Organic Letters
Letter
1n−1s. Although 1n−1q could be obtained in excellent yields at
120 °C, 150 °C had to be used to obtain an excellent yield of 1r−
1s. Very similar to 4a, the commercially available sulfonyliso-
cyanates 4b and 4c worked well in the syntheses of 1t−1x. Under
conditions A and B, 1a was prepared on a 50 g scale in 95 and
91% yields, respectively. As expected, alkylaldehydes (as
enolizable aldehydes) were not suitable substrates for this
method.
water-free conditions was developed and was characterized by its
unprecedented cleanliness, efficiency, convenience, and scal-
ability. Finally, the method was successfully applied in two
tandem syntheses of fluorenes. It may be expected that this
method will not only change the synthesis of N-sulfonyl
arylaldimines but also change their synthetic transformations
subsequently.
Since the aza-Friedel−Crafts reaction is a typical application5
of N-tosyl arylaldimine 1 and its product easily undergoes further
electrophilic reaction,5d,14 tandem reactions were expected by
using 2-formyl biphenyl (2t) as a substrate. As shown in Scheme
5, the desired tosylimine 1y was obtained in 83% yield by heating
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
1
Experiments, characterization, H and 13C NMR spectra
for all products 1a−1y, 5, and 6 (PDF)
Scheme 5. Tandem Synthesis of Fluorenes 5 and 6
AUTHOR INFORMATION
Corresponding Authors
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was supported by NNSFC (Nos. 21472107 and
21372142).
■
REFERENCES
■
(1) (a) Weinreb, S. M. Top. Curr. Chem. 1997, 190, 131. (b) Bloch, R.
Chem. Rev. 1998, 98, 1407.
(2) (a) Hensel, A.; Nagura, K.; Delvos, L. B.; Oestreich, M. Angew.
Chem., Int. Ed. 2014, 53, 4964. (b) Zhang, F.-L.; Wang, Y.-F.; Lonca, G.
H.; Zhu, X.; Chiba, S. Angew. Chem., Int. Ed. 2014, 53, 4390. (c) Luo, Y.;
Hepburn, H. B.; Chotsaeng, N.; Lam, H. W. Angew. Chem., Int. Ed. 2012,
51, 8309. (d) Hyodo, K.; Nakamura, S.; Shibata, N. Angew. Chem., Int.
Ed. 2012, 51, 10337. (e) Shao, C.; Yu, H.-J.; Wu, N.-Y.; Feng, C.-G.; Lin,
G.-Q. Org. Lett. 2010, 12, 3820.
(3) (a) Lykke, L.; Halskov, K. S.; Carlsen, B. D.; Chen, V. X.; Jørgensen,
K. A. J. Am. Chem. Soc. 2013, 135, 4692. (b) Illa, O.; Namutebi, M.; Saha,
C.; Ostovar, M.; Chen, C. C.; Haddow, M. F.; Nocquet-Thibault, S.;
Lusi, M.; McGarrigle, E. M.; Aggarwal, V. K. J. Am. Chem. Soc. 2013, 135,
11951. (c) Amatore, M.; Leboeuf, D.; Malacria, M.; Gandon, V.; Aubert,
C. J. Am. Chem. Soc. 2013, 135, 4576. (d) Trost, B. M.; Silverman, S. M. J.
Am. Chem. Soc. 2012, 134, 4941. (e) Chen, S.; Salo, E. C.; Wheeler, K. A.;
Kerrigan, N. J. Org. Lett. 2012, 14, 1784.
(4) (a) Guo, Q.; Zhao, J. C.-G. Org. Lett. 2013, 15, 508. (b) Ghorai, M.
K.; Ghosh, K.; Yadav, A. K.; Nanaji, Y.; Halder, S.; Sayyad, M. J. Org.
