References
Harper, M. J. K. & Walpole, A. L. Contrasting endocrine activities of cis and trans isomers in a series of substituted triphenylethylenes. Nature 212, 87 (1966).
CAS PubMed Google Scholar
Caldwell, J. The importance of stereochemistry in drug action and disposition. J. Clin. Pharmacol. 32, 925–929 (1992).
CAS PubMed Google Scholar
Krautwald, S. & Carreira, E. M. Stereodivergence in asymmetric catalysis. J. Am. Chem. Soc. 139, 5627–5639 (2017).
CAS PubMed Google Scholar
Beletskaya, I. P., Nájera, C. & Yus, M. Stereodivergent catalysis. Chem. Rev. 118, 5080–5200 (2018).
CAS PubMed Google Scholar
Lin, L. & Feng, X. Catalytic strategies for diastereodivergent synthesis. Chem. Eur. J. 23, 6464–6482 (2017).
CAS PubMed Google Scholar
Bihani, M. & Zhao, J. C.-G. Advances in asymmetric diastereodivergent catalysis. Adv. Synth. Catal. 359, 534–575 (2017).
CAS Google Scholar
Moser, D., Schmidt, T. A. & Sparr, C. Diastereodivergent catalysis. JACS Au 3, 2612–2630 (2023).
Kim, Y. H. Dual enantioselective control in asymmetric synthesis. Acc. Chem. Res. 34, 955–962 (2001).
CAS PubMed Google Scholar
Zanoni, G., Castronovo, F., Franzini, M., Vidari, G. & Giannini, E. Toggling enantioselective catalysis—a promising paradigm in the development of more efficient and versatile enantioselective synthetic methodologies. Chem. Soc. Rev. 32, 115–129 (2003).
CAS PubMed Google Scholar
Bartok, M. Unexpected inversions in asymmetric reactions: reactions with chiral metal complexes, chiral organocatalysts, and heterogeneous chiral catalysts. Chem. Rev. 110, 1663–1705 (2010).
CAS PubMed Google Scholar
Escorihuela, J., Burguete, M. I. & Luis, S. V. New advances in dual stereocontrol for asymmetric reactions. Chem. Soc. Rev. 42, 5595–5617 (2013).
CAS PubMed Google Scholar
Funken, N., Zhang, Y.-Q. & Gansäuer, A. Regiodivergent catalysis: a powerful tool for selective catalysis. Chem. Eur. J. 23, 19–32 (2017).
CAS PubMed Google Scholar
Nájera, C., Beletskaya, I. P. & Yus, M. Metal-catalyzed regiodivergent organic reactions. Chem. Soc. Rev. 48, 4515–4618 (2019).
Neveselý, T., Wienhold, M., Molloy, J. J. & Gilmour, R. Advances in the E → Z isomerization of alkenes using small molecule photocatalysts. Chem. Rev. 122, 2650–2694 (2022).
Lovering, F., Bikker, J. & Humblet, C. Escape from flatland: increasing saturation as an approach to improving clinical success. J. Med. Chem. 52, 6752–6756 (2009).
CAS PubMed Google Scholar
Lovering, F. Escape from Flatland 2: complexity and promiscuity. MedChemComm 4, 515–519 (2013).
See AlsoJames: The Flyers are a Playoff Team; There, I Said It.Mirror Publisher Adapts to AI and Reader Changes: 600 Jobs at RiskImpact of Eliminating Childhood Vaccine Mandates on Healthcare SystemThe Future of AI: Emotional Intelligence in ChatbotsCAS Google Scholar
Zhan, G., Du, W. & Chen, Y.-C. Switchable divergent asymmetric synthesis via organocatalysis. Chem. Soc. Rev. 46, 1675–1692 (2017).
CAS PubMed Google Scholar
Kalita, S. J., Huang, Y.-Y. & Schneider, U. Stereodivergent catalytic asymmetric allylic alkylation. Sci. Bull. 65, 1865–1868 (2020).
