Abstract
C-oligosaccharides are found in natural products and drug molecules. Despite the considerable progress made during the last decades, modular and stereoselective synthesis of C-oligosaccharides continues to be challenging and underdeveloped compared to the synthesis technology of O-oligosaccharides. Herein, we design a distinct strategy for the stereoselective and efficient synthesis of C-oligosaccharides via palladium-catalyzed nondirected C1–H glycosylation/C2-alkenylation, cyanation, and alkynylation of 2-iodoglycals with glycosyl chloride donors while realizing the difunctionalization of 2-iodoglycals. The catalysis approach tolerates various functional groups, including derivatives of marketed drugs and natural products. Notably, the obtained C-oligosaccharides can be further transformed into various C-glycosides while fully conserving the stereochemistry. The results of density functional theory (DFT) calculations support oxidative addition mechanism of alkenyl-norbornyl-palladacycle (ANP) intermediate with α-mannofuranose chloride and the high stereoselectivity of glycosylation is due to steric hindrance.
Similar content being viewed by others
Introduction
Transition metal-catalyzed C–H glycosylation has surfaced as a powerful tool for synthesizing C-glycosides1,2,3,4,5,6. Iodoglycals can be used as both a useful glycosyl donor in C–H glycosidation reactions7,8,9,10,11,12,13 and as readily available building blocks in functionalization reactions, which have long been of interest to chemists. Monofunctionalization of 2-iodoglycals via palladium-catalyzed cross-couplings can thus be considered as the most reliable strategy. For example, monofunctionalization typically involves palladium-catalyzed Heck7, Stille14, Suzuki–Miyaura15, Sonogashira16,17, aminocarbonylation18, alkenylation19, alkylation20, among others21,22 (Figs. 1, (1), left). Despite these indisputable advances, key challenges remain. First, all studies have as of yet focused on single cross-coupling reactions for the synthesis of 2-C-branched sugars, while difunctionalizations of 2-iodoglycals have not been reported. Second, the C–H activation/glycosylation is highly promising23,24,25,26. In 2021, Chen’s group reported a strategy for the stereoselective synthesis of C-vinyl glycosides via the palladium-catalyzed directed C-H glycosylation of olefins, but has been limited to the directed synthesis C-vinyl glycosides27 (Figs. 1, (2)). In contrast, we herein describe the palladium-catalyzed C1–H glycosylation and C2-alkenylation of 2-iodoglycals through vicinal-difunctionalization without additional directing groups (Fig. 1, (1), right).
Compared with O-oligosaccharides, C-oligosaccharides have remarkable stability in the process of enzyme and chemical hydrolysis and are also widely present in natural products and drug molecules. For example, marine natural products (maitotoxin)28 and drug molecules (dodecodiulose and tunicamine)29,30 featuring interglycosidic C-linkages (Fig. 2, (1)). Therefore, glycosidic C–C bond formation strategies are valuable for enriching the diversity of viable oligosaccharides31. In the last three decades, considerable progress has been made in the synthesis of C-oligosaccharides, among others, through ring-closing alkene metathesis32, a Ramberg-Bäcklund approach33 or Stille-type cross-coupling34. However, these approaches largely rely on highly reactive functionalized coupling partners, specifically designed glycosyl donors, delicate operating conditions, and multistep reaction sequences. In addition, the methods for assembling C-disaccharides that involve directly connecting the anomeric carbon and anomeric carbon are rare. This is most probably attributed to the fact that connecting two sugar units C1–C1 together requires anomer carbon polarity reversal. This challenge has been overcome via Stille couplings35 of glycals (Fig. 2, (2)) and the radical–radical homocouplings36,37 (Fig. 2, (3)) of glycosides, but these reactions form dimeric products and anomeric mixtures with poor diastereoselectivity and have limited substrate scope. In 2022, the Ackermann group reported the Pd-catalyzed aminoquinoline-directed C(sp3)–H glycosylation of glycosides using 1-iodoglycals donors12 (Fig. 2, (4)). This strategy has been proven to be effective, widely applicable, and diastereoselective, highlighting the important prospects of C-oligosaccharides. Despite these formidable advances in directed C–H glycosylation to synthesize C-oligosaccharides, the development of DG (directing group)-free C–H glycosylation has proven elusive (Fig. 2, (5)).
