Organic Letters
Letter
S.; Crochard, J.-P.; Fradet, D.; Jackman, H.; Luan, A.; Madigan, E.;
McDowall, N.; Meldrum, K.; Gordon, C. M.; Widegren, M.; Yeo, S.
The Development of a Practical Multikilogram Synthesis of the Chiral
β-Amino Acid Imagabalin Hydrochloride (PD-0332334) via Asym-
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(c) Benhaim, C.; Bouchard, L.; Pelletier, G.; Sellstedt, J.; Kristofova,
L.; Daigneault, S. Enantioselective Synthesis of β-Trifluoromethyl α-
Amino Acids. Org. Lett. 2010, 12, 2008. (d) Zhang, Z.; Hu, Q.; Wang,
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Stereodivergent Synthesis of Non-Symmetric β,β-Diaryl-α-Amino
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H.; Zhang, X. Highly Enantioselective Hydrogenation of o-Alkoxy
Tetrasubstituted Enamides Catalyzed by a Rh/(R,S)-JosiPhos Catalyst.
Org. Lett. 2015, 17, 1842. (g) Zhang, Z.; Wang, J.; Li, J.; Yang, F.; Liu,
G.; Tang, W.; He, W.; Fu, J.-J.; Shen, Y.-H.; Li, A.; Zhang, W.-D. Total
Synthesis and Stereochemical Assignment of Delavatine A. Rh-
Catalyzed Asymmetric Hydrogenation of Indene-Type Tetrasubsti-
tuted Olefins and Kinetic Resolution through Pd-Catalyzed Triflamide-
Directed C−H Olefination. J. Am. Chem. Soc. 2017, 139, 5558.
(h) Kraft, S.; Ryan, K.; Kargbo, R. B. Recent Advances in Asymmetric
Hydrogenation of Tetrasubstituted Olefins. J. Am. Chem. Soc. 2017,
139, 11630. (i) Guan, Y.-Q.; Gao, M.; Deng, X.; Lv, H.; Zhang, X.
Rhodium-catalyzed asymmetric hydrogenation of tetrasubstituted β-
acetoxy-α-enamido esters and efficient synthesis of droxidopa. Chem.
Commun. 2017, 53, 8136. (j) Li, C.; Wan, F.; Chen, Y.; Peng, H.; Tang,
W.; Yu, S.; McWilliams, J. C.; Mustakis, J.; Samp, L.; Maguire, R. J.
Stereoelectronic Effects in Ligand Design: Enantioselective Rhodium-
Catalyzed Hydrogenation of Aliphatic Cyclic Tetrasubstituted
Enamides and Concise Synthesis of (R)-Tofacitinib. Angew. Chem.,
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T. J.; Kwong, F. Y.; Kok, S. H. L.; Lee, H. W.; Chan, A. S. C.
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a free N−H group for the synthesis of β-amino acid derivatives. Proc.
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Leon, T.; Doran, S.; Etayo, P.; Vidal-Ferran, A.; Riera, A.; Verdaguer, X.
Primary and Secondary Aminophosphines as Novel P-Stereogenic
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9452. (c) Cristobal-Lecina, E.; Etayo, P.; Doran, S.; Reves, M.; Martin-
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C. H. Novel and Efficient Chiral Bisphosphorus Ligands for Rhodium-
Catalyzed Asymmetric Hydrogenation. Org. Lett. 2010, 12, 1104.
(f) Chen, C.; Wen, S.; Geng, M.; Jin, S.; Zhang, Z.; Dong, X.-Q.; Zhang,
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(14) (a) Burk, M. J.; Casy, G.; Johnson, N. B. A Three-Step Procedure
for Asymmetric Catalytic Reductive Amidation of Ketones. J. Org.
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(15) Chi, Y.; Tang, W.; Zhang, X. In Modern Rhodium-Catalyzed
Organic Reactions; Evans, P. A., Ed.; Wiley-VCH: Weinheim, 2005;
Chapter 1, pp 1−31.
(8) Mansell, S. M. Catalytic applications of small bite-angle
diphosphorus ligands with single-atom linkers. Dalton Trans 2017,
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(9) We previously prepared compound (R)-2 by the reaction of (S)-1
with paraformaldehyde in the presence of sodium hydride.10 While the
method provided the product in high yield (95%), we herein used n-
butyllithium in place of sodium hydride with a view to obtaining (R)-2
in an industrial scale.
(10) Imamoto, T.; Horiuchi, Y.; Hamanishi, E.; Takeshita, S.; Tamura,
K.; Sugiya, M.; Yoshida, K. Utilization of optically active secondary
phosphine−boranes: synthesis of P-chiral diphosphines and their
enantioinduction ability in rhodium-catalyzed asymmetric hydro-
genation. Tetrahedron 2015, 71, 6471.