CAS Google Scholar
Huo, X., Li, G., Wang, X. & Zhang, W. Bimetallic catalysis in stereodivergent synthesis. Angew. Chem. Int. Ed. 61, e202210086 (2022).
CAS Google Scholar
Wei, L., Fu, C., Wang, Z.-F., Tao, H.-Y. & Wang, C.-J. Synergistic dual catalysis in stereodivergent synthesis. ACS Catal. 14, 3812–3844 (2024).
CAS Google Scholar
Sun, H., Ma, Y., Xiao, G. & Kong, D. Stereodivergent dual catalysis in organic synthesis. Trends Chem. 6, 684–701 (2024).
CAS Google Scholar
Chen, P., Li, Y., Chen, Z.-C., Du, W. & Chen, Y.-C. Pseudo-stereodivergent synthesis of enantioenriched tetrasubstituted alkenes by cascade 1,3-oxo-allylation/Cope rearrangement. Angew. Chem. Int. Ed. 59, 7083–7088 (2020).
CAS Google Scholar
Tang, M.-Q., Yang, Z.-J. & He, Z.-T. Asymmetric formal sp2-hydrocarbonations of dienes and alkynes via palladium hydride catalysis. Nat. Commun. 14, 6303 (2023).
Li, P. et al. Stereodivergent access to non-natural α-amino acids via enantio- and Z/E-selective catalysis. Science 385, 972–979 (2024).
CAS PubMed Google Scholar
Luo, P. et al. Switchable chemo-, regio- and pseudo-stereodivergence in palladium-catalyzed cycloaddition of allenes. Angew. Chem. Int. Ed. 63, e202412179 (2024).
CAS Google Scholar
Wang, J. et al. Photocatalytic Z/E isomerization unlocking the stereodivergent construction of axially chiral alkene frameworks. Nat. Commun. 15, 3254 (2024).
Koschker, P. & Breit, B. Branching out: rhodium-catalyzed allylation with alkynes and allenes. Acc. Chem. Res. 49, 1524–1536 (2016).
CAS PubMed Google Scholar
Haydl, A. M., Breit, B., Liang, T. & Krische, M. J. Alkynes as electrophilic or nucleophilic allylmetal precursors in transition-metal catalysis. Angew. Chem. Int. Ed. 56, 11312–11325 (2017).
CAS Google Scholar
Li, G., Huo, X., Jiang, X. & Zhang, W. Asymmetric synthesis of allylic compounds via hydrofunctionalisation and difunctionalisation of dienes, allenes, and alkynes. Chem. Soc. Rev. 49, 2060–2118 (2020).
CAS PubMed Google Scholar
Cera, G. & Maestri, G. Palladium/Brøsted acid catalysis for hydrofunctionalizations of alkynes: from Tsuji–Trost allylations to stereoselective methodologies. ChemCatChem 14, e202200295 (2022).
CAS Google Scholar
Kadota, I., Shibuya, A., Gyoung, Y. S. & Yamamoto, Y. Palladium/acetic acid catalyzed allylation of some pronucleophiles with simple alkynes. J. Am. Chem. Soc. 120, 10262–10263 (1998).
CAS Google Scholar
Gellrich, U. et al. Mechanistic investigations of the rhodium catalyzed propargylic C–H activation. J. Am. Chem. Soc. 136, 1097–1104 (2014).
CAS PubMed Google Scholar
Lutete, L. M., Kadota, I. & Yamamoto, Y. Palladium-catalyzed intramolecular asymmetric hydroamination of alkynes. J. Am. Chem. Soc. 126, 1622–1623 (2004).
CAS PubMed Google Scholar
Lumbroso, A., Koschker, P., Vautravers, N. R. & Breit, B. Redox neutral atom economic rhodium-catalyzed coupling of terminal alkynes with carboxylic acids toward branched allylic esters. J. Am. Chem. Soc. 133, 2386–2389 (2011).
CAS PubMed Google Scholar
Koschker, P., Kahny, M. & Breit, B. Enantioselective redox-neutral Rh-catalyzed coupling of terminal alkynes with carboxylic acids toward branched allylic esters. J. Am. Chem. Soc. 137, 3131–3137 (2015).
