Rhenium Chemistry (Chiodi, 2020)

Baran Group Meeting Debora Chiodi Rhenium Chemistry 10/24/20

Applications: Selected books and reviews: Re(s) Properties of rhenium: • High-temperature superalloys (e.g., jet engine • “Rhenium: Properties, Uses • Appearance: silver-gray parts, aircraft turbine blades) and Occurrence”, 2017, Eric • d7 transition metal • Pt–Re cat. for lead-free, high-octane gasoline James, Nova Science • Electronic configuration: [Xe] 4f14 5d5 6s2 • Analysis of meteorites to determine their origin Publishers, Inc. (book) • Oxidation states: from –1 to +7 (e.g., different solar system) • Eur. J. Org. Chem. 2017, • Most common oxidation states in catalysis: • Therapeutics and diagnostics for nuclear medicine 3549–3564. (review) +1, +3, +5, +7 • Catalysts in organic chemistry • Chem. Rev. 2011, 111, • One of the rarest elements in the Earth's crust 1938–1953. (review) • "Rhenium-oxo and rhenium- (average concentration 0.5–1 ppb) peroxo complexes in catalytic • 0.2% Re present in molybdenite (main source) 185 187 oxidations." Springer, Berlin, • Isotopes: Re and Re Heidelberg, 2000. (book) • Melting point = 3180°C, it is the highest melting metal • “Inorganic Syntheses”, after tungsten (3380°C) volume XVII, 1997, chapter molybdenite iron meteorite Pratt & Whitney turbofan engine (U.S. airforce) 31. (book) Historical Timeline 1908 First discovery by Masataka Ogawa 1910 Henry Mosley postulated the existence of 2 missing elements in the periodic table (no. 43 and 75) 1919 Masataka Ogawa isolated Re(s) for the first time Walter Noddack, Ida Noddack, & Otto Berg chalcopyrite 1925 named the element after the river Rhein 1927 120 mg of pure Re were extracted 1928 1 g Re extracted from 660 kg of molybdenite 1928-1930 1st industrial production of Re 1929-1930 MW = 188.71 g/mol accepted by German Atomic Weight Commission 1948 Re production started in USSR

1960 Re world production = 10 tons 75% Re metal in USA was employed 1968 in R&D of refractory metal alloys First organo-rhenium(VII) 1975 synthesis by Mertis and Wilkinson 1979 First synthesis of MTO by Beattie and Jones (low yield) chalcopyrite ore (in Chile) Re first catalytic application: optimized 1987 synthesis of MTO by Herrman

First application of high valent oxo-Re(V) 2003 in organic chemistry by Toste 2005 First application of low valent Re in organic chemistry by Takai and Kuninobu 2008 77% Re in USA employed for alloys

Production of rhenium during copper extraction Walter and Ida Naddock 1 Baran Group Meeting Debora Chiodi Rhenium Chemistry 10/24/20

