-D, Zhang L.-F, Bao X, Zhao X.-H, Zeng C, Du J.-Y, Zhang G.-B, Wang F.-X, Ma X.-Y, Fan C.-A. Angew. Chem. Int. Ed. 2013; 52: 9229
3b Caruana L, Kniep F, Johansen TK, Poulsen PH, Jørgensen KA. J. Am. Chem. Soc. 2014; 136: 15929
3c Ramanjaneyulu BT, Mahesh S, Anand RV. Org. Lett. 2015; 17: 3952
3d Wang Z, Wong YF, Sun J. Angew. Chem. Int. Ed. 2015; 54: 13711
3e Deng Y.-H, Zhang X.-Z, Yu K.-Y, Yan X, Du J.-Y, Huang H, Fan C.-A. Chem. Commun. 2016; 52: 4183
3f Ge L, Lu X, Cheng C, Chen J, Cao W, Wu X, Zhao G. J. Org. Chem. 2016; 81: 9315
3g Ma C, Huang Y, Zhao Y. ACS Catal. 2016; 6: 6408
3h Zhang X.-Z, Deng Y.-H, Yan X, Yu K.-Y, Wang F.-X, Ma X.-Y, Fan C.-A. J. Org. Chem. 2016; 81: 5655
3i Zhao K, Zhi Y, Shu T, Valkonen A, Rissanen K, Enders D. Angew. Chem. Int. Ed. 2016; 55: 12104
3j Goswami P, Singh G, Vijaya Anand R. Org. Lett. 2017; 19: 1982
3k Kang T.-C, Wu L.-P, Yu Q.-W, Wu X.-Y. Chem. Eur. J. 2017; 23: 6509
3l Li S, Liu Y, Huang B, Zhou T, Tao H, Xiao Y, Liu L, Zhang J. ACS Catal. 2017; 7: 2805
3m Liao J.-Y, Ni Q, Zhao Y. Org. Lett. 2017; 19: 4074
3n Zhou T, Li S, Huang B, Li C, Zhao Y, Chen J, Chen A, Xiao Y, Liu L, Zhang J. Org. Biomol. Chem. 2017; 15: 4941
3o Goswami P, Sharma S, Singh G, Vijaya Anand R. J. Org. Chem. 2018; 83: 4213
3p Gupta AK, Ahamad S, Vaishanv NK, Kant R, Mohanan K. Org. Biomol. Chem. 2018; 16: 4623
3q Jadhav AS, Pankhade YA, Anand RV. J. Org. Chem. 2018; 83: 8596
3r Jadhav AS, Pankhade YA, Hazra R, Anand RV. J. Org. Chem. 2018; 83: 10107
3s Wang J, Pan X, Liu J, Zhao L, Zhi Y, Zhao K, Hu L. Org. Lett. 2018; 20: 5995
3t Kale SB, Jori PK, Thatikonda T, Gonnade RG, Das U. Org. Lett. 2019; 21: 7736
3u Singh G, Kumar S, Chowdhury A, Vijaya Anand R. J. Org. Chem. 2019; 84: 15978
3v Wang Y, Wang K, Cao W, Liu X, Feng X. Org. Lett. 2019; 21: 6063

4a Dong N, Zhang Z.-P, Xue X.-S, Li X, Cheng J.-P. Angew. Chem. Int. Ed. 2016; 55: 1460
4b Liu T, Liu J, Xia S, Meng J, Shen X, Zhu X, Chen W, Sun C, Cheng F. ACS Omega 2018; 3: 1409
4c Wu Q.-Y, Ao G.-Z, Liu F. Org. Chem. Front. 2018; 5: 2061
4d Dai L, Yu Q, Zhang J, Wu F, Wang C, Zhang J, Rong L. J. Org. Chem. 2021; 86: 10568
4e Xiong B, Xu S, Liu Y, Tang K.-W, Wong W.-Y. J. Org. Chem. 2021; 86: 1516