CAS PubMed Google Scholar
Chen, Q.-A., Chen, Z.-W. & Dong, V. M. Rhodium-catalyzed enantioselective hydroamination of alkynes with indolines. J. Am. Chem. Soc. 137, 8392–8395 (2015).
Liu, Z. & Breit, B. Rhodium-catalyzed enantioselective intermolecular hydroalkoxylation of allenes and alkynes with alcohols: synthesis of branched allylic ethers. Angew. Chem. Int. Ed. 55, 8440–8443 (2016).
CAS Google Scholar
Cruz, F. A. & Dong, V. M. Stereodivergent coupling of aldehydes and alkynes via synergistic catalysis using Rh and Jacobsen’s amine. J. Am. Chem. Soc. 139, 1029–1032 (2017).
Cruz, F. A., Zhu, Y.-M., Tercenio, Q. D., Shen, Z.-M. & Dong, V. M. Alkyne hydroheteroarylation: enantioselective coupling of indoles and alkynes via Rh-hydride catalysis. J. Am. Chem. Soc. 139, 10641–10644 (2017).
Su, Y.-L. et al. Asymmetric α-allylation of aldehydes with alkynes by integrating chiral hydridopalladium and enamine catalysis. Org. Lett. 20, 2403–2406 (2018).
CAS PubMed Google Scholar
Lee, J. T. D. & Zhao, Y. Direct enantioselective α-allylation of unfunctionalized cyclic ketones with alkynes through Pd-amine cooperative catalysis. Chem. Eur. J. 24, 9520–9524 (2018).
CAS PubMed Google Scholar
Xie, L.-Y., Yang, H.-J., Ma, M.-L. & Xing, D. Rhodium-catalyzed branched and enantioselective direct α-allylic alkylation of simple ketones with alkynes. Org. Lett. 22, 2007–2011 (2020).
CAS PubMed Google Scholar
Wu, M.-S., Han, Z.-Y. & Gong, L.-Z. Asymmetric α‑pentadienylation of aldehydes with cyclopropylacetylenes. Org. Lett. 23, 636–641 (2021).
CAS PubMed Google Scholar
Davison, R. T. et al. Enantioselective addition of α‑nitroesters to alkynes. Angew. Chem. Int. Ed. 60, 4599–4603 (2021).
CAS Google Scholar
Velasco-Rubio, A. ́, Bernárdez, R., Varela, J. A. & Saá, C. Enantioenriched α-vinyl 1,4-benzodiazepines and 1,4-benzoxazepines via enantioselective rhodium-catalyzed hydrofunctionalizations of alkynes and allenes. J. Org. Chem. 86, 10889–10902 (2021).
Zhang, J. et al. Asymmetric coupling of β-ketocarbonyls and alkynes by chiral primary amine/Rh synergistic catalysis. Org. Lett. 24, 1186–1189 (2022).
CAS PubMed Google Scholar
Ma, C., Liang Chen, L. & He, Z.-T. Asymmetric intramolecular O-hydroximation of alkynes. CCS Chem. 7, 1168–1176 (2025).
CAS Google Scholar
Lin, Y. et al. Asymmetric α‑allylation of amino acid esters with alkynes enabled by chiral aldehyde/palladium combined catalysis. Org. Lett. 26, 7908–7913 (2024).
CAS PubMed Google Scholar
Chang, C.-Y. & Aponick, A. Enantioselective synthesis of allylic sulfones via rhodium-catalyzed direct hydrosulfonylation of allenes and alkynes. J. Am. Chem. Soc. 146, 16996–17002 (2024).
Liu, Y., Chen, H. & Wang, X. Synergistic homogeneous asymmetric Cu catalysis with Pd nanoparticle catalysis in stereoselective coupling of alkynes with aldimine esters. J. Am. Chem. Soc. 146, 28427–28436 (2024).
