Recent advances in catalytic asymmetric synthesis of chiral organogermanes

Abstract

Chiral organogermanes hold great potential as bioisosteres in medicinal chemistry and functional materials, yet their development has long been hindered by a scarcity of efficient synthetic strategies. This review offers a comprehensive overview of recent advances in the catalytic asymmetric synthesis of chiral organogermanes, highlighting a shift from traditional resolution methods toward asymmetric catalytic approaches. The content is organized into three main categories: (i) synthesis of C-stereogenic germanes, (ii) synthesis of Ge-stereogenic germanes, and (iii) synthesis of other chiral germanes, including planar, inherent, and axially chiral types. Key synthetic methodologies are systematically examined, such as enantioselective alkene hydrofunctionalization, carbene insertion, coupling reactions, and [2+2+2] cycloaddition, utilizing a variety of catalytic systems ranging from transition metals (Rh, Cu, Ni, Co) and Lewis acids to engineered metalloenzymes. Particular emphasis is placed on the mechanistic insights and ligand design principles that enable stereochemical control in these transformations. We hope this review will inspire chemists working in related areas and contribute to the future advancement of this field.

Keywords

Asymmetric catalysis / chiral organogermanes / C-stereogenic germanes / Ge-stereogenic germanes

Authors contribution

Liu S: Investigation, writing-original draft, visualization. Ke J: Project administration, methodology, writing-review & editing. He C: Conceptualization, funding acquisition, supervision, writing-review & editing.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

We are grateful for financial support from the National Natural Science Foundation of China (No. 22271134), Guangdong Provincial Key Laboratory of Catalysis (No. 2020B121201002), Shenzhen Science and Technology Innovation Commission (No. RCJC20221008092723013 and No. JCYJ20230807093104009).

Copyright

© The Author(s) 2026.

References

[1] Fujii S, Miyajima Y, Masuno H, Kagechika H. Increased hydrophobicity and estrogenic activity of simple phenols with silicon and germanium—containing substituents. J Med Chem. 2013; 56(1): 160-166.

[2] Menchikov LG, Ignatenko MA. Biological activity of organogermanium compounds (a review). Pharm Chem J. 2013; 46(11): 635-638.

[3] Xu MY, Li N, Xiao B. Recently developed organogermanium(IV) compounds as drug candidates and synthetic tools in drug discovery. Org Biomol Chem. 2025; 23(35): 7852-7871.

[4] Buriak JM. Organometallic chemistry on silicon and germanium surfaces. Chem Rev. 2002; 102(5): 1271-1308.

[5] Shimizu M, Ryuse D, Kinoshita T. Germanium—bridged 2—phenylbenzoheteroles as luminophores exhibiting highly efficient solid—state fluorescence. Chemistry. 2017; 23(58): 14623-14630.

[6] Su TA, Li H, Klausen RS, Kim NT, Neupane M, Leighton JL, et al. Silane and germane molecular electronics. Acc Chem Res. 2017; 50(4): 1088-1095.

[7] Xiang X, Zhou Z, Wu X, Ni Z, Gai L, Xiao X, et al. Novel germoles and their ladder—type derivatives: Modular synthesis, luminescence tuning, and electroluminescence. CCS Chem. 2022; 4(12): 3798-3808.

[8] Ke J, Chen D, Ren LQ, Zu B, Li B, He C. Transition—metal—catalyzed C—Ge coupling reactions. Org Chem Front. 2024; 11(22): 6558-6572.

[9] Rogova T, Ahrweiler E, Schoetz MD, Schoenebeck F. Recent developments with organogermanes: Their preparation and application in synthesis and catalysis. Angew Chem Int Ed. 2024; 63(8): e202314709.

[10] Tu JL, Huang B. Catalytic construction of C(sp ³)—Ge bonds: Recent advances and future perspectives . Adv Synth Catal. 2024; 366(22): 4618-4633.

[11] Chang H, Wang R, Wang YM. Asymmetric synthesis of propargylic and allenic silanes, germanes, and stannanes. Chem Asian J. 2025; 20(16): e00105.

[12] Corriu RJP, Moreau JJE. Stereospecific route to asymmetric vinylgermanes: Hydrogermylation of phenylacetylene catalysed by rhodium and platinum complexes. J Chem Soc D. 1971(15): 812.

[13] Nanjo M, Maehara M, Ushida Y, Awamura Y, Mochida K. Convenient access to optically active silyl— and germyllithiums: Synthesis, absolute structure, and reactivity. Tetrahedron Lett. 2005; 46(51): 8945-8947.

