Cobalt-Mediated η⁵-Pentadienyl/Alkyne [5 + 2] Cycloaddition Reactions: Substitution Effects, Bicyclic Synthesis, and Photochemical η⁴-Cycloheptadiene Demetalation

Abstract

The preparation of seven-membered carbocycles via traditional organic synthesis is difficult, yet essential, due to the prevalence of these moieties in bioactive compounds. As we report, the Co-mediated pentadienyl/alkyne [5 + 2] cycloaddition reaction generates kinetically stable η 2 ,η 3 -cycloheptadienyl complexes in high yield at room temperature, which isomerize to the thermodynamically preferred η 5 -cycloheptadienyl complexes upon heating at 60−70°C. Here we describe an extended investigation of this reaction manifold, exploring substituent effects and extending the reaction to tandem cycloaddition/nucleophilic cyclizations, generating fused bicyclic compounds. We also describe a new high-yielding photolytic method for the decomplexation of organic cycloheptadienes from Co(I) complexes. Both C 5 Me 5 (Cp*) and C 5 H 5 (Cp) halfsandwich complexes are active in [5 + 2] cycloaddition with alkynes, with Cp* generally providing higher yields of cycloheptadienyl complexes. Cp cycloheptadienyl complexes, however, are resistant to thermal η 2 ,η 3 → η 5 isomerization. The reaction remains limited to open pentadienyl complexes incorporating substituents in the terminal (1 and 5) positions, except for the unsubstituted CpCo(η 5 -cycloheptadienyl) + complex, which is modestly reactive. Incorporation of tethered latent nucleophiles allows cyclization onto the intermediate cycloheptadienyl cations, producing bicyclo[5.3.0]decadiene and bicyclo[5.4.0]-undecadiene systems with complete diastereocontrol. A selection of intermediate complexes have been crystallographically characterized. Addition of tethered malonate nucleophiles occurs reversibly with equilibration to a thermodynamic elimination product, while enolate nucleophiles cyclize reliably under kinetic control. The resulting bicyclic products are decomplexed in high (>90%) yield by UV photolysis in the presence of allyl bromide to provide the organic bicyclic diene with complete retention of ring fusion geometry and without double-bond isomerization. ■ INTRODUCTIONSince the first report of the Diels−Alder reaction, cycloaddition methodology has become a key component of the synthetic organic chemist's toolbox. This utility is largely due to the formation of multiple carbon−carbon bonds in a single step, often with excellent control of regiochemistry and stereoselectivity. Thermal, photochemical, and metal-mediated cycloaddition reactions for the synthesis of small-and medium-sized carbocycles have been developed, with four-, five-, and sixmembered rings receiving most of the attention (i.e., [2 + 2], [3 + 2], and [4 + 2] cycloaddition reactions). In contrast, the preparation of seven-membered rings by cycloaddition remains less developed, 1 despite the almost continuous discovery of bioactive natural products with seven-membered-ring structures in the core. 2 One important pathway to access the sevenmembered ring is the formal [5 + 2] cycloaddition reaction, which has a rich and varied history. 3 Among unsolved problems in [5 + 2] cycloaddition is the cyclization...

Recent Developments in the [5+2] Cycloaddition

“…[91] In 2015, these authors investigated the extension of this process to variously substituted h 5 -pentadienyl cobalt complexes. [92] As shown in Scheme 42, the cobalt-mediated reaction of a range of mono-and disubstituted h 5 -pentadienyl cobalt complexes 147 with alkynes afforded at room temperature in dichloromethane the corresponding non-conjugated h 2 ,h 3 -cycloheptadienyl cycloadducts 148 in high yields (68-98%) and with excellent selectivity and complete diastereocontrol. These products isomerized quantitatively to the corresponding fully conjugated h 5 -cycloheptadienyl complexes 149 upon heating at 70 8C.…”

Crystal structure of bis(η2-ethylene)(η5-pentamethylcyclopentadienyl)cobalt

“…The utility of the Cp*Co(CH 2 CH 2 ) 2 complex in organometallic synthesis has been explored extensively. Examples include the preparation of high-oxidation state Co V complexes (Brookhart et al, 2000) and the preparation of Cp*Co( 5 -pentadienyl) + complexes (Witherell et al, 2008;Ylijoki et al, 2009Ylijoki et al, , 2015.…”

Ynol Ethers as Ketene Equivalents in Rhodium-Catalyzed Intermolecular [5 + 2] Cycloaddition Reactions

“…As part of our studies on new cycloaddition reactions, , we previously reported a route to seven-membered rings involving the metal-catalyzed [5 + 2] cycloaddition of vinylcyclopropanes (VCPs) and π-components . Rhodium catalysts have proven to be the most general for this CC bond activation process, working thus far intramolecularly with alkynes, alkenes and allenes and intermolecularly with alkynes and activated allenes as 2C components. ,, …”