(11) In regard to air-stable property, BulkyP* resembles tri(1-
adamantyl)phosphine, which is a crystalline solid and subjected to
negligible air-oxidation even over a period of three months. (a) Chen,
L.; Ren, P.; Carrow, B. P. Tri(1-adamantyl)phosphine: Expanding the
Boundary of Electron-Releasing Character Available to Organo-
phosphorus Compounds. J. Am. Chem. Soc. 2016, 138, 6392.
(b) Carrow, B. P.; Chen, L. Tri(1-adamantyl)phosphine: Exceptional
Catalytic Effects Enabled by the Synergy of Chemical Stability,
Donicity, and Polarizability. Synlett 2017, 28, 280.
(12) For selected papers dealing with Rh-catalyzed asymmetric
hydrogenation of tetrasubstituted alkenes, see: (a) Burk, M. J.; Gross,
M. F.; Martinez, J. P. Asymmetric Catalytic Synthesis of β-Branched
Amino Acids via Highly Enantioselective Hydrogenation Reactions. J.
Am. Chem. Soc. 1995, 117, 9375. (b) Sawamura, M.; Kuwano, R.; Ito, Y.
Enantioselective Hydrogenation of β-Disubstituted α-Acetamidoacry-
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Chiral Phosphine Ligands. J. Am. Chem. Soc. 1995, 117, 9602. (c) Roff,
G. J.; Lloyd, R. C.; Turner, N. J. A Versatile Chemo-Enzymatic Route to
Enantiomerically Pure β-Branched α-Amino Acids. J. Am. Chem. Soc.
2004, 126, 4098. (d) Benhaim, C.; Bouchard, L.; Pelletier, G.; Sellstedt,
J.; Kristofova, L.; Daigneault, S. Enantioselectiove Synthesis of β-
Trifluoromethyl α-Amino Acids. Org. Lett. 2010, 12, 2008.
(16) Li, Tang, Senanayake, and their coworkers reported that N-(1-(4-
bromophenyl)vinyl)acetamide was hydrogenated quantitatively in the
presence of MeO-BIBOP-Rh catalyst (S/C = 200 000) under 300 psi
H2 pressure at 25−30 °C for 40 h to give the corresponding product
with 90.6% ee: Li, W.; Rodriguez, S.; Duran, A.; Sun, X.; Tang, W.;
Premasiri, A.; Wang, J.; Sidhu, K.; Patel, N. D.; Savoie, J.; Qu, B.; Lee,
H.; Haddad, N.; Lorenz, J. C.; Nummy, L.; Hossain, A.; Yee, N.; Lu, B.;
Senanayake, C. H. The P-Chiral Phosphane Ligand (MeO-BIBOP) for
Efficient and Practical Large-Scale Rh-Catalyzed Asymmetric Hydro-
genation of N-Acetyl Enamides with High TONs. Org. Process Res. Dev.
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(17) (a) Zupancic, B.; Mohar, B.; Stephan, M. Heavyweight “R-SMS-
Phos” Ligands in the Olefins’ Hydrogenation Arena. Org. Lett. 2010, 12,
1296. (b) Sieber, J. D.; Rodriguez, S.; Frutos, R.; Buono, F.; Zhang, Y.;
Li, N.; Qu, B.; Premasiri, A.; Li, Z.; Han, Z. S.; Xu, Y.; Byrne, D.;
Haddad, N.; Lorenz, J.; Grinberg, N.; Kurouski, D.; Lee, H.; Narayanan,
B.; Nummy, L.; Mulder, J.; Brown, J. D.; Granger, A.; Gao, J.; Krawiec,
M.; Williams, Z.; Pennino, S.; Song, J. J.; Hossain, A.; Yee, N. K.;
Busacca, C.; Roschangar, F.; Xin, Y.; Mao, Z.; Zhang, X.; Hong, Y.;
Senanayake, C. H. Development of a Scalable, Chromatography-Free
Synthesis of t-Bu-SMS-Phos and Application to the Synthesis of an
Important Chiral CF3-Alcohol Derivative with High Enantioselectivity
Using Rh-Catalyzed Asymmetric Hydrogenation. J. Org. Chem. 2018,
83, 1448.
́
(e) Molinaro, C.; Scott, J. P.; Shevlin, M.; Wise, C.; Menard, A.;
Gibb, A.; Junker, E. M.; Lieberman, D. Catalytic, Asymmetric, and
E
Org. Lett. XXXX, XXX, XXX−XXX