86% yield respectively with complete conversion in 48 h. p-CO2Et aniline was also feasible substrate and was successfully converted
to 4h, albeit in a slightly decreased yield of 43%. The reaction of 4-F aniline proceeded smoothly to provide pyrrolidinol 4i in 73%
yield. N-Aryl-3-pyrrolidinols 4j-4m with Cl or Br substitution were also achieved in moderate yields indicating that these two
venerable halide substitutions on the aniline are compatible with this transition metal catalyzed process in reflux toluene although
relative complicated reaction mixtures were observed. Interestingly, p-CF3 5n aniline was partially transformed into 4n (24% yield)
with ca. 70% recovery of starting aniline even after 3 days reaction. The reactions to form 4o and 4p were pretty slower than
previous ones and significant amount of starting anilines 5o and 5p remained after 48 h. It can reasonably be attributed to the steric
effects and was further confirmed by the entire failure of reactions of the triol with 2,6-dimethylaniline 5q and 1-naphylamine 5r. m-
OH aniline 5s was also inert for this reaction, apparently the phenolic OH deactivated the catalytic system.
Next, to further test the potential of this catalytic system, 1,3,4-hexanetriol 6b was submitted to the standard conditions with
aniline 5a as the alkylation acceptor. Pleasingly, 2-ethyl pyrrolidinol 4t was also produced, albeit in only 38% yield (Scheme 4, top).
When 1,2,5-pentanetriol 6c was used as the alkylating agent, the same reaction with aniline 5a gave rise to a pyrrolidine/piperidine
pair 4u/4u' in good combined yield and equal selectivity. Analogous results were obtained for m-Me aniline 5c (Scheme 4, bottom).
Related experiment details, characteristics of compounds, copies of NMR spectra can be found in Supporting information for this
article.
In summary, a ruthenium catalyzed hydrogen autotransfer amination of triols has been developed for 3-pyrrolidinol synthesis.
This catalytic system is proved to be compatible with the additional free hydroxyl group. A variety of substituted anilines are
successfully transferred into highly valuable 3-pyrrolidinol derivatives from abound and cheap 1,2,4-butanetriol with high efficiency.
This extremely environmental benign and low-cost protocol would stimulate further investigations.
Acknowledgments
We thank the National Natural Science Foundation of China (No. 21672027), QingLan Project of Jiangsu Province (2016) and
Six-Talent-Peaks Program of Jiangsu (2016) for financial support. This work was also supported by High-Level Entrepreneurial
Talent Team of Jiangsu Province (2017-37).
References
[1] (a) T. Irrgang; R. Kempe, Chem. Rev. 119 (2019) 2524-2549;
(b) A. Corma, J. Navas, M.J. Sabater, Chem. Rev. 118 (2018) 1410-1459;
(c) X. Ma, C. Su, Q. Xu, Top. Curr. Chem. 374 (2016) 1-74;
(d) Q. Yang, Q. Wang, Z. Yu, Chem. Soc. Rev. 44 (2015) 2305-2329.
[2] (a) S. Whitney, R. Grigg, A. Derrick, A. Keep, Org. Lett. 9 (2007) 3299-3302;
(b) C. Loefberg, R. Grigg, M.A. Whittaker, A. Keep, A. Derrick, J. Org. Chem. 71 (2006) 8023-8027;
(c) R. Grigg, T.R.B. Mitchell, S. Sutthivaiyakit, N. Tongpenyai, Chem. Commun. (1981) 611-612.
[3] Y. Watanabe, Y. Tsuji, Y. Ohsugi, Tetrahedron Lett. 22 (1981 2667-2670.
[4] (a) S. Elangovan, J. Neumann, J.B. Sortais, et al., Nat. Commun. 7 (2016) 12641;
(b) S. Baehn, S. Imm, K. Mevius, et al., Chem. -Eur. J. 16 (2010) 3590-3593;
(c) S. Imm, S. Baehn, L. Neubert, H. Neumann, M. Beller, Angew. Chem. Int. Ed. 49 (2010) 8126-8129.
[5] (a) R. Kawahara, K.I. Fujita, R. Yamaguchi, Adv. Synth. Catal. 353 (2011) 1161-1168;
(b) R. Kawahara, K.I. Fujita, R. Yamaguchi, J. Am. Chem. Soc. 132 (2010) 15108-15111.
[6] (a) O. Saidi, A.J. Blacker, M.M. Farah, S.P. Marsden, J.M.J. Williams, Chem. Commun. 46 (2010) 1541-1543;
(b) O. Saidi, A.J. Blacker, G.W. Lamb, et al., Org. Process Res. Dev. 14 (2010) 1046-1049.
[7] (a) R. Martinez, D.J. Ramon, M. Yus, Org. Biomol. Chem. 7 (2009) 2176-2181;
(b) R. Martinez, G.J. Brand, D.J. Ramon, M. Yus, Tetrahedron Lett. 46 (2005) 3683-3686.
[8] (a) S. Michlik, R. Kempe, Chem. -Eur. J. 16 (2010) 13193-13198;
(b) B. Blank, R. Kempe, J. Am. Chem. Soc. 132 (2010) 924-925.
[9] C. Gunanathan, D. Milstein, Angew. Chem. Int. Ed. 47 (2008) 8661-8664.
[10] (a) S. Liu, R. Chen, G.J. Deng, Chem. Lett. 40 (2011) 489-491;
(b) Y. Liu, W. Chen, C. Feng, G. Deng, Chem. - Asian J. 6 (2011) 1142-1146.
[11] S.L. Feng, C.Z. Liu, Q. Li, X.C. Yu, Q. Xu, Chin. Chem. Lett. 22 (2011) 1021-1024.
[12] (a) X. Cui, F. Shi, Y. Zhang, Y. Deng, Tetrahedron Lett. 51 (2010) 2048-2051;
(b) X. Cui, F. Shi, M.K. Tse, et al., Adv. Synth. Catal. 351 (2009) 2949-2958.
[13] (a) B. Emayavaramban, P. Chakraborty, E. Manoury, R. Poli, B. Sundararaju, Org. Chem. Front. 2019, 10.1039/c8qo01389f;
(b) C.M. Hsiao, Y.F. Chen, C.H. Lin, et al., J. Organomet. Chem. 861 (2018 10-16;
(c) G. Zhang, Z. Yin, S. Zheng, Org. Lett. 18 (2016) 300-303;
(d) T. Yan, B.L. Feringa, K. Barta, ACS Catal. 6 (2016) 381-388;
(e) Q. Zou, C. Wang, J. Smith, D. Xue, J. Xiao, Chem. -Eur. J. 21 (2015) 9656-9661;
(f) Y. Zhang, X. Qi, X. Cui, F. Shi, Y. Deng, Tetrahedron Lett. 52 (2011) 1334-1338.