Acquiring and Exploiting Persistency of Propargyl Radicals: Novel

Aug 22, 2016 - Sixth, an ability to reversibly make propargyl radicals resistant to dimerization would allow in unsymmetrical bis-propargyl systems in...
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Acquiring and Exploiting Persistency of Propargyl Radicals: Novel Paradigms Gagik G. Melikyan,* Ryan Davis, and Samantha Cappuccino Department of Chemistry and Biochemistry, California State University Northridge, Northridge, California 91330-8262, United States ABSTRACT: Three complementary methods for altering an intrinsic nature of propargyl radicals, from transient to persistent, were developed by fine-tuning the bulkiness and degree of substitution around the secondary and tertiary propargylic carbons, as well as by sterically enhancing a π-bonded Co2(CO)6 metal core. The latter was employed, as a mechanistic tool, for precluding an acetylene−allene rearrangement, stabilizing propargyl cations, and creating a steric hindrance that could provide for said transition from transient to persistent propargyl radicals. A window of opportunities was identified wherein the steric bulkiness in propargyl radicals remains below the “persistency threshold”, providing good to excellent stereoselectivities in radical dimerization reactions (d,l 62−100%). Along with the persistency threshold for tertiary propargyl radicals (278.2 Å3), two different thresholds for persistency in secondary propargyl radicals were established306.5 and 576.0 Å3 dependent upon the molecular architecture and the nature of the substituents populating the radical centers. Three alternative molecular platforms were designed to exploit a newly acquired dichotomy in allylic radicals (α-persistent-γ-transient) and trichotomy in pentadienyl radicals (α-persistent-γ-transient-εtransient), providing access to molecular assemblies with contiguous 4°−4°, 4°−3°, and 3°−3° carbon atoms.

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INTRODUCTION Organic radicals are odd-electron, highly reactive species undergoing a wide range of chemical reactionscoupling, addition, disproportionation, eliminationat nearly diffusioncontrolled rates.1 A steric factor was recognized early on2 as a key structural parameter that can effectively hinder intermolecular interactions and convert transient radicals into persistent species.3,4 Such an increase in steric hindrance can be achieved by introducing bulky substituents into a close vicinity to the radical center. The drawback of this approach is that the bulky groups introduced into the molecule, such as a phenyl, tertbutyl, or isopropyl group,3,4 are covalently bonded to the carbon framework and are not intended to be removable or to act as auxiliary groups. In this account, we developed a conceptually different strategy for converting organic transient radicals into their persistent counterparts by attaching a bulky, π-bonded, and removable metal core to the unsaturated functionality in proradical substrates. In particular, propargyl radical A was chosen as the transient organic species, and a Co2(CO)6 cluster5,6 was selected as a bulky auxiliary group that could potentially convert propargyl radicals into persistent species B (Figure 1). Thus, the main task was to experimentally determine whether the said metal cluster in combination with other determinants, i.e. a degree of substitution (1°, 2°, 3°) of the α radical center (R1, R2 = H, Alk, Ar) and the bulkiness of an axial ligand L (CO, PR3), could provide sufficient steric protection that would make propargyl radicals increasingly resistant to dimerization. The transition at issuefrom transiency to persistencycould serve six different objectives pertaining to synthetic, analytical, and fundamental chemistry. The first was to identify the composition of the α radical © XXXX American Chemical Society

Figure 1.

centerthe degree of substitution, nature, and bulkiness of substituentsthat would allow for dimerization to occur as an activated, not diffusion-controlled process and for stereoselectivities to be effectively controlled by the steric factors. In other words, we wanted to exploit a narrow window of opportunity for achieving high stereoselectivities in dimerization reactions of organometallic radicals before the requisite species would turn persistent. Second, achieving persistency with respect to the dimerization reaction7 between bulky metalcomplexed propargyl radicals would allow for studying the intermolecular radical additions to the activated double bonds, a synthetic area that remains scarcely studied because of the competing self-coupling reactions. Third, with an α-radical center made persistent, an introduction of the conjugated double bonds would allow for projecting a radical center away from the metal coordination site and studying dimerization reactions at the remote locations, such as γ- or ε-carbon atoms (C and D; Figure 1). Fourth, projecting a radical center into the Received: May 31, 2016

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DOI: 10.1021/acs.organomet.6b00435 Organometallics XXXX, XXX, XXX−XXX

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Figure 2.

predefined, select locations in the carbon chain (γ, ε, η, ι, or λ depending upon the number of alternating double bonds, from one to five) represents a novel, convenient method for selectively generating radicals in highly conjugated yne-polyene systems. Fifth, making an α position to the metal core persistent would allow for probing and determining the largest number of the double bonds that could be involved in the radical site projection or the largest distance over which the actual reaction center could travel in the course of the radical reaction. Sixth, an ability to reversibly make propargyl radicals resistant to dimerization would allow in unsymmetrical bispropargyl systems introduction of a persistent−transient dichotomy providing for selective participation of the propargyl triads in radical carbon−carbon bond-forming reactions.

propargyl alcohols 1 with HBF4 and isolation of cobaltstabilized propargyl cations 2, followed by reduction to the respective propargyl radicals 3 and subsequent dimerization to 1,5-alkadiynes 4 (Scheme 1). The second protocol11a,b,g,h was Scheme 1a

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RESULTS AND DISCUSSION In an all-carbon environment, organic radicals undergo dimerization reactions either in a stereorandom manner or with low to moderate stereoselectivities that in turn are dependent upon the size of the substituents around the reaction site, as well as radical generation methods, temperature, physical state, and reaction conditions.1,8 The formation of the radical C−C bonds occurs stereorandomly also in the larger, unsaturated organometallic radicals π-bonded to transition metals, such as Mo, Fe, Cr, and Co9,10 (domain 1, Figure 2). Increasing the steric hindrance around the reaction site in organic radicals can preserve their transiency, while exhibiting a certain level of stereoselectivity (domain 2, Figure 2). The secondary α-alkyl, α-phenyl radicals represent one of the first examples of successful stereodifferentiation, albeit moderate, with α-Me and α-Et radicals dimerizing stereorandomly (d,l:meso 1:1), while α-t-Bu radicals exhibit preference for the d,l configuration (d,l:meso 62:38).8a The qualitative change is observed when the cumulative bulkiness of substituents achieves some critical levels sufficient for persistency, with organic radicals becoming kinetically stable monomeric species which either are not susceptible to radical coupling reactions or dimerize reversibly1,3,4 (domain 3, Figure 2). In the purely organic setting, a combination of three phenyl groups, three tert-butyl groups, or select combinations thereof makes radicals persistent.4 At the inception of this project, no examples on persistent π-bonded organometallic radicals have ever been reported (domain 3, Figure 2).5,9,10 Therefore, the main goal was to probe dimerization reactions of cobaltcomplexed propargyl radicals by gradually increasing the bulkiness and degree of substitution at the α carbon atom in order to achieve the said persistency and find the threshold between domains 2 and 3, with the higher end of the former being the most suitable for achieving diastereoselectivity in radical C−C bond formation reactions and with the lower end of the latter being the most suitable for exploiting a newly acquired persistency. Alternative experimental protocols were developed for conducting radical dimerization reactions and assessing the transiency vs persistency of Co2(CO)6-complexed propargyl radicals. The first protocol11a−g involves treatment of π-bonded

a 1

R , R2 = H, alkyl, aryl, naphthyl, alkenyl, alkynyl, alkoxy.

specifically developed to avoid the use of strong acids, such as HBF4, thus making the reaction sequence benign to acidsensitive functionalities (Scheme 2). In particular, the requisite methyl propargyl ethers 5 were treated with triflic anhydride at low temperatures to convert to ionic triflates 6, with the latter being reducible with cobaltocene, a 19e− reducing agent.12 Methodologically, an adopted criterion for radicals to be categorized as transient in nature was the rate of dimerization reaction for radicals 3, forming respective dimeric products 4 at reasonable rates, in good to excellent yields (Scheme 3). In contrast, with the substituents R1 and R2 increasing in size, and creating more steric crowding α to the metal core, radicals 3 could become persistent, thus surrendering their ability to dimerize and resorting instead to an H atom abstraction reaction as the only mechanistic pathway allowing for conversion to stable end products (HAA 7). It is also conceivable that the certain combinations of α substituents R1 and R2 could make propargyl cations 2 persistent toward reduction, especially with a reducing agent such as cobaltocene;12 the latter is relatively large in size (V = 199.6 Å3) and comparable with requisite metal complexes (e.g., HC CCH(OH)PhCo2(CO)6 V = 327.6 Å3). TLC and NMR monitoring of those cations would reveal the absence of radical dimers 4 and HAA products 7, with the unreacted cations being quantitatively converted to methyl propargyl ethers 5 by methanol quenching (Scheme 3). In the search for secondary persistent propargyl radicals, we studied dimerization reactions of propargyl radicals 8−17, in which the triple bonds were protected with bulky Co2(CO)6 moieties (group I, Figure 3). The primary locale for varying requisite structures was an α carbon atom with substituents ranging from alkyl (8, n = 0−2, 6) to phenyl (9−14) to naphthyl (15, 16) to alkynyl (17) groups. In all those cases, the dimerization at issue was observed under a variety of experimental protocols, including the isolation of respective cations and their reduction with either zinc or cobaltocene (Scheme 1) or an in situ generation of respective propargyl triflates with triflic anhydride and a subsequent low-temperB

DOI: 10.1021/acs.organomet.6b00435 Organometallics XXXX, XXX, XXX−XXX

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Organometallics Scheme 2a

a 1

R , R2 = H, alkyl, aryl, naphthyl, alkenyl, alkynyl, alkoxy.