[14] Zhao Z, Zhang F, Wang D, Deng L. Advances in transition—metal—catalyzed hydrogermylation of alkenes and alkynes. Chin J Chem. 2023; 41(22): 3063-3081.

[15] Lin W, You L, Yuan W, He C. Cu—catalyzed enantioselective hydrogermylation: Asymmetric synthesis of unnatural β—germyl α—amino acids. ACS Catal. 2022; 12(23): 14592-14600.

[16] Liu RY, Buchwald SL. CuH—catalyzed olefin functionalization: From hydroamination to carbonyl addition. Acc Chem Res. 2020; 53(6): 1229-1243.

[17] Lin W, Ren LQ, Chen D, Han X, Zhang L, Chen Z, et al. Cu—catalyzed asymmetric hydrogermylation towards C— and Ge—stereogenic germanes. CCS Chem. 2025; 7(4): 1157-1167.

[18] Cao W, Liu X, Feng X. Asymmetric catalytic radical reactions enabled by chiral N,N'—dioxide—metal complexes . Acc Chem Res. 2025; 58(15): 2496-2510.

[19] Chen X, Zhou Y, Yang M, Yang Y, Feng X, Cao W. Merging photocatalysis with chiral lewis acid catalysis for enantioselective hydrosilylation/hydrogermylation of electron—deficient alkenes. Angew Chem Int Ed. 2025; 64(35): e202504676.

[20] Levi Knippel J, Ni AZ, Schuppe AW, Buchwald SL. A general strategy for the asymmetric preparation of α—stereogenic allyl silanes, germanes, and boronate esters via dual copper hydride— and palladium—catalysis. Angew Chem Int Ed. 2022; 61(47): e202212630.

[21] Xu MY, Jiang WT, Xia MZ, An ZL, Xie XY, Xiao B. Orthogonal sp ³—Ge/B bimetallic modules: Enantioselective construction and enantiospecific cross—coupling . Angew Chem Int Ed. 2024; 63(16): e202317284.

[22] Li Z, Liu B, Yao CY, Gao GW, Zhang JY, Tong YZ, et al. Ligand—controlled cobalt—catalyzed regio—, enantio—, and diastereoselective oxyheterocyclic alkene hydroalkylation. J Am Chem Soc. 2024; 146(5): 3405-3415.

[23] Hu X, Wang C, Yu L, Tong YZ, Li Z, Li Y, et al. Modular construction of α— or β—stereogenic organosilanes and organogermanes via enantioselective alkene hydroalkylation. Nat Synth. 2025; 4(11): 1442-1452.

[24] Huang MY, Zhu SF. Uncommon carbene insertion reactions. Chem Sci. 2021; 12(48): 15790-15801.

[25] Bergstrom BD, Nickerson LA, Shaw JT, Souza LW. Transition metal catalyzed insertion reactions with donor/donor carbenes. Angew Chem Int Ed. 2021; 60(13): 6864-6878.

[26] Huang MY, Zhu SF. Catalytic reactions for enantioselective transfers of donor—substituted carbenes. Chem Catal. 2022; 2(11): 3112-3139.

[27] Zhang S, Xu MH. Recent advances in catalytic asymmetric metalloid—hydrogen bond insertion of transition—metal carbenes. Chem Soc Rev. 2025; 54(13): 6505-6524.

[28] Hyde S, Veliks J, Ascough DMH, Szpera R, Paton RS, Gouverneur V. Enantioselective rhodium—catalysed insertion of trifluorodiazoethanes into tin hydrides. Tetrahedron. 2019; 75(1): 17-25.

[29] Han AC, Zhang XG, Yang LL, Pan JB, Zou HN, Li ML, et al. Rhodium—catalyzed enantioselective C−Ge bond formation by carbene insertion: Efficient access to chiral organogermanes. Chem Catal. 2024; 4(1): 100826.

[30] Zhu SF, Zhou QL. Transition—metal—catalyzed enantioselective heteroatom—hydrogen bond insertion reactions. Acc Chem Res. 2012; 45(8): 1365-1377.

[31] Yang LL, Ouyang J, Zou HN, Zhu SF, Zhou QL. Enantioselective insertion of alkynyl carbenes into Si—H bonds: An efficient access to chiral propargylsilanes and allenylsilanes. J Am Chem Soc. 2021; 143(17): 6401-6406.