Most commonly encountered Re compounds Features of rhenium Oxidations using Re(V) and Re(VII) • Manganese-group transition metal (Group 7) O prices from • Characteristics of both early and late transition metal species cat. MTO R • Lower electronegativity than late transition metals such as Rh, Ru, Pd, etc. R1 R R1 H2O2 +7 • Re–X (X = C, N, O) bonds are more polarized than the corresponding O Me O ⎤ M–X bonds of late transition metals under the same conditions O O byproducts: O • Re–X (X = C, N, O) bond has stronger nucleophilicity than M–X bonds of Re K Re Re O O Re late transition metals O O O O O O + 1 O O O O • Also has a similar reactivity to late-transition metal complexes (oxidative R OH R OH addition, reductive elimination, and -H elimination, etc.) MTO β • Wide range of oxidation states ranging from –1 to +7 J. Org. Chem. 1995, 60, 7728–7732. 2 g $327.00 5 g $188.00 1 g $197.00 2 Some examples of Re complex synthesis R R cat. MTO O R R2 1 3 H O +6 Me OSnMe3 R R 2 2 1 3 O PPh3 [O] number not R R I O very common, THF Re Re2O7 + Me4Sn Re + Re Angew. Chem. Int. Ed. 1991, 30, Re O I more frequent O O O O 1638–1641. O O PPh as intermediate O O Inorg. Chem. 1998, 37, 467–472. 3 Angew. Chem. Int. Ed. 1988, 27, 394. Inorg. Chem. Commun. 1 g $201.00 O 2015, 51, 83–86. Me Me Me cat. KReO4 1 2 H H + H2O2 O + H2O2 O O R R H O Re O Re Re 2 2 R1 R2 O O - H2O O - H2O O O +5 O Ph O O O Chem. Commun. 2015, 51, 3399–3402. O O Ph Cl Cl Cl PPh Cl P Re Re 3 Re J. Organomet. Chem. 1995, 500, 149. Cl SMe Cl PPh Cl cat. oxo-Re(V) 2 3 P Ph O OPPh3 Cl Cl ⎤ Ph TBHP Ph O O O Ph 37% HCl, EtOH Cl PPh3 CHCl Cl P 1 g $225.00 1 g $74.40 1 g $344.00 Re K Re 3 Re Cl PPh Cl Catalyst: O O PPh3, reflux 3 dppm, reflux P Ph O 30 min, Ar Cl 2 h, Ar Cl Ph O L= MeCN +3 H O O N PPh Cl N PPh3 N Cl 3 Cl PPh dry PhMe Cl Re Ph N Cl Cl Re 3 Re N N Re Cl SMe2 O L Re Re Cl PPh3 37% HCl Cl NCMe OPPh tBu O O Cl Cl Cl Cl Cl DMSO, 12 h, rt 3 PPh3 tBu PPh3 Inorg. Chem. 1998, 37, 4979–4985. tBu tBu 1 g $409.00 1 g $248.00 J. Chem. Soc. 1962, 4019–4033. or Inorg. Chim. Acta 1993, 204, 63–71. “Inorganic Syntheses”, Volume XVII, 1997, Chapter 31. O Ph PPh Ph +1 Br Br 3 Cl P OC OC CO OC N N 250 bar, neat, 250 °C Re Re CO Re Re Re2O7 + 17 CO Re2(CO)10 + 7 CO2 Cl OC OC CO Cl CO P dist. hexane, rt, N2, 30 min Cl Ph thf CO PPh Re2(CO)10 + Br2 2 ReBr(CO) Ph 2 3 5 500 mg $218.00 1 g $147.00 "Pentacarbonylrhenium Halides”, Inorganic Syntheses. 1990, 28, 154–159. Cat. Commun. 2009, 10, 720–724. "Organo-Transition Metal Chemistry: A Personal View”, 2009, p.108. Inorg. Chem. 2016, 55, 5973−5982. 2 Baran Group Meeting Debora Chiodi Rhenium Chemistry 10/24/20 O O Oxidations using Re(VII), Re(V), and Re(III) Angew. Chem. Int. Ed. Benzene to benzoquinone: Me Me MTO epoxidation 1991, 30, 1638–1641. MTO, H O Me Inorg. Chem. 1998, 37, 2 2 also: mechanism: O + H2O Me 467–472. AcOH Me Me Men Me + H O n Me Me 2 O vitamin K3 O Me H2O Me Me Me H O H2O H H OH O O 2 O Me O O O Re Me O Re Me O Me Me O O O Re Me Me or O Me O Me O O Me Me O Me Me Me Me O Me Me Re O O repeated twice in order to get the quinone O 2 Me Inorg. Chim. Acta 1998, 270, 55–59. J. Org. Chem. 1994, 59, 8281–8283. Me Me Me OH2 Me O Angew. Chem. Int. Ed. 1995, 33, 2475–2477. Me O O Me Me Re H O Re Me O O O H O 2 O Benzylic 2 2 H2O2 O Me ReOCl3(OPPh3)(SMe2) (5 mol %) Me O O oxidation: TBHP (2 equiv.), 90°C 3 1 ACS Catal. 2012, 2, 163−167. Miscellaneous oxidations using MTO: Pyridine N MTO (0.5 mol%) J. Org. Chem. R O oxidation: X + RCOOH X 1998, 63, HO cat. MTO SH cat. MTO 30% aq. H O (2 equiv.) N+ OH S N 2 2 1740–1741. HO rt, CH Cl - O H2O2 SH DMSO S 2 2 O O Organometallics 1996, 15, 3543–3549. Inorg. Chem. 1999, 38, 1040–1041. Reductions: Re(V) and Re(VII) Deoxygenation of carbonyls and alcohols: OH cat. MTO Me O Me cat. MTO O H2O2 Reaction conditions: 3-pentanol, cat. ReOCl3(SMe2)(OPPh3), 170°C H2O2 OH 1 1 H R R tBuOH R R Me Me tBuOH H + Me R, R1 = alkyl, aryl 19–95% H 98% MeO MeO MeO Me Tetrahedron Lett. 1995, 36, 6415-6418; Tetrahedron Lett. 1996, 37, 6487–6490. Cl O Cl OH Cl Cl O Baeyer–Villiger oxidation using Re(V) and Re(III): Me H O PPh3 + O (by- Re catalysts: N N cat. [Re] Cl Re Cl Cl Cl product) O Ph Cl Cl O H O N N n 2 2 n PPh3 ChemCatChem 2015, 7, 1177–1183. Green Chem. 2016, 18, 2675–2681. O III O O Re SO cat. [Re] N N 3 PPh3 Stereospecific epoxide deoxygenation: Org. Lett. 2015, 17, 3346–3349. R1 1 N Cl O O O R1 R R H2O2 R O N N Re cat. Re2O7 cat. Re2O7 N Cl Cl R R1 App. Cat. A: Gen. 2012, 443, 27–32. R 1 P(OPh)3, 1 P(OPh) , N N R R R 3 R Inorg. Chim. Acta 2017, 455, 390–397. PPh3 toluene, 100°C toluene, 100°C 3 Baran Group Meeting Debora Chiodi Rhenium Chemistry 10/24/20