Over the last two decades, the Catellani-type reaction has allowed for highly efficient molecular polyfunctionalization38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55, which has also provided us with a strategy for the undirected synthesis of C-oligosaccharides. Notably, in contrast to arene-Catellani reactions: (1) the π preactivity of alkene substrates enhances their reactivity and typically can lead to undesired cyclopropanation, (2) the preactivity of alkene substrates might more strongly interfere with the C–H cleavage process, posing a challenge to reaction development27, (3) palladium-catalyzed nonstereoselective alkenyl Catellani reactions have been successful when using primary alkyl halides, their application in the synthesis of complex secondary C-alkenyl glycosides remains elusive. This is expected given the considerable challenges posed by multifunctional, sterically hindered sugar substrates and the additional need to control the diastereoselectivity of C(alkenyl)–C(anomeric) bond formation. Following our continuous interest in Catellani-type reactions and carbohydrate chemistry2,48,49,56,57,58, we questioned whether modular and stereoselective assembly of C-oligosaccharides via modular difunctionalization of glycals.
Here, we show the Catellani-type C–H glycosylation of 2-iodoglycals to afford C-oligosaccharides with excellent diastereoselectivities.
Results
As shown in Table 1, we initiated our study by exploring the conditions for the envisioned palladium/norbornene (NBE)-enabled C–H glycosylation using 2-iodoglycal 1a, glycosyl chloride donor 2a, and ethyl acrylate 3a. Interestingly, the model reaction afforded the C-disaccharide 4a in 64% isolated yield with exclusive diastereoselectivity (entry 1). Compound 4a′ was obtained as byproduct via direct Mizoroki-Heck coupling, which can be inhibited by screening ligands and NBEs. K2CO3 was used to obtain the desired product in low yield (entry 2). Pd(PhCN)2Cl2 was found to be slightly more efficient than Pd(OAc)2 (entry 3). Subsequently, we examined dimethylformamide (DMF) and toluene as solvents and found that the reaction could not proceed efficiently in polar reaction media (entries 4 and 5). Two experiments at high temperature (120 °C) and low temperature (80 °C) did not obtain higher yields (entries 9–10). Control experiments were then conducted to understand the role of each reaction component. Unsurprisingly, no product was detected without palladium, ligand, NBE, or the base. (entries 8, 11–13). Dong had previously reported that the use of structurally modified norbornenes (smNBE) and Buchwald’s Ph-DavePhos (L1) increases the yield of the products. To our delight, we found that the use of Ph-DavePhos increased the yield of 4a (entries 6 and 7 and L2–L5). Notably, the desired product was not formed when smNBE N4 was used, whereas the yield of the direct Heck coupling product was >90%. We conclude that the possible reasons for this observation could be that smNBE forms a spatially crowded ANP and the glycosyl chloride with large steric hindrance cannot undergo oxidative addition, leading to the failure of this domino process. Therefore, we chose simple commercial norbornene to further probe our strategy. Among the investigated norbornenes, N8 was identified as being optimal (N1–N8). We also preliminarily explained the possible reasons why N8 is optimal through density functional theory (DFT) calculations (Supplementary Fig. 5).
Substrate scope
After having established the optimized C–H glycosylation reaction conditions, various 2-iodoglycals, olefins, and glycosyl chloride donors were independently explored to examine the universality of the method to synthesize C-oligosaccharides (Fig. 3). Notably, excellent diastereoselectivity was observed in all cases, and the catalytic system was also compatible with different substitution pattern. The connectivity of the newly formed C-glycosidic bonds for each type of sugar was unambiguously verified via two-dimensional nuclear magnetic resonance spectroscopy. Various olefin terminating reagents, including tert-butyl acrylate, acrylamide, vinyl ketone, and 2-vinylpyridine, well tolerated under the standard conditions, and the corresponding C-disaccharides 4a–4g were obtained in 35–70% yield. Next, we examined the scope of 2-iodoglycals (derived from d-galactose and l-rhamnose), and the reactions of 2-iodoglycals 1c, 1d, and 1e with 2a and 3a resulted in the target products 4i, 4j, and 4k with yields of 59%, 64%, and 50%, respectively. Conversely, the reaction cannot be applied to acetyl (Ac)-protected and unprotected sugars (4t and 4u), possibly due to the coordination effect of ester groups on palladium59 and the influence of O-glycosylation60. Furthermore, we examined the scope of furanosyl and pyranosyl chloride donors. As shown in Fig. 3A, a series of methyl-, benzyl-, and TBDPS-protected α-mannosyl chlorides, α-rhamnosyl chloride, and β-ribofuranosyl chlorides with different substituents reacted to afford the corresponding products in good yields and with excellent stereoselectivities (4l–4s).
