M.C. White, Chem 153 了- allyl chemistry375 Week of december 9. 2002 oT- Trimethylenemethane cyclization Provide a mechanism for the following transformation toluene,Δ SiMe mixture of stereoisomers SiMe L,Pd(o Ph LnPd山 LnPd山 团 Pd(o Trost JACS1980(102)6359,ACS1983(105)2326
M.C. White, Chem 153 π-allyl chemistry -375- Week of December 9, 2002 π-Trimethylenemethane cyclization O O Ph AcO SiMe3 (Ph3P)4Pd O O Ph H H Provide a mechanism for the following transformation. mixture of stereoisomers + toluene, ∆ LnPd Ph (0) AcO SiMe3 Ph SiMe3 OAc Ph LnPd(II) LnPd(II) O O Ph Pd(II)Ln O O Ph Pd(II)Ln O O Ph H H Pd(0)Ln O O Ph H H Pd(0) H Trost JACS 1980 (102) 6359, JACS 1983 (105) 2326
M.C. White, Chem 153 Metal alkylidenes 376 Week of december 9. 2002 Metal carbenes Fischer Carbenes(formally derived from a singlet carbene) Schrock Carbenes(formally derived from a triplet carbene) carbene RV O alkyl(or H) The presence of strong 8+6 I-acceptor ligands on the ts competes LM=CR I-donation from the metal P orbital weak inlet extreme nmr transfered to the C(p,) orbital LnM=CR alkyl (or H) High oxidation state, early metals tal-carbon bonds are more Low oxidation state. late metals carbenes Non-a acceptor ligands on the metal than t -backbonding (often I-donor ligands such as Cp or CI) nature and highly polarized alkyl (or H)substituents on the carbene resulting in a partial negative T-donar substituents on the carbene C resulting in a partial positive charge on the the carbene c arlene carbon likened to a carbonyl: 8 80Me PapA (CO)sCr (CO)4C 18e. Ph (BUcH)3Ta note: that the formal charge for the carbene unit is zero. the # highly oxophilic, early metal of electrons donated is 2 CrCO)+ (CO)4C (A-BucH3Ta 人 (A-BuCH3Ta Ph ome Fischer Chem. Ber. 1972(105)3966 Schrock jACS1974(96)6796,1976(98)5399
M.C. White, Chem 153 Metal alkylidenes -376- Week of December 9, 2002 Metal Carbenes singlet carbene M C X sp2 pz R' R O C LnM=CR2 δ+ δ- Fischer Carbenes (formally derived from a singlet carbene) (CO)5Cr0 OMe Ph OR (CO)5CrII Ph OMe OR (CO)5CrII Ph OMe OR CO Ph RO OMe Cr0(CO)6 Fischer Chem. Ber. 1972 (105) 3966. · Low oxidation state, late metals · π-acceptor ligands on the metal · π-donar substituents on the carbene C δ+ δ- + · electrophilic carbenes · σ-donation is stronger than π-backbonding resulting in a partial positive charge on the carbene carbon note: that the formal charge for the carbene unit is zero, the # of electrons donated is 2. π-donation from the carbene substituents competes w/ π-donation from the metal The presence of strong π-acceptor ligands on the metal renders π-backbonding into the empty carbene p orbital weak. R' X = heteroatoms likened to a carbonyl: O OMe Me δ+ δ- 18 etriplet carbene Schrock Carbenes (formally derived from a triplet carbene) M C R sp2 pz R · The metal-carbon bonds are more covalent in nature and highly polarized towards C resulting in a partial negative charge on the carbene C. alkyl (or H) X R' R' LnM=CR2 δ- δ+ · High oxidation state, early metals · Non- π acceptor ligands on the metal (often π-donor ligands such as Cp or Cl) · alkyl (or H) substituents on the carbene. · nucleophilic carbenes The first characterized Schrock carbene: Ta V t-Bu t-Bu t-Bu t-Bu δ δ+ - + likened to a phosphorus ylide: Ph3P t-Bu δ- δ+ O pentane/N2 O2 and moisture sensitive -2 charge/ 4 electron donor 10 e- (t-BuCH2)3Ta V t-Bu O (t-BuCH2)3Ta V O t-Bu highly oxophilic, early metal (t-BuCH2)3Ta V O t-Bu + 85% Schrock JACS 1974 (96) 6796, 1976 (98) 5399. M C R sp2 pz R alkyl (or H) X R' R' extreme π-backbonding: where the 2e- in the M(dπ) orbital are transfered to the C(pz) orbital