Reductions: Re(V) and Re(VII) Example 1: OH R1 O An alternative to the Corey– HO OH cat. MTO, 2° ROH 1) 1.5 equiv. Me2PhSiH, 1 5 mol% 3 R1 Winter olefination: 140°C R yield% = 71–90% R R1 R DCM, rt 2 ee% = 77–93% R2 2) 1 equiv. TBAF R RCOOH + HO OH 3 R3 Me R1COOH R Me O 1 R R1 OH Example 2: One-pot Meyer–Schuster rearrangement / asymmetric reduction HO OH Re R O 1 O Re R Me Me 3 mol% O O OH Ph O Ph OH O 4 O 4 2.5 mol% 2 semicorrine ligand 1 R R1 R H O Ph 2 2 dioxane R Ph Ph R 2 equiv. Me2PhSiH Ph R Me Main R RT, 3 h + cat. 2 yield% = 38–85% H2O catalytic Re O ee% = 45–92% O cycle Example 3: O P(O)Ph 1.5 equiv. Me PhSiH, P(O)Ph2 MDO Me Me N 2 2 HN Me 5 mol% 3 Me 4 yield% = 51–89% 3 L 1 DCM, rt O Re O R Ar R Ar R ee% = 17–99% Re 2 L O O O R = alkyl, aryl O L= solvent Selected entries: O Me Me 1 R P(O)Ph2 R P(O)Ph2 MTO 4 [Re(III) diolate] HN P(O)Ph2 HN 1 OH HN R 5 Me Me Me Me 4 N Organometallics 2013, 32, 3210–3219; JACS 2002, 124, 3970–3979. F3C yield% = 78% yield% = 89% Ts yield% = 81% ee% = > 99% Racemic ketone O 1) cat. [ReOBr2(hmpbta)(PPh3)] OH ee% = 98% ee% = 95% reduction: PhSiH3, THF, reflux Example 4: 1 1 R R R R P(O)Ph 1.5 equiv. Me PhSiH, P(O)Ph2 2) TBAF N 2 2 HN 5 mol% 3 yield% = 47–83% OH OR O OH 1 OR 1 ee% = 95–99% OH OH R DCM, rt R R = Me, Et; R1 = aryl Me N O O H R An alternative to the HWE olefination: t = 25 min, 89% t = 1 h, 67% t = 1 h 20 min, 61% R = NO , t = 13 min, 93% O 2 hmpbta: 2-(2′-hydroxy-5′-methylphenyl)benzotriazole O R O R = COOMe, 20 min, 87% OEt cat. MTO + + P(O)Ph3 R = SMe, t = 25 min, 85% 1 N N 1 Tetrahedron Lett. 2015, 56, 414–418. R R PPh3, toluene R OEt H Enantioselective reduction of ketones and imines Angew. Chem. Int. Ed. 1991, 30, 1641–1643. Synthesis of semicorrin Re catalyst 3: Ph Ph Ph CN O Reductive OH cat. (Ph P) IReO Chem. Commun. 2016, O O 3 2 2 O coupling: O Cl SMe2 N Cl 52, 7257–7260. Re DCM, rt Ph Ph benzene, 150°C Ph Ph + Cl NC Re N HN Cl OH R R H H N Cl cat. (Ph3P)2IReO2 OPPh3 or Ph Ph Chem. Eur. J. 2010, O OPPh3 R R R R PPh3 R R 1 2 16, 9555–9562. Ph 3 benzene, 150°C 4 Baran Group Meeting Debora Chiodi Rhenium Chemistry 10/24/20