The power of our strategy for selective saccharide assembly of the reaction was demonstrated with the synthesis of trisaccharides, drug-conjugated sugar derivatives, and the late-stage modification of natural products (Fig. 3B). One pot efficient diastereoselective synthesis of trisaccharides was carried out using d-ribofuranose (3h), d-glucose (3i), d-galactose (3j), d-mannose (3k) as terminating reagents. Protected disaccharides (4z and 4aa) were sequentially incorporated at the C1 position of 2-iodoglycals via the C-ribofuranose linkage with exclusive β-selectivity. Alkenes containing natural products, such as menthol, estrone, and metestosterone, were also found to be viable substrates, providing the desired products 4ab, 4ac, and 4ad in 56%, 42%, and 71% yields, respectively. 1-Chloro-mannose-conjugated drug molecules, such as ibuprofen (nonsteroidal anti-inflammatory drug), probenecid (sulfonamide anti-gout drug), and naproxen (nonsteroidal anti-inflammatory drug), were synthesized, and were successfully C–H glycosylation to afford the corresponding products 4ae–4ag.
Synthetic utility
Thereafter, a large-scale attempt at cooperative catalysis was successfully conducted, and late-stage diversifications were carried out to prove the practical utility of our approach. Thus, a gram-scale reaction was carried out to afford 4a in 46% yield. Likewise, cyanation was achieved using zinc cyanide to afford 5a in 30% yield (Fig. 4A). Subsequently, it was demonstrated that Sonogashira-Hagihara termination was also applicable to C–H glycosylation. Desilylated carbohydrate product 7a is a synthetic intermediate used in the preparation of various glycomimetics. For example, the Sonogashira coupling of 7a with 7b afforded C-disaccharide-phenylalanine conjugate 8a in 72% yield. The C-disaccharide-triazole conjugate 9a was synthesized by a reaction using 7c as a raw material in 80% yield. Furthermore, the tetrasaccharide 10a was obtained by copper-catalyzed Glaser coupling of 7a in 65% yield. Finally, under a copper catalyst, amide 11a was efficiently synthesized by alkynyl conversion (Fig. 4B).
Mechanistic investigation
Finally, DFT calculations were exploited to probe the mechanism of the palladium-catalyzed C–H glycosylation and determine the origin of the stereoselectivity. Trimethyl 2-iodoglucal (12a) and α-mannofuranose chloride (2a) were used as model substrates. Our calculated results showed that the energy barrier from 1h to D requires 24.3 kcal/mol, which includes a series of processes such as the migratory insertion of norbornene and, subsequently, C1–H activation to form alkenyl-norbornyl-palladacycle (D) (Fig. 5A). Subsequently, G-α is received through OA (oxidative addition) and RE (reductive elimination) steps. The DFT calculations revealed that the OA proceeds via a concerted three-membered cyclic transition state (4-TS), which directly leads to the form of the d-mannofuranosyl Pd(IV) intermediate (F-α) without the formation of oxocarbenium26,56 (Supplementary Figs. 5 and 10). Subsequently, the RE process gives G-α through the three-membered cyclic transition state (5-TS). In conclusion, the OA and RE transition states in the α-selective pathway have relatively low barriers, whereas the corresponding β-mannofurglycosylation pathway of the β-mannofuranose chloride (2a’) is clearly unfavorable. In F-α, phosphine and α-mannofuranose are on the opposite side of glucal, which leads to small steric hindrances. Nevertheless, there could be strong repulsive interactions between different groups in F-β. Therefore, F-β is located 28.8 kcal/mol higher in energy than F-α, and the energy of 4-TS’ is much higher than 4-TS (Fig. 5B).
