Article pubs.acs.org/Organometallics
Acquiring a Prognostic Power in Co2(CO)6‑Mediated, CobaltoceneInduced Radical Dimerizations of Propargyl Triflates Gagik G. Melikyan,* Ryan Davis, Bryan Anker, Deborah Meron, and Kellyanne Duncan Department of Chemistry and Biochemistry, California State University Northridge, Northridge, California 91330, United States S Supporting Information *
ABSTRACT: Cobalt-complexed propargyl triflates can be generated in situ from methyl propargyl ethers and triflic anhydride and then reduced with cobaltocene to topologically and functionally diverse 1,5-alkadiynes. The electronic effect of an α-substituent is shown to attenuate the ionic nature of an α-C−OTf bond and thus its reducibility with cobaltocene. The powerful π-donors, such as phenyl, naphthyl, alkenyl, alkynyl, and alkoxy groups, provide the ionicity of α-C−OTf bonds and make them suitable recipients for a single-electron delivery from cobaltocene. σDonors (alkyl groups), a H atom, and σ/π-acceptors (ester groups) do not sufficiently stabilize propargyl cations, maintaining the covalent nature of α-C−OTf bonds and making them resistant toward the reducing agent. A newly acquired ability to differentiate between the αC−OTf bonds is used in polyethers for the regioselective reduction and radical dimerization in select propargylic positions, thus paving the way for a long sought after radical-ionic α,α′-functionalization in propargyl systems. Heterolytic bond dissociation energy (BDE) values are used to quantitate the impact of alpha substituents, to identify the “ionic” and “covalent” domains for electronically diverse propargyl triflates (ionic: BDEhet 238−271 kcal/mol; covalent: BDEhet 277−315 kcal/mol), and also to make predictions for new types of substituents and new classes of organic compounds.
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INTRODUCTION Cobalt-complexed propargyl ethers can act as precursors to triflates, which in turn can be reduced with cobaltocene to generate transient propargyl radicals.1 Synthetically, this new method represents a major enhancement to existing methodologies.2,3 First, a new formatmethyl ether + triflic anhydrideallowed us to avoid the use of strong acids, such as HBF4 and others,4 for generation of propargyl cations, thus making the methodology compatible with peripheral acidsensitive functionalities. Second, an in situ generation of propargyl triflates and α-C−OTf bond ionicity allowed for circumventing the laborious cation isolation step.2 Third, establishing an ability of cobaltocene5 to reduce propargyl triflates at temperatures as low as −50 °C substantially expanded the temperature domain for reduction reactions of the metal-stabilized carbocations.2,3 Fourth, lower temperatures for cation generation and reduction allowed us to access propargyl cations of a higher level of conjugation, which are subject to rapid polymerization under standard conditions.6a,b Chronologically, the first substrate successfully dimerized with a Tf2O−Cp2Co tandem contained a phenyl group in α-position to the metal core, Co2(CO)6.1 In this account, we present a systematic study on dimerization of propargyl triflates wherein the electronic effects of alpha substituents were varied to modulate the ionic nature of α-C−OTf bonds and hence their reducibility with cobaltocene. Experimental results were correlated with heterolytic bond dissociation energy (BDE) © XXXX American Chemical Society
values in an attempt to acquire prognostic power for radical generation in electronically and functionally diverse molecular settings.
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RESULTS AND DISCUSSION Substrate Base Expansion and Alpha Covalent Bond Modulation: σ-Donors, π-Donors, and σ/π-Acceptors. The complexation of a triple bond in propargyl alcohols with a dicobalthexacarbonyl core, Co2(CO)6,7 immobilizes it, preventing an unwanted acetylene−allene rearrangement8 and also providing significant stabilization of the propargyl cations.2,3,9,10 Thus, the treatment of cobalt complexes 1 with HBF4 triggers water elimination and formation of cobalt-stabilized propargyl cations 2 (Scheme 1). Reduction with zinc occurs at noticeable rates at temperatures as high as +10 °C, with the standard reaction temperature being +20 °C.6c The formation of the respective head-to-head dimers 3 served as an indirect proof that radicals 4 are in fact formed along the reaction coordinate. The new methodology1 that utilizes methyl propargyl ethers as substrates and triflic anhydride (5) as a reagent was originally optimized for α-phenyl derivative 6, which converted to propargyl triflate 7 via ionic pair 8 (Scheme 2). Experimentally, it was established that cobaltocene is capable of rapidly reducing propargyl triflate 7 even at −50 °C (10 min) and Received: September 17, 2016
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DOI: 10.1021/acs.organomet.6b00730 Organometallics XXXX, XXX, XXX−XXX
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Organometallics
α-Aryl and α-Naphthyl Substituents. The ionic pair 25 represents topologically and functionally diverse cobalt complexes with aromatic rings introduced alpha to the cationic center (Figure 3). Along with an unsubstituted phenyl group (10),1 mono- and bis-functionalized (4-, 3,4-) aromatic rings with π-donors, such as alkoxy groups, were tested as substrates, expanding the scope of the reaction and providing access to radical dimers 26−28 and their structural analogues. Yields varied within the range of 47−73%, with d,l-diastereomers being sterically favored in all substrates studied.1 Lower yields (22−32%) were observed for α- and β-naphthyl dimers (29, 30) due to increased steric hindrance at the dimerization site. Cerium(IV)-induced demetalation reactions proceeded with high yields (47−98%),1,6d providing a four-step access to d,l3,4-disubstituted 1,5-alkadiynes 31−36 hardly accessible by alternative means.11 Most importantly, the formation of radical dimers under standardized conditions serves as an experimental proof that propargyl trif lates 25 maintained their ionicity and thus an ability to be reduced with cobaltocene. α-Alkynyl Substituent. Substrate 18 (Figure 2) represents a