5 Aher YN, Pawar AB. Org. Biomol. Chem. 2019; 17: 7536

6a Lou Y, Cao P, Jia T, Zhang Y, Wang M, Liao J. Angew. Chem. Int. Ed. 2015; 54: 12134
6b Jarava-Barrera C, Parra A, López A, Cruz-Acosta F, Collado-Sanz D, Cárdenas DJ, Tortosa M. ACS Catal. 2016; 6: 442
6c Huang GB, Huang WH, Guo J, Xu DL, Qu XC, Zhai PH, Zheng XH, Weng J, Lu G. Adv. Synth. Catal. 2019; 361: 1241
6d Li X, Gao G, He S, Song Q. Org. Chem. Front. 2021; 8: 4543

7 Li T, Wu Y, Duan W, Ma Y. RSC Adv. 2021; 11: 17860

8a Torán R, Vila C, Sanz-Marco A, Muñoz MC, Pedro JR, Blay G. Eur. J. Org. Chem. 2020; 627
8b Roy D, Panda G. Synthesis 2019; 51: 4434
8c Rai V, Kavyashree P, Harmalkar SS, Dhuri SN, Maddani MR. Org. Biomol. Chem. 2022; 20: 345
8d More SG, Rupanawar BD, Suryavanshi G. J. Org. Chem. 2021; 86: 10129
8e Guin S, Saha HK, Patel AK, Gudimella SK, Biswas S, Samanta S. Tetrahedron 2020; 76: 131338
8f Chen M, Sun J. Angew. Chem. Int. Ed. 2017; 56: 4583

9 Panda SP, Hota SK, Dash R, Roy L, Murarka S. Org. Lett. 2023; 25: 3739

10a Vanparijs O, Marsboom R, Desplenter L. Poult. Sci. 1989; 68: 489
10b Prabhakaran J, Parsey RV, Majo VJ, Hsiung S.-C, Milak MS, Tamir H, Simpson NR, Van Heertum RL, Mann JJ, Dileep Kumar JS. Bioorg. Med. Chem. Lett. 2006; 16: 2101
10c Miller MW, Mylari BL, Howes HL. Jr, Lynch JE, Lynch MJ, Koch RC. J. Med. Chem. 1979; 22: 1483
10d Liu J, Gong Y, Shi J, Hao X, Wang Y, Zhou Y, Hou Y, Liu Y, Ding S, Chen Y. Eur. J. Med. Chem. 2020; 194: 112244
10e Kumar JS. D, Majo VJ, Hsiung S.-C, Millak MS, Liu K.-P, Tamir H, Prabhakaran J, Simpson NR, Van Heertum RL, Mann JJ, Parsey RV. J. Med. Chem. 2006; 49: 125
10f Crance JM, Scaramozzino N, Jouan A, Garin D. Antiviral Res. 2003; 58: 73

11a Sun K, Shi A, Liu Y, Chen X, Xiang P, Wang X, Qu L, Yu B. Chem. Sci. 2022; 13: 5659
11b Hwang L.-C, Yang S.-Y, Chuang C.-L, Lee G.-H. Molecules 2017; 22: 1924

12 Kumar Parida S, Kumar Hota S, Jaiswal S, Singh P, Murarka S. Adv. Synth. Catal. 2022; 364: 1549

13a Parida SK, Jaiswal S, Singh P, Murarka S. Org. Lett. 2021; 23: 6401
13b Hota SK, Panda SP, Das S, Mahapatra SK, Roy L, De Sarkar S, Murarka S. J. Org. Chem. 2023; 88: 2543
13c Das S, Parida SK, Mandal T, Sing L, De Sarkar S, Murarka S. Chem. Asian J. 2020; 15: 568
13d Das S, Parida SK, Mandal T, Hota SK, Roy L, De Sarkar S, Murarka S. Org. Chem. Front. 2021; 8: 2256
13e Das S, Azim A, Hota SK, Panda SP, Murarka S, De Sarkar S. Chem. Commun. 2021; 57: 13130

14a Ghosh P, Byun Y, Kwon NY, Kang JY, Mishra NK, Park JS, Kim IS. Cell Rep. 2022; 3: 100819
14b Tan Y, Xuekun W, Han Y.-P, Zhang Y, Zhang H.-Y, Zhao J. J. Org. Chem. 2022; 87: 8551

Supplementary Material

Supporting Information