Reductions: Re(V) and Re(VII) (continued) C–X bond formation (continued) O C–N bond formation: benzylic amination Carbonyl OSiMe2Ph NHTs hydrosilylation: cat. ReIO2(PPh3)2 1 2 JACS 2003, 125, R R 1 2 1 ReOI2(OEt)(PPh3) (5 mol%) 1 HSiMe Ph R R 4056–4057. R R 2 H aldehydes benzene NH2Ts, NBS, neat, 90°C / ketones R R yields: 60–94% Selected examples: MeO H NBS Br O OSiMe Ph Ts N [Re]I2 + Ts N OSiMe2Ph 2 Br tBu H PhMe2SiO H -HI Ts N V Ph Me [Re]I 87% 69% 68% I V Redox-neutral isomerizations: Re(V) and Re(VII) [Re]BrI NHTs VII Ts N [Re]BrI OH cat. O ReOSiPh OH 3 3 R1 1 R R1 0°C R R JACS 2005, 127, 2842–2843. [3,3]- R Ts R = alkyl, aryl σ (E) selective VII R1 = H, alkyl yield% = 30-98% H N [Re]BrI R1 OH R1 O [ReOCl3(OPPh3)(SMe2)] (5 mol%) R1 ACS Catal. 2012, 2, 163−167. R R2 DME, 80°C R2 R3 R3 C–N bond formation: alkyne hydroamidation Synthetic application for α-ionone: Re2(CO)10 R Me Me Me Me O 2 steps cat. oxo-Re(V) O OH Me cat. Re2(CO)10 R NH + R R Me Me Me Me Me Me toluene, reflux N Re • OH O n dr 6:1 n H Eur. J. Org. Chem. 2016, 4900–4906. n = 0-2 O H Chem. Eur. J. 2009, 15, 3940–3944. Chemistry 2012, 18, 11894–11898. Re O N C–X bond formation Me JACS 2003, 125, Me 6076–6077. Org. Lett., 2007, 9, 5609–5611. n R NH Propargylic alcohol O n SN1-type reaction: O O Me sugar C–N bond formation: S 1-type reaction O N Me OH O Br O O O R1 HN H OH MeO N OH R2 MeO N Br Br cat. ReOCl3(dppm) H Ar R1 Y Ar Br H O TMS cat. ReOCl (dppm) OH 2 MeCN Y 3 TMS R NH PF , MeCN HO R1 Ar = o-OBn-Ph 4 6 Br H 2 pentabromopseudillin Y = -CH2Cl, -CH=CH2 R Org. Lett. 2005, 7, 2501–2504. 5 Baran Group Meeting Debora Chiodi Rhenium Chemistry 10/24/20