nonaromatic type of cobalt−alkyne complexes with an alkynyl group being introduced to the propargyl carbon atom. Its ability to stabilize the cationic center on par with aryl and naphthyl groups would make respective propargyl triflates ionic and thus reducible with cobaltocene. The requisite methyl ether 37 was synthesized from alcohol 38 (85.5%) by methanolysis and then treated with Tf2O and Cp2Co, per the standard protocol6e (Scheme 3). α,α-Dimer 39 was formed in a regioselective manner (51.9%) and with a noticeably higher stereoselectivity (d,l-39:meso-39, 95:5) when compared to the Zn-induced dimerization (d,l-39:meso-39, 82:18).6e It is conceivable that methyl ether 37 reacted with Tf2O by displacing a triflate anion, followed by the formation of the transient species 40. The latter converts to the intermediate propargyl triflate that can be represented by either the covalent form 41 or the ionic form 42.12 The formation of dimer 39 serves as experimental proof that propargyl triflate is best represented by its ionic form 42, which is reduced with cobaltocene, albeit somewhat slower than its “aromatic” counterparts (−50 °C, 15 min; −30 °C, 15 min vs −50 °C, 10 min), to generate propargyl radicals 43. An exclusive formation of d,l-39 was also observed in a high-temperature conversion of propargyl triflates (82 °C, 3 min).6d α-Alkenyl Substituent. Incorporating a double bond at the propargylic carbon introduces a duality to the carbocations, propargylic vs allylic, with the latter maintaining its intrinsic ability to rearrange.13 Isomeric substrates 19 and 20 contain methoxy groups attached to both termini of the allylic triad (Figure 2) and are expected to exhibit similar behavior in Tf2O−Cp2Co reaction due to the formation of the same cationic intermediate. This prediction is based on the previous studies on structurally related alpha and gamma alcohols,6a which afforded a γ,γ-dimeric product in the same yield (α-OH 99%; γ-OH 99%). Thus, γ-methyl ether 44, representing both substrates 19 and 20, was synthesized from α-alcohol 45 (65%)6a and then treated with Tf2O and Cp2Co under standard conditions (−50 to −10 °C, 30 min; −50 °C, 10 min).1 γ,γDimer 46 was formed in a nearly quantitative yield (98%), attesting to the rapid generation of the propargyl-allyl radical 47 and, preceding the reduction step, ionic triflate 48. The latter is a resonance hybrid representing two resonance contributors, 49(γ) and 49(α), which are both ionic in nature, due to the
Scheme 1. Standard Protocol for Acid-Induced Generation of Propargyl Cations
Scheme 2. Original Protocol for Generation of an Ionic Propargyl Triflate
generating propargyl radicals 9, which in turn dimerize to chromatographically separable stereoisomers (d,l-10:meso-10, 62:38).1 Preliminary studies on the scope of the Tf2O−Cp2Co reaction revealed that the reduction rate is dependent upon the nature of the alpha substituent directly attached to the propargylic carbon.1,6 On the basis of these data, we developed a working hypothesis linking the reduction rate of propargyl triflate 11 to the nature of an α-C−OTf bond, i.e., ionic vs covalent (Figure 1). If the level of stabilization provided by an
Figure 1. Testing the working hypothesis: the ionicity of the α-C− OTf bond in propargyl triflates vs its reducibility with cobaltocene.
α-substituent is sufficient for an α-C−OTf bond to undergo ionization, then cobaltocene could deliver an electron, at a reasonable pace, toward the cationic center in ionic triflate 12. In contrast, if the said stabilization remains insufficient, then an α-C−OTf bond could remain covalent, thus making triflate 13 nonreducible with cobaltocene. To establish the qualitative threshold between two categories of alpha substituents, four types of substrates were examined: (1) those containing πdonors at α-carbon atoms (14−21); (2) those containing σdonors in an α-position (22); (3) reference compound 23 with an alpha H atom; and (4) those containing a σ/π-acceptor at the α-carbon atom (24) (Figure 2). B
DOI: 10.1021/acs.organomet.6b00730 Organometallics XXXX, XXX, XXX−XXX
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Figure 2.
Figure 3. α-Aryl and α-naphthyl substituents: radical dimers derived from ionic triflates.1,6d
sufficient, on par with aromatic substituents, stabilization provided by the double bond, as a π-donor. α-Alkoxy Substituent. Among the π-donors tested, an oxygen atom occupies a unique niche, with an electron pair, not a double bond or a phenyl group, being a stabilizing unit. Propargyl acetals 50 (R = Ph, TMS) were synthesized by the condensation of the commercial acetals with Co2(CO)8, followed by the treatment with Tf2O and single-electron reduction with cobaltocene (Scheme 5).6f The nucleophilic substitution and a C−O bond heterolysis in ionic pair 51 resulted in propargyl triflates that can be represented by triflate 52 (covalent form), propargyl cation 52 (ionic form I), and oxonium ion 52 (ionic form II). Reduction with cobaltocene occurred at −50 °C, yielding diastereomeric 3,4-dimethoxy-1,5hexadiynes 53 (R = Ph) and 54 (R = TMS) in the ratio of d,l:meso, 91:9 and 100:0, respectively. The formation of the radical dimers attests to the formation of the requisite radicals
55 as a result of the single-electron reduction of ionic triflates 52 and, thus, an ability of the oxygen atom to provide a level of stabilization on par with that exhibited by the aromatic, alkenyl, and alkynyl substituents. α-Alkyl Substituent: Secondary Propargyl Alcohols. Me ether 56 represents the substrate type 22 (Figure 2) with a σ-donor (methyl group) attached to the propargylic position in the cobalt−alkyne complex (Scheme 6). The treatment with Tf2O was carried out under standard conditions (−50 to −10 °C, 30 min)1 followed by the reduction with Cp2Co at −50 °C for 3 h. The substantially extended reaction time (α-Me 3 h; αPh 10 min1) was applied in order to find out if the reduction of propargyl triflate 57 can in principle take place, forming any detectable amounts of the respective dimer. In a departure from the standard protocol,1 the crude mixture was treated with an excess of tert-butanol (0 °C, 48 h) prior to the aqueous workup in order to be able to differentiate between an unreacted C
