Literature Seminar (D2 Part) 2011/04/06 (Wed) Noriaki Takasu (D2) Diazo-mediated Metal Carbenoid Chemistry ~Recent Developments of Variety Bond Formation Methods~ Cyclopropanation C-H Insertion [4+3] Cyclization R1 R2 N2 R1 LnM 2 LnM R [3+2] Cyclization Metal Carbenoid Ylide Formation Coupling N-H, O-H Insertion Recently, many metal catalyzed C-H activation reactions have been reported, but many reactions have not become reaction using wide range (selectivity, functional group tolerance). The metal-carbenoid intermediates are capable of undergoing a range of unconventional reactions, and due to their high energy, they are ideal for initiating cascade sequences leading to the rapid generation of structural complexity. These species are using for many type C-H activated reactions, C-C or C-heteroatom bond formations, and skeletal constructions. In this seminar, I talk about many type metal-carbenoid reactions from various metal. Contents 1. Carbenoid (P.1-2) 2. Rhodium Carbenoid Induced Reaction (P.3-10) 3. Copper Carbenoid Induced Reaction (P.11-12) 4. Palladium Carbenoid Induced Reaction (P.13-14) 5. Other Metal Carbenoid Induced Reaction (P.15-16) 6. Summary & Perspective (P.17) 1. Carbenoid 1-1. Carbene Carbene is a molecule containing a neutral carbon with a 2 valences R NN R R and 2 unshared electrons. C Carbenes are classified as either singlets or triprets depending upon their NHC R' electronic structure. Most carbenes are very short lived, although persistent carbenes are ref.) Nojiri's Lit known (example of stable carbene: N-Heterocyclic carbene; NHC). (M1 Part) p p R R Singlet Triplet R' R' • unshared electron pair ( orbital) and empty p orbital • 2 electron was shared with p orbital and orbital • resembles carbocation and carboanion united on same • resembles biradical carbon, so have nucleophilicity and electrophilicity • Typical angle (calculated) : 130~150° (reactivity depends on substituted groups). • many R and R' groups can stabilize singlet carbene (more than triplet carbene). • Typical angle (calculated) : 100~110° One of the typical carbene formation : diazo decomposition Diazo compounds readily decompose thermally or photochemically N or h or Metal CO2R N CO2R driving force : formation of N2 bond and generation of N2 gas -N H Generated carbene is high reactivity. H 2 In the case of using transition metal to generated carbene C-H Insertion Metal-Carbenoid species is generated 1,2-migration of alkyl Cyclopropanylation and other reaction... 1-2. Metal-Carbenoid Carbenoid is a vague term used for a molecule in which all carbons are tetravalent but still has properties resembling those of a carbene, typically the carbene-like carbon has multiple bonds with a metal. Carbene is stabilized by Metal. Carbenoid has unique reactivity that carbene has not, keeping the reactivity of free carbene. Carbenoid is structurally related to singlet carbenes and posses similarly reactivity. R Carbenoids can be formed by reacting salts of transition metals. e.g. Cu, Rh, Pd, etc... many metals can be formed. MLn These are formed by metal with carbenoid precursor, typically diazo compound. R' Kind of Diazo Compound (Carbenoid Precursor) Carbenoid can be controled carbene reactivity through substituent (acceptors and donors). Not enough electrophilicity causes less reactivity, and too much electrophilicity causes side-reaction, so control of electrophilicity is important. Metal-carbenoid reaction requires appropriate level of electrophilic ability at the carbenoid carbon center. Acceptor Acceptor/Acceptor Acceptor/Donor •Acceptor/Acceptor and Acceptor/Donor types stabilize O O O O diazo compound (so more active catalyst needed for decomposition). H Y X X Y X • Donor substituent stabilized carbenoid through resonance. N2 N2 N2 • Almost metal-carbenoids have electrophilicity. X = R, OR, NR2 X, Y = R, OR, NR2 X = R, OR, NR2 • Carbenoids formed from Acceptor/Acceptor compounds Y = vinyl, Aryl has high electrophilicity. too much electrophilicity causes side-reaction, so control of electrophilicity is important. Electron Feature of This Type Metal-Carbenoid R lone pair on carbon to M : strong C-M bond M C d electrons to p orbital on carbon : weak~moderate bond, stabilize carbene a little R' but still maintain its enough electrophilicity desired metal : bind to the carbene through strong -acceptor interactions and weak (appropriate) back donation interaction. 