Letter pubs.acs.org/OrgLett
Rh/SPO-WudaPhos-Catalyzed Asymmetric Hydrogenation of α‑Substituted Ethenylphosphonic Acids via Noncovalent Ion-Pair Interaction Xuguang Yin,† Caiyou Chen,† Xiong Li,† Xiu-Qin Dong,*,† and Xumu Zhang*,†,‡ †
College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, Hubei 430072, P. R. China Department of Chemistry, South University of Science and Technology of China, Shenzhen, Guangdong 518055, P. R. China
‡
S Supporting Information *
ABSTRACT: Asymmetric hydrogenation of α-substituted ethenylphosphonic acids has been successfully achieved by Rh/ ferrocenyl chiral bisphosphorus ligand (SPO-Wudaphos) through noncovalent ion-pair interaction between the substrate and catalyst under mild reaction conditions without base. A series of chiral phosphonic acids were obtained with excellent results (up to 98% ee, >99% conversion, 2000 TON). Moreover, the control experiments showed that the noncovalent ion-pair interaction was critical in this asymmetric hydrogenation. Scheme 1. Synthesis of of Chiral α-Substituted Ethylphosphonic Acids via Asymmetric Hydrogenation
T
he utilization of attractive noncovalent interactions between catalyst and substrate to improve reaction reactivity and selectivity has emerged as an important strategy in the field of catalysis.1 Similar to enzymatic catalysis, noncovalent interactions play an important role not only in the rate acceleration, through lowering the kinetic energy barrows, but also in stereoselectivity improvement by suppressing the degree of freedom in the transition state.2 As one of the most common interaction modes, noncovalent ionpair interaction has been widely applied in asymmetric catalysis,3 including asymmetric allylic alkylation,4 asymmetric Griganard cross-coupling,5 asymmetric aldol reaction,6 asymmetric hydrogenation,7 asymmetric Diels−Alder reaction,8 and others.9 Chiral α-substituted ethylphosphonic acids have received considerable attention in bioorganic and medicinal chemistry.10 Owing to their great significance, much effort was devoted to developing synthetic methodologies to approach them. Several methods for the preparation of optically active α-substituted ethylphosphonic acids, including the enantioselective methylation of benzylphosphonic acid derivatives bearing chiral auxiliaries11 and the photo-Arbuzov rearrangement of optically active 2-(1-phenylethoxy)-1,3,2-dioxaphosphorinanes,12 have been reported during the past decades. Catalytic asymmetric hydrogenation of α-substituted ethenylphosphonic acids was regarded as one of the most straightforward and efficient methods to access chiral α-substituted ethylphosphonic acids. However, little research work involved the asymmetric hydrogenation of α,β-unsaturated phosphonic acids.13 In 2001, Genet et al. reported Ru-catalyzed asymmetric hydrogenation of α,β-unsaturated phosphonic acids to prepare optically active 1-arylethylphosphonic acids (Scheme 1a).14 However, this hydrogenation required vigorous conditions and gave only moderate enantioselectivities. Ding et al. reported © XXXX American Chemical Society
excellent asymmetric hydrogenation of α-substituted ethenylphosphonic acids catalyzed by Rh/chiral SPO ligands15 providing various chiral α-aryl and α-alkyl ethylphosphonic acids with excellent enantioselectivities (Scheme 1b).16 Received: July 10, 2017
A
DOI: 10.1021/acs.orglett.7b02098 Org. Lett. XXXX, XXX, XXX−XXX
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Organic Letters
hydrogenation in the presence of NEt3. Poor to moderate results were obtained (39%−81% ee, 20%−>99% conversions, Table 1, entries 1−4). To our delight, Wudaphos L1−L3 and SPO-Wudaphos L4−L5 ligands developed by our group most recently (Figure 1) promoted this transformation completely in the absence of NEt3 (Table 1, entries 5−9). The structure of these ligands had a great effect on the enantioselectivities. Moderate to good enantioselectivities were observed with Wudaphos L1−L2 when the R1 group of phosphorus atom was changed from a phenyl group to a cyclohexyl group (75−88% ee, Table 1, entries 5 and 6). When the R2 group of phosphorus atom was switched from methyl group to phenyl group, poor enantioselectivity was afforded (11% ee, Table 1, entry 7). We can obtain excellent enantioselectivities using SPO-Wudaphos L4 and L5 (92−93% ee, Table 1, entries 8 and 9). Therefore, the best ligand for the asymmetric hydrogenation of αphenylethenylphosphonic acid 1a is SPO-Wudaphos L4.