DOI: 10.1021/acs.organomet.6b00730 Organometallics XXXX, XXX, XXX−XXX
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Organometallics Scheme 3. Tf2O−Cp2Co-Induced Radical Dimerization of Bis-α-alkynyl α-Methyl Ethers
Scheme 4. Tf2O−Cp2Co-Induced Radical Dimerization of γMethoxy Allyl Ethers
Scheme 6. Secondary Methyl Ethers as Substrates
Scheme 5. Tf2O−Cp2Co-Induced Radical Dimerization of α-Alkoxy Methyl Ethers
D
DOI: 10.1021/acs.organomet.6b00730 Organometallics XXXX, XXX, XXX−XXX
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Organometallics amount of methyl ether 56 and covalent propargyl triflate 57. The latter, formed due to the C−O bond heterolysis in the ionic pair 58, should not be reducible with cobaltocene because of the covalent nature of the α-C−OTf bond, but still can undergo a substitution reaction with tert-butanol to form t-Bu ether 59. Thus, the amount of methyl ether 56 present in the crude mixture would be indicative of the amount of the ionic pair 58 that was hydrolyzed to the former in the course of an aqueous workup. On the contrary, the amount of tert-butyl ether 59 in the crude mixture would attest to the formation of the covalent propargyl triflate 57 that is resistant to reduction with cobaltocene and does not convert into the ionic form of triflate 57. A careful examination of the crude mixture by NMR revealed the formation of tert-butyl ether 59: bis-propargyl ether 60:methyl ether 56 in a 43:31:26 ratio. No traces of dimer 61 were detected by spectral means, indicating that the generation of requisite radicals 62 did not occur along the reaction coordinate. The formation of bis-propargyl ether 60 can be explained by the hydrolysis of propargyl triflate 57 (covalent form) in the course of the aqueous workup, formation of the sec-propargyl alcohol [HCCCH(OH)CH3(Co2(CO)6], and its interaction with an in situ generated sec-propargyl cation.14 It is conceivable that the rate of the substitution reaction in propargyl triflate 57 with tert-butanol is relatively low due to steric factors, with a significant portion of the propargyl triflate 57 remaining unreacted even after a 48 h long exposure to tert-butanol. Thus, tert-butyl ether 59 and bispropargyl ether 60 combined represent the covalent propargyl triflate 57, while recovered methyl ether 56 represents an unreacted ionic pair 58. The replacement of an α-methyl group with alternative σ-donors, such α-ethyl and α-n-propyl groups (22, n = 1, 2; Figure 2) did not provide for a critical level of stabilization that could convert respective covalent propargyl triflates to their ionic counterparts and make them reducible with cobaltocene. α-H Substituent: Primary Propargyl Alcohols. Primary methyl ethers 23 represent the reference substrates that separate cobalt complexes with σ- and π-donors and those containing σ- and π-acceptors (Figure 2). Methyl ether 63 was treated with Tf2O (−50 to −10 °C, 30 min), then with Cp2Co (−50 °C, 3 h), followed by solvolysis with tert-butanol (20 °C, 120 h). A careful examination of the crude mixture by NMR did not allow for detecting even trace amounts of radical dimer 64, attesting to the fact that the generation of primary propargyl radicals 65 did not take place. Instead, tert-butyl ether 66, bispropargyl ether 67, and methyl ether 63 were formed in a 10:6:84 ratio. Overall, the reaction profile mimics that of the secondary propargyl systems (Scheme 6), although quantitatively the product distribution differed significantly due to disparity in the relative stabilities of primary and secondary carbocations. A much higher amount of starting material (63, 84%; 56, 26%) suggests that the ionic pair 68 possesses a higher kinetic stability compared with its secondary counterpart 58. The formation of the covalent propargyl triflate 69 still takes place as indicated by the formation of the tert-butyl ether 66,15 a result of the solvolysis reaction with tert-butanol, and bis-propargyl ether 67, a result of the hydrolysis and an in situ trapping of the primary propargyl cations. Apparently, the key conversion of 69 (covalent form) to 69 (ionic form) did not take place, thus preventing cobaltocene from reducing the cationic site and generating requisite radicals 65. α-Ethoxycarbonyl Substituent. In the cobalt−alkyne series, propargyl radicals with σ-/π-acceptors located alpha to
Scheme 7. Primary Methyl Ethers as Substrates
the metal core remain unknown.2,3 Methyl ether 24 (Figure 2) represents the only type of substrate that contains an electronwithdrawing ethoxycarbonyl group directly attached to the propargylic carbon atom. Requisite methyl ether 70, synthesized in one step from propargyl alcohol 71, was treated with a 2-fold excess of Tf2O (−50 to −10 °C, 30 min; −10 °C 30 min) and Cp2Co at −50 °C (30 min) in order to test the ability of propargyl triflate 72 to receive a single electron delivery and to dimerize, via captodative radical 73, to dimer 74 (Scheme 8). Scheme 8. Ethoxycarbonyl Group as an Alpha Substituent
The crude product was quenched with methanol and then carefully studied by NMR in an attempt to detect the formation of dimeric product 74. The only product present was methyl ether 70 isolated by preparative TLC in a nearly quantitative yield (94.5%). The very fact that even trace amounts of dimer 74 were not detected in the crude mixture represents experimental proof that propargyl triflate 72 (ionic) was not formed in the course of the reaction and thus did not undergo reduction to the requisite radicals 73. Dual-Nature Substrates with Covalent and Ionic Propargyl Triflate Moieties: Showcasing a Newly Acquired Site-Differentiation Capability. Having established that the ionicity of α-C−OTf bond in cobalt−alkyne complexes can be varied by changing the electronic nature of E
DOI: 10.1021/acs.organomet.6b00730 Organometallics XXXX, XXX, XXX−XXX
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Organometallics the alpha substituents, we designed the dual-nature substrate 75 in which two triflate groups are introduced α- and α′- to the metal coordination site (Figure 4). With π-donors as
Figure 4. Exploiting ionicity of the α-C−OTf bond: sequential radicalionic functionalization.
