Organogermanium Chemistry
Organogermanium chemistry is the chemical science of organogermanium compounds, which are organometallic compounds containing a C–Ge bond.[1] Germanium shares group 14 in the periodic table with carbon, silicon, tin and lead. Historically, organogermanes are considered as nucleophiles and their reactivity is between that of organosilicon and organotin compounds. But recent research[2] indicated that some organogermanes have enhanced reactivity compared with their organosilicon and organoboron analogues in some cross-coupling reactions.
Organogermanes are advocated as less-toxic alternatives to many toxic organotin reagents. However, the high costs of germanium compounds limit their synthetic value.
Organogermanes in transition-metal-catalyzed cross-coupling reactions
History
The first example of organogermanes used in transition-metal-catalyzed cross-coupling reaction was reported in 2004.[3] 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.[2]
A stoichiometric study by Schoenebeck[4] 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 is 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 their use as nucleophiles in cross-coupling reactions.[4]
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.[5]
Au-catalyzed cross-coupling reactions
In addition to Pd nanoparticle and Pd(TFA)2, other electron-deficient transition-metal complexes, such as Au(III) or cationic Au(I) complexes, are reactive for C–Ge bond activation to give aryl gold (Ar–Au) as transmetallation intermediate. Merging this reactivity with C(aryl)–H activation or photo-induced oxidative addition of ArN2BF4 with gold catalysts, C(aryl)–H functionalization[6][7] or C(aryl)–C(aryl) cross-coupling[8] can be realized via Au(I)/Au(III) catalytic cycle. Under the employed conditions, ArGeEt3 are more reactive compared with its aryl silane or boronic ester analogues. Additionally, gold complexes are unreactive with oxidative addition with (pseudo)halides. In conclusion, these reactions also showed great orthogonal reactivity with different reactive functional groups.
Au-catalyzed C(aryl)–C(alkynyl) cross-coupling was reported with alkynyl germanes as nucleophiles and ArN2BF4 as coupling partners under photoirradiation condition. Not surprisingly, this method showed orthogonality against Sonogashira Coupling.[9]
Organogermanes in transition-metal-free reactions
Ipso halogenation
ArGeEt3 can react with electrophilic halogen sources without transition-metal catalysts to give ipso halogenation product under mild conditions.[10] For the bromination (with NBS) and iodination (with NIS), the reaction is highly chemoselective, with halogenation solely taking place at C–Ge in presence of electron-rich arene, heterocycle substrates or other reactive functional groups. The mechanistic study supports a concerted SEAr-type pathway.
Aryl germanes are stable against selectfluor. The electrophilic fluorination will selectively place at the –Bu3Sn site in presence of –GeEt3. Other Ar–M species, such as aryl boronic acids/esters and silanes, cannot stay intact under this condition.
Based on its unique reactivity, organogermanes can be viewed as masked halides in organic synthesis, which enables the modular synthesis of polyarenes.[11]
Giese-type reaction
C–Ge bonds of alkyl germanes can be homolyzed by photoirradiation, generating alkyl radical, which can be captured by electron-deficient alkenes.[12] This Giese-type reaction has excellent orthogonal selectivity. Reactive functional groups such as halides, boronic esters can be well tolerated.
Miscellaneous Reactivity
The nucleophilicity increases Si < Ge < Sn as well as the hyperconjugation effect known as the β-silicon effect Si < Ge << Sn. The Si–C bond is mainly covalent and the Sn–C relatively polar, bonds with germanium are in between.[13]
Reactivity of M-ene reaction: Si < Ge < Sn < Pb. From Si to Pb, an increasing π-σ* conjugation between the C=C double bond and the C–M bond will enhance the reactivity. It is also likely that there is some interaction between the nucleophilic end of the enophile and the metal in the reaction intermediate which lowers the energy of the transition state.[14]
Other organogermanium compounds:
Propagermanium, also known as germanium sesquioxide or Ge-132, is used as alternative medicine in the treatment of serious diseases such as cancer, HIV infection, and others, although there is no solid evidence on their bioactivity.
Triphenylgermanol (Ph3GeOH) is known, existing as a colorless solid. Like the isostructural silanol, it engages in hydrogen bonding in the solid-state.[15]
Many Ge-centered reactive intermediates are known: germylenes (carbene analogues), germyl free radicals, germynes (carbyne analogues). Digermynes only exist for extremely bulky substituents. XRD structure showed the C–Ge≡Ge–C core of these Digermynes is nonlinear but planar. Such compounds are prepared by the reduction of bulky arylgermanium(II) halides.[16]
Similar as silicon and contrasting with carbon, compounds containing Ge=C (germenes)[17] and Ge=Ge (digermylenes)[18] double bonds are rare and bulky groups are required to stabilize these species. Other examples include the bulky derivatives of germabenzene and 1,2-digermabenzene[19], analogues of benzene.
