Chiral phosphoric acid catalyzed asymmetric hydrogenolysis of racemic 3-aryl-3-hydroxyisoindolin-1-ones

Article abstract of DOI:10.1016/j.tetlet.2013.03.138

The enantioselective hydrogenolysis of racemic 3-aryl-3-hydroxyisoindolin- 1-ones catalyzed by BINOL-derived chiral phosphoric acid with benzothiazoline as the hydride source is described. The corresponding cyclic diaryl methylamines are obtained in good to excellent yields and up to 91% enantioselectivities.

Full text of DOI:10.1016/j.tetlet.2013.03.138

Tetrahedron Letters 54 (2013) 3082–3084
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Chiral phosphoric acid catalyzed asymmetric hydrogenolysis of racemic
3-aryl-3-hydroxyisoindolin-1-ones
⇑
Jian-Qing Zhou, Wei-Jian Sheng, Jian-Hong Jia, Qing Ye, Jian-Rong Gao, Yi-Xia Jia
College of Chemical Engineering and Materials Science, Zhejiang University of Technology, Hangzhou 310014, China
a r t i c l e i n f o
a b s t r a c t
Article history:
The enantioselective hydrogenolysis of racemic 3-aryl-3-hydroxyisoindolin-1-ones catalyzed by BINOL-
derived chiral phosphoric acid with benzothiazoline as the hydride source is described. The correspond-
ing cyclic diaryl methylamines are obtained in good to excellent yields and up to 91% enantioselectivities.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 3 February 2013
Revised 22 March 2013
Accepted 28 March 2013
Available online 12 April 2013
Keywords:
Imine reduction
Asymmetric organocatalysis
Chiral phosphoric acid
Hydrogenolysis
Optically active amines are prevalent substructures in many
drugs and biologically active molecules, and widely applied as chi-
ral reagents, chiral ligands, and chiral catalysts in asymmetric syn-
thesis. Consequently, the development of reliable approaches to
chiral amines has been a focused interest for organic chemists.1
Numerous methods have been intensely established for this pur-
pose, in which the asymmetric reduction of imines is undoubtedly
a direct means of accessing chiral amines.2 In this context, the
organocatalytic transfer hydrogenation of imine has developed as
a facile and powerful process to enantiopure amines.3 Pioneered
by the groups of Rueping and List, BINOL-derived chiral phosphoric
acids4 have been proved to be efficient catalysts in the asymmetric
transfer hydrogenation of C@N double bonds.5 A wide range of
yisoindolin-1-ones to produce cyclic N-carbonyl chiral amines in
modest to excellent enantioselectivities.14 However, the extension
of the 3-aryl substituted substrate to form cyclic diaryl methyl-
amine was not successful. We reported herein a BINOL-derived
chiral phosphoric acid catalyzed asymmetric hydrogenolysis of 3-
aryl-3-hydroxyisoindolin-1-ones 1 with benzothiazoline as effi-
cient hydride source, led to 3-arylisoindolinones 2, a structurally
important unit in many biologically active compounds and natural
products,15 in good to excellent yields and with modest to excel-
lent enantioselectivities (Scheme 1).
Initially, 3-hydroxy-3-p-tolylisoindolin-1-one (1a) was chosen
as the model substrate to study the asymmetric hydrogenolysis
reaction (Table 1). Thus, treatment of 1a with 1.2 equiv 2-phen-
ylbenzothiazoline 4a in the presence of 10 mol % chiral phosphoric
acid 3a in CH2Cl2 at 35 °C for 12 h led to 3-p-tolylisoindolinone 2a
in almost quantitative yield and 23% ee (Table 1, entry 1). This re-
sult inspired us to investigate other acid catalysts bearing different
substituent groups at 3,30-positions of the binaphthyl unit (entries
2–6). Gratifyingly, catalyst 3d containing a 9-phenanthryl substitu-
ent accessed the best enantiomeric excess (entry 4), whereas poor
to modest ee values were obtained for the other catalysts screened.