substituents, a carbon−triflate bond is expected to have an ionic nature and thus be reducible by cobaltocene (primary radical f unctionalization site). In contrast, with σ-donors, an H atom, or σ-/π-acceptors as substituents, a carbon-triflate bond is expected to maintain a covalent nature and remain nonreducible by cobaltocene. These “resistant” carbon triflate bonds can be used in subsequent acid-induced ionic reactions that are known to occur with 1° and 2° methyl ethers2,3c (secondary ionic f unctionalization site). Triether 76 was synthesized by the condensation of lithium acetylide with anisaldehyde 77,16 an in situ methylation1 with Me3O+BF4−, and condensation with Co2(CO)87 (38.3% over three steps; Scheme 9). It contains three types of methoxy groups with one of them being attached to the sp2-hybridized carbon atom and, thus, being intrinsically nonconvertible to the triflate, and other two being propargylic in nature and being introduced to the secondary benzylic-propargylic (α-) and primary propargylic (α′-) positions, respectively. The latter is expected to convert to the 1° propargyl triflate (α′-), which is resistantdue to its covalent natureto reduction with cobaltocene, while the former is expected to produce an ionic propargyl triflate (α-), which is subject to a single electron reduction and subsequent radical C−C bond formation. The treatment with a 2-fold excess of Tf2O (−50 to −10 °C/30 min; −10 °C, 30 min) produced supposedly bis-triflate 78, which was then reduced with an excess of cobaltocene (2 equiv; −78 °C, 30 min) and quenched with methanol in order to convert unreacted 1° propargyl triflate moieties into respective methyl ethers. According to NMR analysis of the crude product, α,α-dimer 79 was formed as a mixture of diastereomers in a 55:45 ratio. Unexpectedly, chromatographic isolation revealed an extreme instability of meso-79, which undergoes a rapid decomposition on the preparative TLC plate even at low temperatures (−16 °C), as well as in the course of concentrating isolated product under reduced pressure at ambient temperatures. As a result, despite its significant presence in the crude mixture (d,l-79:meso-79, 55:45), only minute amounts of meso-79 can be chromatographically isolated, allowing us to obtain 1H NMR and MS spectra. The major diastereomer, d,l-79, was isolated by consecutive preparative TLC separations, with its relative configuration being determined by X-ray crystallography17 (Figure 5). Aromatic rings are arranged in a gauche fashion (θ C11−C4−C5‑C21 46.5°), as are the hydrogen atoms (θH5−C5−C4‑H4 80.0°), both exhibiting a noticeable level of deviation from an ideal staggered conformation. By their
Figure 5. ORTEP diagram of d,l-μ-η2-[1,8-dimethoxy-4,5-di(4′methoxybenzene)octa-2,6-diyne]bis(dicobalthexacarbonyl) (79). Select bond lengths (Å), bond angles (deg), and torsional angles (deg): Co1−Co2 2.46, Co1−C2 1.97, Co1−C3 1.97, Co2−C2 1.97, Co2− C3 1.98, C2−C3 1.34, C4−C5 1.58, C6−C7 1.34, C1−C2−C3 145.8, C2−C3−C4 148.2, C5−C6−C7 148.4, C6−C7−C8 143.9, C1−C2− C3−C4 3.5, C5−C6−C7−C8 6.4, C3−C4−C5−C6 151.2, C11−C4− C5−C21 46.5, H5−C5−C4−H4 80.0.
lengths, the coordinated triple bonds “behave” as pseudodouble bonds (C2−C3 1.34 Å, C6−C7 1.34 Å), with bond angles exhibiting a drastic departure from the linear configuration typical for uncomplexed triple bonds (C1−C2− C3 145.8°, C2−C3−C4 148.2°, C5−C6−C7 148.4°, C6−C7− C8 143.9°).2,3 Treatment with ceric ammonium nitrate18 (8 equiv, −78 to −30 °C) led to decomplexation of the organometallic moieties in a single step, releasing d,l-80 as a pure diastereomer (61.5%). Overall, dif ferentiation-by-design between α- and α′-C−OTf bonds was successf ully achieved with the former participating in the reduction process and forming the carbon−carbon bond, while the latter maintained its integrity and reverted back to the original methoxy group f unctionality. Both α′positions are available in d,l-79/d,l-80 for consecutive ionic f unctionalizations, which can be carried out with a variety of nucleophiles, both in symmetrical and unsymmetrical fashions.2,3c Correlation of the Experimental Data with Heterolytic BDE Values: Can the Radical Dimerization Reaction Be Predicted? The correlation of the experimental data with the heterolytic BDE values was intended to identify the “ionic” and “covalent” domains wherein the propargyl triflates are reducible or nonreducible by cobaltocene, respectively. Numerically, the heterolytic BDE values are determined by the stabilities of the respective carbocations.19,20 For propargyl triflates, the same parameter is the main determinant in either acquiring an ionic nature due to the sufficient stabilization of the carbocation by an alpha substituent or, on the contrary, becoming covalent in nature due to the insufficient transfer of electron density. For the benzylic cation (α-Ph), the BDE value of 238 kcal/mol19b F
DOI: 10.1021/acs.organomet.6b00730 Organometallics XXXX, XXX, XXX−XXX
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Organometallics Scheme 9. Ionicity-Based Site Differentiation: Selective Generation of Propargyl Radicals in Polyethers
represents a reference point for stabilizing α-Ph and α-Naph substituents (14−17, Figure 2) and thus falls into an “ionic domain” (Figure 6). The propargyl cation (BDEhet 271 kcal/
substrate 21 (Figure 2) demonstrate an ability of the O atom to provide sufficient stabilization to the carbocations, on par with aromatic rings and multiple bonds, thus also falling within the “ionic domain”. Conceptually, ionic cobalt-complexed propargyl cations are those for which a critical separation between a propargyl cation and triflate anion is achieved, thus allowing a reducing agent to deliver a single electron to an electrophilic center. No determination can be made if an ionic propargyl cation complexed to the cobalt cluster forms an intimate ionic pair, external or solvent-separate ionic pair, or dissociated ions.21 The reference H atom features the highest BDE value of 315 kcal/mol,19a with the stability of the carbocation being inferior to those stabilized by π-donors and with primary propargyl triflates remaining covalent and nonreducible by cobaltocene. Introducing a methyl group provides for a significant decrease in the BDE value (277 kcal/ mol19a), although secondary propargyl triflates still remain covalent and nonreducible by cobaltocene. An ester group, for which the heterolytic BDE value has not been found by us in the literature, is represented by the surrogate cyano group with a BDE of 305 kcal/mol.19b Thus, the “ionic domain” can be def ined as consisting of the cobalt propargyl complexes with alpha substituents for which the heterolytic BDE values are lower than 271 kcal/mol with a range of 238−271 kcal/mol being supported by the dimerization data presented. The “covalent domain” spans the range of 277−315 kcal/mol, with a narrow area of 271−277 kcal/mol representing an “uncertainty domain”. The predictions can be made with respect to the prospective substrates in order to expand the substrate base and also to exclude, a priori, the substrates that cannot acquire an ionic nature and thus participate in the radical C−C bond-forming reactions alpha to the metal core.22 Thus, any substituents with BDE values higher than 277 kcal/mol, including but not limited to alkyl groups of any length and topology (σ-donors), σ- and πacceptors of any composition (aldehyde, ester, ketone, amide, nitrile groups), are expected to deactivate respective alpha positions in Tf2O−Cp2Co reactions and be the spectator propargyl moieties in dual-nature, higher complexity molecular assemblies. In contrast, the alpha substituents with heterolytic BDE values lower than 271 kcal/mol can be anticipated to
Figure 6. Heterolytic BDE-based quantification of the ionicity of propargyl triflates.
