Intercepting a labile anti-π-allyl-iridium complex before its isomerization

The stereodefined installation of chiral centers adjacent to thermodynamically unstable Z-olefins is a challenge in synthetic chemistry. In recent work published Science, You and coworkers reported an iridium-catalyzed, Z-retentive asymmetric allylic allylation with variety Z-allyl esters, providing elegant access important Z-olefins. Transition-metal-catalyzed allylations are among the most powerful tools for forging carbon-carbon carbon-heteroatom bonds modern chemistry.1Kazmaier U. Transition Metal Catalyzed Enantioselective Allylic Substitution Organic Synthesis. Springer, 2012Crossref Google Scholar particular, their counterparts, termed (AAAs), can selectively install stereogenic alkene units, thus versatile building blocks accessing natural products, drugs, perfumes.2Trost B.M. Crawley M.L. Asymmetric transition-metal-catalyzed alkylations: applications total synthesis.Chem. Rev. 2003; 103: 2921-2944Crossref PubMed Scopus (2228) As exemplified carbon nucleophiles, general reaction pathway briefly illustrated Figure 1A: first, oxidative addition low-valent metals allyl alcohols or derivatives generates π-allyl-metal intermediates; subsequently, these transient species react Csp3- Csp2-type nucleophiles via outer- inner-sphere mechanism, delivering products I–III. Regarding selectivity AAA reactions, three major aspects must be considered: (1) regioselectivity, which usually controls whether inner (C3, branch [B]) terminal (C1, linear [L]) complex reacts nucleophiles; (2) enantioselectivity, defines spatial orientation as well branch-selective reaction; (3) geometric selectivity, results E- Z-olefinic products. By continuous endeavors, communities have successfully addressed first two problems by rationally choosing suitable ligands using noncovalent interactions between donors acceptors.3Wang Y.-N. Lu L.-Q. Xiao W.-J. Non-bonding enable selective formation branched palladium-catalyzed substitution reactions.Chem. Asian J. 2018; 13: 2174-2183Crossref (20) Except unconventional case,4Lin H.-C. Xie P.-P. Dai Z.-Y. Zhang S.-Q. Wang P.-S. Chen Y.-G. T.-C. Hong X. Gong L.-Z. Nucleophile-dependent Z/E- regioselectivity C–H alkylation 1,4-dienes.J. Am. Chem. Soc. 2019; 141: 5824-5834Crossref (49) reactions always afford E-olefinic through isomerization originally generated anti-π-allyl-metal intermediate into its more stable syn-variant. Therefore, from precursors remains reactions. Very recently, coworkers5Jiang R. Ding L. Zheng C. S.-L. Iridium-catalyzed reactions.Science. 2021; 371: 380-386Crossref (24) iridium (Ir)-catalyzed indole-type aldimine esters efficient practical method synthesizing (Figure 1B). With combination [Ir(COD)Cl]2 (COD = 1,5-cyclooctadiene) Carreira-type P,olefin-ligand catalyst (Ir-Cat. A, R′ I),6Rössler S.L. Petrone D.A. Carreira E.M. synthesis functionally rich molecules enabled (phosphoramidite,olefin) ligands.Acc. Res. 52: 2657-2672Crossref (108) dearomatization-cyclization cascade 3-nucleophile-subsititued indoles took place presence stoichiometric In(OTf)3 (OTf trifluoromethesulfonate), producing diverse range enantioenriched polycyclic indolines. Moreover, combining Ir B)7Hartwig J.F. Stanley L.M. Mechanistically driven development catalysts substitution.Acc. 2010; 43: 1461-1475Crossref (432) derived Feringa-type P-ligand copper consisting Cu(MeCN)4OTf P,N-ligand (S,Sp)-L, authors further achieved α-amino-acid-derived affording α-amino acid quaternary stereocenters. It worth mentioning that both catalytic systems allow units high enantioselectivity either acidic A) basic B) conditions. Additionally, there some differences donor scopes systems: former tolerates aryl-, alkyl-, iodide-substituted whereas latter seems exhibit good only aliphatic ones. limited generality system might result comparable rates capture anti-π-allyl-Ir nucleophile syn-variant given product isomer were produced 1:1 mixture when Z-cinnamyl acetate was used. example, performed extensive mechanistic studies illuminate especially Z-geometric 1C). structure active catalyst, Ir-Cat. A (R′ H), established time nuclear magnetic resonance (NMR) X-ray crystallographic analysis. precursor, 1:2 Ir(COD)Cl]2 Carreira’s ligand H) π-allyl-Ir complexes (anti syn) characterized NMR high-resolution mass spectrometry. also confirmed electrospray ionization spectrometry 31P On basis experimental results, possible mechanism proposed. First, coordinates (Ir/L 1:1) generate help AgOTf In(OTf)3. Next, it ester form anti-allyl-Ir intermediate. Before unimolecular relatively syn-variant, this labile rapidly trapped nucleophile, Z-allylation finally delivered conformation olefins untouched, regeneration Ir(I) catalyst. excellent unusual observed work. For compared colleagues’ previous on Ir-catalyzed tryptophols tryptamine E-allyl alcohols, opposite enantio-induction recorded even same-configuration under conditions.8Zhang Han intermolecular dearomatization indoles.Chem. Sci. 2014; 5: 1059-1063Crossref (94) contrast works Wang9Wei Zhu Q. Xu S.-M. Chang C.-J. Stereodivergent α,α-disubstituted acids synergistic Cu/Ir catalysis.J. 140: 1508-1513Crossref (134) Zhang10Huo Fu He W. Ir/Cu dual catalysis: enantio- diastereodivergent bearing vicinal stereocenters.J. 2080-2084Crossref (144) groups, where found Ir- Cu-cocatalyzed observed. These phenomena unknown properties intermediates. additional structural information reactivity still needed fully elucidate regio- enantioselectivity. conclusion, skillfully demonstrated if chosen. In-depth revealed key success quick nucleophilic attack before isomerizes This represents new promising arsenal Z-olefin (e.g., Z-allylboron ketones imines, cross-couplings, Z-selective cross-metathesis). Perhaps interestingly, we expect intercepting will strategy could extended other metal-catalyst systems, such those ruthenium, rhodium, molybdenum. L.-Q.L. W.-J.X. acknowledge financial support National Natural Science Foundation China ( 21822103 , 21820102003 21772052 21772053 ).