After the solvent examination, we found CHCl3 was the best choice
substrates, such as acyclic ketimines,6 cyclic ketimines,7
a-imino
esters,8 enamides,9 and nitrogen aromatics10 have been enantiose-
lectively reduced to the corresponding chiral amines. Hantzsch es-
ter was the commonly used organic hydride source in these
transformations, while benzothiazoline has been demonstrated
by Akiyama and co-workers as a unique and efficient hydride-
transfer reagent.11 Moreover, by applying the same protocol the
enantioselective hydrogenation of in situ generated imines has also
been successfully established.12 In spite of these notable advances,
efficient approaches to chiral diaryl methylamine still remained
less exploited.
O
O
Recently, hemiaminals have been extensively involved in asym-
metric organocatalysis as stable imine precursors through the for-
mation of N-carbonyl iminium in situ.13 Zhou and co-workers
disclosed an enantioselective hydrogenolysis of 3-alkyl-3-hydrox-
chiral phosphoric acid
[H]
NH
OH
NH
∗
Ar
Ar
1
2
⇑
Corresponding author. Tel.: +86 15558028971.
E-mail address: yxjia@zjut.edu.cn (Y.-X. Jia).
Scheme 1. Asymmetric hydrogenolysis of racemic 3-aryl-3-hydroxyisoindolin-1-
ones.
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.03.138

J.-Q. Zhou et al. / Tetrahedron Letters 54 (2013) 3082–3084
3083
Table 1
Table 2
Optimization of the asymmetric hydrogenolysis reactiona
Substrate scope for the asymmetric hydrogenolysis reactiona
O
O
O
O
S
10 mol% 3d
Ar
10 mol% 3
NH
NH
OH
NH
OH
NH
N
H
1.2 eq. 4a
*
*
CHCl3, 25 oC, 12 h
1.2 eq. hydride
4a
4b
4c
: R = Ph
Ar
Ar
solvent, 35 oC, 12 h
: R = 2-Br-Ph
: R = 3-Br-Ph
1
2
4d: 1-Naphthyl
4e: 2-Naphthyl
4f: 4-NO2-Ph
1a
2a
Entry
R
Yieldb (%)
eec (%)
R
3a
3b
: R = Ph
: R = 1-Naphthyl
3c: R = 2-Naphthyl
3d: R = 9-phenanthryl
1
2
3
4
5
6
7
8
9
4-Me-Ph (1a)
3-Me-Ph (1b)
2-Me-Ph (1c)
Ph (1d)
99
89
91
99
99
99
99
97
98
92
82
99
95
89
72
<5
EtO2C
CO2Et
O
O
O
P
OH
70 (S)
91
N
H
5
3e
: R = Mesityl
4-MeO-Ph (1e)
4-Et-Ph (1f)
3f: 3,5-(tBu)2-Ph
85
67
83
86
83
32
<5
79
R
4-tBu-Ph (1g)
4-nPr-Ph (1h)
4-Vinyl-Ph (1i)
4-Cl-Ph (1j)
Entry
Catalyst
Hydride
Solvent
Yieldb (%)
eec (%)
10d
11
12
13d
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16d
3a
3b
3c
3d
3e
3f
3d
3d
3d
3d
3d
3d
3d
3d
3d
3d
4a
4a
4a
4a
4a
4a
4a
4a
4a
4b
4c
4d
4e
4f
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CHCl3
Toluene
Et2O
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
99
98
89
99
97
90
99
92
98
95
99
99
99
99
76
99
23
66
39
83
32
19
85
81
69
47
85
75
81
83
59
89
3-MeO-Ph (1k)
3,5-Me2-Ph (1l)
2-Naph (1m)
a
Reaction conditions: 1 (0.2 mmol), 4a (0.24 mmol), and 3d (10 mol %) in CHCl3
(2.0 mL) at 25 °C for 12 h.
b
Isolated yield.
c
Determined by HPLC analysis.
d
At 50 °C.
5
4a
1m proceeded smoothly at 50 °C to afford the product in excellent
yield and good enantioselectivity (entry 13). Although only modest
enantiomeric excess of 70% was detected for the phenyl-substrate
1d (entry 4), the introduction of suitable substituents at the para-
position of phenyl ring could favorably improve the enantioselec-
tivity. Thus, the reactions of substrates bearing Me, MeO, Et, nPr, vi-
nyl, and Cl groups afforded the corresponding products in good to
excellent enantioseletivities (83–91% ee). Exception was that mod-
est ee value was obtained in the reaction of para-tBu substrate 1g
(entry 7). Noticeably, the absolute configuration of product 1d
was determined to be S by the comparison of its optical rotation
with that reported in Ref. 13.
