Highly Strained Tertiary sp³ Scaffolds: Synthesis of Functionalized Cubanes and Exploration of Their Reactivity under Pd(II) Catalysis

Abstract

A series of chemically distinct, highly strained, activated cubane scaffolds was synthesized through optimization of the metal-halogen exchange reactions of iodinated cubane derivatives. This included the first reported successful attachment of both boron and phosphorous; key elements in potential transition metal-catalyzed cross coupling reactions; on the cubane scaffold. Additionally, Zn, Sn, Si, S and various C-based systems were also attached in a high-yielding, one-pot reaction from readily available precursors. A comprehensive program investigating the reactivity of these tertiary cubane nucleophiles towards Suzuki-Miyaura, Negishi and Stille cross-coupling methods, never previously reported with the cubane scaffold; is also described, but proved unsuccessful.

Cubane Cross‐Coupling and Cubane–Porphyrin Arrays

“…Our own initial approach for applying palladium‐catalyzed cross‐coupling chemistry on cubanes, failed, unfortunately, owing to the instability of the cubane core in presence of palladium . With this knowledge, we turned our attention to a single‐electron‐transfer (SET) mechanism, circumventing the requirement of the oxidative addition of the transition metal to the cubane core.…”

“…A major limitation right now is to overcome the sterical hindrance of ortho ‐substituents (entry 2 e , 25 %) and to extend the scope for further heteroaromatic coupling partners. With the direct‐coupled cubane‐aryl systems in hand, we decided to go back to our initial approach of palladium‐catalyzed cross‐coupling chemistry with cubanes …”

Nonconjugated Hydrocarbons as Rigid‐Linear Motifs: Isosteres for Material Sciences and Bioorganic and Medicinal Chemistry

“…To access cubane for use in palladium cross‐coupling reactions a series of chemically distinct, highly strained, activated cubane scaffolds were synthesized (Scheme ). This was achieved by using iodinated cubane derivatives 154 to optimize lithium–halogen exchange reactions . Boron 155 a , phosphorus 155 b , tin 155 c , silicon 155 d , sulfur 155 e, and alkyl 155 f groups were attached to the cubane scaffold with this method.…”

“…This was achieved by using iodinated cubane derivatives 154 to optimize lithium-halogen exchange reactions. [207] Boron 155 a, phosphorus 155 b,t in 155 c,s ilicon 155 d,s ulfur 155 e, and alkyl 155 f groups were attached to the cubane scaffold with this method. The optimum conditions found for the metal-halogen exchange reactionallowedf or the generation of the lithiated intermediate through the reactiono fc ubanyl iodide 154 with two equivalents of tBuLi at À78 8Ci nT HF for 1h.T he reaction mixture wast hen allowed to warm to room temperature after two equivalents of the relevant RÀXr eagent were added.T hese electrophilicc ubanes were then investigated for their use in Suzuki-Miyaura, Negishi, and Stille cross-coupling reactionsw ith various halogenatedp henylg roups,b ut all coupling reactions proved unsuccessful.…”

Bridging and Conformational Control of Porphyrin Units through Non‐Traditional Rigid Scaffolds

“…Pd‐Catalyzed cross‐coupling reactions are versatile and straightforward approaches for porphyrins to form carbon−carbon bonds with a wide range of functionalities . In contrast to cubane, the BCP ring is more tolerant towards Pd‐catalyzed cross‐coupling reactions . The first BCP‐porphyrin array 44 was afforded using Suzuki–Miyaura cross‐coupling reaction of [5‐(4′,4′,5′,5′‐tetramethyl‐1′,3′,2′‐dioxaborolan‐2′‐yl)‐10,20‐bis(4′‐methylphenyl)‐15‐phenylporphyrinato]zinc(II) ( 41 ) and BCP ( 33 ).…”