mol19b), representing substrate 18 with an α-alkynyl substituent attached to the cationic center (Figure 2), significantly raises the upper BDE limit of the “ionic domain”. Per heterolytic BDE values, alpha double bonds provide a better stabilization in allylic cations (BDEhet 256 kcal/mol19b) in comparison to the triple bond (BDEhet 271 kcal/mol 19b ), which is fully corroborated by the experimental evidence for substrates 19 and 20 (Figure 2). An alkoxy stabilizing group is represented by the BDE value of 252 kcal/mol19b measured for an αhydroxymethyl cation, HOCH2+. Experimental data for G
DOI: 10.1021/acs.organomet.6b00730 Organometallics XXXX, XXX, XXX−XXX
Article
Organometallics
(E), petroleum ether (PE), and pentane (P). Mass spectra were run at the Regional Center on Mass-Spectroscopy, UC Riverside, Riverside, CA, USA (FAB, ZAB-SE; CI-NH3, 7070EHF; Micromass; TOF Agilent 6210 LCTOF instrument with a multimode source). μ-η 2 -(3-Methoxy-1,5-diphenylpenta-1,4-diyne)]dicobalt Hexacarbonyl (37). Under an atmosphere of nitrogen, HBF4·Me2O (161 mg, 1.20 mmol) was added to a solution of alcohol 38 (104 mg, 0.20 mmol) in dry pentane (20 mL) at −20 °C. The reaction mixture was stirred for 45 min at −10 °C, the precipitate was allowed to settle at −30 °C, and the pentane layer was removed. Dry pentane (20 mL) was added along the inner wall of the flask, stirring was resumed for 15 min, cation was allowed to settle, and the pentane layer was removed. The washing was repeated twice with additional portions of dry pentane (20 mL). Additional pentane (20 mL) was then added, followed by methanol (0.5 mL), and the reaction mixture was stirred vigorously for 30 min at −30 °C. The mixture was warmed to −10 °C, treated with degassed saturated NaClaq solution (15 mL), and extracted with ether (3 × 20 mL). Combined ethereal fractions were dried (Na2SO4), concentrated under reduced pressure, and fractionated by preparative TLC (PE:E, 7:1) to afford 37 (91 mg, 85.5%) as red crystals. Tdecomp = 64−67 °C (with sealed capillary; dried by coevaporation with benzene, 3 × 1 mL). TLC (PE:E, 6:1): Rf 0.55. 1 H NMR (400 MHz, CDCl3): δ 3.69 (3H, s, OCH3), 5.56 (1H, s, CH), 7.25−7.39 (6H, m, aromatic H), 7.39−7.48 (2H, m, aromatic H), 7.64−7.77 (2H, m, aromatic H). 13C NMR (100 MHz, CDCl3): δ 57.0, 72.3 (CH, OCH3), 86.5, 86.9, 89.8, 94.9 (CC), 122.2, 127.8, 128.3, 128.6, 128.7, 129.9, 131.7, 137.7 (aromatic C), 199.1 (CO). MS TOF FD+: m/z M+ 532. MS HR TOF FD+: m/z calcd for C24H14O7Co2 M+ 531.9398, found 531.9413. d,l-μ-η 2 -[1,6-Diphenyl-3,4-di(2′-phenylethynyl)hexa-1,5diyne]bis(dicobalthexacarbonyl) (39). Tf2O−Cp2Co Low-Temperature Protocol. Under an atmosphere of nitrogen, Tf2O (59 mg, 0.21 mmol) was added dropwise (2 min) to a solution of 37 (106 mg, 0.20 mmol) in CH2Cl2 (4 mL) at −50 °C, and the reaction temperature was raised to −10 °C in 3 h. The temperature was brought down to −50 °C, and the reaction mixture was treated with a solution of Cp2Co (57 mg, 0.30 mmol) in CH2Cl2 (1.5 mL). The reaction mixture was stirred at −50 °C for 15 min, warmed to −30 °C, and stirred for another 15 min (TLC control). The mixture was then warmed to −10 °C, quenched with degassed saturated NaClaq solution (10 mL), and diluted with CH2Cl2 (10 mL). The organic layer was washed with water (3 × 10 mL) and dried (Na2SO4). The crude mixture was evaporated to dryness, dissolved in CH2Cl2 (25 mL), treated with dicobaltoctacarbonyl (10.3 mg, 0.03 mmol, N2 atmosphere, 4 h), and fractionated by preparative TLC (2 plates, PE:E, 12:1) to afford an inseparable mixture of d,l-39 and meso-39 (52 mg, 51.9%, d,l-39:meso39, 95:5). Spontaneous Tf2O-Induced High-Temperature Protocol. Under an atmosphere of nitrogen, Tf2O (59 mg, 0.21 mmol) was added dropwise (2 min) to a solution of 37 (106 mg, 0.20 mmol) in C2H4Cl2 (5 mL) at −20 °C. The reaction mixture was stirred 10 min at −20 °C, warmed to +20 °C, stirred for another 10 min, then submerged into an 82 °C preheated oil bath, and stirred for 3 min. The reaction flask was immersed into a water bath (+20 °C), stirred for 10 min, then cooled to −10 °C, and quenched with degassed saturated NaClaq solution (10 mL). Upon dilution with ether (10 mL), the organic layer was washed with water (3 × 10 mL), dried (Na2SO4), and concentrated under reduced pressure. The crude mixture (by NMR, d,l-39:monocomplex of d,l-39, 92:8; d,l-39:meso-39, 100:0) was dissolved in dry ether (10 mL) and treated with dicobaltoctacarbonyl (2 mg, 0.006 mmol) under an atmosphere of nitrogen. The reaction mixture was stirred for 3 h at 20 °C, then evaporated under reduced pressure, and fractionated by preparative TLC (1 plate, PE:E, 10:1; repurification, 1/2 plate, P:E, 10:1) to afford isomerically pure d,l-39 (17 mg, 33.9%) as a tar-like red solid. 1H NMR (400 MHz, C6D6): δ 5.10 (2H, s, CH), 6.95 (8H, m, aromatic H), 7.04 (4H, t, aromatic H, J = 7.4), 7.49 (4H, dd, aromatic H, J = 8.0, J = 1.6), 7.95 (4H, spl d, aromatic H, J = 8.0, J = 1.2). 13C NMR (100 MHz, CDCl3): δ 44.3 (C3, C4), 87.7, 88.2, 92.1, 97.1 (CC), 122.9, 127.9, 128.2, 128.8, 129.6, 131.5, 137.7 (aromatic C), 199.2 (CO). MS TOF FD+: m/z M+ 1002. MS HR TOF FD+: m/z
acquire an ionic nature and allow for the radical reactions to proceed in select propargylic positions. The substrates in question can be structurally related to those already experimentally tested (aromatics of any topology, mono- and polyenes, mono- and polyynes, and oxygen-containing structural units) and also to their counterparts that could provide for an enhanced stabilization to the propargyl cations. In particular, amino groups of various degrees of substitution could cause a significant downward expansion of the “ionic domain” [BDEhet α-NH2 218 kcal/mol (1° amine); BDEhet αCH3NH 205 kcal/mol (2° amine)],19b further expanding the substrate scope and providing access to 3,4-diamino-1,5alkadiynes, the vicinal diamines with 1,5-disposed triple bonds.