In conclusion, we have developed an efficient asymmetric
hydrogenolysis of racemic 3-aryl-3-hydroxyisoindolin-1-ones, led
to chiral cyclic diaryl methylamines in good to excellent yields
and up to 91% enantioselectivities. The present process utilized
chiral BINOL-derived phosphoric acid 3d as a catalyst to form sta-
ble N-carbonyl iminium ions by dehydration and benzothiazoline
as the hydrogen donor to reduce enantioselectively the iminium
to N-carbonyl amines. Further extension of this methodology to
asymmetric synthesis is underway in our laboratory.
a
Reaction conditions: 1a (0.2 mmol), hydride source 4 or 5 (0.24 mmol), 3
(10 mol %) in the solvent (2.0 mL) at 35 °C for 12 h.
b
Isolated yield.
Determined by chiral HPLC analysis.
At 25 °C.
c
d
for this transformation to give the product in 85% ee (entry 7). The
reactions proceeded smoothly in toluene and ether but with lower
enantioselectivities (entries 8 and 9). In order to further improve
the ee value, other hydride sources 4b–f and Hantzsch ester 5 were
investigated in CHCl3 at 35 °C with 3d as a catalyst. However, no
improvement of the enantioselectivity resulted from the modifica-
tion of the substituted aryl groups of benzothiazoline (entries 10–
14), showing 4a was the best hydride source for this reaction.
When Hantzsch ester 5 was used, only 59% ee and modest yield
were obtained (entry 15). Finally, decreasing the temperature from
35 to 25 °C resulted in a slight improvement in the enantioselectiv-
ity from 85% to 89% (entry 16).
With the optimized reaction conditions in hand, the substrate
scope was then investigated and a range of 3-aryl-3-hydroxyisoin-
dolin-1-ones 1a–o were tested. As shown in Table 2, all the reac-
tions proceeded smoothly to give the desired products with good
to excellent yields, whereas the enentioselectivities were dramati-
cally influenced by the steric effect. For instance, almost all racemic
products were isolated in the reaction of 2-methylphenyl substrate
1c and 3,5-dimethylphenyl substrate 1l (entries 3 and 12). Signifi-
cantly lower enantioselectivity was also observed for 3-methoxyl-
phenyl substrate 1k (entry 11). The reaction was also affected by
the electronic property of the aryl group. Low reaction rate was ob-
served for the hydrogenolysis of para-Cl-substrate 1j at 25 °C and
the reaction needed to take place at 50 °C to ensure good conver-
sion (entry 10). To our delight, the reaction of 2-naphthyl-substrate
Acknowledgments
We are grateful for the generous financial supports by the Na-
tional Natural Science Foundation of China (21002089), New Cen-
tury Excellent Talents in University (NCET-12-1086), and young
scholarship for the doctoral program of higher education
(20103317120001).
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2013.03.
138.

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1001–1006; (f) Rueping, M.; Theissmann, T. Chem. Sci. 2010, 1, 473–476; (g)
References and notes
Rueping, M.; Theissmann, T.; Stoeckel, M.; Antonchick, A. P. Org. Biomol. Chem.
2011, 9, 6844–6850.
1. (a) Nugent, T. C. Chiral Amine Synthesis: Methods, Developments, and
Applications; Wiley: Weilhem, 2010; (b) Nugent, T. C.; Mohamed, E.-S. Adv.
Synth. Catal. 2010, 352, 753–819.
2. (a) Spindler, F.; Blaser, H.-U. In Handbook of Homogeneous Hydrogenation III; de
Vries, J., Elsevier, C. J., Eds.; Wiley-VCH: Weinheim, 2007; (b) Brunel, J. M.
Recent Res. Dev. Org. Chem. 2003, 7, 155–190.
11. (a) Zhu, C.; Akiyama, T. Org. Lett. 2009, 11, 4180–4183; (b) Zhu, C.; Akiyama, T.
Adv. Synth. Catal. 2010, 352, 1846–1850; (c) Zhu, C.; Akiyama, T. ChemCatChem
2011, 3, 2850–2851; (d) Henseler, A.; Kato, M.; Mori, K.; Akiyama, T. Angew.