Discussion
In conclusion, we have developed the palladium-catalyzed nondirected late-stage C(sp2)–H glycosylation of 2-iodoglycals, resulting in the modular assembly of unnatural C-disaccharides, C-trisaccharides, and drug glycoconjugates. This strategy does not require multiple steps during synthesis to prepare the complex precursor and does not need directing groups, along with their introduction and removal. The strategy of cooperative catalysis was highly diastereoselective, widely applicable, and operationally simple. Based on density functional theory (DFT) calculations, we suggest that the stereo-selective C–H glycosylation undergoes oxidative addition/reduction elimination. We anticipate that our strategy may aid the future design of new synthesis strategies for bio-relevant C-oligosaccharides in carbohydrate chemistry.
Methods
Experimental procedure: stereoselective assembly of C-oligosaccharides
In a dried 10 ml tube equipped with a stirring bar, 1 (0.15 mmol, 1.5 equiv), 2 (0.2 mmol, 2.0 equiv), Pd(PhCN)2Cl2 (0.01 mmol, 0.1 equiv), Ph-Davephos (0.02 mmol, 0.2 equiv), and Cs2CO3 (0.2 mmol, 2.0 equiv) were added. The tube charged with argon more than three times. 3 (0.1 mmol, 1.0 equiv), N8 (0.2 mmol, 2.0 equiv), and 1,4-dioxane (1.0 ml) were injected into the tube via microsyringe and plastic syringes, respectively. The resulting suspension was placed in an oil bath that had been preheated to 100 °C for 16 h, and then the mixture was cooled to r.t. The reaction mixture was filtered and concentrated in vacuo. The residue was purified with a chromatography column on silica gel to give 4 (petroleum ether/EtOAc).
Data availability
The data generated or analyzed during this study are included in this article and the supplementary information. The Cartesian coordinates are available from the Source Data. Details about materials and methods, experimental procedures, characterization data, computational details, and NMR spectra are available in the Supplementary Information. All data are available from the corresponding author upon request. Source data are provided with this paper.
References
Chen, A., Yang, B., Zhou, Z. & Zhu, F. Recent advances in transition-metal-catalyzed glycosyl cross-coupling reactions. Chem. Catal. 2, 3430–3470 (2022).
Gou, X.-Y., Zhu, X.-Y., Zhang, B.-S. & Liang, Y.-M. Synthesis of C-aryl glycosides by C−H functionalization. Chem. Eur. J. 29, e202203351 (2023).
Jiang, Y., Zhang, Y., Lee, B. C. & Koh, M. J. Diversification of glycosyl compounds via glycosyl radicals. Angew. Chem. Int. Ed. 62, e202305138 (2023).
Yang, Y. & Yu, B. Recent advances in the chemical synthesis of C-glycosides. Chem. Rev. 117, 12281–12356 (2017).
Ghouilem, J., De Robichon, M., Le Bideau, F., Ferry, A. & Messaoudi, S. Emerging organometallic methods for the synthesis of C-branched (hetero)aryl, alkenyl, and alkyl glycosides: C−H functionalization and dual photoredox approaches. Chem. Eur. J. 27, 491–511 (2021).
Shang, W. & Niu, D. Radical pathway glycosylation empowered by bench-stable glycosyl donors. Acc. Chem. Res. 56, 2473–2488 (2023).
Dharuman, S. & Vankar, Y. D. N-Halosuccinimide/AgNO3-efficient reagent systems for one-step synthesis of 2-haloglycals from glycals: application in the synthesis of 2C-branched sugars via Heck coupling reactions. Org. Lett. 16, 1172–1175 (2014).
Gong, X.-P. et al. Palladium-catalyzed one-step synthesis of stereodefined difunctionalized glycals. CCS Chem. 5, 741–749 (2022).
Liu, M., Niu, Y., Wu, Y.-F. & Ye, X.-S. Ligand-controlled monoselective C-aryl glycoside synthesis via palladium-catalyzed C–H functionalization of N-quinolyl benzamides with 1-iodoglycals. Org. Lett. 18, 1836–1839 (2016).