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CONCLUSIONS Departure from the “classical” generation of a Nicholas cation, which utilizes isolated propargyl cations as electrophiles, allowed us to discover the dual-nature propargyl triflates as new precursors to propargyl radicals. A key structural element is an α-O−Tf bond that fluctuates in nature between ionic and covalent: π-donors provide a critical amount of electron density to make the triflates ionic and, thus, reducible by cobaltocene (Ph, Naph, CC, CC, OR), while σ-donors (alkyl groups, C1−C8), H atoms, and σ,π-acceptors (COOR) lack the ability to sufficiently stabilize propargyl cations. In the substrates of dual nature, one of two triflate groups can selectively be “activated”, thus becoming the locale of the site-selective radical reaction. A newly acquired site-differentiation capability paves the way for a radical-ionic α,α′-functionalization sequence, wherein the radical reaction is initially used for creating a C−C bond alpha to the metal core, while the peripheral triflates can be subsequently engaged in the secondary functionalization by an ionic mechanism. The knowledge thus acquired has a prognostic power, enabling us to predict reaction outcomes for new types of substituents and new classes of organic compounds by using, as a quantitative criterion, the heterolytic BDE values.
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EXPERIMENTAL SECTION
All manipulations of air-sensitive materials were carried out in flamedried Schlenk-type glassware on a dual-manifold Schlenk line interfaced to a vacuum line. Argon and nitrogen (Airgas, ultrahigh purity) were dried by passing through a Drierite tube (Hammond). Methylene chloride was stored over CaCl2 and distilled under dry nitrogen from CaH2; ether was stored over sodium and filtered through an alumina−silica gel column. All reagents and solvents (pentane, THF, acetone, benzene, methanol) were purchased from Acros, TCI, Alpha Aesar, and Sigma-Aldrich and used as received. Co2(CO)8 and Ce(NH4)2(NO3)4 were purchased from Strem. Zinc was acquired from Aldrich (dust, 10 mm). NMR solvents were supplied by Cambridge Isotope Laboratories. 1H and 13C NMR spectra were recorded on Bruker Avance III-400 (1H, 400 MHz) and Varian 400-MR (1H, 400 MHz) spectrometers. Chemical shifts were referenced to internal solvent resonances and are reported relative to tetramethylsilane. Spin−spin coupling constants (J) are given in hertz. Elemental analyses were performed by Galbraith Laboratories (Knoxville, TN, USA). Melting temperatures (uncorrected) were measured on a Stanford Research Systems apparatus, EZ-Melt MPA120. Silica gel standard grade (63−200 mm; Sorbent Technologies) was used for flash column chromatography. Analytical and preparative TLC analyses were conducted on silica gel TLC plates, w/UV254 (Sorbent Technologies; aluminum sheets), and silica gel for TLC, UV/254 (Sorbent Technologies; w/gypsum; 20 × 20 cm), respectively. Visualization was carried out with potassium permanganate aqueous solution unless indicated otherwise. Eluents are ether H
DOI: 10.1021/acs.organomet.6b00730 Organometallics XXXX, XXX, XXX−XXX
Article
Organometallics
solution was diluted with pentane (20 mL), washed with water (3 × 10 mL), dried (Na2SO4), and concentrated under reduced pressure (250 mbar), and the residue was fractionated by preparative TLC (P:E, 10:1) to afford 66 (89 mg, 89.0%; 350 mbar, 14 h) as a dark red oil. TLC (P:E, 10:1): Rf 0.88. 1H NMR (400 MHz, δ, CDCl3): 1.26 (9H, s, 3CH3), 4.53 (2H, s, CH2), 6.02 (1H, s, HCC). 13C NMR (100 MHz, δ, CDCl3): 27.64 (3CH3), 62.31 (CH2), 71.45, 73.92 (CMe3, HCC), 94.83 (HCC), 200.04 (CO). MS TOF FD+: m/z M+ 397.7. MS HR TOF FD+: m/z calcd for C13H12O7Co2 M+ 397.9242, found 397.9253. μ-η 2 -[Ethyl 2-methoxy-4-(trimethylsilyl)but-3-ynoate]dicobalt Hexacarbonyl (70). Under an atmosphere of nitrogen, HBF4·Et2O (680 mg, 4.20 mmol) was added dropwise (2 min) to a solution of alcohol 71 (340 mg, 0.70 mmol) in dry pentane (15 mL) at −30 °C and stirred for 2 h. The precipitated cation was washed with pentane (4 × 15 mL) at −30 °C, pentane (15 mL) was added to the flask, and the mixture was treated with methanol (1 mL) and stirred (3 h) at −30 °C. The reaction mixture was treated with water (10 mL) at −20 °C, allowed to warm to 20 °C, and diluted with pentane (30 mL), and the organic layer was washed with water (3 × 15 mL) and dried (Na2SO4). The crude mixture was concentrated under reduced pressure, and the residue was fractionated by preparative TLC (SiO2, P:E, 10:1, −12 °C) to afford 70 (180 mg, 51.4%) as a dark red oil. TLC (PE:E, 5:1): Rf 0.54. 