Scheme 3a

a 1

R , R2 = H, alkyl, aryl, naphthyl, alkenyl, alkynyl, alkoxy.

into two distinct categories: i.e., 2°/sp3 (8) and 3°/sp2 (9−16). The third category, 2°/sp, is represented by α-alkynyl propargyl radicals 17 which dimerize with an excellent regioselectivity, α to the metal core, and form d,l-1,1,2,2-tetraethynylethanes with high diastereoselectivities (82−93%).11i Given the topology of 1,4-alkadiynes, the only locale available to the structural variations are γ,γ′-acetylenic termini. In particular, a bulky substituent in the γ′ position could potentially affect the course of the reaction, given its demonstrated ability for inducing a 1,3-steric induction.11f Introducing duplicate TMS and phenyl groups in the γ and γ′ positions did not provide persistency, with the latter (γ = Ph, γ′ = Ph) affording higher yields and enhanced stereoselectivity in the formation of the respective α,α dimers.11i Arranged in group II are propargyl radicals 18− 20 (Figure 3), which contain the α-alkoxy groups and can sterically mimic 2° propargyl radicals with sp3-hybridized αcarbon atoms such as 8.11j Requisite radicals were generated from the respective acetals according to the Tf2O−Cp2Co protocol11h that provides for an in situ generation of ionic propargyl triflates and their low-temperature reduction with cobaltocene (−50 °C). While an absolute volume of the substituent in the α-position was gradually increasing (VOMe = 35.4 Å3, VOEt = 53.8 Å3, VOiPr = 72.2 Å3), radicals 18−20 were able to maintain transiency and to form 3,4-dialkoxy-1,5alkadiynes in moderate yields and with high d,l diastereoselectivity (83−92%).11j Quantitatively, given the calculated volume of the cobalt−alkyne core, the total volume of both

ature reduction with cobaltocene (Scheme 2). The formation of respective radical dimers such as 4 (Scheme 3) was observed in good to high yields (45−75%) with predominant formation of d,l diastereomers (63−98%).11a In an α-methoxyphenyl series,11a relocation of the substituent along the periphery of the aromatic nucleus (10, 4-OMe; 11, 3-OMe; 12, 2-OMe) did not provide for a noticeable level of persistency despite a close proximity of the 2-OMe group to the radical center (Zn, 61− 70%; Cp2Co, 52−63%). Introducing a larger naphthyl group α to the radical center (15, 16) did not impede the dimerization reaction with zinc as a reducing agent (Zn, 49−58%), although the yields were systematically lower in the case of a bulky and homogeneous reductant (Cp2Co, 22−32%).11h An X-ray crystallographic analyses indicated that d,l dimers derived from α-Ph11a−c (9) and α-2-naphthyl radicals (16)11h are conformationally similar with flat aromatic rings positioned gauche to each other. Given the planarity of aromatic nuclei, and a lack of conformational constraints in place, it was concluded that any further increase in size, or the number of aromatic rings, could hardly lead to a desired level of persistency. Quantitatively, an experimentally established transiency for secondary propargyl radicals 8−16 is best expressed by the total bulkiness around the radical centers that varies within the range of 227−377 Å3. Other determinants to consider are the degree of substitution of the carbon atom directly attached to the radical center (2°, 3°, 4°) and its hybridization state. Accordingly, radicals 8−16 can be separated C

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Figure 3.

Scheme 4

complex 22 was synthesized in two steps (condensation/ complexation)13 and then converted to the requisite cation 23 by a low-temperature treatment with HBF4 (Scheme 4). Reduction with cobaltocene11 was carried out at −50 °C to initiate a radical reaction, and then the reaction mixture was treated with methanol in order to retrieve any unreacted cation 23. A careful examination of the crude mixture by means of

substituents in the pseudo 2° propargyl radicals 18−20 fell within the range of 262−299 Å3. α Quaternary Carbon Induced Persistency of the Secondary Propargyl Radical. In propargyl radical 21, a degree of substitution of the α substituent was further elevated, moving from tertiary toward quaternary carbon atoms (group III, Figure 3). To probe this class of propargyl radicals, cobalt D

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Organometallics Scheme 5

agent. The fact that the cation 23 exhibited an unexpected compatibility with cobaltocene shows that both entities cannot communicate effectively due to their steric bulkiness, topology, and probably an unfavorable electronic distribution in redox components. Axial Ligand Induced Persistency of the Secondary Propargyl Radical. Introducing a phosphorus ligand into a cobalt core represents an alternative strategy for making propargyl radicals persistent (group IV, Figure 3). Two different topologies were tested by replacing carbon monoxide with trimethylphosphine and triphenylphosphine in α-alkoxy and α-phenyl derivatives 28 and 29, respectively (Figure 3). The most attractive feature of this approach is that the structural alteration to the carbon framework, intended by design to control the kinetic stability of propargyl radicals, is not introduced in the π-bonded ligand but into the metal core14 that can be oxidatively removed15 after the radical reaction, releasing an organic product. In the propargyl acetal series,11j trimethylphosphine was tested in an α-OEt-substituted propargyl radical, expecting that a much larger phosphorus ligand (VPMe3 = 94.6 Å3; VCO = 33.8 Å3) might block an α carbon atom and impede a dimerization reaction. Under the standard conditions,11h,j dimerization did in fact occur, providing access to 3,4-diethoxy-1,5-hexadiynes with an enhanced diastereoselectivity (d,l 93%). These data indicated that the combination of an alkoxy group in an α position and a PMe3 group in an axial position (28, Figure 3) did not provide for the critical level of steric hindrance that is needed for radical persistency. Sterically, substrate 29 (Figure 3) represents enhancements in two dimensions: i.e., a larger α substituent (VPh = 91.5 Å3; VOEt = 53.8 Å3) and a larger axial ligand (VPPh3 = 291.7 Å3; VPMe3 = 94.6 Å3). A triphenylphosphine ligand was introduced in cobalt complex 30 according to the literature protocol16 that involves treatment of the requisite alcohol 31 with an equimolar amount of the phosphorus ligand at elevated temperatures (Scheme 5). The formation of the cation 32 was substantially facilitated due to the powerful stabilizing effect of the axial ligand.16 Reduction with zinc to generate radical 33 was followed by decomplexation with Ce(NH4)2(NO3)615 and reverse complexation with Co2(CO)8.13b This reaction sequence allowed for release of the products of the initial

NMR spectroscopy indicated that an in situ generation of radical 24 did take place, although no detectable amounts of dimeric product 25 were present. Instead, the HAA product 26 was isolated (10.5%) along with Me ether 27 (52.4%), a solvolysis product of the unreacted cation 23 (Scheme 4). Thus, radical 24 is the f irst persistent secondary propargyl radical ever reported (Vtotal = 306.5 Å3). It proves that there is not a single determinant of the persistency of the propargyl radicals. Along with the cumulative bulkiness determined by the substituents directly attached to the radical center, a degree of substitution of the β carbon atom (2°, 3°, 4°) appears to be as critical: radical 20 with an α OiPr group is sterically similar to radical 24 with a t-Bu substituent (VOiPr = 72.2 Å3 vs VtBu = 79.9 Å3), but there is a profound difference in their behavior transient vs persistentdue to the fact that radical 24 contains the quaternary carbon atom directly attached to the radical center. Attendant with it is another parameter that can be identified as an additional determinant: type of hybridization of the β atom directly attached to the α radical center. The persistency of radical 24 shows that an sp3 hybridization with the local tetrahedral geometry is more efficient in impeding dimerization than a flat geometry of the sp2-hybridized carbon atoms, in either phenyl (9−14) or naphthyl (15, 16) substituents. The kinetic stability of radical 24 also indicates that the scope of persistency can be expanded by introducing structural homologues of the tert-butyl group with the larger number of carbon atoms, such as CR3 (R = Et, Pr, Bu) as well as main-group elements bulkier than carbon itself (Si, Ge, Sn, Pb). The formation of Me ether 27 as the main product (Me ether 27, 52.4%; HAA 26, 10.5%) suggests that the cation 23 is the f irst Co2(CO)6-complexed propargyl cation persistent to reduction with cobaltocene. This phenomenon has never been observed in radical dimerizations of the metal-complexed propargyl radicals.5,9−11 In contrast, given the very nature of cobaltocene as a powerful one-electron reducing agent,12 the reaction times are usually measured in minutes, even at temperatures as low as −78 °C.11a,b,d,g,j Thus, the strategy adopted by us (Scheme 3) allows for differentiating between the cation persistency toward reduction and radical persistency toward dimerization. In other words, two determinants for the successful radical generation are the cumulative bulkiness around the cationic center and the volume of the reducing E

DOI: 10.1021/acs.organomet.6b00435 Organometallics XXXX, XXX, XXX−XXX

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Organometallics Scheme 6

Scheme 7

radical reaction (34, 35) from chiral metal bondages and subsequent complexation of organic dimer 36 and HAA product 37 to form the easily identifiable11k bis-cluster 38 (3%) and HAA product 39 (2%). The very fact that both products were formed in trace amounts is indicative of the fact that radical 33 acquired a long sought after persistency due to the close proximity of the bulky axial ligand (PPh3) to the radical center that effectively blocked the convergence of radical species. It is noteworthy that the treatment of the crude radical mixture with methanol did not form any detectable amounts of the respective Me ether, [(HCC)CH(OMe)Ph]Co2(CO)6,11k thus attesting to the fact that the reduction did indeed take place and it was not impeded by the substrate topology. Thus, introducing an axial ligand in the cobalt core represents a facile method for making the transient secondary propargyl radicals persistent, with the chiral metal cluster acting as a removable molecular template. In quantitative terms, the threshold for achieving persistency is equal to 576.0 Å3 (V(HCC)CH2Co2(CO)6 (226.6 Å3) − VCO (33.8 Å3) + VPh (91.5 Å3) + VPPh3 (291.7 Å3)). For comparison, in secondary propargyl radicals carrying an α tert-butyl group, such as 24, the total volume required for persistency was only 306.5 Å3, indicating that there are two dif ferent thresholds for persistency in secondary propargyl radicals dependent upon the molecular architecture and the nature of the substituents around the radical center. Persistent Tertiary Propargyl Radicals. Having developed two methods for achieving persistency in secondary propargyl radicals, we turned to tertiary radicals in order to

interrogate their structural requirements toward the bulkiness of α substituents. Two types of tertiary radicals, 40 and 41, were probed (group V, Figure 3) along with the structurally related pseudo-3° propargyl radical 42 (group VI, Figure 3). Of particular interest was the simplest tertiary propargyl radical 43, containing an unsubstituted acetylenic terminus and α,α-methyl groups directly attached to the radical center (Scheme 6). Cobalt complex 44 was synthesized from the commercially available tertiary alcohol by complexation with dicobalt octacarbonyl13b and then treatment with HBF45,11 to form tertiary propargyl cation 45. Its reduction with cobaltocene was carried out at −50 °C with the crude mixture being treated with methanol to trap any unreacted tertiary cation 45. A careful NMR examination of the crude mixture showed that no radical dimer 46 was formed, with HAA product 47 (52.0%) and Me ether 48 (11.5%) being two major products. These data indicate that intermediate 43 represents the smallest persistent tertiary propargyl radical with a cumulative volume of 278.2 Å3. This value can serve as a lowest reference point in designing the persistent tertiary radicals with the alternative all-carbon or heteroatom-containing substituents. Thus, the steric threshold was exceeded in an α-methyl α-ethyl tertiary propargyl alcohol (type 41, γ′-Ph; Figure 3), which failed to dimerize, affording the respective HAA product (34.0%) and Me ether (8.3%).11j A pseudo tertiary propargyl radical containing α-methyl and αmethoxy substituents (type 42, γ′-Ph; Figure 3) also failed to dimerize, undergoing rapid β scission (46.3%) and H atom transfer (33.7%) reactions.11j Having developed three alternative methods for building the persistent 2° (two) and 3° (one) propargyl radicals, we F

