Article Cite This: J. Am. Chem. Soc. 2017, 139, 18034−18043
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Catalytic Enantioselective Hetero-dimerization of Acrylates and 1,3Dienes Stanley M. Jing, Vagulejan Balasanthiran, Vinayak Pagar, Judith C. Gallucci, and T. V. RajanBabu* Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18th Avenue, Columbus, Ohio 43210, United States S Supporting Information *
ABSTRACT: 1,3-Dienes are ubiquitous and easily synthesized starting materials for organic synthesis, and alkyl acrylates are among the most abundant and cheapest feedstock carbon sources. A practical, highly enantioselective union of these two readily available precursors giving valuable, enantio-pure skipped 1,4diene esters (with two configurationally defined double bonds) is reported. The process uses commercially available cobalt salts and chiral ligands. As illustrated by the use of 20 different substrates, including 17 prochiral 1,3-dienes and 3 acrylates, this heterodimerization reaction is tolerant of a number of common organic functional groups (e.g., aromatic substituents, halides, isolated mono- and di-substituted double bonds, esters, silyl ethers, and silyl enol ethers). The novel results including ligand, counterion, and solvent effects uncovered during the course of these investigations show a unique role of a possible cationic Co(I) intermediate in these reactions. The rational evolution of a mechanism-based strategy that led to the eventual successful outcome and the attendant support studies may have further implications for the expanding use of low-valent group 9 metal complexes in organic synthesis.
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INTRODUCTION Studies aimed at the development of highly efficient and enantioselective methods for the preparation of various classes of organic compounds are among the most active areas of research in modern organic synthesis.1 Successful outcome of such research, especially when it involves catalytic reactions between readily available starting materials and feedstock carbon sources,2 can greatly impact the design, synthesis, and manufacture of molecules of interest from medicine to materials.3 Development of enantioselective versions of coupling reactions (hetero-dimerizations) between two different, stable alkenes for the synthesis of chiral intermediates has huge potential, yet presents significant challenges on two fronts, activation of the relatively unreactive molecules and selectivity (chemo-, regio-, and enantioselectivity) in the reactions between them.4 In this context, we have reported highly enantioselective hetero-dimerization between ethylene and activated alkenes using nickel catalysts (eq 1),5a and between ethylene and 1,3-dienes using cobalt catalysts (eq 2).6a,b While the reactions of ethylene are highly efficient and selective, and applicable for the syntheses of several biologically important molecules (e.g., 2-arylpropionic acids,7a steroid analogues,7b pseudopterosins,7c trikentrins7d), the utility of this reaction would be vastly enhanced if instead of ethylene a functionalized alkene such as methyl acrylate can be used. Even though acrylates are among the largest volume feedstocks (>2,000,000 t annual production), they are seldom used in catalytic enantioselective reactions, and, for known dimerization © 2017 American Chemical Society
reactions involving acrylates and other alkenes, the reported substrate scope, yields, and selectivities are somewhat limited.8 In the best example in the literature of an enantioselective codimerization of an alkyl acrylate and a diene, Hirano et al. reported obtaining 31% yield and 58% ee in the reaction between 1,2,3,4-tetramethylbutadiene and tert-butyl acrylate in the presence of 10 mol% of a Ru(0) complex. A less substituted butadiene gave mixture of three products (total yield 73%) in ee’s in the range of 10−29%.8f Since our protocols for ethylene/1,3-diene hetero-dimerization that uses cobalt/ alkylaluminum (eq 2) failed to work for the Lewis basic acrylate, a new catalyst system had to be developed. In this Article we report the development of a practical and highly regio- and enantioselective catalytic reaction that combines a range of 1,3-dienes with alkyl acrylates (1:1.1 ratio, 23 °C) in the presence of 1−5 mol% of readily available bis-phosphine cobalt halide complexes (eq 3b) and an activator, sodium tetrakis-3,5-bis-(trifluoromethylphenyl)borate (NaBARF). The products are nearly enantio-pure, conjugated 1,4-diene esters (5) bearing a chiral center between the configurationally defined double bonds. Since these double bonds have distinctly different reactivities we expect these chiral synthons to be of significant value for further synthetic applications. Reactions of 20 different substrates are reported, including 17 different prochiral dienes, giving yields in the range of 70−90% and Received: September 20, 2017 Published: November 9, 2017 18034
DOI: 10.1021/jacs.7b10055 J. Am. Chem. Soc. 2017, 139, 18034−18043
Article
Journal of the American Chemical Society
Figure 1. Oxidative route to dimerization of alkenes.