Liu, Y. et al. Palladium-catalysed C(sp3)−H glycosylation for the synthesis of C-Alkyl glycoamino acids. Angew. Chem. Int. Ed. 59, 3491–3494 (2020).
Wu, J., Kaplaneris, N., Ni, S., Kaltenhäuser, F. & Ackermann, L. Late-stage C(sp2)–H and C(sp3)–H glycosylation of C-aryl/alkyl glycopeptides: mechanistic insights and fluorescence labeling. Chem. Sci. 11, 6521–6526 (2020).
Wu, J., Kopp, A. & Ackermann, L. Synthesis of C-oligosaccharides through versatile C(sp3)−H glycosylation of glycosides. Angew. Chem. Int. Ed. 61, e202114993 (2022).
Zhang, S., Niu, Y.-H. & Ye, X.-S. General approach to five-membered nitrogen heteroaryl C-glycosides using a palladium/copper cocatalyzed C–H functionalization strategy. Org. Lett. 19, 3608–3611 (2017).
Chemler, S. R., Iserloh, U. & Danishefsky, S. J. Enantioselective synthesis of the oxadecalin core of phomactin A via a highly stereoselective Diels−Alder reaction. Org. Lett. 3, 2949–2951 (2001).
Cobo, I., Matheu, M. I., Castillón, S., Boutureira, O. & Davis, B. G. Phosphine-free Suzuki–Miyaura cross-coupling in aqueous media enables access to 2-C-aryl-glycosides. Org. Lett. 14, 1728–1731 (2012).
Fan, W., Chen, Y., Lou, Q., Zhuang, L. & Yang, Y. Synthesis of 3-C-branched Kdo analogues via sonogashira coupling of 3-Iodo Kdo glycal with terminal alkynes. J. Org. Chem. 83, 6171–6177 (2018).
Shamim, A., Souza, F. B., Vasconcelos, S. N. S. & Stefani, H. A. Synthesis of a library of glucal-derived triazoles via copper-catalyzed azide–alkyne cyclization. Tetrahedron Lett. 58, 884–888 (2017).
Bordessa, A., Ferry, A. & Lubin-Germain, N. Access to complex C2-branched glycoconjugates via palladium-catalyzed aminocarbonylation reaction of 2-iodoglycals. J. Org. Chem. 81, 12459–12465 (2016).
Liu, J. et al. Palladium-catalyzed cross-coupling of 2-iodoglycals with N-tosylhydrazones: access to 2-C-branched glycoconjugates and oxadecalins. J. Org. Chem. 84, 9344–9352 (2019).
Polák, P. & Cossy, J. Ni-catalyzed cross-coupling of 2-iodoglycals and 2-iodoribals with Grignard reagents: a route to 2-C-glycosides and 2’-C-nucleosides. Chem. Eur. J. 28, e202104311 (2022).
Malinowski, M., Van Tran, T., De Robichon, M., Lubin-Germain, N. & Ferry, A. Mild palladium-catalyzed cyanation of unprotected 2-iodoglycals in aqueous media as versatile tool to access diverse C2-glycoanalogues. Adv. Synth. Catal. 362, 1184–1189 (2020).
Monasson, O., Malinowski, M., Lubin-Germain, N. & Ferry, A. Hirao cross-coupling reaction as an efficient tool to build non-natural C2-phosphonylated sugars. Synthesis 54, 3414–3420 (2022).
Cai, S., Sun, Q., Wang, Q., He, G. & Chen, G. Ruthenium-catalyzed pyridine-directed aryl C–H glycosylation with glycosyl chlorides. J. Org. Chem. 87, 8811–8818 (2022).
Qi, R. et al. Visible-light-promoted stereoselective C(sp3)−H glycosylation for the synthesis of C-glycoamino acids and C-glycopeptides. Angew. Chem. Int. Ed. 61, e202200822 (2022).
Wang, Q. et al. Palladium-catalysed C−H glycosylation for synthesis of C-aryl glycosides. Nat. Catal. 2, 793–800 (2019).
Wang, Q. et al. Total synthesis of C-α-mannosyl tryptophan via palladium-catalyzed C–H glycosylation. CCS Chem. 3, 1729–1736 (2020).