[32] Chen SH, Zhang S, Chen ZY, Wu Y, Wang P. Cu—catalyzed enantioselective carbene insertion into Ge—H and Si—H bonds enabled by SPSiBox with a tunable chiral pocket. J Am Chem Soc. 2025; 147(18): 15666-15675.

[33] Jennifer Kan SB, Lewis RD, Chen K, Arnold FH. Directed evolution of cytochrome c for carbon—silicon bond formation: Bringing silicon to life. Science. 2016; 354(6315): 1048-1051.

[34] Jennifer Kan SBJ, Huang X, Gumulya Y, Chen K, Arnold FH. Genetically programmed chiral organoborane synthesis. Nature. 2017; 552(7683): 132-136.

[35] Huang W, Adornato GM, Horst M, Alturaifi TM, Hou K, Liu P, et al. De novo design, directed evolution and computational study of heme—binding helical bundle protein catalysts for biocatalytic enantioselective Ge—H insertion. J Am Chem Soc. 2025; 147(44): 40869-40878.

[36] Fu GC. Transition—metal catalysis of nucleophilic substitution reactions: A radical alternative to S_N1 and S_N2 processes . ACS Cent Sci. 2017; 3(7): 692-700.

[37] Lucas EL, Jarvo ER. Stereospecific and stereoconvergent cross—couplings between alkyl electrophiles. Nat Rev Chem. 2017; 1: 65.

[38] Gu QS, Li ZL, Liu XY. Copper(I)—catalyzed asymmetric reactions involving radicals. Acc Chem Res. 2020; 53(1): 170-181.

[39] Gao Z, Liu L, Gu QS, Liu XY. Enantioconvergent cyclopropyl radical C−C coupling. Trends Chem. 2024; 6(12): 786-787.

[40] Han GY, Su PF, Pan QQ, Liu XY, Shu XZ. Enantioconvergent and regioselective reductive coupling of propargylic esters with chlorogermanes by nickel catalysis. Nat Catal. 2024; 7(1): 12-20.

[41] Brösamlen D, Oestreich M. Enantio— and regioconvergent synthesis of γ—stereogenic vinyl germanes and their use as masked vinyl halides. Org Lett. 2023; 25(11): 1901-1906.

[42] Han AC, Xiao LJ, Zhou QL. Construction of Ge—stereogenic center by desymmetric carbene insertion of dihydrogermanes. J Am Chem Soc. 2024; 146(8): 5643-5649.

[43] Shintani R, Takagi C, Ito T, Naito M, Nozaki K. Rhodium—catalyzed asymmetric synthesis of silicon—stereogenic dibenzosiloles by enantioselective [2+2+2] cycloaddition. Angew Chem Int Ed. 2015; 54(5): 1616-1620.

[44] Zheng JL, Yuan WH, Zheng HW, Du W, Chen YC. Diastereoselective and enantioselective construction of 1,4—nonadjacent alkyne—tethered products through CuI—promoted deprotonation and addition of terminal alkynes. Org Chem Front. 2025; 12(23): 6407-6414.

[45] Wang K, Liu XY, Dong Z. Synthesis of chiral germanium center enabled by poly—deborylative alkylation and desymmetrization. Nat Commun. 2025; 16(1): 5013.

[46] Murai M, Matsumoto K, Takeuchi Y, Takai K. Rhodium—catalyzed synthesis of benzosilolometallocenes via the dehydrogenative silylation of C(sp ²)—H bonds . Org Lett. 2015; 17(12): 3102-3105.

[47] Zhang QW, An K, Liu LC, Yue Y, He W. Rhodium—catalyzed enantioselective intramolecular C—H silylation for the syntheses of planar—chiral metallocene siloles. Angew Chem Int Ed. 2015; 54(23): 6918-6921.

[48] Shibata T, Shizuno T, Sasaki T. Enantioselective synthesis of planar—chiral benzosiloloferrocenes by Rh—catalyzed intramolecular C—H silylation. Chem Commun. 2015; 51(37): 7802-7804.

[49] Qian CG, Yan H, Li JY, Zhang ZS, An ZL, Xiao B. Synthesis of inherently chiral germepins via Rh—catalyzed enantioselective C—H germylation. Org Lett. 2025; 27(16): 4118-4123.

[50] Cao YX, Chauvin AS, Tong S, Alama L, Cramer N. Accessing carbon, boron and germanium spiro stereocentres in a unified catalytic enantioselective approach. Nat Catal. 2025; 8(6): 569-578.