Chem., Int. Ed. 2011, 50, 8180–8183; (e) Zhu, C.; Akiyama, T. Synlett 2011,
1251–1254; (f) Sakamoto, T.; Mori, K.; Akiyama, T. Org. Lett. 2012, 14, 3312–
3315; (g) Zhu, C.; Akiyama, T. Tetrahedron Lett. 2012, 53, 416–418; (h) Saito, K.;
Akiyama, T. Chem. Commun. 2012, 48, 4573–4575.
3. (a) de Vries, J. G.; Mrsic, N. Catal. Sci. Technol. 2011, 1, 727–735; (b) Zheng, C.;
You, S.-L. Chem. Soc. Rev. 2012, 41, 2498–2518.
12. Storer, R. I.; Carrera, D. E.; Ni, Y.; MacMillan, D. W. C. J. Am. Chem. Soc. 2006, 128,
84–86; (b) Hoffmann, S.; Nicoletti, M.; List, B. J. Am. Chem. Soc. 2006, 128,
13074–13075; (c) Zhou, J.; List, B. J. Am. Chem. Soc. 2007, 129, 7498–7499; (d)
Rueping, M.; Antonchick, A. P. Angew. Chem., Int. Ed. 2008, 47, 5836–5838; (e)
Liu, X.-Y.; Che, C.-M. Org. Lett. 2009, 11, 4204–4207; (f) Han, Z.-Y.; Xiao, H.;
Chen, X.-H.; Gong, L.-Z. J. Am. Chem. Soc. 2009, 131, 9182–9183; (g) Kumar, A.;
Sharma, S.; Maurya, R. A. Adv. Synth. Catal. 2010, 352, 2227–2232; (h)
Wakchaure, V. N.; Zhou, J.; Hoffmann, S.; List, B. Angew. Chem., Int. Ed. 2010,
49, 4612–4614; (i) Enders, D.; Liebich, J. X.; Raabe, G. Chem. Eur. J. 2010, 16,
9763–9766; (j) Rueping, M.; Hubener, L. Synlett 2011, 1243–1246.
13. (a) Myers, E. L.; De Vries, J. G.; Aggarwal, V. K. Angew. Chem., Int. Ed. 2007, 46,
1893–1896; (b) Raheem, I. T.; Thiara, P. S.; Peterson, E. A.; Jacobsen, E. N. J. Am.
Chem. Soc. 2007, 129, 13404–13405; (c) Mergott, D. J.; Zuend, S. J.; Jacobsen, E.
N. Org. Lett. 2008, 10, 745–748; (d) Raheem, I. T.; Thiara, P. S.; Jacobsen, E. N.
Org. Lett. 2008, 10, 1577–1580; (e) Peterson, E. A.; Jacobsen, E. N. Angew. Chem.,
Int. Ed. 2009, 48, 6328–6331; (f) Muratore, M. E.; Holloway, C. A.; Pilling, A. W.;
Storer, R. I.; Trevitt, G.; Dixon, D. J. J. Am. Chem. Soc. 2009, 131, 10796–10797;
(g) Rueping, M.; Nachtsheim, B. J. Synlett 2010, 119–122; (h) Knowles, R. R.; Lin,
S.; Jacobsen, E. N. J. Am. Chem. Soc. 2010, 132, 5030–5032; (i) Yu, X.; Lu, A.;
Wang, Y.; Wu, G.; Song, H.; Zhou, Z.; Tang, C. Eur. J. Org. Chem. 2011, 892–897;
(j) Yu, X.; Wang, Y.; Wu, G.; Song, H.; Zhou, Z.; Tang, C. Eur. J. Org. Chem. 2011,
3060–3066.
4. For recent reviews of chiral phosphoric acid catalysis, see: (a) Akiyama, T.; Itoh,
J.; Fuchibe, K. Adv. Synth. Catal. 2006, 348, 999–1010; (b) Akiyama, T. Chem. Rev.
2007, 107, 5744–5758; (c) Terada, M. Chem. Commun. 2008, 4097–4112; (d)
Terada, M. Synthesis 2010, 1929–1982; (e) Terada, M. Curr. Org. Chem. 2011, 15,
2227–2256; (f) Rueping, M.; Kuenkel, A.; Atodiresei, I. Chem. Soc. Rev. 2011, 40,
4539–4549.