Sun, Q. et al. Stereoselective synthesis of C-vinyl glycosides via palladium-catalyzed C−H glycosylation of alkenes. Angew. Chem. Int. Ed. 60, 19620–19625 (2021).
Nicolaou, K. C. et al. Chemical synthesis of the GHIJKLMNO ring system of maitotoxin. J. Am. Chem. Soc. 130, 7466–7476 (2008).
Mochizuki, T. & Shiozaki, M. Synthesis of (6R,7R)-d-gluco-l-gulo-6,7-dodecodiulose-(6,2),(7,11). Chem. Lett. 26, 801–802 (1997).
Mahoney, W. C. & Duksin, D. Separation of tunicamycin homologues by reversed-phase high-performance liquid chromatography. J. Chromatogr. A. 198, 506–510 (1980).
Yuan, X. & Linhardt, J. R. Recent advances in the synthesis of C-oligosaccharides. Curr. Top. Med. Chem. 5, 1393–1430 (2005).
Liu, L. & Postema, M. H. D. A unified approach to differentially linked β-C-disaccharides by ring-closing metathesis. J. Am. Chem. Soc. 123, 8602–8603 (2001).
Mcallister, G. D., Paterson, D. E. & Taylor, R. J. K. A simplified Ramberg–Bäcklund approach to novel C-glycosides and C-linked disaccharides. Angew. Chem. Int. Ed. 42, 1387–1391 (2003).
Koester, D. C., Kriemen, E. & Werz, D. B. Flexible synthesis of 2-deoxy-C-glycosides and (1 → 2)-, (1 → 3)-, and (1 → 4)-linked C-glycosides. Angew. Chem. Int. Ed. 52, 2985–2989 (2013).
Bayer, M., Bächle, F. & Ziegler, T. Synthesis and Pd-catalyzed coupling of 1-C-stannylated glycals. J. Carbohydr. Chem. 37, 347–369 (2018).
Guerrini, M., Guglieri, S., Santarsiero, R. & Vismara, E. Synthesis and characterisation of hexa- and tetrasaccharide mimics from acetobromomaltotriose and acetobromomaltose, and of C-disaccharide mimics from acetobromoglucose, obtained by electrochemical reduction on silver. Tetrahedron: Asymmetry 16, 243–253 (2005).
Masuda, K., Nagatomo, M. & Inoue, M. Direct assembly of multiply oxygenated carbon chains by decarbonylative radical–radical coupling reactions. Nat. Chem. 9, 207–212 (2017).
Cheng, H.-G., Chen, S., Chen, R. & Zhou, Q. Palladium(II)-initiated Catellani-type reactions. Angew. Chem. Int. Ed. 58, 5832–5844 (2019).
Wang, J. & Dong, G. Palladium/norbornene cooperative catalysis. Chem. Rev. 119, 7478–7528 (2019).
Catellani, M., Frignani, F. & Rangoni, A. A complex catalytic cycle leading to a regioselective synthesis of o, o′-disubstituted vinylarenes. Angew. Chem. Int. Ed. 36, 119–122 (1997).
Della Ca’, N., Fontana, M., Motti, E. & Catellani, M. Pd/norbornene: a winning combination for selective aromatic functionalization via C–H bond activation. Acc. Chem. Res. 49, 1389–1400 (2016).
Della Ca, N., Maestri, G., Malacria, M., Derat, E. & Catellani, M. Palladium-catalyzed reaction of aryl iodides with ortho-bromoanilines and norbornene/norbornadiene: unexpected formation of dibenzoazepine derivatives. Angew. Chem. Int. Ed. 50, 12257–12261 (2011).
Lautens, M., Paquin, J.-F., Piguel, S. & Dahlmann, M. Palladium-catalyzed sequential alkylation−alkenylation reactions and their application to the synthesis of fused aromatic rings. J. Org. Chem. 66, 8127–8134 (2001).
Lautens, M. & Piguel, S. A new route to fused aromatic compounds by using a palladium-catalyzed alkylation – alkenylation sequence. Angew. Chem. Int. Ed. 39, 1045–1046 (2000).