Synthesis of organogermanes
The first organogermanium compound, tetraethylgermane, was synthesized by Winkler in 1887[20], by the reaction of germanium tetrachloride with diethylzinc. Generally, organogermanes are prepared by nucleophilic substitution or Pd-catalyzed cross-coupling reactions.[2] In recent years, some modern methods, such as hydrogermylation of alkenes are reported to enrich the toolkit for organogermane synthesis.[21]
References
- ↑ Yamamoto, Hisashi; Oshima, Koichiro (2004). Main Group Metals in Organic Synthesis. ISBN 3-527-30508-4. Search this book on
- ↑ 2.0 2.1 2.2 Fricke, Christoph; Schoenebeck, Franziska (2020-11-17). "Organogermanes as Orthogonal Coupling Partners in Synthesis and Catalysis". Accounts of Chemical Research. 53 (11): 2715–2725. doi:10.1021/acs.accounts.0c00527. ISSN 0001-4842. PMID 33118804 Check
|pmid=value (help). Unknown parameter|s2cid=ignored (help) - ↑ Enokido, Tatsuki; Fugami, Keigo; Endo, Mayuko; Kameyama, Masayuki; Kosugi, Masanori (2004). "Palladium-Catalyzed Cross-Coupling Reaction by Means of Organogermanium Trichlorides". Advanced Synthesis & Catalysis. 346 (13–15): 1685–1688. doi:10.1002/adsc.200404187.
- ↑ 4.0 4.1 Fricke, Christoph; Sherborne, Grant J.; Funes‐Ardoiz, Ignacio; Senol, Erdem; Guven, Sinem; Schoenebeck, Franziska (2019-12-02). "Orthogonal Nanoparticle Catalysis with Organogermanes". Angewandte Chemie International Edition. 58 (10): 17788–17795. doi:10.1002/anie.201910060. ISSN 1433-7851. PMC 6899604 Check
|pmc=value (help). PMID 31562670. - ↑ Dahiya, Amit; Gevondian, Avetik G.; Schoenebeck, Franziska (2023-04-12). "Orthogonal C–O Bond Construction with Organogermanes". Journal of the American Chemical Society. 145 (14): 7729–7735. doi:10.1021/jacs.3c01081. ISSN 0002-7863. PMID 36994920 Check
|pmid=value (help). Unknown parameter|s2cid=ignored (help) - ↑ Dahiya, Amit; Fricke, Christoph; Schoenebeck, Franziska (2020-04-29). "Gold-Catalyzed Chemoselective Couplings of Polyfluoroarenes with Aryl Germanes and Downstream Diversification". Journal of the American Chemical Society. 142 (17): 7754–7759. doi:10.1021/jacs.0c02860. ISSN 0002-7863. PMID 32249568 Check
|pmid=value (help). Unknown parameter|s2cid=ignored (help) - ↑ Fricke, Christoph; Dahiya, Amit; Reid, William B.; Schoenebeck, Franziska (2019-10-04). "Gold-Catalyzed C–H Functionalization with Aryl Germanes". ACS Catalysis. 9 (10): 9231–9236. doi:10.1021/acscatal.9b02841. ISSN 2155-5435. PMC 6781487 Check
|pmc=value (help). PMID 31608162. - ↑ Sherborne, Grant J.; Gevondian, Avetik G.; Funes‐Ardoiz, Ignacio; Dahiya, Amit; Fricke, Christoph; Schoenebeck, Franziska (2020). "Modular and Selective Arylation of Aryl Germanes (C−GeEt 3 ) over C−Bpin, C−SiR 3 and Halogens Enabled by Light‐Activated Gold Catalysis". Angewandte Chemie International Edition. 59 (36): 15543–15548. doi:10.1002/anie.202005066. ISSN 1433-7851. PMC 7496160 Check
|pmc=value (help). PMID 32392397 Check|pmid=value (help). - ↑ Dahiya, Amit; Schoenebeck, Franziska (2022-07-01). "Orthogonal and Modular Arylation of Alkynylgermanes". ACS Catalysis. 12 (13): 8048–8054. doi:10.1021/acscatal.2c00852. ISSN 2155-5435. Unknown parameter
|s2cid=ignored (help) - ↑ Fricke, Christoph; Deckers, Kristina; Schoenebeck, Franziska (2020-10-12). "Orthogonal Stability and Reactivity of Aryl Germanes Enables Rapid and Selective (Multi)Halogenations". Angewandte Chemie International Edition. 59 (42): 18717–18722. doi:10.1002/anie.202008372. ISSN 1433-7851. PMC 7590071 Check