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Organometallics Scheme 8

Scheme 9

to the metal core was the first attempt to trigger an allylic rearrangement in the persistent tertiary radical 49(α) and escape a steric congestion that was builtby designaround a propargyl position (Scheme 7).11g Alcohol 50 was converted to cation 51, which was then reduced with zinc to generate the tertiary radical 49(α). As anticipated, the latter exhibited a complete persistency with respect to radical dimerization reactions, forming no detectable amounts of α,α dimer 52. The presence of a double bond provided for an “escape route”, rearranging a spin density from the α to γ position within an

designed three topologically diverse molecular platforms to demonstrate that the newly acquired persistency can be exploited for controlling the regioselectivity of the radical reactions and for projecting reaction sites away from the locale of the initial cation generation. In all cases, the double bond was used as a molecular vehicle for repositioning the reaction site toward the periphery of the molecules, in both acyclic and cyclic settings. Exploiting Persistency I: Projection α to γ in Acyclic Systems. Chronologically, introducing an isobutenyl group α G

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isolation of cation 63 was still complicated by the formation of pentane-soluble side products supposedly derived from electrophilic addition reactions across the conjugated double bonds. Treatment with methanol allowed us to determine that, under the conditions chosen, alcohol 61 undergoes complete conversion to cation 63, although its sizable fraction (ca. 43%) could not be precipitated due to a multitude of side reactions. Reduction of cation 63 with a 2-fold excess of Cp2Co at low temperatures (−78 to −20 °C) allowed for an in situ generation of radical 64, which is trichotomic by design: i.e., an α radical should exhibit the persistency, while the γ and ε locations should retain the transiency (persistent−transient− transient trichotomy). The crude mixture contained γ,ε dimer 65 and γ,γ dimer 66 in a 93:7 ratio, attesting to the high regioselectivity of the radical coupling reaction (Scheme 9). No detectable amounts of the respective ε,ε dimer 67 were found in a careful examination of the NMR spectrum. In addition to dimeric products, α-HAA 68 was also formed, with the reaction chemoselectivity being equal to (γ,ε-65 + γ,γ-66):α-HAA 68 74:26. Dimeric products proved to be inseparable by means of preparative TLC on silica gel at low temperatures (−15 °C; 52.4%), but a careful examination of their thermal stabilities established that the heating of the isomeric mixture at 70 °C for 3 h allows isolation of γ,ε-dimer 65 in pure form (61.1%).21 Decomplexation with ceric ammonium nitrate afforded organic γ,ε dimer 69 (77.8%), rich in unsaturation and unique in topology (Scheme 9). Its carbon framework contains contiguous 3°−4° carbon atoms, a common structural motif in natural product chemistry,17,22 and also represents multiple classes of unsaturated compounds (1,3-/1,4-/1,5-/1,7-diene; 1,3-/1,6-/1,7-/1,9-enyne; 1,11-diyne; 1,3-dien-5-yne) ripe for transition-metal-induced cyclizations.23 The steric and electronic reasons for the regioselective formation of γ,ε-dimer 65 as a major product are not entirely clear at this stage. According to computational studies, among the organic products the most stable isomer is in fact the γ,ε dimer 69 (E = 51.2 kcal/mol), with the ε,ε dimer being the second most stable isomer (E = 52.9 kcal/mol), followed by the least stable γ,γ dimer (E = 55.2 kcal/mol). In our previous studies on cobalt-complexed propargyl radicals, formation of the cross-coupling products varied from nearly statistical to minor amounts depending upon the charge distribution in the requisite propargyl cations.11b In unsymmetrical allylic systems, formation of the new carbon−carbon bond predominantly occurs at the less-substituted terminus of the allylic triad.24 In 3,3-dimethylallyl radical, the ratio 16:30:54 of head to head (3°−3°), head to tail (3°−1°), and tail to tail (1°−1°) products was reported that apparently correlates with a decrease in the aggregate steric hindrance.25a In isoprenoid series with barium as a reducing agent, cross-coupling products (α,γ′; 1°−3°) were reported to form in quantities (23−49%) comparable to that of the major homocoupling products (α,α′; 1°−1°).25b Overall, the formation of γ,ε dimer 65, as a major product, represents a proof of concept that the dimerization reaction can be fully impeded at the α position with the reaction center being projected over three (α to γ), or even five (α to ε) atoms away from the site of the cation generation.

allylic triad. The tertiary radical 49(γ) exhibited transiency due to the much lower level of steric hindrance (α-C3° V (HC C )CH 2 Co 2 ( CO) 6 +( CH CH 2 )+ CH 3 = 292.6 Å 3 ; γ-C3° VCH2CHCMe2 = 94.3 Å3), thus forming γ,γ dimer 53 in high yield (86%).11g Its decomplexation proceeded smoothly at low temperatures, yielding the 1,5-diene-1,9-diyne 54 (70%) with contiguous quaternary carbon atoms.11g,17 Due to the very design of this reaction, we created the persistent−transient dichotomy in an allylic system wherein radical 49(α) is made persistent (due to the presence of a bulky cobalt−alkyne core), while radical 49(γ) exhibits transiency with said properties being mutually exclusive and jointly exhaustive. Exploiting Persistency II: Projection α to γ in Cyclic Systems. Alcohol 55 represents a cyclic version of its counterpart 50 wherein the carbon atom, α to the metal core, is made tertiary, while the ring carbon, γ to the metal core, remains secondary (Scheme 8). Accordingly, radical 56 becomes dichotomous in nature with Cα(persistent) and Cγ(transient) reaction sites being positioned at both ends of the allylic triad. Synthesized from cyclohexenone by the condensation−complexation sequence,13 alcohol 55 (77.5%) was converted to cyclic cation 57 under acidic conditions5,11 with subsequent reduction with a 3-fold excess of cobaltocene11,12 at low temperatures (−78 to −30 °C). Radical 56 followed two independent reaction pathways: i.e., dimerization in the γ position that involves secondary γ-radicals as transient species and hydrogen atom abstraction at both ends of the allylic triad. The former afforded γ,γ dimer 58 (59.5%) as an inseparable diastereomeric mixture (54:46), while the latter yielded α-HAA 59 and γ-HAA 60 in a 74:26 ratio (10.3%). For the purposes of characterization, γ-HAA 60 was also independently synthesized from alcohol 55 by treatment with CF3COOH−NaBH4 (56.0%).18 Overall, the product distribution favored a radical coupling reaction (γ,γ-58:α-HAA 59:γHAA 60 72:21:7), providing access to 3,3′-diethynyl-1,1′dicyclohex-2,2′-ene derivatives as a result of the regioselective dimerization of cyclohexenyl radicals of dual α-persistent−γtransient nature. Alternative approaches to the carbon framework at issue are severely limited:19 i.e., 3,3′-dialkynyl derivatives have never been reported in the literature, with only a 3,3′-dimethyl analogue being synthesized by the reduction of the respective allylic alcohol with ZnI 2− NaCNBH319a and by the Ti/Pd-mediated coupling of the respective ethyl carbonate (α,α′:α,γ′ 1:1; syn:anti 1:1).19b Exploiting Persistency III: Projection α to ε in Acyclic Systems. Having successfully blocked the dimerization reaction α to the metal core in cyclic and acyclic systems (Schemes 7 and 8), we turned our attention to more complex molecules containing two conjugated double bonds as an α substituent (D, Figure 1). Among the three alternative methods for making propargyl radicals persistent (Schemes 4−6), that employing a higher degree of substitution (3° vs 2°) at the α carbon atom was chosen as a tool for controlling the regioselectivity of the process (Scheme 6). Alcohol 61 was synthesized in two steps13 from commercially available dienone 62, which was treated with HBF45,11 to generate the requisite cation 63 (Scheme 9). The standard protocols11,20 applying a 4−10-fold excess of strong acid failed to work at any temperature regimen, given the cation’s strong susceptibility to polymerization. An empirically optimized procedure included a stepwise addition of 2 equiv of HBF4 at −40 °C with prolonged stirring after each addition step (1.5 h). The

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CONCLUSION An intrinsic transiency of propargyl radicals can be altered by exploiting, and fine-tuning, the main determinants involved: i.e., (1) bulkiness around the radical center, (2) degree of substitution of the radical center (2°, 3°), (3) degree of H

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Article

Organometallics

analyses (one plate unless indicated otherwise) were conducted on silica gel 60 F254 (EM Science; aluminum sheets) and silica gel 60 PF254 (EM Science; w/gypsum; 20 × 20 cm), respectively. Visualization was carried out with potassium permanganate aqueous solution unless indicated otherwise. Eluents are ether (E), petroleum ether (PE), pentane (P), and benzene (B). Mass spectra were run at the Regional Center on Mass Spectroscopy, UC Riverside, Riverside, CA (LIFDI, GCT Premier, Micromass; TOF Agilent 6210 LC-TOF instrument with a Multimode source). Computational work was carried out with Spartan’10, version 1.0.1 (Wave function Inc., Irvine, CA). Full characterization for compounds 53 and 54 is given in ref 11g. Radical Dimerizations of Cobalt-Complexed Propargyl Alcohols with Zinc as a Reducing Agent (General Protocol I). Under an atmosphere of nitrogen, HBF4·Me2O (1.50 mmol) was added dropwise (10 min) to a solution of propargyl alcohol (0.25 mmol) in dry ether (20 mL) at −20 °C. The reaction mixture was stirred for 5 min at −20 °C and then 1 h at 0 °C. The precipitate was allowed to settle at −20 °C, and the ethereal layer was removed. Dry ether (20 mL) was added along the inner wall of the flask, stirring was resumed for 15 min, the propargyl cation was allowed to settle, and the ethereal layer was removed. The washing was repeated twice (2 × 20 mL), the residual amount of ether was removed under reduced pressure, and the propargyl cation was dissolved in dry CH2Cl2 (5 mL) at −20 °C. The reaction mixture was then treated with zinc (2.50 mmol) and stirred for 5 min at −20 °C and then for 4 h at 20 °C (TLC control). Zinc was filtered off on a short bed of Florisil (1 in.), and the crude mixture was analyzed by NMR to determine the diastereometic composition (d,l:meso). Individual diastereomers were isolated by means of preparative TLC (silica gel) or column chromatography (silica gel or Florisil) in good to high yields. Radical Dimerizations of Cobalt-Complexed Propargyl Alcohols with Cobaltocene as a Reducing Agent (General Protocol II). Under an atmosphere of nitrogen, HBF4·Me2O (1.50 mmol) was added dropwise (10 min) to a solution of propargyl alcohol (0.25 mmol) in dry ether (20 mL) at −20 °C. The reaction mixture was stirred for 5 min at −20 °C and then 1 h at 0 °C. The precipitate was allowed to settle at −20 °C, and the ethereal layer was removed. Dry ether (20 mL) was added along the inner wall of the flask, stirring was resumed for 15 min, the propargyl cation was allowed to settle, and the ethereal layer was removed. The washing was repeated twice (2 × 20 mL), the residual amount of ether was removed under reduced pressure, and the propargyl cation was dissolved in dry CH2Cl2 (3 mL) at −20 °C. At−78 °C, a solution of Cp2Co (0.50 mmol/2 mL of dry CH2Cl2) was added dropwise (5 min), and the reaction mixture was stirred 15 min (TLC control). The crude mixture was filtered through a short bed of Florisil (1 in.) and analyzed by NMR to determine the diastereometic composition (d,l:meso). Individual diastereomers were isolated by means of preparative TLC (silica gel) or column chromatography (silica gel or Florisil) in good to high yields. Radical Dimerizations of Cobalt-Complexed Methyl Propargyl Ethers with Tf2O as a Mediator and Cp2Co as a Reducing Agent (General Protocol III). Under an atmosphere of nitrogen, Tf2O (0.26 mmol) was added dropwise to a solution of methyl propargyl ether (0.25 mmol) in dry CH2Cl2 (4 mL) at −50 °C. The reaction mixture was brought to −10 °C in 30 min (NMR control), and then a solution of Cp2Co (0.26 mmol) in dry CH2Cl2 (1 mL) was added dropwise at −50 °C. The reaction mixture was stirred for 10 min, diluted with saturated brine (10 mL), warmed to 0 °C in 40 min, and then extracted with ether (10 mL), washed with water (2 × 15 mL), and dried (Na2SO4). The diastereometic composition (d,l:meso) was determined by NMR, organic solvents were evaporated under reduced pressure, and individual diastereomers were isolated by means of preparative TLC (silica gel) or column chromatography (silica gel or Florisil) in good to high yields. (μ-η2-4,4-Dimethylpent-1-yn-3-ol)dicobalt Hexacarbonyl (22). Under an atmosphere of nitrogen, ethynylmagnesium chloride (1.25 g, 14.74 mmol; 24.6 mL, 0.6 M in THF) was added dropwise (15 min) to a solution of pivaloyl aldehyde (1.15 g, 13.40 mmol) in