M.C. White, Chem 153 Metal alkylidenes-377 Week of december 9. 2002 The first isolated and characterized Schrock carbenes The first characterized Schrock carbene a-agostic Interaction w/extra electron density (t-BuCH2)( ciTa CI -Bu 2eqA-BuCH)Li (-BuCH2k( CI)Ta ([-BuCH2hTa (- BuCH2)Ta≌ 10 LiCI LiCI steric conjestion induces direct a-proton abstraction by one of the neopentane ligands resulting in the metal alkylidene Schrock JACS 1974(96)6796, Acc Chem. Res 1979(12)98 solated Schrock carbene B +C(Ph CH MeC(Ph) 16e- Schrock Jacs1975(97)657706579 is suggestive of a significant amount of db character
M.C. White, Chem 153 Metal alkylidenes -377- Week of December 9, 2002 The first isolated and characterized Schrock carbenes The first isolated Schrock carbene: TaV Me Me Me 18 eC(Ph)3 BF4 MeC(Ph)3 TaV Me CH2 16 eH BF4 base TaV Me CH2 18 eSchrock JACS 1975 (97) 6577, 6579. 2.026 Å 2.246Å ~ 10 % shorter Ta-C bond is suggestive of a significant amount of db character The first characterized Schrock carbene: (t-BuCH2)2(Cl)Ta V t-Bu Cl H 10 e- complex α-agostic interaction provides the metal w/extra electron density 2 eq t-BuCH2Li (t-BuCH2)2(Cl)Ta V t-Bu H t-Bu steric conjestion induces direct α-proton abstraction by one of the neopentane ligands resulting in the metal alkylidene. (t-BuCH2)2TaV t-Bu Cl CMe4 (t-BuCH2)3Ta V t-Bu LiCl LiCl Schrock JACS 1974 (96) 6796, Acc. Chem. Res. 1979 (12) 98
M.C. White, Chem 153 Metal alkylidenes-378- Week of december 9. 2002 Carbonyl methylenation: Tebbe's reagent Tebbe's reagent: Tebbe JACS 1978(100)3611 Ti.aiMe CH2 stoichiometric toluene AMe toluene,-15°C 2 AlMe 65% 16e AlMe,CI Tebbe's reagent 0.5M soln 100 mL/S363 In situ prep: Grubbs JOC 1985(50)2386 (Aldrich 2001) i\AlMy R Synthetic applications OTBS OBn oTBs O OTBS OBn OTBS 2TICH, CIAIMe? Eto,C tol-THF-Py, Eto,C 8Cto-15°C otBs OBI otbs otbs OBI otbs Schreiber JAcs 1990(112)9657 key intermediate in the total synth of Hikizimycin CpTiCH2CIAIMe2 THF, rt, Ih Nicolaou ACIEE1994(33.,2184,2187,2190 key intermediate in the total synthesis of Zaragozic acid
M.C. White, Chem 153 Metal alkylidenes -378- Week of December 9, 2002 Carbonyl methylenation: Tebbe’s reagent TiIV Cl Cl 16 e- + 2 AlMe3 toluene rt TiIV Cl 16 eAlMe2 CH4, AlMe2Cl Tebbe's reagent: Tebbe JACS 1978 (100) 3611. Tebbe's reagent 0.5M soln 100 mL/$363 (Aldrich 2001) TiIV Cl AlMe2 TiIV O TiIV O R R CH2 16 eTiIV Cl AlMe2 stoichiometric toluene, -15 o C 65% Synthetic applications: EtO2C O OTBS OTBS OBn OBn OTBS OTBS Cp2TiCH2ClAlMe2 tol-THF-Py, -78oC to -15o C 82% EtO2C OTBS OTBS OBn OBn OTBS OTBS key intermediate in the total synthesis of Hikizimycin Schreiber JACS 1990 (112) 9657. OR O O O Cp2TiCH2ClAlMe2 THF, rt, 1h 85% O OR O Nicolaou ACIEE 1994 (33), 2184, 2187, 2190 key intermediate in the total synthesis of Zaragozic acid In situ prep: Grubbs JOC 1985 (50) 2386
M.C. White, Chem 153 Metal alkylidenes- 379 Week of december 9. 2002 Tebbe's reagent Tebbe's reagent reacts with olefins to give metallocyclobutanes AICIMe Grubbs OM 1982(1)1658 Titanium metallocyclobutane I reacts with acid chlorides to form Ti enolates OTiCICp2 PhCHO CI tol, -20C to 0%C Ph Grubbs JACS 1983(105)1665
M.C. White, Chem 153 Metal alkylidenes -379- Week of December 9, 2002 Tebbe’s reagent TiIV Cl AlMe2 TiIV 16 e- + AlClMe2 TiIV TiIV Tebbe's reagent reacts with olefins to give metallocyclobutanes: Titanium metallocyclobutane 1 reacts with acid chlorides to form Ti enolates. 1 Grubbs OM 1982 (1) 1658. O Cl Ph tol, -20oC to 0o C OTiClCp2 Ph PhCHO O Ph OH Ph 69% TiIV TiIV O Cl Ph O Cl Ph Grubbs JACS 1983 (105) 1665