Secondary Orbital Effect Involving Fluorine is Responsible for Substrate-Controlled Diastereodivergence in the Catalyzed syn-aza-Henry Reaction of α-Fluoronitroalkanes
Ivor Smajlagic
Department of Chemistry, Brock University, 1812 Sir Isaac Brock Way, St., Catharines, ON L2S 3A1 Canada
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Prof. Dr. Jeffrey N. Johnston
Department of Chemistry and Institute of Chemical Biology, Vanderbilt University Nashville, Tennessee, 37235 USA
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Prof. Dr. Travis Dudding
Department of Chemistry, Brock University, 1812 Sir Isaac Brock Way, St., Catharines, ON L2S 3A1 Canada
Search for more papers by this authorIvor Smajlagic
Department of Chemistry, Brock University, 1812 Sir Isaac Brock Way, St., Catharines, ON L2S 3A1 Canada
Search for more papers by this authorCorresponding Author
Prof. Dr. Jeffrey N. Johnston
Department of Chemistry and Institute of Chemical Biology, Vanderbilt University Nashville, Tennessee, 37235 USA
Search for more papers by this authorCorresponding Author
Prof. Dr. Travis Dudding
Department of Chemistry, Brock University, 1812 Sir Isaac Brock Way, St., Catharines, ON L2S 3A1 Canada
Search for more papers by this authorGraphical Abstract
Evidence for a secondary orbital interaction between fluorine and a hydrogen-bond-activated azomethine (C=N) is found to be a driving force for fluorine-induced diastereodivergence observed in a rare syn-selective aza-Henry reaction. This study examines BAM catalysis in detail, but the phenomenon is expected to be more general given similar observations in enantioselective phase transfer catalysis.
Abstract
The fluorine atom is a powerful, yet enigmatic influence on chemical reactions. True to form, fluorine was recently discovered to effect diastereodivergence in an enantioselective aza-Henry reaction, resulting in a very rare case of syn-β-amino nitroalkane products. More bewildering was the observation of an apparent hierarchy of substituents within this substrate-controlled behavior: Ph>F>alkyl. These cases have now been examined comprehensively by computational methods, including both non-fluorinated and α-fluoro nitronate additions to aldimines catalyzed by a chiral bis(amidine) [BAM] proton complex. This study revealed the network of non-covalent interactions that dictate anti- (α-aryl) versus syn-selectivity (α-alkyl) using α-fluoronitronate nucleophiles, and an underlying secondary orbital interaction between fluorine and the activated azomethine.
Conflict of interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available in the supplementary material of this article.
Supporting Information
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References
- 1For reviews on the aza-Henry reaction see:
- 1aM. F. P. Ana, Current Organocatalysis 2016, 3, 222–242;
10.2174/2213337202666150908210627 Google Scholar
- 1bA. Noble, J. C. Anderson, Chem. Rev. 2013, 113, 2887–2939;
- 1cE. Marqués-López, P. Merino, T. Tejero, R. P. Herrera, Eur. J. Org. Chem. 2009, 2009, 2401–2420;
- 1dB. Westermann, Angew. Chem. Int. Ed. 2003, 42, 151–153;
Angew. Chem. 2003, 115, 161–163.
10.1002/ange.200390039 Google Scholar
- 2D. Lucet, T. Le Gall, C. Mioskowski, Angew. Chem. Int. Ed. 1998, 37, 2580–2627;
10.1002/(SICI)1521-3773(19981016)37:19<2580::AID-ANIE2580>3.0.CO;2-L CASPubMedWeb of Science®Google ScholarAngew. Chem. 1998, 110, 2724–2772.10.1002/(SICI)1521-3757(19981002)110:19<2724::AID-ANGE2724>3.0.CO;2-4 Google Scholar
- 3A. Y. Sukhorukov, A. A. Sukhanova, S. G. Zlotin, Tetrahedron 2016, 72, 6191–6281.