substitution of the carbon atom directly attached to the radical center (2°, 3°, 4°), (4) hybridization state of the carbon atom attached to the propargylic position, and (5) size of the metal core. A bulky, removable, and π-bonded Co2(CO)6 cluster provided for stabilization of the requisite propargyl cations, exclusion of the acetylene−allene rearrangement, and siteselective generation of radicals by a single-electron transfer and also created the molecular template for attenuating the bulkiness by altering the volume of an axial substituent. In contrast to organic radicals dimerizing mostly stereorandomly in an all-carbon environment, for cobalt-complexed propargyl radicals a “window of opportunities” was identified wherein good to excellent stereoselectivities in radical coupling reactions can be achieved (d,l 62−100%) without surpassing the newly defined persistency thresholds (3° radicals, 278.2 Å3; 2° radicals, 306.5 or 576.0 Å3). Secondary propargyl radicals were made persistent by introducing quaternary, sp3-hybridized carbon atoms at the propargylic position or by replacing an axial carbon monoxide with bulkier phosphine ligands in the cobalt−alkyne complexes. Tertiary propargyl radicals, even with relatively small substituents such as methyl groups connected to the radical center, can be made persistent by complexation with a dicobalt hexacarbonyl core. Double bonds were used in persistent propargyl radicals for “escaping” highly congested areas and for projecting reaction sites toward the periphery of the carbon frameworks. The phenomena of dichotomy in allylic radicals (α-persistent−γ-transient) and trichotomy in pentadienyl radicals (α-persistent−γ-transient−ε-transient) were observed with radical coupling reactions, providing access to molecular assemblies with contiguous tertiary and quaternary carbon atoms. New methods for assembling highly congested molecular units (4°−4°, 4°−3°, 3°−3°) can be used as key steps in targeted syntheses of organic compounds of relevance to medicinal chemistry, materials science, and natural product syntheses. Novel methodologies for creating persistency in πbonded organic radicals can be expanded toward new types of π-bonded unsaturated units (dienes, arenes, diynes, enynes) and transition metals other than cobalt (Fe, Cr, Mo, W, Mn) and could also allow for ESR detection of intermediate radicals, shedding light upon intimate structural details and a mode of the interaction of an unpaired electron with a π-bonded metal core.

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EXPERIMENTAL SECTION

General Considerations. All manipulations of air-sensitive materials were carried out in flame-dried 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, Alfa Aesar, and Sigma-Aldrich and used as received. Zinc was acquired from Aldrich (dust, 10 mm). Co2(CO)8, Cp2Co, and Ce(NH4)2(NO3)4 were purchased from Strem. NMR solvents were supplied by Cambridge Isotope Laboratories. 1H and 13 C NMR spectra were recorded on a Bruker Avance III-400 (1H, 400 MHz) spectrometer. Chemical shifts were referenced to internal solvent resonances and are reported relative to tetramethylsilane. Spin−spin coupling constants (JHH) are given in hertz. Elemental analyses were performed by Columbia Analytical Services (Kelso, WA). Melting temperatures (uncorrected) were measured on a MelTemp II (Laboratory Devices) apparatus and EZ-Melt (Stanford Research Systems). Silica gel S735-1 (60−100 mesh; Fisher) was used for flash column chromatography. Analytical and preparative TLC I

DOI: 10.1021/acs.organomet.6b00435 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics dry THF (30 mL) at −20 °C. Upon addition, the reaction mixture was stirred for 20 min at −20 °C, brought to 20 °C, and stirred for 10 min (TLC control). The crude mixture was quenched with saturated NH4Cl(aq) (10 mL) at 0 °C, stirred for 15 min, diluted with water (50 mL), and extracted with ether (25 mL). An aqueous layer was separated, combined ethereal layers were washed with water (3 × 20 mL) and dried (Na2SO4), and solvents were evaporated under reduced pressure. Under an atmosphere of nitrogen, the crude alcohol (1.128 g, 10.07 mmol) was dissolved in dry ether (10 mL) and added dropwise (10 min) to a solution of dicobalt octacarbonyl (3.44 g, 10.07 mmol) in dry ether (20 mL) at 20 °C. The reaction mixture was stirred for 3 h (TLC control), concentrated under reduced pressure, and fractionated on silica gel (200 g, anaerobic conditions, dry ice jacket; PE:E, 10:1) to afford 22 (904 mg, 17.0% over two steps) as a dark red oil. TLC (PE:E, 5:1): Rf 0.47. 1H NMR (400 MHz, δ, CDCl3): 1.05 (s, 9H, 3CH3), 1.83 (d, J = 5.2, 1H, OH), 4.47 (d, 1H, CH, J = 5.6), 6.06 (s, 1H, HC). 13C NMR (100 MHz, δ, CDCl3): 26.4 (3CH3), 36.9 (C4), 72.7, 81.0 (C3, HCC), 96.4 (HCC), 199.9 (CO). MS TOF FD+: m/z M+ 398. MS HR TOF FD+: m/z calcd for C13H12O7Co2 M+ 397.9242, found 397.9260. Anal. Found: C, 38.62; H, 3.02. Calcd for C13H12O7Co2: C, 39.22; H, 3.04. (μ-η2-4,4-Dimethylpent-1-yne)dicobalt Hexacarbonyl (26) and (μ-η2-3-methoxy-4,4-dimethylpent-1-yne)dicobalt Hexacarbonyl (27). Cp2Co-mediated dimerization reaction: under an atmosphere of nitrogen, HBF4·Et2O (243 mg, 1.50 mmol) was added dropwise (5 min) to a solution of alcohol 22 (99.5 mg, 0.25 mmol) in dry pentane (20 mL) at −20 °C. The reaction mixture was stirred for 20 min at −20 °C until the solution became colorless. The precipitate was washed with pentane (2 × 20 mL) at −20 °C, and residual organic solvent was evaporated under reduced pressure (−20 °C). The cation 23 was dissolved in dry CH2Cl2 (4 mL), and a solution of Cp2Co (94.5 mg, 0.50 mmol) in dry CH2Cl2 (2 mL) was added dropwise (10 min) at −30 °C. The solution was stirred for 8 h at −30 °C and treated with MeOH (1 mL), and stirring was continued for an additional 1 h at −30 °C. The reaction mixture was diluted with ether (30 mL), washed with water (20 mL), extracted with ether (3 × 10 mL), and dried (Na2SO4). The crude mixture (NMR: HAA 26:Me ether 27 17:83) was concentrated under reduced pressure (350 mbar), and the residue was fractionated by preparative TLC (pentane, −16 °C) to afford HAA 26 (10 mg, 10.5%; 350 mbar, 6 h) and Me ether 27 (54 mg, 52.4%; 350 mbar, 4 h). HAA 26: dark red oil. TLC (PE): Rf 0.68. 1H NMR (400 MHz, δ, CDCl3): 1.04 (9H, s, 3CH3), 3.02 (2H, s, CH2), 6.08 (1H, s, HC). MS TOF FD+: m/z M+ 382. MS HR TOF FD+: m/z calcd for C13H12O6Co2 M+ 381.9292, found 381.9291. Me ether 27: dark red oil. TLC (PE:E, 5:1): Rf 0.68. 1H NMR (400 MHz, δ, CDCl3): 1.03 (9H, s, Me3C), 3.61 (3H, s, OCH3), 3.95 (1H, d, CH, J = 0.4), 6.03 (1H, d, HC). 13C NMR (100 MHz, δ, CDCl3): 26.8 (Me3C), 38.1 (C-4), 61.0 (OMe), 73.1 (HCC), 91.5 (C-3), 93.0 (HCC). MS TOF FD+: m/z M+ 412. MS HR TOF FD+: m/z calcd for C14H14O7Co2 M+ 411.9398, found 411.9412. Anal. Found: C, 40.87; H, 3.43. Calcd for C14H14O7Co2: C, 40.80; H, 3.42. (μ-η2-d,l-3,4-Diphenyl-1,5-hexadiyne)- and (μ-η2-meso-3,4Diphenyl-1,5-hexadiyne)bis(dicobalt hexacarbonyl) (38) and (μ-η2-3-phenyl-1-propyne)dicobalt Hexacarbonyl (39). Under an atmosphere of nitrogen, HBF4·Et2O (243 mg, 1.50 mmol) was added dropwise to a solution of alcohol 30 (163 mg, 0.25 mmol) in degassed pentane (20 mL) and ether (20 mL) at −20 °C. The reaction mixture was stirred at −20 °C (15 min), and the precipitant was allowed to settle. The cation 32 was washed with degassed pentane (2 × 20 mL) at −20 °C, and residual solvent was evaporated under reduced pressure (30 min, −20 °C). The residue was dissolved in dry CH2Cl2 (5 mL) and stirred for 5 min at −20 °C. Degassed zinc (163 mg, 2.50 mmol) was added in one portion at −20 °C, and the reaction mixture was stirred for 5 min, warmed to 20 °C, and stirred for an additional 2 h (TLC control). At −10 °C, quenching was performed with MeOH (1 mL) and the temperature was raised to 20 °C over 20 min. Zinc was filtered off on a short bed of Florisil (1 in.), and the crude mixture (34 + 35) was concentrated under reduced pressure, dissolved in degassed acetone (5 mL), and treated at −78 °C with a solution of Ce(NH4)2(NO3)6 (1.10 g, 2.00 mmol) in degassed acetone