1H NMR (400 MHz, δ, CDCl3): 0.31 (9H, s, Me3Si), 1.35 (3H, t, CH3, J = 6.8), 3.54 (3H, s, OMe), 4.25 (2H, ABX3, CHAHBCH3, Jav(HA−HB) = 17.8, J(HA−CH3) = 6.8, J(HB−CH3) = 7.2), 4.88 (1H, s, CH). 13C NMR (100 MHz, δ, CDCl3): 0.69 (Me3Si), 14.26 (CH3), 58.58, 61.82 (OMe, OCH2), 79.30 (CC), 81.77 (CH), 105.33 (CC), 169.91 (CO), 199.95 (CO). MS TOF FD+: m/z M+ 500. MS HR TOF FD+: m/z calcd for C16H18O9Co2Si M+ 499.9379, found 499.9370. Attempted Dimerization of μ-η 2 -[Ethyl 2-methoxy-4(trimethylsilyl)but-3-ynoate]dicobalt Hexacarbonyl (70). Under an atmosphere of nitrogen, Tf2O (124 mg, 0.44 mmol) was added dropwise (5 min) to a solution of methyl ether 70 (110 mg, 0.22 mmol) in dry CH2Cl2 (4 mL) at −50 °C. The reaction was warmed to −10 °C over 30 min, kept at −10 °C for 30 min, and cooled to −50 °C. A solution of Cp2Co (83 mg, 0.44 mmol) in dry CH2Cl2 (2 mL) was added dropwise (5 min) and stirred for 30 min at −50 °C. The reaction mixture was treated with methanol (1 mL) at −50 °C, stirred 20 min, warmed to 0 °C, stirred 20 min, and quenched with saturated brine (10 mL) at 0 °C. The mixture was diluted with pentane (30 mL), washed with water (4 × 15 mL), and filtered through a short bed of Na2SO4 (2 in.). The crude mixture was concentrated under reduced pressure (350 mbar, 12 h), and the residue was fractionated by preparative TLC (SiO2, P:E, 15:1, −12 °C) to recover methyl ether 70 (104 mg, 94.5%). μ-η2-[1-(1′,4′-Dimethoxybut-2′-yn-1′-yl)-4methoxybenzene]dicobalt Hexacarbonyl (76). Under an atmosphere of N2, n-BuLi (352 mg, 5.50 mmol) was added dropwise (15 min) to a solution of 3-methoxyprop-1-yne (385 mg, 5.50 mmol) in dry THF (20 mL) at −10 °C. The reaction mixture was stirred for 5 h at −10 °C, a solution of p-anisaldehyde 77 (680 mg, 5.00 mmol) in dry THF (5 mL) was added dropwise (15 min) at −10 °C, and the stirring was continued for an additional 14 h at 20 °C (TLC control). Me3O+BF4− (814 mg, 5.50 mmol) was added in one portion at −20 °C, the reaction mixture was stirred for 3 h at −20 °C (TLC control) and quenched with H2O (25 mL) at −20 °C, the aqueous layer was extracted with ether (3 × 20 mL), and the combined organic fractions were filtered through a short bed of Na2SO4 (2 in.). Under an atmosphere of N2, the crude methyl ether (1.10 g, 5.00 mmol; assuming 100%) was dissolved in ether (10 mL) and was added dropwise (15 min) to a solution of dicobaltoctacarbonyl (1.37 g, 4.00 mmol) in ether (20 mL) at 20 °C. The mixture was stirred for 3 h at 20 °C, concentrated under reduced pressure, and fractionated on silica gel (200 g, anaerobic conditions, −10 °C; PE:E, 50:1) to afford 76 (968 mg, 38.3% over three steps) as a brick red solid. Mp: 32.8−33.5 °C (sealed capillary, dried by coevaporation with benzene, 3 × 1 mL). TLC (PE:E, 5:1). Rf 0.49. 1H NMR (400 MHz, δ, CDCl3): 3.41 (3H, s, OMe), 3.50 (3H, s, OMe), 3.81 (3H, s, OMe), 4.46 (2H, CHAHB, Jav
calcd for C46H22O12Co4 M+ 1001.8434, found 1001.8480. Microanalysis: Found: C, 54.84; H 2.47. C46H22O12Co4 requires: C, 55.12; H 2.21.6e μ-η2-[3-(tert-Butoxy)but-1-yne]dicobalt Hexacarbonyl (59) and μ-η2-[3-(But-3-yn-2-yloxy)but-1-yne]bis(dicobalthexacarbonyl) (60). Under an atmosphere of N2, Tf2O (141 mg, 0.50 mmol) was added dropwise (5 min) to a solution of methyl ether 56 (93 mg, 0.25 mmol) in dry CH2Cl2 (4 mL) at −50 °C. The reaction mixture was warmed to −10 °C over 30 min and cooled to −50 °C, and a solution of Cp2Co (95 mg, 0.50 mmol) in dry CH2Cl2 (2 mL) was added dropwise (5 min). The reaction mixture was stirred for 3 h at −50 °C, treated with tert-butanol (1 mL) at −50 °C, stirred 5 min, warmed to 0 °C, and stirred for an additional 48 h. The solution was quenched with saturated NaCl (10 mL) at 0 °C, stirred 30 min, diluted with pentane (30 mL), washed with H2O (3 × 15 mL), and dried (Na2SO4). The complex crude mixture was concentrated under reduced pressure (300 mbar, 14 h; NMR: tertbutyl ether 59:bis-propargyl ether 60:methyl ether 56, 43:31:26), and the residue was fractionated by preparative TLC (SiO2, pentane, −16 °C, 2 runs) to afford, as major products, an inseparable mixture of tertbutyl ether 59 and bis-propargyl ether 60 (35 mg, 59:60, 61:39; 59 17 mg, 16.5%; 60 18 mg, 20.7%), methyl ether 56 (12 mg; recovery 12.9%), and [HCCCH(CH3)(OH)]Co2(CO)6 (∼2 mg) (last two complexes were repurified on preparative TLC, SiO2, P:E, 5:1, −16 °C). tert-Butyl ether 59 + bis-propargyl ether 60: TLC (P:E, 5:1): Rf 0.74. 