- 4B. M. Nugent, R. A. Yoder, J. N. Johnston, J. Am. Chem. Soc. 2004, 126, 3418–3419.
- 5A. Singh, J. N. Johnston, J. Am. Chem. Soc. 2008, 130, 5866–5867.
- 6D. Uraguchi, K. Koshimoto, T. Ooi, J. Am. Chem. Soc. 2008, 130, 10878–10879.
- 7Ketimine electrophiles in enantioselective aza-Henry reactions are far less common, but syn-selective variants are known: X. Wang, Y.-F. Chen, L.-F. Niu, P.-F. Xu, Org. Lett. 2009, 11, 3310–3313.
- 8T. J. Struble, I. Smajlagic, H. Foy, T. Dudding, J. N. Johnston, J. Org. Chem. 2021, 86, 15606–15617.
- 9
- 9aS. Handa, V. Gnanadesikan, S. Matsunaga, M. Shibasaki, J. Am. Chem. Soc. 2007, 129, 4900-++;
- 9bS. Handa, V. Gnanadesikan, S. Matsunaga, M. Shibasaki, J. Am. Chem. Soc. 2010, 132, 4925–4934.
- 10J. A. Bing, N. D. Schley, J. N. Johnston, Chem. Sci. 2022, 13, 2614–2623.
- 11
- 11aH. G. Adolph, M. J. Kamlet, J. Am. Chem. Soc. 1966, 88, 4761–4763;
- 11bB. A. Vara, J. N. Johnston, J. Am. Chem. Soc. 2016, 138, 13794–13797.
- 12The stabilizing effect of fluorine on other nitroalkane derivatives has also been studied: M. S. Crocker, H. Foy, K. Tokumaru, T. Dudding, M. Pink, J. N. Johnston, Chem 2019, 5, 1248–1264.
- 13
- 13aL. E. Zimmer, C. Sparr, R. Gilmour, Angew. Chem. Int. Ed. 2011, 50, 11860–11871; Angew. Chem. 2011, 123, 12062–12074;
- 13bC. Thiehoff, Y. P. Rey, R. Gilmour, Isr. J. Chem. 2017, 57, 92–100;
- 13cM. Aufiero, R. Gilmour, Acc. Chem. Res. 2018, 51, 1701–1710.
- 14For DFT studies of interesting fluorine effects on carbanion reactivity, see:
- 14aM. Suenaga, K. Nakata, J.-L. M. Abboud, M. Mishima, Bull. Chem. Soc. Jpn. 2017, 90, 289–297;
- 14bT. Kang, N. Kim, P. T. Cheng, H. Zhang, K. Foo, K. M. Engle, J. Am. Chem. Soc. 2021, 143, 13962–13970.
- 15D. Cahard, V. Bizet, Chem. Soc. Rev. 2014, 43, 135–147.
- 16
- 16aC. Ni, J. Hu, Chem. Soc. Rev. 2016, 45, 5441–5454;
- 16bT. Sugiishi, M. Matsugi, H. Hamamoto, H. Amii, RSC Adv. 2015, 5, 17269–17282;
- 16cW. Zhang, C. Ni, J. Hu, in Fluorous Chemistry (Ed.: I. T. Horváth), Springer Berlin Heidelberg, Berlin, Heidelberg, 2012, pp. 25–44.
- 17
- 17aS. Krautwald, E. M. Carreira, J. Am. Chem. Soc. 2017, 139, 5627–5639;
- 17bD. Uraguchi, K. Yoshioka, T. Ooi, Nat. Commun. 2017, 8, 14793;
- 17cX. Huo, G. Li, X. Wang, W. Zhang, Angew. Chem. Int. Ed., n/a, e202210086.
