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J.-H. Tay, P. Nagorny
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Synlett
nificantly lower than for BINOL- or BINOL-derived methyl
phosphate (Table 2, entry 1). Thus, only 4% loss in enantio-
meric excess was observed after 24 hours. The increase in
temperature to 220 °C resulted in a faster racemization rate,
and the measured enantiopurity of 1a was 84% ee after 18
hours (Table 2, entry 2). Further elevation of the tempera-
ture to 250 °C resulted in decomposition of 1a (Table 1, en-
try 3). Interestingly, the H8-BINOL counterpart of 1a, acid
2a exhibited higher stability to racemization, and the enan-
tiopure sample for 2a was isolated even after being heated
at 220 °C for 18 hours (Table 2, entry 4). These experiments
demonstrate that BINOL-based CPA with saturated back-
bone is more configurationally stable in comparison to its
unsaturated analogue, which is consistent with the prior
studies on comparative racemization of H8-BINOL and
BINOL derivatives.14
In conclusion, we have developed a quick, easy, and reli-
able protocol15 to determine the enantiopurity of chiral
phosphoric acids using 31P NMR spectroscopy and commer-
cially available chiral amines as discriminating agents. The
protocol is shown to be general for a series of CPA and it
gives excellent resolution in most cases. Utilizing this pro-
tocol, we were able to study the racemization behavior of
chiral phosphoric acids under hydrogenation and thermal
conditions.
(2) For selected reviews, please read: (a) Terada, M. Synthesis 2010,
12, 1929. (b) Zamfir, A.; Schenker, S.; Freund, M.; Tsogoeva, S. B.
Org. Biomol. Chem. 2010, 8, 5262. (c) Parmar, D.; Sugiono, E.;
Raja, S.; Rueping, M. Chem. Rev. 2014, 114, 9047.
(3) Selected examples of other C2-symmetric CPA
– SPINOL:
(a) Coric, I.; Muller, S.; List, B. J. Am. Chem. Soc. 2010, 132, 17370.
(b) Xu, F.; Huang, D.; Shen, W.; Lin, X.; Wang, Y. J. Org. Chem.
2010, 75, 8677. VINOL and VAPOL: (c) Desai, A. A.; Huang, L.;
Wulf, W. D.; Rowland, G. B.; Antilla, J. C. Synthesis 2010, 2106.
CPA with multiple chiral axis: (d) Momiyama, N.; Konno, T.;
Furiya, Y.; Iwamoto, T.; Terada, M. J. Am. Chem. Soc. 2011, 133,
19294. (e) Guo, Q.-S.; Du, D.-M.; Xu, J. Angew. Chem. Int. Ed.
2008, 47, 759.
(4) (a) Sun, Z.; Winschel, G. A.; Borovika, A.; Nagorny, P. J. Am.
Chem. Soc. 2012, 134, 8074. (b) Nagorny, P.; Sun, Z.; Winschel, G.
A. Synlett 2013, 24, 661. (c) Borovika, A.; Nagorny, P. Tetrahedron
2013, 69, 5719. (d) Mensah, E.; Camasso, N.; Kaplan, W.;
Nagorny, P. Angew. Chem. Int. Ed. 2013, 52, 13939. (e) Borovika,
A.; Tang, P.-I.; Klapman, S.; Nagorny, P. Angew. Chem. Int. Ed.
2013, 52, 13424. (f) Bhattarai, B.; Tay, J.-H.; Nagorny, P. Chem.
Commun. 2015, 51, 5398. (g) Sun, Z.; Winschel, G. A.;
Zimmerman, P.; Nagorny, P. Angew. Chem. Int. Ed. 2014, 53,
11194.
(5) Tay, J. H.; Arguelles, A. J.; Nagorny, P. Org. Lett. 2015, 17, 3774.
(6) Korostylev, A.; Taranov, V. I.; Fischer, C.; Monsees, A.; Borner, A.
J. Org. Chem. 2004, 69, 3220.
(7) Klussmann, M.; Ratjen, L.; Hoffmann, S.; Wakchaure, V.;
Goddard, R.; List, B. Synlett 2010, 2189.
(8) Hanato, M.; Moriyama, K.; Maki, T.; Ishihara, K. Angew. Chem.
Int. Ed. 2010, 49, 3823.
(9) (a) Arnold, W.; Dly, J. J.; Imhof, R.; Kyburz, E. Tetrahedron Lett.
1983, 24, 343. (b) Wilen, S. H.; Qi, J. Z.; Williard, P. G. J. Org.
Chem. 1991, 56, 485.
(10) For selected examples, please read: (a) Omelańczuk, J.;
Mikolajczky, M. Tetrahedron: Asymmetry 1996, 7, 2687.
(b) Gunderson, K. G.; Shapiro, M. J.; Doti, R. A.; Skiles, J. W. Tet-
rahedron: Asymmetry 1999, 10, 3263. (c) Shapiro, M. J.;
Archinal, A. E.; Jarema, M. A. J. Org. Chem. 1989, 54, 5826.
(d) Ravard, A.; Crooks, P. A. Chirality 1996, 8, 295.
Acknowledgment
This work has been supported by the National Science Foundation
CAREER Award (CHE-1350060). P.N. is a Sloan Foundation Fellow. We
would like to thanks Prof. Sanford for the useful suggestion during the
preparation of this manuscript.
Supporting Information
(11) Wenzel, T. J.; Chisholm, C. D. Prog. Nucl. Magn. Reson. Spectrosc.
2011, 59, 1.
Supporting information for this article is available online at
(12) Meca, L.; Řeha, D.; Havlas, Z. J. Org. Chem. 2003, 68, 5677.
(13) Hoyano, Y. Y.; Pincock, R. E. Can. J. Chem. 1980, 58, 134.
(14) Albrow, V.; Biswas, K.; Crane, A.; Chaplin, N.; Easun, T.; Gladiali,
S.; Lygo, B.; Woodward, S. Tetrahedron: Asymmetry 2003, 14,
2813.
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References and Notes
(1) Selected reviews: (a) Akiyama, T. Chem. Rev. 2007, 107, 5744.
(b) Doyle, A. G.; Jacobsen, E. N. Chem. Rev. 2007, 107, 5713.
(c) Yamamoto, H.; Boxer, M. Chimia 2007, 61, 279.
(15) General Procedures for the NMR Discrimination Experi-
ments
Nonracemic CPA (10 mg) was mixed with discriminating agent
(1.5 equiv) in CDCl3 (0.6 mL) in NMR tubes (all CPA was washed
with 6 N HCl prior to analysis). The 31P spectrum of the mixture
was measured using a Varian VNRMS 700.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 551–554