Yang, S.-Q., Wang, Y.-F., Zhao, W.-C., Lin, G.-Q. & He, Z.-T. Stereodivergent synthesis of tertiary fluoride-tethered allenes via copper and palladium dual catalysis. J. Am. Chem. Soc. 143, 7285–7291 (2021).
CAS PubMed Google Scholar
Chen, Y.-W., Liu, Y., Lu, H.-Y., Lin, G.-Q. & He, Z.-T. Palladium-catalyzed regio- and enantioselective migratory allylic C(sp3)–H functionalization. Nat. Commun. 12, 5626 (2021).
Wang, Y.-C. et al. Umpolung asymmetric 1,5-conjugate addition via palladium hydride catalysis. Angew. Chem. Int. Ed. 62, e202215568 (2023).
CAS Google Scholar
Yang, S.-Q. et al. Catalytic asymmetric hydroalkoxylation and formal hydration and hydroaminoxylation of conjugated dienes. J. Am. Chem. Soc. 145, 3915–3925 (2023).
CAS Google Scholar
Chen, X.-X., Luo, H., Chen, Y.-W., Liu, Y. & He, Z.-T. Enantioselective palladium-catalyzed directed migratory allylation of remote dienes. Angew. Chem. Int. Ed. 62, e202307628 (2023).
CAS Google Scholar
Tang, M.-Q., Yang, Z.-J., Han, A.-J. & He, Z.-T. Diastereoselective and enantioselective hydrophosphinylations of conjugated enynes, allenes and dienes via synergistic Pd/Co catalysis. Angew. Chem. Int. Ed. 64, e202413428 (2025).
CAS Google Scholar
Jiang, R., Ding, L., Zheng, C. & You, S.-L. Iridium-catalyzed Z-retentive asymmetric allylic substitution reactions. Science 371, 380–386 (2021).
CAS PubMed Google Scholar
Roberts, C. C., Matías, D. M., Goldfogel, M. J. & Meek, S. J. Lewis acid activation of carbodicarbene catalysts for Rh-catalyzed hydroarylation of dienes. J. Am. Chem. Soc. 137, 6488–6491 (2015).
CAS PubMed Google Scholar
Goldfogel, M. L. & Meek, S. J. Diastereoselective synthesis of vicinal tertiary and N-substituted quaternary stereogenic centers by catalytic hydroalkylation of dienes. Chem. Sci. 7, 4079–4084 (2016).
Cooke, M. L., Xu, K. & Breit, B. Enantioselective rhodium-catalyzed synthesis of branched allylic amines by intermolecular hydroamination of terminal allenes. Angew. Chem. Int. Ed. 51, 10876–10879 (2012).
CAS Google Scholar
Beck, T. M. & Breit, B. Regioselective rhodium-catalyzed addition of 1,3-dicarbonyl compounds to terminal alkynes. Org. Lett. 18, 124–127 (2016).
CAS PubMed Google Scholar
Pritzius, A. B. & Breit, B. Z-selective hydrothiolation of racemic 1,3-disubstituted allenes: an atom-economic rhodium-catalyzed dynamic kinetic resolution. Angew. Chem. Int. Ed. 54, 15818–15822 (2015).
CAS Google Scholar
Hilpert, L. J. & Breit, B. Rhodium-catalyzed parallel kinetic resolution of racemic internal allenes towards enantiopure allylic 1,3-diketones. Angew. Chem. Int. Ed. 58, 9939–9943 (2019).
CAS Google Scholar
Correia, J. T. M., List, B. & Coelho, F. Catalytic asymmetric conjugate addition of indolizines to α,β-unsaturated ketones. Angew. Chem. Int. Ed. 56, 7967–7970 (2017).
CAS Google Scholar
Zhang, Y.-Z. et al. Organocatalytic C3-functionalization of indolizines: synthesis of biologically important indolizine derivatives. Org. Biomol. Chem. 18, 5688–5696 (2020).
CAS PubMed Google Scholar
Singh, K., Staig, S. J. & Weaver, J. D. Facile synthesis of Z-alkenes via uphill catalysis. J. Am. Chem. Soc. 136, 5275–5278 (2014).
CAS PubMed Google Scholar