- 18
- 18aD. J. Sprague, J. N. Johnston, Org. Lett. 2020, 22, 8496–8499;
- 18bB. A. Vara, A. Mayasundari, J. C. Tellis, M. W. Danneman, V. Arredondo, T. A. Davis, J. Min, K. Finch, R. K. Guy, J. N. Johnston, J. Org. Chem. 2014, 79, 6913–6938;
- 18cT. A. Davis, A. E. Vilgelm, A. Richmond, J. N. Johnston, J. Org. Chem. 2013, 78, 10605–10616;
- 18dT. A. Davis, J. N. Johnston, Chem. Sci. 2011, 2, 1076–1079.
- 19E. Gomez-Bengoa, A. Linden, R. Lopez, I. Mugica-Mendiola, M. Oiarbide, C. Palomo, J. Am. Chem. Soc. 2008, 130, 7955–7966.
- 20Y. Xue, Y. Wang, Z. Cao, J. Zhou, Z.-X. Chen, Org. Biomol. Chem. 2016, 14, 9588–9597.
- 21L. Belding, S. M. Taimoory, T. Dudding, ACS Catal. 2015, 5, 343–349.
- 22B. Wang, T. Xu, L. Zhu, Y. Lan, J. Wang, N. Lu, Z. Wei, Y. Lin, H. Duan, Org. Chem. Front. 2017, 4, 1266–1271.
- 23Y. Xue, Y. Wang, Z. Cao, J. Zhou, Z.-X. Chen, Org. Biomol. Chem. 2016, 14, 9588–9597.
- 24J. He, D. Tang, C. Hu, Z. Su, Molecules 2021, 26, 1965.
- 25N. Yasukawa, A. Yamanoue, T. Takehara, T. Suzuki, S. Nakamura, Chem. Commun. 2022, 58, 1318–1321.
- 26B. Han, Q.-P. Liu, R. Li, X. Tian, X.-F. Xiong, J.-G. Deng, Y.-C. Chen, Chem. Eur. J. 2008, 14, 8094–8097.
- 27S. M. Taimoory, T. Dudding, J. Org. Chem. 2016, 81, 3286–3295.
- 28N. Lu, F. Bai, Y. Fang, Z. Wei, J. Cao, D. Liang, Y. Lin, H. Duan, Adv. Synth. Catal. 2017, 359, 4111–4116.
- 29C. A. Hunter, J. K. M. Sanders, J. Am. Chem. Soc. 1990, 112, 5525–5534.
- 30P. Li, J. M. Maier, E. C. Vik, C. J. Yehl, B. E. Dial, A. E. Rickher, M. D. Smith, P. J. Pellechia, K. D. Shimizu, Angew. Chem. Int. Ed. 2017, 56, 7209–7212;
Angew. Chem. 2017, 129, 7315–7318.
10.1002/ange.201702950 Google Scholar
- 31For an outline of Types 1–4, see Ref. [10].
- 32L. Kang, Y. Lin, Z. Gao, J. Zhang, H. Yang, J. Qian, Q. Peng, G. Jiang, CCS Chemistry 2021, 3, 1678–1689.
- 33See Supporting Information for additional details.
- 34During the preparation of this manuscript, a report documenting n(F)→π*(amide) interactions appeared: S. A. Harry, M. Kazim, P. M. Nguyen, A. Zhu, M. R. Xiang, J. Catazaro, M. Siegler, T. Lectka, Angew. Chem. Int. Ed. 2022, 61, e202207966.
- 35C. Reep, S. Sun, N. Takenaka, Asian J. Org. Chem. 2019, 8, 1306–1316.
- 36R. A. Cormanich, M. P. Freitas, C. F. Tormena, R. Rittner, RSC Adv. 2012, 2, 4169–4174.
- 37
- 37aP. A. Champagne, J. Desroches, J. F. Paquin, Synthesis 2015, 47, 306–322;
- 37bY. J.-S. Hao Yong-Jia, Zhou Ying, Wang Xin, Zhou Jian, Acta Chim. Sin. 2018, 76, 925–939.
- 38T. J. Auvil, A. G. Schafer, A. E. Mattson, Eur. J. Org. Chem. 2014, 2633–2646.