C–X bond formation (continued) C–C bond formation: Coupling (continued) JACS 2003, 125, Oxocarbenium / anomeric carbon functionalization: Sakurai-type reaction: OBn OBn 15760–15761. OH OBn PhSH O TMS BnO BnO 94% (α only) cat. ReOCl3(dppm) O [ReOCl3(SMe2)(OPPh3)] SPh TMS BnO NH4PF6 TMS 89% OBn O Br Br (1 mol%) OBn MeNO , 65°C O TsNH2 O 2 O O BnO NHTs HO TMS OBn 81% (1:3.3 α:β) OH BzO O BnO O MeO cat. ReOCl3(dppm) MeO Bz O OBn BzO NH PF BnO OMe BnO Me 4 6 Me 90% [ReOCl (SMe )(OPPh )] O MeO MeNO , 65°C MeO O 3 2 3 2 O Cl Cl BnO BzO (1 mol%) O Bz BzO OMe OH TMS JACS 2004, 126, 4510–4511. 86% α cat. ReOCl3(dppm) NH PF Me 4 6 Me 99% Chem. MeO MeNO2, 65°C MeO C–B bond 1 cat. [ReBr(CO)3(thf)]2 1 R N N R Commun. N N S 1-type trapping with electron- formation: 9-BBN-H B 2015, 51, N toluene, 125°C 4583–4586. rich (hetero)aromatics: furan O R2 R2 (release of H2 gas)

SiMePh OH TMS C–Si bond cat. Re2(CO)10 2 cat. ReOCl (dppm) formation: 3 OMe OMe HSiMePh2 Eur. J. Org. Chem. 120°C 2006, 5495–5498. TMS KPF6 OMe OMe MeNO2, 65°C C–C bond formation: Coupling OMe OMe Dimerization of alkynes: cat. Re2(CO)10 Org. Lett. 2004, 6, 1325–1327. cat. Bu4NF Ph Ph H TMS PhMe, 80°C, 8 h Ph Chem. Lett. (2 equiv.) 2009, 38, 836. Synthetic application: 50% Me Me Propargylic alcohol coupling with acidic methylenes: OH Re(V) O O MeO MeO Me OH O O cat. [ReBr(CO)3(thf)]2 Me Me TMS N Me R3 + R2 Me Me 50°C R3 TMS 1 Me Me R R2 Chem. Lett. 2008, 37, 878–879. R1 O-Me-detrol 6 Baran Group Meeting Debora Chiodi Rhenium Chemistry 10/24/20