(8 mL; dropwise, 10 min; N2 atmosphere). The reaction mixture was stirred for 1 h at −78 °C, brought to −30 °C, stirred an additional 1 h, and warmed to −15 °C over 1 h. Saturated brine (15 mL) was added at −10 °C, and stirring was continued for another 15 min. An aqueous layer was extracted with ether (3 × 10 mL), the combined ethereal layers were filtered over a short bed of MgSO4 (2 in.), and concentrated under reduced pressure (200 mbar). Under an atmosphere of nitrogen, the residue (36 + 37) was dissolved in ether (5 mL) and added dropwise (10 min) to a solution of Co2(CO)8 (85.5 mg, 0.25 mmol) in ether (30 mL) at 20 °C. The reaction mixture was stirred for 3 h at 20 °C, concentrated under reduced pressure (250 mbar), and fractionated by preparative TLC (pentane, two runs) to afford 38 (3 mg, 3.0%, d,l-38:meso-38 86:14) and HAA 39 (2 mg, 2.0%). (μ-η2-3-Methylbut-1-yne)dicobalt Hexacarbonyl (47) and (μη2-3-methoxy-3-methylbut-1-yne)dicobalt Hexacarbonyl (48). Under an atmosphere of nitrogen, HBF4·Et2O (243 mg, 1.50 mmol) was added dropwise (5 min) to a solution of alcohol 44 (92.5 mg, 0.25 mmol) in dry pentane (20 mL) and ether (2 mL) at −20 °C. The reaction mixture was stirred for 20 min at −20 °C until the solution became colorless. The cation 45 was washed with dry pentane (2 × 20 mL; 30 min stirring for each cycle) at −20 °C, and residual organic solvents were evaporated under reduced pressure (−20 °C, 30 min). The cation 45 was dissolved in dry CH2Cl2 (5 mL), and a solution of Cp2Co (94.5 mg, 0.50 mmol) in dry CH2Cl2 (2 mL) was added dropwise (10 min) at −78 °C. The reaction mixture was stirred for 1 h at −78 °C, an additional 1 equiv of Cp2Co (47.3 mg, 0.25 mmol; dry CH2Cl2, 1 mL) was added dropwise (10 min) at −78 °C, and stirring was continued for an additional 1 h. The solution was brought to −30 °C, stirred for 2 h, treated with methanol (0.5 mL) at −20 °C, and stirred for another 20 min at the same temperature. The crude mixture was washed with water (2 × 10 mL), extracted with pentane (3 × 10 mL), and dried (Na2SO4). The reaction mixture (NMR: HAA 47:Me ether 48 69:31) was concentrated under reduced pressure (350 mbar), and the residue was fractionated by preparative TLC (pentane) to afford HAA 47 (46 mg, 52.0%; 4 h, 350 mbar) and Me ether 48 (repurified by preparative TLC, P:E, 5:1, 11 mg, 11.5%; 4 h, 400 mbar). HAA 47: Dark red oil. TLC (PE): Rf 0.57. 1H NMR (400 MHz, δ, CDCl3): 1.28 (6H, d, 2CH3, J = 6.4), 3.05 (1H, septet of doublets, H-3, J = 6.7, J = 1.0), 6.04 (1H, d, HC, J = 1.2). 13C NMR (100 MHz, δ, CDCl3): 25.3 (3-Me, C4), 32.7 (C3), 72.8 (HCC), 106.5 (HCC), 200.3 (CO). MS TOF FD+: m/z M+ 354. MS HR TOF FD+: m/z calcd for C11H8O6Co2 M+ 353.8979, found 353.8970. Anal. Found: C, 37.43; H, 2.33. Calcd for C11H8O6Co2: C, 37.32; H, 2.28. Me ether 48: brick red oil. TLC (PE:E, 5:1): Rf 0.53. 1H NMR (400 MHz, δ, C6D6): 1.32 (6H, s, 2CH3), 2.98 (3H, s, OCH3), 5.48 (1H, s, HC). 13C NMR (100 MHz, δ, CDCl3): 29.5 (3-Me, C4), 50.4 (OMe), 73.2 (HCC), 77.2 (C3), 101.0 (HCC), 200.0 (CO). MS TOF FD+: m/z M+ 384. MS HR TOF ESI/APCI: calcd for C12H10O7Co2 M+ 383.9085, found 383.9095. Anal. Found: C, 37.52; H, 2.64. Calcd for C12H10O7Co2: C, 37.53; H, 2.62. {μ-η2-1-[(Trimethylsilyl)ethynyl]cyclohex-2-en-1-ol}dicobalt Hexacarbonyl (55). Under an atmosphere of nitrogen, n-butyllithium (352 mg, 5.50 mmol; 3.44 mL, 1.6 M in hexane) was added dropwise (5 min) to a solution of (trimethylsilyl)acetylene (539 mg, 5.50 mmol) in dry THF (20 mL) at −10 °C. Upon addition, the reaction mixture was stirred for 5 h at −10 °C, a solution of cyclohex-2-en-1-one (480 mg, 5.00 mmol) in dry THF (5 mL) was added dropwise (8 min) at −10 °C, and the reaction mixture was stirred for 2 h at 20 °C (TLC control). The crude mixture was quenched with saturated NaCl(aq) (50 mL) at −10 °C and diluted with ether (40 mL), and an aqueous layer was separated and extracted with ether (3 × 20 mL). The combined ethereal layers were dried (Na2SO4), and organic solvents were evaporated under reduced pressure. Under an atmosphere of nitrogen, the crude alcohol (970 mg, 5.00 mmol, assuming 100% yield) was redissolved in dry ether (20 mL) and added dropwise (22 min) to a solution of dicobalt octacarbonyl (1.80 g, 5.25 mmol) in dry ether (20 mL) at 20 °C. The reaction mixture was stirred for 3 h at 20 °C (TLC control), concentrated under reduced pressure, and fractionated on silica gel (250 g, anaerobic conditions, dry ice jacket; J

DOI: 10.1021/acs.organomet.6b00435 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics

56.0%; γ-HAA 60:α-HAA 59 98:2) as a dark red solid. TLC (P): Rf 0.60. 1H NMR (400 MHz, δ, C6D6): 0.31 (9H, s, Me3Si), 1.36 (2H, m, CH2), 1.52 (2H, m, CH2), 1.85 (2H, m, CH2), 2.33 (2H, m, CH2), 6.31 (1H, m, 2-H). 13C NMR (100 MHz, δ, CDCl3): 1.0 (Me3Si), 22.2, 23.3, 26.6, 31.4 (C3−C6), 79.9, 109.9 (CC), 131.0 (C2), 134.7 (C1), 200.8 (CO). MS TOF FD+: m/z M+ 464. MS HR TOF FD+: m/z calcd for C17H18O6SiCo2 M+ 463.9531, found 463.9511. [μ-η2-(E)-3,7-Dimethyl-1-(trimethylsilyl)octa-4,6-dien-1-yn-3ol]dicobalt Hexacarbonyl (61). Under an atmosphere of nitrogen, ethylmagnesium bromide (732 mg, 5.50 mmol; 1.83 mL, 3 M/ether) was added dropwise (5 min) to a solution of (trimethylsilyl)acetylene (539 mg, 5.50 mmol) in dry THF (20 mL) at −10 °C. Upon addition, the reaction mixture was stirred for 5 h at −10 °C, a solution of ketone 62 (620 mg, 5.00 mmol) in dry THF (5 mL) was added dropwise (5 min) at −10 °C, and stirring was continued for additional 2.5 h at 20 °C (TLC control). The crude product was treated with saturated NaCl(aq) (25 mL) at 0 °C and diluted with ether (25 mL), and an aqueous layer was separated and extracted with ether (3 × 25 mL). The combined organic layer was dried (Na2SO4), and volatile solvents were evaporated under reduced pressure. Under an atmosphere of nitrogen, the crude alcohol (1.11 g, 5.00 mmol, assuming 100% yield) was dissolved in ether (10 mL) and added dropwise (10 min) to a solution of dicobalt octacarbonyl (1.71 g, 5.00 mmol) in ether (20 mL) at 20 °C. The reaction mixture was stirred for 3 h at 20 °C (TLC control), concentrated under reduced pressure, and fractionated on Florisil (100 g, anaerobic conditions, dry ice jacket, PE:E, 10:1; repurification 75 g, anaerobic conditions, dry ice jacket, PE:E, 10:1) to afford 61 (1.46 g, 57.5%; over two steps) as a brick red solid. Mp: 52.7−54.0 °C (sealed capillary, dried by coevaporation with benzene, 3 × 1 mL). TLC (PE:E, 5:1): Rf 0.55. 1H NMR (400 MHz, δ, CDCl3): 0.33 (9H, s, Me3Si), 1.66 (3H, s, 3-CH3), 1.789, 1.791 (3H/3H, s/s, CH3, 7-CH3; baseline separation can be achieved in C6D6), 1.85 (1H, s, OH), 5.72 (1H, d, 4-H, J = 15.2), 5.77 (1H, spl d, 6-H, Jav = 11.0, Jav = 0.6), 6.58 (1H, dd, 5-H, J = 10.8). 13C NMR (100 MHz, δ, CDCl3): 1.16 (Me3Si), 18.59 (CH3), 26.29 (CH3), 32.29 (CH3), 74.90 (C3), 78.03, 121.31 (CC), 123.90, 124.33, 137.17, 137.66 (C4−C7), 200.42 (CO). MS TOF FD+: m/z M+ 508. MS HR TOF FD+: m/z calcd for C19H22O7SiCo2 M+ 507.9793, found 507.9769. Anal. Found: C, 44.82; H, 4.27. Calcd for C19H22O7SiCo2: C, 44.89; H, 4.36. [μ-η2-3,7,7,10-Tetramethyl-8-(2′-methylprop-1′-en-1′-yl)dodeca-3E,5E,9E-triene-1,11-diyne-1,12-bis(trimethylsilyl)]bis(dicobalt hexacarbonyl) (65), [μ-η2-3,8-Dimethyl-5,6-bis(2′methylprop-1′-en-1′-yl)deca-3E,7E-diene-1,9-diyne-1,10-bis(trimethylsilyl)]bis(dicobalt hexacarbonyl) (66), and [μ-η2-[(2,6dimethylocta-2,4E-dien-7-yn-8-trimethylsilyl)]dicobalt Hexacarbonyl (68). Under an atmosphere of nitrogen, HBF4·Et2O (40.5 mg, 0.25 mmol) was added to a solution of alcohol 61 (127 mg, 0.25 mmol) in degassed pentane (20 mL) at −40 °C. The reaction mixture was stirred for 1.5 h at −40 °C, an additional 1 equiv of HBF4·Et2O (40.5 mg, 0.25 mmol) was added, and stirring was continued for another 1.5 h at −40 °C. The cation 63 was allowed to precipitate, the supernatant solution was added dropwise to methanol (5 mL) at −20 °C, and this mixture was stirred for 20 min, warmed to 20 °C, diluted with water (10 mL), and extracted with pentane (30 mL). By NMR, the solvolysis product (54 mg) contained no unreacted alcohol 61, or its Me ether, but a myriad of side products. The cation 63 was washed with precooled, degassed pentane (−40 °C, 2 × 20 mL, 30 min each) and, upon evaporation of the residual solvent under reduced pressure (−50 °C, 30 min), was dissolved in dry, precooled CH2Cl2 (−40 °C, 5 mL). A solution of Cp2Co (95.0 mg, 0.50 mmol) in dry, precooled CH2Cl2 (−40 °C, 2 mL) was added dropwise (2 min) at −78 °C, and the reaction mixture was stirred for 20 min (TLC control). The temperature was raised to −20 °C, and the crude mixture was quenched with saturated brine (20 mL), warmed to +20 °C over 20 min, and extracted with pentane (30 mL). The organic layer was washed with water (3 × 30 mL), dried (Na2SO4), and concentrated under reduced pressure. The crude mixture (NMR: γ,ε-65:γ,γ-66:αHAA 68 69:5:26; regioselectivity γ,ε-65: γ,γ-66 93:7; chemoselectivity (γ,ε-65 + γ,γ-66):α-HAA 68 74:26) was fractionated by preparative TLC (two plates, pentane, −16 °C; loading was carried out at −16 °C

