Organoruthenium Chemistry Dongmin Xu 03/02/19 d 8 , second-row, - PowerPoint PPT Presentation

Baran Group Meeting Organoruthenium Chemistry Dongmin Xu 03/02/19 d 8 , second-row, variable ox. states and geometries = versatile reactivity Ruthenium • Hydrogenation Useful Reviews: d 8 second-row transition metal • Oxidation • Murahashi, Chem. Rev. 1998 , 2599. Silvery-white, metallic appearance • Trost, Chem. Rev. 2001 , 2067. • Ruthenacycle mediated reactions Possible oxidation states: -2 to +8 • Alcaide, Chem. Rev. 2009 , 3817. • Addition to Ru π complexes Toxicity not well studied except RuO 4 • Ru-catalyzed olefin metathesis: • Ru vinylidene mediated reactions Density = 12.45 g/cm 3 , m.p. = 2334 °C (8 th in metals) Grubbs, Chem. Soc. Rev. , 2018 , 4510. • C-H activation Hoveyda, JOC , 2014 , 4763. 6 th rarest element in Earth’s crust (after Os, Rh, Ir, Re, Pd) • Metathesis • Photoredox: MacMillan, Chem. Rev. • Olefin isomerization 2013 , 5322. Important events in the history of Ru: • Cyclopropanation NOT covered in this group meeting: • 1650s: Platinum alloy (contains Pt, Ru, Os, Rh, Pd, Ir) was discovered • Radical addition • Reactions using Ru as a Lewis acid • 1844: Karl Ernst Claus discovered ruthenium by dissolving crude Pt with aqua • Photochemistry • Ru-catalyzed click reaction regia and examining the residues • 1953: Djerassi discovered the oxidizing capability of RuO 4 • Cross coupling In the appendices: • 1965: Allen and Senoff reported an unprecedented [Ru(NH 3 ) 5 (N 2 )]X 2 complex • Syntheses of common Ru complexes • 1987: TPAP was first synthesized by Ley and Griffith • 1992: Grubbs et al reported the first Ru carbene catalyst for olefin metathesis Hydrogenation: Applications: Chemoselective hydrogenation with H 2 : • Adding 0.1% Ru to titanium increases its corrosion resistance by 100 times “Compared to Rh, Ir, and Co, ruthenium complexes generally have less • Hardening of Pt and Pd; used in effective catalytic activities for hydrogenation of simple alkenes.” manufacture of jewelry and electrical contacts O O Me Me • Ru-Mo superconductors RuCl 2 (PPh 3 ) 3 (cat.) Fun Facts: Me Me H 2 (100 atm), 50 °C • Named after Ruthenia , a Latin word that refers to Russia 94% • Ru has 7 natural stable isotopes, along with 34 radioisotopes • Global production ~12 tons per year; projected world reserve ~5000 tons O O - Mostly as byproduct of copper, nickel, or platinum mining Tsuneda, Bull. Chem. Soc. Jpn. 1973 , 279. • Current market price: $266/ozt, or $8.55/g Aldrich price: $112/g (200 mesh powder, 99.9% trace metal basis) • Percentage of Ru in mined platinum group metal mixture varies greatly RuCl 2 (CO)(PPh 3 ) 3 (cat.) - e.g. 11% in South Africa vs. 2% in certain parts of Russia H 2 (14 atm), 158 °C • Parker 51 fountain pen has a 14K gold nib tipped with 96.2% Ru and 3.8% Ir 95% Fahey, JOC 1973 , 80. [Ru], ZrO 2 , ZnSO 4 (aq) “bilayer catalytic system” • Developed by Asahi H 2 (50 atm), 150 °C Chemical Co., Japan >60% • >50000 tons annually Nagahara, Rev. J. Surf. Sci. Technol. Avant-Garde 1992 , 951.