1H NMR (400 MHz, δ, CDCl3): 59 1.26 (9H, s, 3CH3), 1.47 (3H, d, CH3, J = 6.0), 4.75 (1H, q, CH, J = 6.4), 5.99 (1H, s, HCC); 60 1.54 (6H, d, 2CH3, J = 6.4), 4.98 (2H, q, CH), 6.10 (2H, s, HC C). The NMR spectrum of bis-propargyl ether 60 is in full agreement with previously published data.14 Methyl ether 56: dark red oil. TLC (P:E, 5:1): Rf 0.77. 1H NMR (400 MHz, δ, CDCl3): 1.52 (3H, d, CH3, J = 6.4), 3.47 (3H, s, OMe), 4.47 (1H, q, CH, J = 6.0), 6.11 (1H, s, HCC).23 μ-η2-[3-(tert-Butoxy)prop-1-yne]dicobalt Hexacarbonyl (66) and μ-η2-[3-(Prop-2-yn-1-yloxy)prop-1-yne]bis(dicobalthexacarbonyl) (67). Under an atmosphere of N2, Tf2O (141 mg, 0.50 mmol) was added dropwise (5 min) to a solution of methyl ether 63 (89 mg, 0.25 mmol) in dry CH2Cl2 (4 mL) at −50 °C. The reaction mixture was warmed to −10 °C over 30 min and cooled to −50 °C, and a solution of Cp2Co (95 mg, 0.50 mmol) in dry CH2Cl2 (2 mL) was added dropwise (5 min) and stirred for 3 h at −50 °C. The solution was treated with tert-butanol (1 mL) at −50 °C, stirred 20 min, warmed to 20 °C, and stirred for an additional 120 h. The reaction mixture was quenched with saturated brine (10 mL) at 0 °C, stirred 20 min, warmed to 20 °C, stirred an additional 20 min, diluted with pentane (20 mL), washed with H2O (3 × 15 mL), and dried (Na2SO4). The complex crude mixture was concentrated under reduced pressure (300 mbar, 4 h; NMR: tert-butyl ether 66:bispropargyl ether 67:methyl ether 63, 10:6:84), and the residue was fractionated by preparative TLC (SiO2, pentane, −12 °C, 2 runs) and repurified by preparative TLC (SiO2, P:E, 20:1, −12 °C) to afford, as major products, an inseparable mixture of tert-butyl ether 66 and bispropargyl ether 67 (8 mg, 66:67, 59:41; 66 3.7 mg, 3.7%; 67 4.3 mg, 5.2%) and methyl ether 63 (35 mg, 39.3% recovery). The spectral (NMR) and chromatographic (TLC) data for tert-butyl ether 66 and bis-propargyl ether 67 were consistent with those of authentic samples synthesized by the solvolysis of the primary propargyl cation with tertbutanol (next experiment) and by the complexation of the commercial bis-propargyl ether (Alpha Aesar) with dicobaltoctacarbonyl, respectively. μ-η2-[3-(tert-Butoxy)prop-1-yne]dicobalt Hexacarbonyl (66; Independent Synthesis). Under an atmosphere of nitrogen, HBF4· Et2O (243 mg, 1.50 mmol) was added dropwise to a solution of [HCCCH2(OH)]Co2(CO)6 (86 mg, 0.25 mmol) in pentane (10 mL) and ether (1 mL) at −20 °C and stirred 20 min until the solution was colorless. The precipitated cation was washed with pentane (2 × 10 mL) at −20 °C, a portion of pentane (5 mL) was added to the reaction flask, and tert-butanol (0.5 mL) was added at −20 °C. The mixture was warmed to 0 °C, stirred for 20 min, warmed to 20 °C, and stirred an additional 10 min until all of the precipitate dissolved. The I
DOI: 10.1021/acs.organomet.6b00730 Organometallics XXXX, XXX, XXX−XXX
Article
Organometallics = 13.4), 5.26 (1H, s, CH), 6.90 (2H, d, 3′-H, 5′-H, J = 8.4), 7.29 (2H, d, 2′-H, 6′-H). 13C NMR (100 MHz, δ, CDCl3): 55.50, 57.37, 59.05 (4-OCH3, 1′-OCH3, 4′-OCH3), 73.02 (4′-C), 83.46 (1′-C), 92.24, 99.31 (CC), 114.12, 127.56, 134.35, 159.73 (aromatic C), 199.59 (CO). MS TOF FD+: m/z M+ 506. MS HR TOF FD+: m/z calcd for C19H16O9Co2 M+ 505.9453, found 505.9470. Anal. Found: C, 45.08; H, 3.41. C19H16O9Co2 requires: C, 45.08; H, 3.19. d,l- and meso-μ-η2-[1,8-Dimethoxy-4,5-di(4′methoxyphenyl)octa-2,6-diyne]bis(dicobalthexacarbonyl) (79). Under an atmosphere of N2, Tf2O (141 mg, 0.50 mmol) was added dropwise (10 min) to a solution of methyl ether 76 (127 mg, 0.25 mmol) in dry CH2Cl2 (4 mL) at −50 °C. The reaction mixture was warmed to −10 °C over 30 min, stirred for 30 min at −10 °C, and cooled to −78 °C. A solution of Cp2Co (95 mg, 0.50 mmol) in precooled dry CH2Cl2 (−50 °C, 2 mL) was added dropwise (7 min) to the reaction mixture at −78 °C and stirred for an additional 30 min at −78 °C (TLC control). The solution was treated with methanol (1 mL) at −78 °C, stirred 20 min, quenched with saturated brine (10 mL) at 0 °C, stirred 20 min, warmed to 20 °C, and stirred for an additional 20 min. The reaction mixture was diluted with pentane (30 mL), and the organic layer was washed with H2O (3 × 20 mL) and dried (Na2SO4). The complex crude mixture (NMR: d,l-79:meso-79, 55:45) was concentrated under reduced pressure, and the residue was fractionated by preparative TLC (SiO2, P:E, 10:1, −16 °C, 2 plates, 1 run) to yield d,l-79 (repurification: SiO2, P:E, 10:1, −16 °C, 1 plate, 2 runs; SiO2, P:E, 10:1, −16 °C, 1 plate, 6 runs; 32 mg, 26.9%) as a dark red solid and meso-79 (
