Organogermanium compounds in cross-coupling reactions
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Organogermanium compounds in cross-coupling reactions refers to a type of cross-coupling reaction where one of the coupling partners is an organogermanium compound. Usually these reactions are catalyzed by transition metal complexes.
The first example of organogermanes used in transition-metal-catalyzed cross-coupling reaction was reported in 2004.[1] However, due to the toxicity, low reactivity (compared with other Ar–[M] nucleophiles) and poor stability of ArGeCl3, this reaction was demonstrated not to be synthetically applicable.
After that, various organogermanes were designed to increase their robustness and decrease their toxicity. However, most of them are not trivial to synthesize and have the least reactivity in Pd(0)/Pd(II) catalytic system. As a result, these organogermanes have limited utilization in organic synthesis.[citation needed]
A stoichiometric study by Schoenebeck[2] confirmed that ArGeEt3 are inert species in the transmetallation step with Pd(II) complex. DFT calculation indicated that the conventional concerted transmetallation mechanism has an extremely high energy barrier and not viable under the reaction conditions. Instead, electrophilic aromatic substitution (SEAr)-type pathway is kinetically more favored to activate C–Ge bonds.
Based on this concept, if the transition metal catalyst is electron-deficient or electrophilic enough, the activation of C–Ge bond can be achievable via SEAr mechanism. And due to this unique reactivity, the transformations of organogermanes can exhibit excellent chemoselectivity and tolerate other reactive functional groups, which can provide a platform to functionalize different groups orthogonally.
Pd-catalyzed cross-coupling reactions
Highly electrophilic cationic Pd nanoparticle can activate the C–Ge bond of ArGeEt3. The Pd nanoparticle is exclusively reactive towards organogermanes with aryl iodides (ArI) or aryl iodonium salts (Ar2I+) as electrophilic coupling partners. Other cross-coupling-reactive functional groups, such as other (psudo)halides, aryl boronic esters, stayed intact during the reaction. In comparison, under traditional Pd(0)-catalyzed cross-coupling conditions, ArGeEt3 are inert while aryl boronic acids/esters are reactive. Besides, ArGeEt3 bearing electron-deficient aryl groups, whose aryl boronic acid analogues are highly unstable, have excellent stability instead, allowing the use of them as nucleophiles in cross-coupling reactions.[2]
Pd(TFA)2 is another reactive catalyst for transmetallation of ArGeEt3. It has an electron-deficient Pd center and provides thermodynamic driving force by forming TFA–GeEt3. Based on this strategy, an oxidative C–O cross-coupling method catalyzed by Pd(TFA)2 was reported. The reaction proceeded through a Pd(II)/Pd(IV) catalytic cycle. Similarly, other reactive functional groups for cross-coupling such as (pseudo)halides and boronic esters are well tolerated.[3]