5. (a) Rueping, M.; Sugiono, E.; Azap, C.; Theissmann, T.; Bolte, M. Org. Lett. 2005,
7, 3781–3783; (b) Hoffmann, S.; Seayad, A. M.; List, B. Angew. Chem., Int. Ed.
2005, 44, 7424–7427.
6. (a) Nguyen, T. B.; Bousserouel, H.; Wang, Q.; Guéritte, F. Org. Lett. 2010, 12,
4705–4707; (b) Nguyen, T. B.; Bousserouel, H.; Wang, Q.; Guéritte, F. Adv. Synth.
Catal. 2011, 353, 257–262.
7. (a) Rueping, M.; Antonchick, A. P.; Theissmann, T. Angew. Chem., Int. Ed. 2006,
45, 6751–6755; (b) Han, Z.-Y.; Xiao, H.; Gong, L.-Z. Bioorg. Med. Chem. Lett.
2009, 19, 3729–3732; (c) Rueping, M.; Tato, F.; Schoepke, F. R. Chem. Eur. J.
2010, 16, 2688–2691; (d) Rueping, M.; Stoeckel, M.; Sugiono, E.; Theissmann, T.
Tetrahedron 2010, 66, 6565–6568; (e) Rueping, M.; Sugiono, E.; Steck, A.;
Theissmann, T. Adv. Synth. Catal. 2010, 352, 281–287; (f) Rueping, M.; Merino,
E.; Koenigsa, R. M. Adv. Synth. Catal. 2010, 352, 2629–2634; (g) Rueping, M.;
Brinkmann, C.; Antonchick, A. P.; Atodiresei, I. Org. Lett. 2010, 12, 4604–4607;
(h) Chen, Q.-A.; Chen, M.-W.; Yu, C.-B.; Shi, L.; Wang, D.-S.; Yang, Y.; Zhou, Y.-G.
J. Am. Chem. Soc. 2011, 133, 16432–16435.
14. Chen, M.-W.; Chen, Q.-A.; Duan, Y.; Ye, Z.-S.; Zhou, Y.-G. Chem. Commun. 2012,
48, 1698–1700.
8. (a) Li, G.-L.; Liang, Y.-X.; Antilla, J. C. J. Am. Chem. Soc. 2007, 129, 5830–5831; (b)
Kang, Q.; Zhao, Z.-A.; You, S.-L. Adv. Synth. Catal. 2007, 349, 1657–1660; (c)
Kang, Q.; Zhao, Z.-A.; You, S.-L. Org. Lett. 2008, 10, 2031–2034.
15. (a) Belliotti, T. R.; Brink, W. A.; Kesten, S. R.; Rubin, J. R.; Wustrow, D. J.; Zoski, K.
T.; Whetzel, S. Z.; Corbin, A. E.; Pugsley, T. A.; Heffner, T. G.; Wise, L. D. Bioorg.
Med. Chem. Lett. 1998, 8, 1499–1502; (b) Bishop, A. C.; Ubersax, J. A.; Petsch, D.
T.; Matheos, D. P.; Grayk, N. S.; Blethrow, J.; Shimizu, E.; Tsien, J. Z.; Schultzk, P.
G.; Rose, M. D.; Wood, J. L.; Morgan, D. O.; Shokat, K. M. Nature 2000, 407, 395–
401; (c) Fuchs, J. R.; Funk, R. L. Org. Lett. 2001, 3, 3923–3925; (d) Comins, D. L.;
Schilling, S.; Zhang, Y. Org. Lett. 2005, 7, 95–98.
9. Li, G.-L.; Antilla, J. C. Org. Lett. 2009, 11, 1075–1078.
10. (a) Rueping, M.; Antonchick, A. P.; Theissmann, T. Angew. Chem., Int. Ed. 2006,
45, 3683–3686; (b) Rueping, M.; Antonchick, A. P. Angew. Chem., Int. Ed. 2007,
46, 4562–4565; (c) Guo, Q.-S.; Du, D.-M.; Xu, J.-X. Angew. Chem., Int. Ed. 2008,
47, 759–762; (d) Metallinos, C.; Barrett, F. B.; Xu, S. Synlett 2008, 720–724; (e)
Rueping, M.; Theissmann, T.; Raja, S.; Batsa, J. W. Adv. Synth. Catal. 2008, 350,