Baran Group Meeting Organoruthenium Chemistry Dongmin Xu 03/02/19 - Olefin dihydroxylation Transfer hydrogenation: OH Pros: homogeneous reaction RuCl 3 (7 mol%) AH 2 M R OH avoids hazardous H 2 NaIO 4 no pressurization needed OH EtOAc-H 2 O-MeCN Cons: limited scope Shing, ACIEE 1994 , 2312 O 58% 0.5 - 3 min lower efficiency than direct [H] MH 2 A no universal proton donor • Low yield if diol too water-soluble; cleavage in the aqueous phase by NaIO 4 R H (screening needed) - Olefin epoxidation H RuCl 2 (PPh 3 ) 3 RuCl 3 (cat.) O Ph Ph (1 mol%) Ph Ph t Bu t Bu OH O Me Me MeOH, 150 °C, 5 h H ( cis:trans = 1:4) 78% Me Me 90% N N Maitlis, J. Organomet. Chem. 1984 , c7 NaIO 4 Eskenazi, J. Chem. Soc. RuCl 2 (PPh 3 ) 3 CH 2 Cl 2 -H 2 O Chem. Commun. 1985 , 1111. (0.25 mol%) - α -oxidation of ethers O HCOOH, 180 °C, 6 h N N 76% H O RuO 2 (cat.) O Ph Watanabe, Bull. Chem. Soc. Jpn. 1984 , 2440. C 9 H 19 OMe NaIO 4 C 9 H 19 OMe CCl 4 -H 2 O-MeCN Oxidation: 85% 83% Sharpless, JOC 1981 , 3936 Ley-Griffith oxidation : TPAP, NMO - Oxidation of allenes and alkynes RuO 4 oxidation: often generated in situ with cat. RuCl 3 /RuO 2 and NaIO 4 - Oxidation of 1° and 2° alcohols - Degradation of aromatic rings to carboxylic acid - Oxidative cleavage of olefins - C-H oxidation O RuCl 3 (2 mol%) (+ 80% unreacted SM) Oxidation via oxoruthenium species NaIO 4 H • Generation of Ru oxo species from peroxyacids CCl 4 -H 2 O Ru n+1 O OR nBu Ru n + ROOOH 17% Ru n+2 O nBu * Can also be generated under aerobic conditions O RuCl 3 (2 mol%) Me Me Me OH NaIO 4 OH RuCl 3 (cat.) O CCl 4 -H 2 O-MeCN O 88% (if NaIO 4 is used) AcOOH Sharpless, JOC, 1981 , 3936 DCM-H 2 O-MeCN CO 2 H 67% • Sluggish reaction due to formation of insoluble Ru-carboxylate complexes 91% • Addition of MeCN causes rapid decomplexation of carboxylates and restores Murahashi, JOC 1993 , 2929. Mechanism: Ru IV catalytic activity of Ru O (If no H 2 O, get O H 2 O O “To our disadvantage, we organic chemists too often ignore even the most ele- epoxidation mentary aspects of the coordination chemistry of the metals we employ as Ru V H then β -H instead) catalysts or reactants” – Barry Sharpless elim. OH

Baran Group Meeting Organoruthenium Chemistry Dongmin Xu 03/02/19 - When no allylic protons are present: Ruthenacycle Mediated Transformations: Ph Ph 4% Ru(cod)(cot) Alkyne + simple olefin: formal ene reaction + Ph CO 2 Me CO 2 Me pyridine, 80 °C RuClCp(cod) R EtO 2 C 85% EtO 2 C + Ph 3 R DMF, 100 °C Wantanabe, Chem. Soc. Chem. Commun. 1991 , 598. 