PE:E, 10:1) to afford 55 (1.86 g, 77.5% over two steps) as dark red crystals. Tdecomp = 56.3−110.5 °C (by TLC, partial decomposition; sealed capillary, dried by coevaporation with benzene, 3 × 1 mL). TLC (PE:E, 5:1): Rf 0.42. 1H NMR (400 MHz, δ, CDCl3): 0.31 (9H, s, 3CH3), 1.76−1.88 (3H, m, 3CH), 1.92 (1H, s, OH), 1.99−2.23 (3H, m, 3CH), 5.67 (1H, spl d, 2-H, J = 9.6), 5.91 (1H, ddd, 3-H, J = 4.8, J = 2.4). 13C NMR (100 MHz, δ, CDCl3): 1.1 (3CH3), 19.7, 25.5 (C5, C6), 40.9 (C4), 71.6 (C1), 78.4, 121.1 (CC), 130.5, 133.3 (C2, C3), 200.6 (CO). MS TOF FD+: m/z M+ 480. MS HR TOF FD+: m/ z calcd for C17H18O7SiCo2 M+ 479.9480, found 479.9469. Anal. Found: C, 42.52; H, 3.63. Calcd for C17H18O7SiCo2: C, 42.51; H, 3.78. {μ-η2-3,3′-[Bis(trimethylsilyl)ethynyl]-1,1′-dicyclohex-2,2′ene]}bis(dicobalt hexacarbonyl) (58), {μ-η2-3-[(Trimethylsilyl)ethynyl]cyclohexene}dicobalt Hexacarbonyl (59), and {μ-η2-2[(Trimethylsilyl)ethynyl]cyclohexene}dicobalt Hexacarbonyl (60). Under an atmosphere of nitrogen, HBF4·Et2O (243 mg, 1.50 mmol) was added dropwise (1 min) to a solution of alcohol 55 (120 mg, 0.25 mmol) in dry pentane (20 mL) at −20 °C. The reaction mixture was stirred for 30 min at −20 °C, and the precipitate was washed with dry pentane (2 × 20 mL; precooled, −20 °C; stirring 20 min per wash) at −20 °C. The cation 57 was dissolved in dry CH2Cl2 (5 mL) at −20 °C, stirred for 5 min, and Cp2Co (142 mg, 0.75 mmol; precooled, −50 °C; degassed, 5 min) was added in one portion at −78 °C. The reaction mixture was stirred for 1 h at −78 °C and then for an additional 1 h at −30 °C (TLC control). A saturated NaCl(aq) solution (10 mL) was added dropwise at −20 °C, and stirring was continued for 5 min. The organic layer was washed with DI water (3 × 15 mL) and dried (Na2SO4). The crude mixture (by NMR, (d,l-58 + meso-58):α-HAA 59:γ-HAA 60 72:21:7; d,l-58:meso-58, 54:46, relative configurations unassigned; α-HAA 59:γ-HAA 60, 74:26) was fractionated by preparative TLC (two plates, P; loading/development at −13 °C) to isolate inseparable mixtures of d,l-58 + meso-58 (74 mg) and α-HAA 59 + γ-HAA 60 (30 mg; α-HAA 59:γ-HAA 60 76:24). Both fractions were repurified by preparative TLC to afford d,l-58 + meso-58 (69 mg, 59.5%; P; loading/development at −13 °C; d,l58:meso-58, 54:46; purity 98%) and α-HAA 59 + γ-HAA 60 (12 mg, 10.3% by NMR, 99.4% purity; P, two runs; loading/development at −13 °C; α-HAA 59:γ-HAA 60, 56:44; α-HAA 60 partially decomposes on the preparative TLC plate, altering the original ratio of HAA products). d,l-58 + meso-58: dark red crystals. TLC (P): Rf 0.52. 1H NMR (400 MHz, δ, CDCl3): minor 0.32 (18H, s, 6CH3), major 0.34 (18H, s, 6CH3), minor + major 1.24−1.44, 1.59−1.72, 1.75−1.84, 1.86−1.96 (8H + 8H, m, 5-H, 6-H, 5′-H, 6′-H), 2.19−2.45 (6H + 6H, m, 1-H, 4-H, 1′-H, 4′-H), minor 6.03 (2H, s, 2-H, 2′-H), major 6.11 (2H, s, 2-H, 2′-H). 13C NMR (100 MHz, δ, CDCl3): minor + major 1.1 (Me3Si), 23.1 (C5, C5′), 80.2, 80.4, 109.5 (CCSiMe3), 200.6 (CO); minor 25.9, 31.9 (C4, C6, C4′, C6′), 42.1 (C1, C1′), 133.8 (C2, C2′), 136.5 (C3, C3′); major 24.1, 31.7 (C4, C6, C4′, C6′), 41.7 (C1, C1′), 134.3 (C2, C2′), 136.0 (C3, C3′). MS TOF FD+: m/z M+ 926. MS HR TOF FD+: m/z calcd for C34H34O12Si2Co4 M+ 925.8911, found 925.8937. Anal. Found: C, 42.94; H, 3.83. Calcd for C34H34O12Si2Co4: C, 44.08; H, 3.70. α-HAA 59 + γ-HAA 60: red viscous oil. TLC (P): Rf 0.60. 1H NMR (400 MHz, δ, C6D6): α-HAA 59 0.27 (9H, s, Me3Si), 1.41, 1.58, 1.79, 2.05 (1H, 2H, 2H, 1H, all multiplets, 3CH2), 3.50 (1H, m/10 lines, 3-H, Jav = 2.83), 5.69 (2H, AB/unsymm splitting pattern, 1-H, 2-H, JH(A)‑H(B) = 10.4); γ-HAA 60, for 1H NMR spectrum, see the next experiment. MS TOF FD+: m/z M+ 464. MS HR TOF FD+: m/z calcd for C17H18O6SiCo2 M+ 463.9531, found 463.9546. {μ-η2-2-[(Trimethylsilyl)ethynyl]cyclohexene}dicobalt Hexacarbonyl (60). Under an atmosphere of nitrogen, NaBH4 (5.7 mg, 0.15 mmol) and CF3COOH (74 mg, 0.65 mmol) were consecutively added to a solution of alcohol 55 (48 mg, 0.10 mmol) in dry CH2Cl2 (7 mL) at 0 °C. The suspension was stirred for 75 min at 0 °C (TLC control). The crude mixture was quenched with degassed saturated NaCl(aq) (10 mL) and diluted with water (10 mL). The aqueous layer was extracted with pentane (3 × 10 mL), and combined organic fractions were dried (Na2SO4) and concentrated under reduced pressure. The crude product was fractionated and then repurified by preparative TLC (P, −13 °C; P, −13 °C), affording γ-HAA 60 (26 mg, K