Chem. 2013, 78, 2311. (c) Shi, S.-H.; Huang, F.-P.; Zhu, P.; Dong, Z.-W.;
Hui, X.-P. Org. Lett. 2012, 14, 2010. (d) Kobayashi, S.; Kiyohara, H.;
Yamaguchi, M. J. Am. Chem. Soc. 2011, 133, 708. (e) Colpaert, F.;
Mangelinckx, S.; De Kimpe, N. Org. Lett. 2010, 12, 1904.
(5) (a) Bai, S.; Liao, Y.; Lin, L.; Luo, W.; Liu, X.; Feng, X. J. Org. Chem.
2014, 79, 10662. (b) Fan, X.; Lv, H.; Guan, Y.-H.; Zhu, H.-B.; Cui, X.-
M.; Guo, K. Chem. Commun. 2014, 50, 4119. (c) Liu, G.; Zhang, S.; Li,
H.; Zhang, T.; Wang, W. Org. Lett. 2011, 13, 828. (d) Esquivias, J.;
a mixture of 2t and TsNCO together. The same reaction gave 9-
tosylaminofluorene 5 in 87% yield in the presence of Bi(OTf)3
(10 mol %). When the same reaction was treated by FeCl3 (10
mol %) in the presence of 1,2,4-trimethoxybenzene, 9-
arylfluorene 6 was obtained in 90% yield. Further conditional
experiment showed that 6 was obtained in very low yield in the
absence of TsNCO. The higher yields of 5 and 6 (compared to
that of 1y) may derive from the fact that 1y was not isolated and
purified in these tandem reactions. In fact, most products of 1a−
1x were synthesized in quantitative yield. Their isolated yields
were decreased by purification, especially by SiO2 flash
chromatography, because they are sensitive to hydrolysis. That
was the reason that 1a−1y were purified by a standard
recrystallization procedure: 1/EtOAc/petroleum ether (60−90
°C) = 5 mmol/2 mL/12 mL.
The shorter reaction times in the syntheses of 5 and 6
(compared to that of 1y) proved that the synthesis of 1y was
catalyzed by Lewis acids. However, this idea was not used in the
synthesis of 1a−1x because these products can be decomposed
by Lewis acids. We believe that the success for the tandem
syntheses of 5 and 6 mainly stems from the fact that our method
has two specific advantages compared to the other existing
methods: the synthesis of 1y proceeded under catalyst-/additive-
free conditions and without the formation of H2O, following
which Friedel−Crafts reactions and their catalysts were not
disturbed at all.
́
Gomez Arrayas, R.; Carretero, J. C. Angew. Chem., Int. Ed. 2006, 45, 629.
(e) Luo, Y.; Li, C.-J. Chem. Commun. 2004, 1930.
(6) (a) Parthasarathy, K.; Azcargorta, A. R.; Cheng, Y.; Bolm, C. Org.
Lett. 2014, 16, 2538. (b) Yoshino, T.; Ikemoto, H.; Matsunaga, S.; Kanai,
M. Angew. Chem., Int. Ed. 2013, 52, 2207. (c) Zhang, T.; Wu, L.; Li, X.
Org. Lett. 2013, 15, 6294. (d) Hesp, K. D.; Bergman, R. G.; Ellman, J. A.
Org. Lett. 2012, 14, 2304. (e) Tsai, A. S.; Tauchert, M. E.; Bergman, R.
G.; Ellman, J. A. J. Am. Chem. Soc. 2011, 133, 1248.
In conclusion, four items have been included in this article.
First, we found that King’s experiment and explanation in 1960
was wrong. Second, King’s experiment was retested, and its
problems were revealed. Third, the first practical method for the
prparation of N-sulfonylimines under catalyst-, additive-, and
(7) Methods other than dehydration: (a) Chawla, R.; Singh, A. K.;
Yadav, L. D. S. Tetrahedron Lett. 2014, 55, 3553. (b) Cui, X.; Shi, F.;
C
Org. Lett. XXXX, XXX, XXX−XXX