3 50% (R = COCH 3 ) H R 3 R 2 R 2 (6:1 branched:linear) R 3 • Ru forced to eliminate R.E. β -H elim. with endocyclic hydride Trost, JACS 1995 , 615. PDT • Higher energy process, R 1 R 4 R 4 O RuClCp*(cod) R 1 not observed when Ru RuH OH Ph + Ph H allylic protons are H DMF, 100 °C present Alkyne + norbornene: formal [2+2] 85% CO 2 Me (3:1 branched:linear) RuH 2 (CO)[PR 3 ] Mechanism: CO 2 Me (cat.) + R 2 cyclo- H a R 3 R 2 R 3 H a PhH, 80 °C 87% R 2 CO 2 Me β -H elim. R.E. R 3 metalation CO 2 Me H b PDT H b Mitsudo, JOC 1979 , 4492 R 1 R 2 R 1 R 2 H R 3 R 2 R 3 R 1 R 3 Ru R 4 R 4 β -H elim. Ru R.E. R 4 RuH R 1 R 4 R 4 faster • Only H b can easily adopt syn conformation with Ru slower R 1 R 4 R 1 Ru RuH • Thus, olefins with allylic protons yield 1,4-dienes, or a formal ene reaction • Exocyclic β -H elimination will result in unfavorable anti-Bredt olefin • Sterics determines branched vs. linear selectivity • Steric bulk of norbornene accelerates reductive elimination, outcompetes - TMS/TES alkynes give excellent regioselectivity endocyclic β -H elimination R 1 Fe(CO) 3 R R 1 R 3 CpRu(MeCN) 3 PF 6 RuH 2 (CO)[PR 3 ] R 3 R R 1 R 3 R + (cat.) + R 2 R 2 A B R R then CAN R 2 R R R 1 R 2 R 3 A : B Yield R iterative synthesis of CO 2 Me TMS >98:2 78% ladderanes TsHN 7 R Warrener , JACS 1994 , 3645 n -pentyl R >98:2 79% TMS HO Alkyne + olefin + CO: formal Pauson-Khand Et O O via Me O Et >98:2 61% TMS Ru 3 (CO) 12 Et Me Ru MeO 2 C R O OAc CO (1 atm) >98:2 88% nBu TES MeO 2 C R DMF, 140 °C Mitsudo, JACS 1997 , 6187 Dérien, J. Chem. Soc. Chem. Commun. 1994 , 2551

Baran Group Meeting Organoruthenium Chemistry Dongmin Xu 03/02/19 Homo Diels-Alder: Norbornene + propargyl alcohol: facile cyclopropanation RuClCp(cod) CO 2 Et OH (cat.) Cp*Ru(MeCN) 3 PF 6 + EtO 2 C O + MeOH, reflux (quant.) MeOH, rt 91% Me Mechanism: Takahashi, Chem Lett 1997 , 1273 R R Ru Ru migratory reductive insertion elimination R O OH Ru II Me R.E. Trost JACS 1993 , 8831 Formal [5+2] cycloaddition: HO R R Ru II Ru IV Ru IV OH R.E. β -OH 1,2-M.I. elim. R R • Ru IV Ru IV Ru IV OH Takahashi, Bull. Chem. Soc. Jpn. 1999 , 2475 1,2-insertion Enone-allene cycloetherification/amination: Trost JACS 2000 , 2379 Formal [6+2] cycloaddition (stoichiometric): 10% OH O H CpRu(MeCN) 3 PF 6 O Cy reductive + acetylene elimination 15% CeCl 3 •7H 2 O H O • DMF, 60 °C 0 °C H 72% Ru 67% Ru Ru(nbd) 10% O Itoh, Chem. Lett. 1983 , 499 O CpRu(MeCN) 3 PF 6 [2+2+2] alkyne trimerization: + BnHN • Ph 15% TiCl 4 3 Me N Ph Me Cp*Ru(cod)Cl nBu DMF, 60 °C Bn (1 mol%) nBu Me MeO 2 C via O + 62% DCE, rt Ru MeO 2 C Nu R 85% nBu H n Trost, JACS 1999 , 10842 93:7 A : B A B Trost, JACS 2000 , 12007 Itoh, Chem. Commun. 2000 , 549