Although great progress has been made, the development of a new catalytic system to construct chiral ethylphosphonic acids is still worthy of achieving. Based on our previous investigation of ferrocenyl chiral bisphosphorus ligands Wudaphos and SPOWudaphos in the application of asymmetric hydrogenation of unsaturated acids via noncovalent ion pair interaction,17 we herein successfully introduce this interaction in the asymmetric hydrogenation of 2-substituted ethenylphosphonic acids under base-free and mild conditions, providing various chiral phosphonic acids with excellent enantioselectivities for the first time (Scheme 1). We began our initial investigation of Rh-catalyzed asymmetric hydrogenation of α-substituted ethenylphosphonic acids by evaluating ligand effects using α-phenylethenylphosphonic acid 1a as a model substrate with 1.0 mol % of catalysts under a pressure of 30 atm H2 in MeOH at room temperature for 12 h (Table 1). Several important bisphosphine ligands such as (S)Table 1. Screening Ligands for the Asymmetric Hydrogenation of α-Phenylethenylphosphonic Acid 1aa
entry
ligands
additive
conv (%)b
ee (%)c
1 2 3 4 5 6 7 8 9
(S)-Binap (RC, SP)-Duanphos (S)-Segphos (S)-Binapine L1 L2 L3 L4 L5
NEt3 NEt3 NEt3 NEt3 none none none none none
99 99 99 20 >99 >99 >99 >99 >99
81 39 63 62 75 88 11 93 92
Table 2. Screening Solvents for the Asymmetric Hydrogenation of α-Phenylethenylphosphonic Acids 1aa
a
All reactions were carried out with a substrate/catalyst ratio of 100:1 at room temperature under 30 atm of H2 pressure for 12 h, 0.2 mmol of 1a, 1.0 equiv of NEt3, and 1.0 mL of MeOH. bDetermined by 1H NMR spectroscopy. cThe ee value was determined by the methyl ester by HPLC on a chiral phase.
entry
solvent
convb (%)
eec (%)
1 2 3 4 5 6 7 8 9 10 11d
MeOH EtOH i PrOH TFE THF CH2Cl2 CHCl3 1,4-dioxane ethyl acetate toluene EtOH
>99 >99 >99 >99 >99 >99 99 >99 99
93 96 95 91 94 85 57 77 87 45 96
a
Binap, (RC, SP)-Duanphos, (S)-Segphos, and (S)-Binapine (Figure 1) were applied in this Rh-catalyzed asymmetric
All reactions were carried out with a substrate/catalyst ratio of 100:1 at room temperature under 30 atm of hydrogen pressure for 12 h, 0.2 mmol of 1a, and 1.0 mL of solvent. bDetermined by 1H NMR spectroscopy. cThe ee value was determined by the methyl ester by HPLC on a chiral phase. d0.5 mol % of catalyst, 10 atm of H2, 6 h.
Figure 1. Structure of phosphine ligands for this asymmetric hydrogenation.
Subsequently, we turned our attention to inspect the solvent effect (Table 2). Alcoholic solvents, such as MeOH, EtOH, i PrOH, and trifluoroethanol (TFE), displayed both high reactivities and excellent enantioselectivities (>99% conversions, 91−96% ee, Table 2, entries 1−4). Moderate to good enantioselectivities were provided in THF, CH2Cl2, 1,4dioxane, and ethyl acetate (>99% conversion, 77−94% ee, Table 2, entries 5, 6, 8, and 9). Trace conversions and poor enantioselectivities were obtained when chloroform (CHCl3) and toluene were used as solvents (99% conversion, 96% ee, Table 2, entry 2). Furthermore, when this reaction was performed with catalyst loading of 0.5 mol % under 10 atm of H2 at room temperature for 6 h, the same result was provided (>99% conversion, 96% ee, Table 2, entry 11 vs entry 2). With the optimized conditions in hand, a series of αsubstituted ethenylphosphonic acids were hydrogenated to explore the substrate scope. These results are summarized in B
DOI: 10.1021/acs.orglett.7b02098 Org. Lett. XXXX, XXX, XXX−XXX
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the model substrate. As shown in Scheme 3, the desired hydrogenation product 2a was obtained with 95% yield and 92% ee.