in catalytic carbon−carbon bond-forming reactions,11 these reagents are almost invariably generated in situ in the presence of excess reducing agents and other metal salts, and the oxidation state of cobalt and the nature of the intermediates (radicals or low-valent organometallic C−Co species) in many of these reactions are often open to speculation. A dearth of reports on well-characterized phosphine-Co(I) complexes related to their catalytic properties and reaction chemistry has also been recognized in the literature by others.12 Thus, we decided to examine the role of discrete, well-characterized Co(I) complexes for the hetero-dimerization reactions of 1,3dienes with the goal of overcoming the limitations of our original procedure. Development of a Modified Protocol for the Hydrovinylation of 1,3-Dienes. To test the viability of an oxidative route (Figure 1) for the dimerization, we prepared and characterized several well-defined Co(I) complexes (Figure 2) and examined their utility in the catalyzed hetero-dimerization reactions between (E)-1,3-dodecadiene and ethylene as a test reaction (eq 4, Table 1). Details of the preparation and characterization of the compounds listed in Figure 2 are described in the Supporting Information.
enantiomeric excesses up to 99%. Mechanistic studies including isolation and characterization of intermediates (multi-nuclear NMR, X-ray crystallography), solvent and counteranion effects, and isotopic labeling studies suggest the unique role of cationic Co(I) intermediates in these reactions.
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RESULTS AND DISCUSSION A Mechanistic Proposal. In detailed scouting studies (see Table S1 in the Supporting Information for details) we found that our broadly applicable original procedures for hydrovinylation of dienes using various bis-phosphine complexes (P∼P)CoX2 and an activator, trimethylaluminum or methyl aluminoxane (MAO), led to very low conversions to the desired adducts 5 (eq 3a). We reasoned that the failure of this reaction involving various alkyl aluminum promoters might be related to the incompatibility of these reagents with the reactive, Lewis basic alkyl acrylate substrate (3), vis-à-vis ethylene that was used in the successful reactions depicted in eq 2. We wondered if we could circumvent the use of aluminum alkyls in this protocol by exploiting a discrete and identifiable Co(I)/Co(III) redox cycle (Figure 1) as a possible pathway for this reaction that maybe approached differently by modifying the reaction conditions. This would involve an oxidative dimerization of the two olefins assisted by the low-valent cobalt species (3 + 4 + 6 → 7), a mechanistic possibility that has been advanced before in other ruthenium-9 and cobalt-catalyzed10 hetero-dimerization reactions, but without much supporting evidence. Even though lowvalent cobalt phosphine complexes have been used extensively
The most significant findings from the initial scouting experiments are shown in the Table 1. More extensive details describing the effect of ligands and activators on this reaction can be found in the Supporting Information (Table S2). Not surprisingly, the coordinately saturated complex (dppe)2CoH (9)13 and the Co(I) complexes 11a, 12a, 12b, 13a, 14, and 15a do not catalyze the dimerization reaction under ambient conditions in the absence of an activator (entry 1). However, in the presence of a Lewis acid, various Co(I) complexes become viable catalysts for this reaction (entries 2−14). Thus, fully characterized Co(I) complexes, (dppe)2CoH (9)13 and [(dppp)3Co2Br2] (11a), are excellent catalysts for this dimerization reaction in the presence of (C6F5)3B (entries 2, 3). Sodium tetrakis-3,5-(bis-3,5-trifluoromethylphenyl)borate (NaBARF) is also an excellent activator of 11a (entry 4). This complex is readily prepared by reduction of the corresponding (P∼P)CoBr2 (10a) with EtMgBr, activated Zn, or Mn. The identities of the starting (dppp)CoBr2 (10a) and the reduced species (11a) derived from reactions of 10a 18035
DOI: 10.1021/jacs.7b10055 J. Am. Chem. Soc. 2017, 139, 18034−18043
Article
Journal of the American Chemical Society
Figure 2. Cobalt(I) and cobalt(II) bis-phosphine complexes for hetero-dimerization of alkenes. See Supporting Information, page S26, for full structures of ligands and the details of the X-ray structural determinations.