Maestri, G. et al. Of the ortho effect in palladium/norbornene-catalyzed reactions: a theoretical investigation. J. Am. Chem. Soc. 133, 8574–8585 (2011).
Weinstabl, H., Suhartono, M., Qureshi, Z. & Lautens, M. Total synthesis of (+)-linoxepin by utilizing the catellani reaction. Angew. Chem. Int. Ed. 52, 5305–5308 (2013).
Ye, J. & Lautens, M. Palladium-catalysed norbornene-mediated C–H functionalization of arenes. Nat. Chem. 7, 863–870 (2015).
Zhang, B.-S. et al. Carboxylate ligand-exchanged amination/C(sp3)–H arylation reaction via Pd/norbornene cooperative catalysis. ACS Catal. 8, 11827–11833 (2018).
Ding, Y.-N. et al. Palladium-catalyzed ortho-C–H glycosylation/ipso-alkenylation of aryl iodides. J. Org. Chem. 85, 11280–11296 (2020).
Lv, W., Chen, Y., Wen, S., Ba, D. & Cheng, G. Modular and stereoselective synthesis of C-Aryl glycosides via Catellani reaction. J. Am. Chem. Soc. 142, 14864–14870 (2020).
Wang, J., Dong, Z., Yang, C. & Dong, G. Modular and regioselective synthesis of all-carbon tetrasubstituted olefins enabled by an alkenyl Catellani reaction. Nat. Chem. 11, 1106–1112 (2019).
Li, J.-J. et al. Atroposelective remote meta-C–H activation. Chem 9, 1452–1463 (2023).
Zhou, L. et al. Synthesis of planar chiral ferrocenes via enantioselective remote C–H activation. Nat. Chem. 15, 815–823 (2023).
Yamamoto, Y., Murayama, T., Jiang, J., Yasui, T. & Shibuya, M. The vinylogous Catellani reaction: a combined computational and experimental study. Chem. Sci. 9, 1191–1199 (2018).
Huang, Y., Zhu, R., Zhao, K. & Gu, Z. Palladium-catalyzed Catellani ortho-acylation reaction: an efficient and regiospecific synthesis of diaryl ketones. Angew. Chem. Int. Ed. 54, 12669–12672 (2015).
Gou, X.-Y. et al. Ruthenium-catalyzed stereo- and site-selective ortho-and meta-C−H glycosylation and mechanistic studies. Angew. Chem. Int. Ed. 61, e202205656 (2022).
An, Y. et al. Palladium-catalyzed C–H glycosylation and retro Diels–Alder tandem reaction via structurally modified norbornadienes (smNBDs). Chem. Sci. 12, 13144–13150 (2021).
Zhang, B.-S. et al. Synthesis of C4-aminated indoles via a Catellani and retro-Diels–Alder strategy. J. Am. Chem. Soc. 141, 9731–9738 (2019).
Probst, N. et al. Palladium(II)-catalyzed diastereoselective 2,3-trans C(sp3)–H arylation of glycosides. ACS Catal. 8, 7781–7786 (2018).
An, S. et al. Palladium-catalyzed O- and N-glycosylation with glycosyl chlorides. CCS Chem. 3, 1821–1829 (2020).
Acknowledgements
We are grateful to the National Natural Science Foundation of China (22171114, Y.-M.L. and 22371097, Y.-M. L.).
Author information
Authors and Affiliations
Contributions
X.-Y.L. and Y.-M.L. conceived the projects. Y.-N.D, M.-Z.X. and Y.-C.H. performed the experiments under the supervision of Y.-M.L. Y.-M.L. and L.A. wrote the manuscript with the feedback of all other authors. Theoretical calculations were carried out by X.-T.K.
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing interests.
Peer review
Peer review information
Nature Communications thanks the anonymous reviewer(s) for their contribution to the peer review of this work. A peer review file is available.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Source data
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Ding, YN., Xu, MZ., Huang, YC. et al. Stereoselective assembly of C-oligosaccharides via modular difunctionalization of glycals. Nat Commun 15, 2794 (2024). https://doi.org/10.1038/s41467-024-47060-7
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s41467-024-47060-7
- Springer Nature Limited