Scheme 2. The electric property and position of the substituent groups on the phenyl group of the substrates had little influence Scheme 2. Scope Study for the Asymmetric Hydrogenation of α-Substituted Ethenylphosphonic Acids 1Catalyzed by Rh/SPO-Wudaphosa,b
Scheme 3. High TON Experiment for Asymmetric Hydrogenation of 1a
In order to investigate the important role of ion-pair noncovalent interaction, the asymmetric hydrogenation of 1phenylethenylphosphonate 316 was conducted under the optimized conditions. No reaction was observed in this transformation (Scheme 4a). Moreover, poor reaction results Scheme 4. Control Experiments for the Investigation the Ion-Pair Noncovalent Interaction Effect
were obtained when 0.5 equiv of Cs2CO3 and 1.0 equiv of NEt3 were added in the asymmetric hydrogenation of α-phenylethenylphosphonic acid 1a (Scheme 4b). These results demonstrated that the ion-pair noncovalent interaction between the ligand and ethenylphosphonic acid substrate played an important role in achieving high reactivity and excellent enantioselectivity. In conclusion, we successfully developed Rh-catalyzed asymmetric hydrogenation of α-aryl and α-alkyl ethenylphosphonic acids using chiral SPO-Wudaphos ligand without base under mild reaction conditions via a noncovalent ion-pair interaction activation strategy. A series of chiral α-substituted ethenylphosphonic acids were obtained in full conversions with excellent enantioselectivities (93−98% ee). Importantly, control experiments showed that the attractive noncovalent ion-pair interaction between the ligand and ethenylphosphonic acid substrates played a critical role in achieving high reactivity and excellent enantioselectivity in this asymmetric hydrogenation.
a
All reactions were performed with 0.2 mmol of substrate/[Rh(NBD)2]BF4/ligand = 1/0.005/0.0055 at room temperature under 10 atm H2 in 1.0 mL of EtOH for 6 h. Conversion was determined by 1 HNMR spectroscopy. Isolated yields. The ee values were determined by the corresponding methyl ester by HPLC or GC on a chiral column. bS/C = 100.
on both the reactivity and enantioselectivity. The substrates bearing electron-donating groups (1b−g) and electron-withdrawing groups (1h−j) on the phenyl ring proceeded smoothly with excellent results (>99% conversions, 93−97% ee). Moreover, the 6-methoxyl-2-naphthyl (1k) substituted ethenylphosphonic acid was hydrogenated well with full conversion and 96% ee. In addition, α-alkyl-substituted substrates cyclohexyl (1l) and benzoyloxyl (1m) ethenylphosphonic acids also converted efficiently into the corresponding α-alkyl ethylphosphonic acids products with excellent enantioselectivities (>99% conversion, 98% ee). However, the trisubstituted substrate (E)-(1-phenylprop-1-en-1-yl)phosphonic acid (1n) was hydrogenated with only 40% conversion and 28% ee under the optimized conditions. Our catalyst still shows high reactivity and excellent enantioselectivity in this asymmetric hydrogenation with a low catalyst loading of 0.05 mol % (S/C = 2000) using 1a as
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ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.7b02098. Experimental details and characterization data (PDF) C
DOI: 10.1021/acs.orglett.7b02098 Org. Lett. XXXX, XXX, XXX−XXX
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AUTHOR INFORMATION
Corresponding Authors
*E-mail:
[email protected]. *E-mail:
[email protected]. ORCID
Xumu Zhang: 0000-0001-5700-0608 Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS We thank the grant support of the Important Sci-Tech Innovative Project of Hubei Province (2015ACA058), the National Natural Science Foundation of China (Grant Nos. 21372179, 21432007, and 21502145), and the Natural Science Foundation of Hubei Province (Grant No. 2016CFB449).
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DOI: 10.1021/acs.orglett.7b02098 Org. Lett. XXXX, XXX, XXX−XXX