|pmc=value (help). PMID 32656881 Check|pmid=value (help). - ↑ Kreisel, Tatjana; Mendel, Marvin; Queen, Adele E.; Deckers, Kristina; Hupperich, Daniel; Riegger, Julian; Fricke, Christoph; Schoenebeck, Franziska (2022-05-09). "Modular Generation of (Iodinated) Polyarenes Using Triethylgermane as Orthogonal Masking Group". Angewandte Chemie International Edition. 61 (20): e202201475. doi:10.1002/anie.202201475. ISSN 1433-7851. PMC 9314983 Check
|pmc=value (help). PMID 35263493 Check|pmid=value (help). - ↑ Selmani, Aymane; Schoetz, Markus D.; Queen, Adele E.; Schoenebeck, Franziska (2022-05-06). "Modularity in the C sp3 Space─Alkyl Germanes as Orthogonal Molecular Handles for Chemoselective Diversification". ACS Catalysis. 12 (9): 4833–4839. doi:10.1021/acscatal.2c00852. ISSN 2155-5435. Unknown parameter
|s2cid=ignored (help) - ↑ Hagen, Gisela; Mayr, Herbert (1991). "Kinetics of the reactions of allylsilanes, allylgermanes, and allylstannanes with carbenium ions". Journal of the American Chemical Society. 113 (13): 4954–4961. doi:10.1021/ja00013a035. ISSN 0002-7863.
- ↑ Cai, Jiaqiang; Davies, Alwyn G. (1992). "Ene reactions of allylic derivatives of silicon, germanium, tin and lead with N-phenyltriazolinedione: the effect of varying the metal". Journal of the Chemical Society, Perkin Transactions 2 (10): 1743–1746. doi:10.1039/p29920001743. ISSN 0300-9580.
- ↑ Ferguson, G.; Gallagher, J. F.; Murphy, D.; Spalding, T. R.; Glidewell, C.; Holden, H. D. (1992-07-15). "The structure of triphenylgermanium hydroxide". Acta Crystallographica Section C Crystal Structure Communications. 48 (7): 1228–1231. doi:10.1107/S0108270191015056.
- ↑ Sugiyama, Yusuke; Sasamori, Takahiro; Hosoi, Yoshinobu; Furukawa, Yukio; Takagi, Nozomi; Nagase, Shigeru; Tokitoh, Norihiro (2006-01-01). "Synthesis and Properties of a New Kinetically Stabilized Digermyne: New Insights for a Germanium Analogue of an Alkyne". Journal of the American Chemical Society. 128 (3): 1023–1031. doi:10.1021/ja057205y. ISSN 0002-7863. PMID 16417395.
- ↑ Meiners, Frank; Saak, Wolfgang; Weidenbruch, Manfred (2000-07-01). "Acetylene-Linked Bis(germaethenes): The First Molecules with Conjugated Germanium−Carbon Double Bonds 1". Organometallics. 19 (15): 2835–2836. doi:10.1021/om000284w. ISSN 0276-7333.
- ↑ Schäfer, Helmut; Saak, Wolfgang; Weidenbruch, Manfred (1999-08-01). "Azadigermiridines by Addition of Diazomethane or Trimethylsilyldiazomethane to a Digermene 1". Organometallics. 18 (16): 3159–3163. doi:10.1021/om990337d. ISSN 0276-7333.
- ↑ Sasamori, Takahiro; Sugahara, Tomohiro; Agou, Tomohiro; Guo, Jing-Dong; Nagase, Shigeru; Streubel, Rainer; Tokitoh, Norihiro (2015-06-08). "Synthesis and Characterization of a 1,2-Digermabenzene". Organometallics. 34 (11): 2106–2109. doi:10.1021/om501204u. ISSN 0276-7333.
- ↑ Winkler, Clemens (1887-08-27). "Mittheilungen über das Germanium". Journal für Praktische Chemie. 36 (1): 177–209. doi:10.1002/prac.18870360119.
- ↑ Selmani, Aymane; Schoenebeck, Franziska (2023). "Anti-Markovnikov Hydrogermylation of Alkenes via Lewis Acid Catalysis". Synthesis. 55 (11): 1792–1798. doi:10.1055/a-2036-3868. ISSN 0039-7881. Unknown parameter
|s2cid=ignored (help)
This article "Organogermanium Chemistry" is from Wikipedia. The list of its authors can be seen in its historical and/or the page Edithistory:Organogermanium Chemistry. Articles copied from Draft Namespace on Wikipedia could be seen on the Draft Namespace of Wikipedia and not main one.
