Letter pubs.acs.org/acscatalysis
Cyclobutadiene Metal Complexes: A New Class of Highly Selective Catalysts. An Application to Direct Reductive Amination Oleg I. Afanasyev, Alexey A. Tsygankov, Dmitry L. Usanov,§ Dmitry S. Perekalin, Nikita V. Shvydkiy, Victor I. Maleev, Alexander R. Kudinov, and Denis Chusov* Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow 119991, Russia S Supporting Information *
ABSTRACT: A catalyst of a new type, cyclobutadiene complex [(C4Et4)Rh(p-xylene)]PF6, was found to promote selective reductive amination in the presence of carbon monoxide under mild conditions (1−3 bar, 90 °C). The reaction demonstrated perfect compatibility with a wide range of functional groups prone to reduction by conventional reducing agents. The developed system represents the first systematic investigation of cyclobutadiene metal complexes as catalysts. KEYWORDS: rhodium, cyclobutadiene, reductive amination, homogeneous catalysis, chemoselectivity, amines
S
ince the discovery of ferrocene in 1951,1 sandwich and halfsandwich complexes with cyclopentadienyl ligands have been extensively utilized in catalysis.2 Owing to its electronic and steric properties, the cyclopentadienyl ligand provides effective stabilization of the catalytic species3 and in many cases allows precise tuning of the catalytic activity. At the same time, substantially less attention has been paid to other types of cyclic π-ligands. For instance, catalytic applications of cyclobutadiene analogues so far have been restricted to their use as intact planar chiral moieties in ligands for palladium and platinum.4 Surprisingly, despite the interesting electronic properties of cyclobutadiene ligands, cyclobutadiene metal complexes have never been used as catalysts themselves. In 2014, Chusov and List reported a novel approach to reductive condensation processes.5 It was found that reductive amination of aldehydes and ketones with primary and secondary amines can proceed without any external hydrogen source and requires only carbon monooxide as a deoxygenative agent and Rh2(OAc)4 as a catalyst. The developed system was notable for favorable green chemistry metrics, such as Efactors.6 Subsequent studies revealed that the concept could be applied not only to reductive amination7,8 but also to reductive Knoevenagel condensation.9 No requirement for an external hydrogen source rendered CO-assisted reductive condensations potentially suitable for substrates which are not compatible with standard reductants, such as dihydrogen or hydrides. However, the substrate scope investigations of the reported studies5,7−9 did not involve systematic screening of potentially labile functional groups, and therefore, one of the key potential advantages of the developed paradigm remained unexplored. Moreover, the state-of-the-art methodology of CO-assisted reductive amination still required high pressures (20−90 bar) and temperatures (120−140 °C).5 © 2016 American Chemical Society
In all reported systems, the catalytic species were generated from simple inorganic salts without introduction of any ligands.5,7−9 Therefore, we envisioned that metal complexes could be fundamentally superior catalysts for CO-mediated reductive condensations, which would be active at pressures compatible with standard laboratory equipment and would tolerate a broad range of functional groups. Herein we report a new type of catalyst, namely, rhodium cyclobutadiene complex 1 (Figure 1). We found complex 1 to be especially well-matched for reductive amination, which
Figure 1. Conventional rhodium catalysts and the catalyst of a new type (1). Received: December 21, 2015 Revised: February 8, 2016 Published: February 11, 2016 2043
DOI: 10.1021/acscatal.5b02916 ACS Catal. 2016, 6, 2043−2046
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ACS Catalysis