1/17 Observation of Carbenoid Cu-Carbenoid P. Hofmann et al., ACIE, 2001, 40, 1288. TMS TMS CO Me CO Me tBu N 2 tBu N 2 2 P Cu + N P Cu tBu 2 tBu N Ph N Ph 5 TMS TMS Cu-Carbenoid In toliene-d8 or benzene-d6 at rt, 15-25% Cu-complex was detected. atropisomer Caractarization from 1H NMR (Figure 2), 13C NMR (229.9 ppm of 5 + (C=N2), 177.9 ppm (C=O), MS (FAB; 531.2, [M ]). (At -33 C, this comoplex was maintained for several hours without significant evolution of nitrogen.) Rh2-Carbenoid J. P. Snyder et al., JACS, 2001, 123, 11318. tBu O tBu N O O Rh (OCOtBu) + Rh O 2 4 toluene O Rh Me X-ray structure N O N rt t O MeN Bu O tBu 1-3. Early Example of Metal-Carbenoid Reaction Insertion P. Yate, JACS, 1952, 74, 5376. :NuH O Cu O O -N2 N2 H H R R Nu = RO, RS, R2N R (complex with Cu) Nu Cyclopropanyration Cl A. F. Noels et al., Tetrahedron, 1983, 39, 2169. Cl Metal Metal; Cl Rh (OAc) : 54% 2 4 In this paper, other example, Cl N HC CO R Cu(OTf) : 42% 2 2 2 reactivity is [Rh] > [Cu] > [Pd] Pd(OAc)2 : 12% CO2R Dimerization (Homometathesis) Ph Ph Ph O O Cu + N OO 2 toluene Ph Ph Ph 86% R. Noyori et al., TL, 1966, 1, 59. general metal of metal-carbenoid reaction : Rh, Cu, Pd ; most useful metal is Rhodium. Dirhodium carboxylate (Rh2L4) H. Reimlinger et al., TL, 1973, 24, 2233. Catalyst diazo/Catalyst R Yield First example of Rhodium carbenoid generation from diazo decomposition. Rh2(OAc)4 600 Et 88 catalyst i R OH + N CO Et RO CO Et Rh2(OAc)4 600 Pr 83 2 2 2 t 25 C Rh2(OAc)4 600 Bu 82 Reactivity using Rh2(OAc)4 (Rh(II)) was higher than Rh(I), Rh(III). Rh2(OAc)4 600 H 80 Rh2(OAc)4 600 Ac 93 RhCl3•3H2O 125 Et 64 t RhCl3•3H2O 125 Bu 58 RhCl(PPh3)3 125 Et 49 2/17 2. Rhodium Carbenoid Induced Reaction 2-1. C-H Insertion ref.) Yamaguchi's Lit (M1 Part) Trend in Selectivity In simple case, Reactivity is determined with both electric effect and steric effect. D. F. Taver et al., JACS, 1986, 108, 7686. O O O R1 CO Et Rh (OAc) 1 2 3 2 2 4 CO Et CO Et R = Me, R = Me, R = Me (3 vs 2 ) 23 : 1 R3 2 R1 2 2 1 1 2 3 t R N2 R R = Me, R = H, R = Bu (2 vs 2 bulky) 34 : 1 R2 R2 R3 steric effect R3 tertially > secondary > primary (electric effect; electron density in the C-H bond) G. Stork et al., TL, 1988, 29, 2283. O O COCHN2 Rh (OAc) COCHN2 Rh2(OAc)4 2 4 CO Me CO2Et 2 CH2Cl2 (0.01 M) CO Me CH2Cl2 (0.01 M) CO2Et 2 rt rt 81% 0% dimer : 33% O COCHN2 Rh2(OAc)4 O COCHN2 Rh2(OAc)4 CH2Cl2 (0.01 M) CO2Me rt CO2Me CH2Cl2 (0.01 M) CO2Me 64% rt CO2Me 0% • electron-withdrawing groups inhibit adjacent C-H bond dimer : 31% Mechanism M. P. Doyle et al., JACS, 1993, 115, 958. D. F. Taber et al., JACS, 1996, 118, 547. C-Rh-Rh is 180 from calculation. They didn't perfom DFT calculation, but they expected from alined ligand (L) effect of C-H insertion. This mechanism was expected from experiments results, low EWG : general selectivity and ZINDO calculation was performed to ylide intermediate. high EWG : selectivity is decreased (attack low steric barrier) These mechanisms were plausible and widely accepted, but additional analysis of mechanism was performed for further development of the C-H activation chemistry. Proposed mechanism from DFT calculation E. Nakamura et al., JACS, 2002, 124, 7181. DFT using B3LYP on Rh2(O2CR)4 C-H activation/C-C bond formation reaction. calclated for [Rh2(O2CH)4 - CH2N2 - metane or propane] and [Rh2(O2CH)4 -N2CHCO2Et - metane or propane] 2 -Donation • carboxylate groups serves as anchors of the Rh atom • electron-withdrawing group (E) enhances the electrophilicity of the carbene carbon center • Rh1 has positive charge which increases the electrophilicity Rh2 Rh1 Rh Carbenoid of carbon center Formation • electron donation from Rh2 to Rh1 assist the C-C bond formation and catalyst regeneration. • If chiral ligand was used, it also serves as the site to harness chirarity. C-H Activation Activated energy is decreased, so C-H Insertion is enhanced. C-H Insertion compared to Cu-carbenoid and Ru-carbenoid, energy of C-H insertion to carbenoid is lower (diazomethane-methane). Dissociation H of NH Rh-Catalyst Cl O H H N Ru Cu (HCO2)4Rh2 CH2 C-C Bond H H Cl O Formation NH H 27.6 kcal/mol > 15.6 kcal/mol > 5.7 kcal/mol 3/17 Stereo-/Chemo-Selective Reaction Review; H. M. L. Davies et al., Chem. Rev., 2003, 103, 2861. H. M. L. Davies, ACIE, 2006, 45, 6422. Intramolecular reaction H. M. L. Davies et al., Nature, 2008, 451, 417. H. M. L. Davies et al., Chem. Soc. Rev., 2009, 38, 3061. M. P. Doyle et al., JACS, 1996, 118, 8837. M. P. Doyle et al., JOC, 2005, 70, 5291. 1.0 mol% I II Rh2(OAc)4 10 7 Rh2(4S-MPPIM)4 53 19 Rh2(5S-MEPY)4 62 23 Rh2(4S-MEOX)4 87 trace Rh2(4S-MPPIM)4 Rh2(5S-MEPY)4 Rh2(4S-MEOX)4 In this type reaction, it was thought that Rh-carbenoid reacts with equatrial C-H, because access to axial C-H is prevented by crowding of the cyclohexane ring.