Table 1. Co-dimerization of (E)-1,3-Dodecadiene and Ethylene Using Co(I) Complexesa entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Co(I) source (amount, mol%) 9, 11a, 12a, 12b, 14, 15a 9 (dppe)2CoH (20) 11a (dppp)3Co2Br2 (5) 11a (dppp)3Co2Br2 (5) 12ab ‘(dppp)CoBr’ (10) 12ab ‘(dppp)CoBr’ (10) 12bb ‘(dppp)CoCl’ (10) 12bb ‘(dppp)CoCl’ (10) 12bb ‘(dppp)CoCl’ (10) 12bb ‘(dppp)CoCl’ (10) 14 (COD)Co(COE-) (10) 15b (dppb)Co(COE-) (10) 15c (S,S)-DIOPCo(COE-) (5) 15d (S,S)-BDPPCo(COE-) (10)
activator (amount, mol%) none (C6F5)3B (20) (C6F5)3B (60) NaBARF (20) (C6F5)3B (15) NaBARF (30) (C6F5)3B (30) NaBARF (25) ZnCl2 (50) ZnI2 (30) (C6F5)3B (30) (C6F5)3B (30) (C6F5)3B (10) (C6F5)3B (30)
temp (°C), time (h) a
various 23, 4 23, 1 23, 1 23, 1 23, 1 23, 1.5 23, 1.5 23, 3 23, 6 23, 12 23, 1 −20, 12 0 to 23, 2
conv (%)
16a/17a
99 100 100 100 100 90 55 100 100 25 100
− 78/20 80/20 82/17 80/20 79/20 76/19 77/17 78/22 40/11 76/11 71/3 34c/5 77d/21
a
See eq 4 and Supporting Information for details. A more detailed list of cobalt(I) sources and corresponding reaction conditions is also included there (Table S2). The conversion and composition of products 16 and 17 (eq 4) were determined by gas chromatography and confirmed by NMR spectroscopy. See Supporting Information for details. bSynthesized by reduction of the corresponding (P∼P)CoX2 by Zn. c87% ee. d80% ee.
with various reagents (EtMgBr, Zn) were established by X-ray crystallography since NMR spectra often resulted in broad
peaks and were generally not reliable, presumably because of the presence of trace amounts of Co(II) species and/or high18036
DOI: 10.1021/jacs.7b10055 J. Am. Chem. Soc. 2017, 139, 18034−18043
Article
Journal of the American Chemical Society Table 2. Optimization of 1,3-Diene-Acrylate Dimerization: Ligand and Counter Ion Effectsa
products (%)c b
entry
Co(I) source (amount, mol%)
activator (amount, mol%)
1 2d 3e 4f 5 6 7 8 9 10 11 12
12a (dppp)CoBr (10) 12a (dppp)CoBr (5) 12a (dppp)CoBr (5) 12a (dppp)CoBr (5) 12a (dppp)CoBr (10) 12a (dppp)CoBr (10) 12a (dppp)CoBr (10) 12b (dppp)CoCl (10) 13a (dppb)CoCl (10) (dppe)CoBr (10) [(S,S)-BDPP]CoBr (10) [L3a]CoBr (5)
none NaBARF (10) NaBARF (15) NaBARF (15) ZnCl2 (100) (C6F5)3B (30) Me3Al (60) NaBARF (30) NaBARF (30) NaBARF (30) NaBARF (30) NaBARF (15)
temp (°C), time (h) 23, 23, 23, 23, 23, 23, 23, 23, 23, 23, 23, 23,
18 12 0.5 12 18 20 20 12 12 12 12 12
conv (%)
18a
19a
0 100 100 0 100 9