not undergo ligand exchange reactions and therefore are catalytically inactive. We managed to synthesize the first cyclobutadiene-arene rhodium complex [(C4Et4)Rh(p-xylene)]PF6 (1) in just one step from commercially available starting materials: complex 2c, silver hexafluorophosphate, 3-hexyne, and p-xylene. The complex is air-stable and is robust enough to be compatible even with 50% aqueous sulfuric acid. The p-xylene ligand in 1 is readily replaced by two-electron ligands, such as CO or amine, generating catalytically active species [(C4Et4)RhLx].12 To our delight, in the presence of complex 1, the model reaction of panisidine with p-methylbenzaldehyde reached 74% conversion over 6 h under mild conditions (3 bar of CO, 90 °C; Table 1, entry 6). The amount of the catalyst could be reduced to 0.05 mol % provided that the reaction time was increased up to 100 h (Table 1, entries 7−8). These results demonstrated that the catalytic species generated from complex 1 is robust enough to achieve turnover numbers of at least 1300. Solvent screening (see Supporting Information) demonstrated that reactions conducted in aprotic solvents (except THF and dioxane) gave low yields of the product. Whereas the process was sluggish in water, reactions in various alcohols proceeded in good yields.13 Despite the fact that tert-butanol showed the highest yield of the model reaction, we chose ethanol as a solvent for further screening for reasons of convenience. Importantly, the reaction is fast enough under low pressure (3 bar) which enables the use of Schlenk glassware instead of autoclaves. Moreover, complex 1 was found to be active even at atmospheric pressure of CO (see Supporting Information). Notably, the amount of carbon monoxide used in the described experiments did not exceed 1.5 equiv, which is advantageous in comparison with reductants conventionally used in large excess. With the optimized conditions in hand, we proceeded to investigation of the substrate scope of the developed methodology (Scheme 2). A wide range of aldehydes could be successfully employed, including variously substituted aromatic (3a, 3b), heteroaromatic (3c), and aliphatic (3d) substrates, which underwent reductive amination in 70−83% isolated yields. The method was also perfectly applicable to ketones (3e) and secondary amines (3f). Notably, a free phenol group was shown to be suitable for this reaction; product 3g was isolated in 75% yield. We were particularly interested in screening the developed catalytic system with the substrates containing functional groups which often appear to be unstable under reductive conditions. To our delight, high yields were obtained for the products containing such functional groups as carboxybenzyl (3j), trifluoroacetamido- (3k), aromatic cyano(3h), aromatic bromo- (3i), and even aromatic nitro-group (3l). The lowered yield of product 3l (60%) is due to crystallization of the corresponding Schiff base from the reaction mixture (the nitro-group stays intact under the reaction conditions). Table 2 compares compatibility of a range of synthetically important functional groups with a number of common reducing conditions, including the catalytic methodology reported herein. Whereas the lability of functional groups is certainly substrate- and condition-dependent, the general trends clearly demonstrate the unique synthetic utility of the new catalytic system. We were interested in the comparison of the developed methodology with complex hydrides of high functional group tolerance which are conventionally used for reductive
enabled highly selective synthesis of amines with reductively labile functional groups (Scheme 1). The developed system represents the first general application of cyclobutadiene metal complexes as catalysts. Scheme 1. Comparison of the Catalyst Described Herein with the Best Reported System for CO-Mediated Reductive Amination
We began our studies by testing some commonly used rhodium catalysts in the model reductive amination reaction between p-anisidine and p-methylbenzaldehyde under substantially milder conditions than those previously reported (3 bar of CO, 90 °C, 6 h).5 Rh(III) complexes 2a and 2b did not show any catalytic activity (Table 1, entries 1−2). On the other hand, Table 1. Screening of Rhodium Complexes as Catalysts for Reductive Aminationa
entry b
1 2b 3b 4b 5b 6b 7c 8c
catalyst
catalyst loading, [mol %]
yield 3, [%]
2a 2b 2c 2d 2e 1 1 1
0.25 0.5 0.25 0.25 0.2 0.5 0.05 0.1
trace trace 6 trace trace 74 67 93
a
Yields were determined by NMR. bHNR1R2 = p-anisidine (1.2 equiv). cHNR1R2 = 1.0 eq of dibenzylamine, 100 h reaction time.