DOI: 10.1021/acs.organomet.6b00435 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics using a PTLC plate which was precooled at −16 °C for 40 min), affording the inseparable dimers γ,ε-65 and γ,γ-66 (γ,ε:γ,γ 92:8; 36 mg, 52.4% based on the amount of cation dimerized, i.e. 127 mg − 54 mg = 73 mg (0.14 mmol)) as a dark brown oil and highly unstable α-HAA 68 (13 mg, 18.9% based on the amount of cation dimerized) as a dark red oil. γ,ε-65 + γ,γ-66 (92:8): TLC (P): Rf 0.70. 1H NMR (400 MHz, δ, C6D6): γ,ε-65 0.34 (9H, s, Me3Si), 0.35 (9H, s, Me3Si), 1.09 (6H, s, 7-Me, 7-Me), 1.53 (3H, s, HCCMeMe), 1.56 (3H, s, HC CMeMe), 2.04, 2.13 (3H/3H, s/s, 3-Me/10-Me), 3.14 (1H, t, 8-H, J = 10.0), 5.16 (1H, d, HCCMeMe, J = 9.6), 6.09 (1H, d, 6-H, J = 15.2), 6.15 (1H, d, 9-H), 6.43 (1H, dd, 5-H, J = 11.2), 6.89 (1H, d, 4H, J = 10.8); γ,γ-66 0.33 (18H, s, 2Me3Si), 1.63 (6H, s, 2HC CMeMe), 1.67 (6H, s, 2HCCMeMe), 2.08 (6H, s, 3-Me, 8-Me),26 3.56 (2H, m/five lines, 5-H, 6-H, Jav = 6.4), 5.31 (2H, br d, 2HC CMeMe, J = 8.4), ∼6.17 (4-H, 7-H; partially overlapped with vinylic H atoms of γ,ε-65). 13C NMR (100 MHz, δ, CDCl3): γ,ε-65 0.87 (Me3Si), 1.09 (Me3Si), 18.7, 19.2, 19.6 (3-Me, 10-Me, MeEMeZCC), 24.9, 25.6, 26.3 (7-Me, 7-Me, MeEMeZCC), 41.7 (C8), 48.8 (C7), 79.6, 80.6, 111.1, 112.1 (CC), 123.0, 124.3, 131.2, 132.1, 132.9, 133.3, 134.9 (CC), 144.7 (C6), 200.6 (CO); γ,γ-66 0.93 (Me3Si), 18.4, 19.5, 23.3, 26.1, 29.9, 42.4, 43.2 (6Me), 77.9, 112.0 (CC), 123.6, 124.8, 131.1, 131.8, 133.1, 135.1, 144.9 (CC).26 MS TOF FD +: m/z M+ 982. MS HR TOF FD+: m/z calcd for C38H42O12Si2Co4 M+ 981.9537, found 981.9498. Anal. Found: C, 45.57; H, 4.46. Calcd for C38H42O12Si2Co4: C, 46.45; H, 4.31. α-HAA 68: TLC (P): Rf 0.75. 1 H NMR (400 MHz, δ, C6D6): 0.27 (9H, s, Me3Si), 1.32 (3H, d, 6Me, J = 6.8), 1.63 (6H, s, 2-Me, CH3), 3.51 (1H, quintet, 6-H, Jav = 7.1), 5.56 (1H, dd, 5-H, J = 14.8, J = 8.4), 5.88 (1H, spl d, 3-H, J = 10.8, J = 0.8), 6.34 (1H, dd, 4-H). MS TOF FD+: m/z M+ 492. MS HR TOF FD+: m/z calcd for C19H22O6SiCo2 M+ 491.9844, found 491.9864. Isolation of γ,ε-65 in an Individual Form. Under an atmosphere of N2, an inseparable mixture of γ,ε-65 and γ,γ-66 (36 mg, 0.037 mmol; ε,γ:γ,γ 92:8) in benzene (3 mL) was heated at 70 °C for 3 h and concentrated under reduced pressure. The crude mixture was fractionated by preparative TLC (pentane, −16 °C; loading was carried at −16 °C using a PTLC plate which was precooled at −16 °C for 40 min), affording pure γ,ε-65 (22 mg, 61.1%) as a dark brown oil. 1 H NMR (400 MHz, δ, C6D6): 0.34 (9H, s, Me3Si), 0.35 (9H, s, Me3Si), 1.088 (3H, s, 7-Me), 1.090 (3H, s, 7-Me), 1.53 (3H, d, HC CMeMe, J = 1.2), 1.56 (3H, s, HCCMeMe, J = 0.8), 2.04 (3H, d, 3Me or 10-Me, J = 1.2), 2.12 (3H, d, 3-Me or 10-Me, J = 1.2), 3.14 (1H, t, 8-H, J = 10.0), 5.16 (1H, spl d, HCCMeMe, J = 8.4, J = 1.2), 6.09 (1H, d, 6-H, J = 15.2), 6.15 (1H, spl d, 9-H, J = 1.2), 6.43 (1H, dd, 5H, Jav = 15.4, Jav = 11.0), 6.90 (1H, d, 4-H, J = 10.8). 3,7,7,10-Tetramethyl-8-(2′-methylprop-1′-en-1′-yl)dodeca3E,5E,9E-triene-1,11-diyne-1,12-bis(trimethylsilyl) (69). Under an atmosphere of N2, a solution of Ce(NH4)2(NO3)6 (48 mg, 0.088 mmol) in degassed acetone (3 mL) was added dropwise (5 min) to a solution of γ,ε-65 (22 mg, 0.022 mmol) in degassed acetone (5 mL) at −78 °C and stirred for 2 h. An additional portion of Ce(NH4)2(NO3)6 (48 mg, 0.088 mmol) in degassed acetone (3 mL) was added dropwise (5 min) at −78 °C, and the reaction mixture was stirred for 2 h at −78 °C and for another 2 h at −50 °C (TLC control). The crude mixture was warmed to −10 °C, treated with saturated NaCl(aq) (11 mL), and diluted with pentane (30 mL). The aqueous layer was extracted with pentane (3 × 10 mL), dried (Na2SO4), and concentrated under reduced pressure. The crude mixture was fractionated by preparative TLC (pentane, −16 °C; loading was carried out at −16 °C using a PTLC plate which was precooled at −16 °C for 40 min), affording 69 (7 mg, 77.8%) as a colorless viscous oil. TLC (P): Rf 0.29. 1H NMR (400 MHz, δ, C6D6): 0.24 (9H, s, Me3Si), 0.28 (9H, s, Me3Si), 0.92 (6H, s, 7-Me, 7-Me), 1.45 (3H, d, HCCMeMe, J = 1.2), 1.60 (3H, s, HCCMeMe, J = 1.2), 1.82 (6H, d, 3-Me/10-Me, J = 1.2), 3.04 (1H, t, 8-H, Jav = 10.2), 4.98 (1H, spl d, HCCMeMe, J = 10.0, J = 1.2), 5.68 (1H, d, 6-H, J = 15.6), 6.09 (1H, spl d, 9-H, J = 10.4, J = 1.6), 6.22 (1H, dd, 5-H, Jav = 15.4, Jav = 11.0), 6.58 (1H, d, 4-H, J = 11.2). 13 C NMR (100 MHz, δ, CDCl3): 0.32 (Me3Si), 0.34 (Me3Si), 17.6, 17.9, 18.6 (3-Me, 10-Me, MeEMeZCC), 25.3, 26.3 (7-Me/7-Me, MeEMeZCC), 41.2 (C8), 48.2 (C7), 90.3, 92.9, 109.0, 109.5 (C

C), 116.6, 117.6, 123.2, 123.3, 132.9, 137.8, 139.3 (CC), 145.2 (C6). MS TOF FD+: m/z MH+ 411. MS HR ESI-APCI+: m/z calcd for C26H43Si2 MH+ 411.2898, found 411.2900.

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AUTHOR INFORMATION

Corresponding Author

*E-mail for G.G.M.: [email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This material is based upon work supported by the National Science Foundation under CHE-1112129. The authors are greatly indebted to the Office of Graduate Studies, Research and International Programs, University Corporation, and College of Science and Mathematics, California State University Northridge, for their generous support.

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REFERENCES

(1) (a) Encyclopedia of Radicals in Chemistry, Biology, and Materials; Chatgilialoglu, C., Studer, A., Eds.; Wiley: New York, 2012, Vols. 1 and 2. (b) Rowlands, G. J. Tetrahedron 2009, 65, 8603−8655. (c) Zard, S. Z. Radical Reactions in Organic Synthesis; Oxford University Press: New York, 2003; pp 1−256. (d) Bar, G.; Parsons, A. F. Chem. Soc. Rev. 2003, 32, 251−263. (e) Radicals in Organic Synthesis; Renaub, P.; Sibi, M. P., Eds.; Wiley: Weinheim, Germany, 2001; Vols. 1 and 2. (f) Malacria, M. Chem. Rev. 1996, 96, 289−306. (g) Curran, D. P. Radical Addition Reactions. In Comprehensive Organic Synthesis; Trost, B. M., Ed.; Pergamon Press: London, 1992; Vol. 5, Chapters 4.1 and 4.2. (h) Jasperse, C. P.; Curran, D. P.; Fevig, T. L. Chem. Rev. 1991, 91, 1237−1286. (i) Giese, B. Radicals in Organic Synthesis: Formation of Carbon-Carbon Bonds; Pergamon: Oxford, U.K., 1986; pp 1−282. (j) Smith, M. B. March’s Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 7th ed.; Wiley: Hoboken, NJ, 2013; pp 234−248. (k) Gibian, M. J.; Corley, R. C. Chem. Rev. 1973, 73, 441− 464. (2) Gomberg, M. J. Am. Chem. Soc. 1900, 22, 757−771. (3) (a) Ruchardt, C. Steric Effects in Free Radical Chemistry. In Topics in Current Chemistry: Organic Chemistry: Syntheses and Reactivity; Springer-Verlag: Berlin, 1980; Vol. 88, pp 1−32. . For reviews on persistent radicals see: (b) Griller, D.; Ingold, K. U. Acc. Chem. Res. 1976, 9, 13−19. (c) Fischer, H. Chem. Rev. 2001, 101, 3581−3610. (d) Studer, A. Chem. - Eur. J. 2001, 7, 1159−1164. (4) (a) Schreiner, K.; Berndt, A. Angew. Chem., Int. Ed. Engl. 1975, 14, 366−367. (b) Mendenhall, G. D.; Griller, D.; Lindsay, D.; Tidwell, T. T.; Ingold, K. U. J. Am. Chem. Soc. 1974, 96, 2441−2447. (c) Griller, D.; Icli, S.; Thankachan, C.; Tidwell, T. T. J. Chem. Soc., Chem. Commun. 1974, 913−914. (d) Hart, D. J.; Seely, F. L. J. Am. Chem. Soc. 1988, 110, 1631−1633. (e) Neumann, W. P.; Hillgartner, H.; Baines, K. M.; Dicke, R.; Vorspohl, K.; Kobs, U.; Nussbutel, U. Tetrahedron 1989, 45, 951−960. (5) Melikyan, G. G. Acc. Chem. Res. 2015, 48, 1065−1079. (6) Melikyan, G. G.; Bright, S.; Monroe, T.; Hardcastle, K. M.; Ciurash, J. Angew. Chem., Int. Ed. 1998, 37, 161−164. (7) Persistency in radical dimerization reactions should be distinguished from the persistency in radical addition reactions, since the volume of the recipient of the radical attack, such as the compound with an activated double bond, is much lower than the volume of the bulky radical itself. In other words, a given radical can be persistent in a dimerization reaction when it reacts with the counterpart of the same size and, in contrast, be transient in addition reactions when the smaller size of the recipient of the radical attack makes the rate constant of the bimolecular addition reactions much higher than that in self-coupling reactions. (8) (a) Eichin, K.; McCullough, K.; Beckhaus, H.; Ruchardt, C. Angew. Chem., Int. Ed. Engl. 1978, 17, 934−935. (b) Greene, F. D.; Berwick, M. A.; Stowell, J. C. J. Am. Chem. Soc. 1970, 92, 867−874. L