C–C bond formation: Coupling (continued) HC(COOEt)3 Alkyne coupling [Re] catalyst Formal synthesis of podophyllotoxin: C H C10H21 with acidic 10 21 C(COOEt) OMe methines: 135°C, toluene 3 O cat. ReOCl (dppm) MeO 3 Re2(CO)10 yield = 48% JACS 2015, 137, CO2Et catalysts: [HRe(CO) ] + O AgPF6 4 n yield = 53% 1452–1457. n = 2,3 MeO MeNO2, 65°C 2 66% 1 OH Intramolecular ortho-alkylation of esters: OMe OMe MeO OMe Me O Me Me O MeO OMe Chem. Commun. cat. Re2(CO)10 1) NaI, AcOH, 115°C O OH 2011, 47, 10791– 2) DIBAL-H CH2ClCH2Cl, 135°C 10793. yield = 20% O 3) Pd(OAc)2, PPh3 O Ag2CO3, 50°C CO Et O OH 64% over 3 steps O 2 Intermolecular ortho-alkylation of phenols: 4 1) TBSCl, TEA, DMAP OH OH Me 2) O , hυ, TPP 3 2 cat. Re2(CO)10 3) Al(Hg), H2O + C6H13 C H toluene, 50°C 68% over 3 steps 6 13 JACS 2009, 131, 9914–9915. OMe R R OMe MeO OMe MeO OMe Alkene coupling with benzylic alcohols: Ph OTBS catalyst: O 1) TBAF Ph cat. [Re(V)] PPh O Ph 22% 3 O OH O OH 2) Pb(OAc) , + Ph PPh3, benzene, 4 O + Re I NaHCO then PDC O 150°C Ph O OH 3 O 37% over 2 steps -apopicropodophyllin PPh β Ph 3 5 OMe 18% MeO OMe J. Org. Chem. 2020, 85, 3320−3327. Alkynylation of imines (alternative to Cu acetylide): R1 O R1 HN N cat. [ReBr(CO)3(thf)]2 O + TMS O neat, 25°C R R H O TMS Chem. Lett. 2006, 35, 1376–1377. Org. Lett. 2004, 6, 1325–1327. OH (±)-podophyllotoxin Regio- and stereoselective synthesis of N-alkylideneallylamines: Alkyne coupling with acidic methylenes: OH O Ph C H O O 6 13 cat. [ReBr(CO)3(thf)]2 cat. [ReBr(CO)5]n + Me Me C H Ph N Ph R 6 13 + N C neat, 50°C P(C6F5)3 Me Me H H R C toluene, 110°C Ph R = alkyl, vinyl, aryl H H Org. Lett. 2005, 7, 4823. C = 13C 70% JACS 2012, 134, 8762−8765. 7 Baran Group Meeting Debora Chiodi Rhenium Chemistry 10/24/20 C–C bond formation: Coupling (continued) Imine–directed thiophene amidation with isocyanates: Reductive alkylation of imine: H tBu H H tBu Ph N O H HN N N cat. [ReBr(CO)3(thf)]2 H+ cat. [HRe(CO) ] + R C Ph 4 n O NHR NHR N + Ph CH2ClCH2Cl, 1 toluene, 180°C 1 S S R R S reflux O O Ph Chem. Lett. 2007, 36, 872–873. 61–81% J. Organomet. Chem. 2011, 696, 348–351. C–C bond formation: Cyclizations Alkylation of enamine (no enolate chemistry): Regio- and stereoselective addition reaction of 1 β-keto phosphonates with alkynes: O OR3 OR R 2 R1 cat. Re2(CO)10 N 1) cat. Re (CO) P R N + O O 2 10 O regio- and O toluene, 135°C OR 3 toluene, 120°C, 24h 2 1 P OR stereoselective R R 3 + Ar 1 R2 OR 2) 160°C, 8h R Ar O R2 R = Me 1 O O OH O HO R Org. Lett. 2009, 11, 2711–2714. R2 3 Me P OR3 3 Ar OR 1 1 P OR Re 3 R OR3 R 3 P OR C–H aminocarbonylation of azobenzenes with isocyanates: OR Re (CO) R2 R2 2 10 O O N Ph 1 N Ph N Path A Ar 2 N C cat. Re2(CO)10 + NHAr Path B reductive Re (CO) –Re N toluene, 130°C 2 10 elimination H Ar Ar O O O H 3 not observed Re Re OR O NHAr O P 3 H H O OR ArHN O O O –Re R1 3 R2 N Ph 3 P OR N N P OR 1 reductive Org. Biomol. Chem. 2015, 13, 7619–7623. N R1 3 R Ar OR3 3 Ar Ar OR elimination NHAr NHAr 2 R2 R 4 5 retro- aldol-type O O Org. Lett. 2014, 16, 5784–5787. C–H activation of carbonyl compounds in the OH hypervalent Re(VII) O presence of a nitrile: 3 catalyst: O OR 3 2 3 2 (R O)2P R O NH 2 (R O)2P R O 2 P R 3 Ph3P H O –R OH O cat. ReH7(PPh3)2 H O 1 H + R3 N R1 R3 R H Re H 1 toluene, 180°C R1 Ar 1 R Ar 2 R2 H R Ar R 6 Ph P H H 8 7 yield = 37-97% 3 JACS 2009, 131, 10824–10825. Synthesis of polysubstituted pyridine: Insertion of terminal alkynes into the C–S bond: 6 3 SPh O R = Me, OMe R O O R5 cat. [HRe(CO) ] regio- and 6 5 4 n R NH O R4 R N Org. Lett. 2012, 14, SPh + Ph Ph Ph stereoselective Ph toluene, 100°C 3182–3185. 1 3 cat. Re2(CO)10 R1 R4 Me 99% Me R R octane, 180 °C, 24 h 2 Org. Lett. 2012, 14, 6116–6118. R2 42–85% R 8 Baran Group Meeting Debora Chiodi Rhenium Chemistry 10/24/20