Rh(I) complex [(C2H4)2RhCl]2 (2c) gave product 3a in 6% yield (Table 1, entry 3). Superior performance of 2c can be attributed to the lower oxidation state of rhodium, which is more favorable for the oxidative addition step of the plausible catalytic cycle. Yet, low activity of 2c can be explained by fast dissociation of the ethylene ligands followed by aggregation of nonstabilized RhCl species. We therefore tested Rh(I) complexes 2d and 2e with less labile ligands; however, no catalytic activity was detected (Table 1, entries 4−5). At this point, we decided to design a new type of Rh(I) catalyst with a carefully tuned cyclic π-ligand, which would effectively stabilize the metal center during the catalytic cycle.3 In our efforts to maintain low oxidation state of rhodium, neutral cyclobutadiene ligand appeared to be the best choice. Despite the wide application of rhodium complexes with cyclopentadienyl ligands,10 their cyclobutadiene analogues are almost unexplored. Several sandwich compounds of general formulas CpRh(C4R4) and Cp*Rh(C4R4) have been prepared by reactions of alkynes with CpRh(CO)2, [Cp*RhCl2]2, or similar rhodium precursors.11 However, these compounds do 2044
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in light of ecological and economic impacts. For instance, pHsensitive sodium cyanoborohydride reductions require preparatively inconvenient workup and specialized disposal of highly toxic water-soluble reaction products,14 whereas sodium triacetoxyborohydride generates even larger amounts of waste and is unstable in protic solvents.15 Notably, the average Efactors6 of CO-assisted catalytic preparation of Scheme 2 products are almost 2-fold and 5-fold lower than those for NaBH3CN and NaBH(OAc)3, respectively (0.18 vs 0.32 and 0.92, if counted for stoichiometric ratios). Also, for an arbitrarily chosen subset of substrates from Scheme 2, we observed considerably higher yields of the desired products using our system (88−98% yields by NMR analysis) vs sodium cyanoborohydride (33−68%, see Supporting Information), which is an inspiring example of the highly selective nature of the developed catalyst. Excellent performance of catalyst 1 together with the atom-economical profile is promising for semi-industrial and industrial applications. In summary, we discovered a catalyst of a new type with unique activity and selectivity. The use of complex 1 enabled development of an unusually mild protocol for direct reductive amination, which is compatible with a wide range of functional and protective groups, including those conventionally unstable under reductive conditions. A representative set of functionalized amines was synthesized in 70−90% isolated yields. In contrast to the best-performing method of CO-mediated reductive amination reported to date,5 the developed catalytic system is active at a CO pressure compatible with standard laboratory glassware, such as Schlenk tubes. We believe that cyclobutadiene complexes of rhodium and other metals have a great potential in other types of reactions; studies in these directions are currently ongoing in our group and will be reported in due course.
Scheme 2. Substrate Scope Studies of Reductive Amination Catalyzed by Complex 1a
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a
NMR yields and isolated yields (in parentheses). Cyan circles highlight the functional groups which are poorly compatible with conventional reducing agents. [a] See text.
ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acscatal.5b02916. Experimental methods, optimization of reaction conditions, and other supplemental data (PDF)
Table 2. Generalized Comparison of Functional and Protective Group Stability under Reductive Conditions
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AUTHOR INFORMATION
Corresponding Author
*E-mails for D.C.:
[email protected]; denis.chusov@gmail. com. Present Address §
(D.L.U.) Department of Chemistry and Chemical Biology, Harvard University 12 Oxford Street, Cambridge, MA 02138, United States Notes [a]
The authors declare no competing financial interest.
amination, namely, sodium cyanoborohydride (NaBH3CN) and sodium triacetoxyborohydride (NaBH(OAc)3). Whereas the convenience of these reagents on a small laboratory scale is evident and widely exploited, a large number of disadvantages render these reagents highly inconvenient for scaled-up synthesis and barely compatible with industrial manufacturing
ACKNOWLEDGMENTS We thank Prof. Valentine Ananikov for his support. Highresolution mass spectra were recorded in the Department of Structural Studies of Zelinsky Institute of Organic Chemistry, Moscow. We thank the Russian Foundation for Basic Research (grant no. 15-03-02548A) and the Council of the President of the Russian Federation (grant for young scientists no. MK6137.2015.3) for financial support. D.S.P. thanks the Council of the President of the Russian Federation (grant for young scientists no.MK-6254.2016.3.
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ref 16. [b]this work. [c]ref 17. [d]ref 18; however, reduction of nitriles with NaBH4 is known (ref 17). [e]ref 19. Ar−Br bond is stable at room temperature but is reduced by LiAlH4 at elevated temperature (ref 21). [f]ref 20. [g]ref 22. [h]ref 23. [i]ref 24. [j]ref 25.
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DEDICATION Dedicated to Professor Benjamin List on the occasion of his 47th birthday.
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