DOI: 10.1021/acs.organomet.6b00435 Organometallics XXXX, XXX, XXX−XXX

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Organometallics (c) Eisch, J. J.; Kaska, D. D.; Peterson, C. J. J. Org. Chem. 1966, 31, 453−456. (d) Beroza, M.; Schechter, M. S. J. Am. Chem. Soc. 1956, 78, 1242−1247. (e) Irie, H.; Maruyama, J.; Shimada, M.; Zhang, Y.; Kouno, I.; Shimamoto, K.; Ohfune, Y. Synlett 1990, 1990, 421−423. For dimerization of photochemically generated radicals see: (f) Shiraki, S.; Natarajan, A.; Garcia-Garibay, M. A. Photochem. Photobiol. Sci. 2011, 10, 1480−1487. (g) Mortko, C. J.; Garcia-Garibay, M. A. J. Am. Chem. Soc. 2005, 127, 7994−7995. (h) Ng, D.; Yang, Z.; GarciaGaribay, M. A. Org. Lett. 2004, 6, 645−647. For cobalt-mediated coupling of tertiary benzylic radicals see: (i) Movassaghi, M.; Schmidt, M. A. Angew. Chem., Int. Ed. 2007, 46, 3725−3728. For dimerization of captodative radicals see: (j) Viehe, H. G.; Janousek, Z.; Merenyi, R.; Stella, L. Acc. Chem. Res. 1985, 18, 148−154. For related Vitamin B12 catalyzed dimerization of alkenes see: (k) Shey, J.; McGinley, C. M.; McCauley, K. M.; Dearth, A. S.; Young, B. T.; van der Donk, W. A. J. Org. Chem. 2002, 67, 837−846. (9) (a) Organometallic Radical Processes; Trogler, W. C., Ed.; Elsevier: Amsterdam, 1990; Chapters 3, 4, 9, and 10. (b) Astruc, D. Acc. Chem. Res. 1991, 24, 36−42. (c) Astruc, D. Electron Transfer and Radical Processes in Transition-Metal Chemistry; VCH: New York, 1995; Chapters 3, 5, and 6. (d) Torraca, K. E.; McElwee-White, L. Coord. Chem. Rev. 2000, 206−207, 469−491. (e) Melikyan, G. G. LigandBased Organometallic Radical Chemistry: an Emerging Interdisciplinary Field. In Frontiers in Organometallic Chemistry; Cato, M. A., Ed.; Nova Science: New York, 2006; pp 155−190. (f) Dzik, W. I.; de Bruin, B. Organometallic Chem. 2011, 37, 46−78. (10) (a) Mahler, J. E.; Gibson, D. H.; Pettit, R. J. Am. Chem. Soc. 1963, 85, 3959−3963. (b) Sapienza, R. S.; Riley, P. E.; Davis, R. E.; Pettit, R. J. Organomet. Chem. 1976, 121, C35−C40. (c) Pearson, A. J.; Chen, Y.-S.; Daroux, M. L.; Tanaka, A. A.; Zettler, M. J. Chem. Soc., Chem. Commun. 1987, 155−157. (d) Hwang, W. S.; Liao, R. L.; Horng, Y. L.; Ong, C. W. Polyhedron 1989, 8, 479−482. (e) Le BerreCosquer, N.; Kergoat, R.; L’Haridon, P. Organometallics 1992, 11, 721−728. (f) Top, S.; Jaouen, G. J. Organomet. Chem. 1987, 336, 143− 151. (g) Cais, M.; Eisenstadt, A. J. Org. Chem. 1965, 30, 1148−1154. (h) Geiger, W. E.; Genneth, Th.; Lane, G. A.; Salzer, A.; Rheingold, A. L. Organometallics 1986, 5, 1352−1359. (i) Padmanabhan, S.; Nicholas, K. M. J. Organomet. Chem. 1981, 212, 115−124. (j) Kaldis, J. H.; McGlinchey, M. J. Tetrahedron Lett. 2002, 43, 4049−4053. (k) Kaldis, J. H.; Brook, M. A.; McGlinchey, M. J. Chem. - Eur. J. 2008, 14, 10074−10084. (11) (a) Melikyan, G. G.; Carlson, L.; Sahakyan, N.; Floruti, A.; Garrison, M. Dalton Transactions 2013, 42, 14801−14812. (b) Melikyan, G. G.; Floruti, A.; Devletyan, L.; Toure, P.; Dean, N.; Carlson, L. Organometallics 2007, 26, 3173−3182. (c) Melikyan, G. G.; Wild, C.; Toure, P. Organometallics 2008, 27, 1569−1581. (d) Melikyan, G. G.; Voorhees, E.; Wild, C.; Spencer, R.; Molnar, J. Tetrahedron Lett. 2010, 51, 2287−2290. (e) Melikyan, G. G.; Spencer, R. Tetrahedron 2010, 66, 5321−5328. (f) Melikyan, G. G.; Spencer, R.; Rowe, A. Organometallics 2010, 29, 3556−3562. (g) Melikyan, G. G.; Hughes, R.; Rivas, B.; Duncan, K.; Sahakyan, N. Organometallics 2015, 34, 242−253. (h) Melikyan, G. G.; Rivas, B.; Harutyunyan, S.; Carlson, L.; Sepanian, R. Organometallics 2012, 31, 1653−1663. (i) Melikyan, G. G.; Anker, B. Organometallics 2015, 34, 4194−4197. (j) Melikyan, G. G.; Voorhees, E.; Sepanian, R. Organometallics 2014, 33, 69−83. (k) Melikyan, G. G.; Villena, F.; Florut, A.; Sepanian, S.; Sarkissian, H.; Rowe, A.; Toure, P.; Mehta, D.; Christian, N.; Myer, S.; Miller, D.; Scanlon, S.; Porazik, M.; Gruselle, M. Organometallics 2006, 25, 4680− 4690. (12) (a) Tyler, D. R. Acc. Chem. Res. 1991, 24, 325−331. (b) Zavarine, I. S.; Kubiak, C. P. Coord. Chem. Rev. 1998, 171, 419−438. (13) (a) Brandsma, L.; Verkruijsse, H. D. Synthesis of Acetylenes, Allenes and Cumulenes; Elsevier: New York, 1981; pp 78−81. (b) Greenfield, H.; Sternberg, H. W.; Friedel, R. A.; Wotiz, J. H.; Markby, R.; Wender, I. J. Am. Chem. Soc. 1956, 78, 120−124. (14) (a) Albers, M. O.; Coville, N. J. Coord. Chem. Rev. 1984, 53, 227−259. (b) Kochi, J. K. Activation of Diamagnetic Metal Carbonyls

by Electrochemical, Thermal, and Photochemical Electron Transfer. In ref 9a ; pp 201−269. (15) Seyferth, D.; Nestle, M. O.; Wehman, A. T. J. Am. Chem. Soc. 1975, 97, 7417−7426. (16) Bradley, D. H.; Khan, M. A.; Nicholas, K. M. Organometallics 1989, 8, 554−556. (b) Bradley, D. H.; Khan, M. A.; Nicholas, K. M. Organometallics 1992, 11, 2598−2607. (17) (a) Peterson, E. A.; Overman, L. E. Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 11943−11948. (b) Trost, B. M.; Jiang, C. Synthesis 2006, 369−396. (c) Nicolaou, K. C.; Sorensen, E. J. Classics in Total Synthesis: Targets, Strategies, Methods; Wiley-VCH: Weinheim, Germany, 1996. (d) Nicolaou, K. C.; Snyder, S. A. Classics in Total Synthesis II: More Targets, Strategies, Methods; Wiley-VCH: Weinheim, Germany, 2003; Vol.2. For radical coupling reactions at the γ position in allyl porphyrin complexes, see: (e) Lu, H.; Dzik, W. I.; Xu, X.; Wojtas, L.; de Bruin, B.; Zhang, X. P. J. Am. Chem. Soc. 2011, 133, 8518−8521. (18) Nicholas, K. M.; Siegel, J. J. Am. Chem. Soc. 1985, 107, 4999− 5001. (19) (a) Lau, C. K.; Dufresne, C.; Belanger, P. C.; Pietre, S.; Scheigetz, J. J. Org. Chem. 1986, 51, 3038−3043. (b) Millan, A.; Campana, A. G.; Bazdi, B.; Miguel, D.; Cienfuegos, L. A.; Echavarren, A. M.; Cuerva, J. M. Chem. - Eur. J. 2011, 17, 3985−3994. (20) (a) Melikyan, G. G.; Nicholas, K. M. The Chemistry of MetalAlkyne Complexes. In Modern Acetylene Chemistry; Stang, P. J., Diederich, F., Eds.; VCH: Weinheim, Germany, 1995; Chapter 4, pp 99−138. (b) McGlinchey, M. J.; Girard, L.; Ruffolo, R. Coord. Chem. Rev. 1995, 143, 331−381. (c) Went, M. Adv. Organomet. Chem. 1997, 41, 69−125. (d) Green, J. R. Curr. Org. Chem. 2001, 5, 809−826. (e) Muller, T. J. J. Eur. J. Org. Chem. 2001, 2001, 2021−2033. (f) Teobald, B. J. Tetrahedron 2002, 58, 4133−4169. (g) Omae, I. Appl. Organomet. Chem. 2007, 21, 318−344. (21) Given the low concentration of γ,γ-dimer 66 present, the actual thermal conversion of γ,γ-dimer 66 to γ,ε-dimer 65 could not be unambiguously established by NMR even in the presence of an internal standard, CHCl2CHCl2. (22) (a) Liu, Y.; Han, S.; Liu, W.; Stoltz, B. M. Acc. Chem. Res. 2015, 48, 740−751. (b) Lednicer, D. Steroid Chemistry at a Glance; Wiley: Chichester, U.K., 2011; pp 1−134. (23) For representative examples of transition metal (Ru, Pt, Pd, Rh, Mo, Cr) induced cyclizations of unsaturated compounds see the following. 1,5-Dienes: (a) Croteau, R. Chem. Rev. 1987, 87, 929−954. (b) Van Tamelen, E. E. Acc. Chem. Res. 1968, 1, 111−120. (c) Abdel Ghani, S. B.; Chapman, J. M.; Figadere, B.; Herniman, J. M.; Langley, G. J.; Niemann, S.; Brown, R. C. D. J. Org. Chem. 2009, 74, 6924− 6928. (d) Alvarez, E.; Diaz, M. T.; Perez, R.; Ravelo, J. L.; Regueiro, A.; Vera, J. A.; Zurita, D.; Martin, J. D. J. Org. Chem. 1994, 59, 2848− 2876. 1,7-Enynes: (e) Trost, B. M.; Toste, F. D. J. Am. Chem. Soc. 2000, 122, 714−715. (f) Dolhem, F.; Lievre, C.; Demailly, G. J. Org. Chem. 2004, 69, 3400−3407. (g) Ota, K.; Lee, S. I.; Tang, J.; Takachi, M.; Nakai, H.; Morimoto, T.; Sakurai, H.; Kataoka, K.; Chatani, N. J. Am. Chem. Soc. 2009, 131, 15203−15211. (h) Bajracharya, G. B.; Nakamura, I.; Yamamoto, Y. J. Org. Chem. 2005, 70, 892−897. (i) Okamoto, R.; Okazaki, E.; Noguchi, K.; Tanaka, K. Org. Lett. 2011, 13, 4894−4897. 1,9-Diynes: (j) Shu, X.; Li, X.; Shu, D.; Huang, S.; Schienebeck, C. M.; Zhou, X.; Robichaux, P. J.; Tang, W. J. Am. Chem. Soc. 2012, 134, 5211−5221 and references cited therein. (24) (a) See ref 1j, pp 512−515 and references cited therein. (b) Billington, D. C. Chem. Soc. Rev. 1985, 14, 93−120. (c) Baker, R. Chem. Rev. 1973, 73, 487−530. (d) Semmelhack, M. F. Org. React. 1972, 19, 115−198. (e) Courtois, G.; Miginiac, L. J. Organomet. Chem. 1974, 69, 1−44. (25) (a) Engel, P. S.; Bishop, D. J. J. Am. Chem. Soc. 1972, 94, 2148− 2149. (b) Yanagisawa, A.; Hibino, H.; Habaue, S.; Hisada, Y.; Yamamoto, H. J. Org. Chem. 1992, 57, 6386−6387 and references cited therein. (26) Stereochemical assignment (3E,7E) was carried out on the basis of NMR analogies with a structurally related γ,γ dimer11g for which the geometry was independently verified by means of X-ray crystallogM

DOI: 10.1021/acs.organomet.6b00435 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics raphy. The number of resonances in the 13C NMR spectrum for methyl groups and vinylic carbon atoms was indicative of the presence of two diastereomers.

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DOI: 10.1021/acs.organomet.6b00435 Organometallics XXXX, XXX, XXX−XXX