C–C bond formation: Cyclizations (continued) [3+2] annulations of N-carbamoyl indoles with alkynes: ortho-Alkenylation with concomitant cyclization: R1 R2 1 H R Simple alkenylation: 3 N cat. Re2(CO)10 N 3 R OH R OH cat. Me2Zn 2 NR2 R cat. Re2(CO)10 O cat. ZnCl2 O R2 R1 + R1 PhCl, 160°C, 4 h 1 2 R2 R R (1.5 equiv.) N N cat. Re2(CO)10 Alkenylation–cyclization: Me Ar H NR2 cat. [MeZnNPh ] 1 O O 2 2 R Me cat. Zn(OTf) OH Me O 2 R2 1) cat. Re2(CO)10, PhCl, 160°C, 4 h 1 + Ph R Re (CO) 2) cat. [Re(OPh)(CO)3(thf)]2 N 2 10 Ph Ar-C≡C-Me (3 equiv.), 160°C, 48 h Ph N[Zn] 3 R2 2 H (1.3 equiv.) (75% over 2 steps) Ar = 4-ClC6H4 O N Re(CO)n(NPh2) 1 NR General mechanism: O 2 Me [Re] A H [Re] H Me R1 OH Me O O+ N + [Re] Ph S Ar Ph F R2 H E H R N 2 ORe(CO) N Ph n Re(CO)n(NPh2) O R1 B –[Re] R N Me 2 Ph R2 H [Re] N [Re] Me H H Me H Me Re(CO) O O O n HNPh H O R2N 2 Me Ph Ph Ph E H R1 Ph C–H [Re] 2 Re(CO) R N n activation O Re(CO)n N C –[Re] O R2N

Ph Ph R2N D Me Ph Chem. Eur. J. 2019, 25, 8245–8248. R1 R2 H Me H Me 2 Me O O O Synthesis of isobenzofurans: Me Me Ph Ph 1,7-H shift 6π Ph Ph O JACS 2006, 128, Ph Ph cat. [ReBr(CO)3(thf)]2 N + O 12376–12377. Ph PhMe, 115 °C, 24 h Org. Lett. 2019, 21, 3441–3445. Ph 9 Baran Group Meeting Debora Chiodi Rhenium Chemistry 10/24/20

C–C bond formation: Cyclizations (continued) Ring expansion: O Multicomponent reaction: O O cat. [ReBr(CO) (thf)] R R1 R1 3 2 cat. ReBr(CO)3(thf)]2 OEt + R 2 R MS 4Å, PhMe, 115 °C MS 4Å O N (1.2 equiv.) + neat, 40°C, 24 h OEt O + then H2SO4, AcOH OH O O 3 R3 R Tetrahedron 2007, 63, 8463–8468. OEt R Synthesis of polysubstituted aromatic rings: [ReBr(CO)3(thf)]2 + O O 1 R4 cat. R6 R O O 2 OEt R 5 6 5 2 7 [ReBr(CO)3(thf)]2 O R R R R R1 OEt + III O III 2 MS 4Å 1 4 Re Re R 3 R R PhMe, 150°C 1 4 HO R R PhMe, 180°C R R R3 O R R3 O Org. Lett. 2008, 10, 3133–3135; OEt OH O 2 Chem. Commun. 2008, 6360–6362. OEt +HO III R1 OEt Re 6 R6 R2 R R5 R2 reductive + – [ReBr(CO)3(thf)]2 elimination O 3 4 R R 1 1 4 R R 3 OEt 3 R +HO HO R R –CO2 O – 1 O HO R O OEt R2 R1 R2 R2 5 OEt ReIII ReIII CO Et R6 4 Chem. Asian J. 2009, 4, 1424–1433. CO2Et 2 O R4 O Formation of bicyclo[3.3.1]nonene frameworks: R3 R4 R3 R4 O R 3 cat. 2 Path A 3 5 R O O [ReBr(CO)3(thf)]2 O Org. Lett. 2009, reductive reductive OEt + R 5 6 11, 2535–2537. elimination elimination R R then cat. TBAF neat, 40°C, 4 h R O O 1 2 Phenol synthesis: R R EtO H 2 OH O HO CO Et 2 R 2 O R O O O cat. Re2(CO)10 R + R OMe 3 4 R1 R4 R1 R4 MeO OMe MS 4Å R R retro- –EtOH aldol-type 3 3 PhMe, 135°C R 5 R 6 R 7 Chem. Lett. 2010, 39, 894–895. 10 Baran Group Meeting Debora Chiodi Rhenium Chemistry 10/24/20 C–C bond formation: Cyclizations (continued) Formation of 2-iodo-1H-indenes (continued): Ph Ph Ph Formal [2+2] cycloaddition: O [Re(I)] O H 1,5–H O CO2Me CO2Me Ar 1,2–I shift shift Ar cat. ReBr(CO)3(thf)]2 Ar • [Re] [Re] + Ar Ar Ar PhMe, 115 °C, 24 h I I I CO2Me Ar CO2Me MeO Chem. Lett. 2007, 36, 1162. Ar –PhCHO –[Re] I Ar [Re] Cyclopentenone formation: 1 R R H - I Ar [Re] R R1 MeO H CO Et n 2 cat. Re2(CO)10 aromatization 1 + 2 Org. Lett. 2019, 21, 6756–6760. n + I EtO2C CO2Et dioxane, 135°C CO Et 2 Alkyne–imine cyclization: O CO2Et tBu NHtBu NHtBu N Angew. Chem. Int. Ed. 2017, 56, 1–6. 2 R R R R Ph R R R R1 Ph + R1 R2 cat. [ReBr(CO) (thf)] O R1 3 2 3 PhMe, reflux, 24 h 2 R O2C cat. Re2(CO)10 R Ph + R1 O or R1 dioxane, 135°C 3 JACS 2005, 127, 13498–13499; Angew. Chem. Int. Ed. 2007, 46, 2144–2146. X HO CO2R Intramolecular diene–alkyne cyclization: CO2Et O X X OTIPS TIPSO H TIPSO H R1 Trimerization: cat. ReCl(CO)5 R1 + R1 O R2 MS 4Å CHO cat. ReBr(CO)5 cat. PhNHCOMe hυ, toluene 2 R3 2 R3 Org. Lett. 2010, 3 R R Ph R 12, 2948. (51–92%) Angew. Chem. Int. Ed. 2005, 117, 468. PhMe, 180 °C, 24 h (98%) (3 equiv.) Ph Enone–imine cyclization: Ph Me N cat. ReBr(CO)3(thf)]2 Formation of 2-iodo-1H-indenes: OEt PhMe, 150 °C, 24 h O + Ph Me Ar O (85%) OEt cat. ReBr(CO)3(thf)]2 MeO dioxane, 80 °C, 3 h (1.5 equiv.) Angew. Chem. Int. Ed. 2006, 45, 2766–2768. O I Ar 1: 64% (1 : 2 = 79 : 21) Allene–imine cyclization: Ar Ar H I Me Me N Ph Ph cat. [HRe(CO)4]n Ar = 3-MeOC H I N + • Ph 6 4 2: neat, 115°C (88%) Ph Org. Lett. 2019, 21, 6756–6760. OMe Org. Lett. 2010, 12, 4275. 11 Baran Group Meeting Debora Chiodi Rhenium Chemistry 10/24/20

O O HO R1 cat. Re2(CO)10 3 “Only three of the naturally occurring elements were manufactured in 4 CO2R 1 3 R R4 the big bang. The rest were forged in the high-temperature hearts R OR + R2 • neat, 115°C, 30 h and explosive remains of dying stars, enabling subsequent R2 γ α γ β β generations of star systems to incorporate this enrichment, forming Me α planets and, in our case, people. Examples of substrate scope: For many, the Periodic Table of Chemical Elements is a forgotten oddity—a chart of boxes filled with mysterious, O OAc HO Me HO Me HO Me cryptic letters last encountered on the wall of high school CO Et CO Et 2 2 O chemistry class. As the organizing principle for the chemical Me Ph Ph behavior of all known and yet-to-be-discovered elements in the universe, the table instead ought to be a cultural icon, a Me Me Me testimony to the enterprise of science as an international human 73% 61% 50% adventure conducted in laboratories, particle accelerators, and on the frontier of the cosmos itself.” Mechanism: 1 R OH ― Neil deGrasse Tyson, Astrophysics for People in a Hurry R4 R2 OH O D D CO R3 D 2 R4 R1 OR3 + D • R2 [Re] H H O 1 O O R1 O R [Re] 3 [Re] OR3 2 OR R2 R 4 R4 D R D 1 D 4 D

H H 1 O O O R R1 O [Re] 3 D 2 OR [Re] OR3 R R2 R4 D 4 R 2 D 3 D - The reaction proceeds at the β- and γ-positions of the allene, whereas the previously known reactions usually occur at the three carbon atoms of the α-, β-, and γ-positions. - The annulation shows very high stereoselectivity in the final products, presumably controlled by hydrogen bonding between the hydroxy and ester groups. Angew. Chem. Int. Ed. 2008, 47, 9318–9321.