M.C. White/Q Chen, Chem 153 Q&A-342 Week of december 2. 2002 An interesting synthesis of cyclopropanes has been recently reported by gri Propose a mechanism for this transformation. Pd dba)3, TFP NHMe P KCO3, DMF TFP= 68% NMe NHMe reductive elimination oxidative addition Pdln Attack of amide at central carbon of NMe NAMe Wacker-like process KHCO3 InsertIo CNHMe CO3 NAMe Insertion Attack of nucleophiles at the central carbon of(n-allyl)palladium complexes is much less common than attack at the termini. Central attack results in the formatic of a palladacyclobutane, which in the absence of a good leaving group can undergo reductive elimination to form a cyclopropane and regenerate pd(o) Grigg, R. Eur J. Org. Chem. 2001, 707-712
M.C. White/Q. Chen, Chem 153 Q&A -342- Week of December 2, 2002 NMe O Ln Pd K2CO3 NHMe O PdLn I O P PdLn NHMe O I NMe O I NHMe O I NHMe O An interesting synthesis of cyclopropanes has been recently reported by Grigg. Propose a mechanism for this transformation. + Pd2(dba)3, TFP K2CO3, DMF 68% TFP = 3 PdLn insertion Attack of amide at central carbon of the π-allyl is considered to be a Wacker-like process. Grigg, R. Eur. J. Org. Chem. 2001, 707-712. NHMe O PdL2 I NMe O oxidative addition insertion reductive elimination Attack of nucleophiles at the central carbon of (η3-allyl)palladium complexes is much less common than attack at the termini. Central attack results in the formation of a palladacyclobutane, which in the absence of a good leaving group can undergo reductive elimination to form a cyclopropane and regenerate Pd(0). KHCO3 KI
M.C. White/Q Chen, Chem 153 Q&A-343 Week of december 2. 2002 Murai has described the synthesis of butanolides from a three component coupling shown below Propose a mechanism for this process Ru3 CO12(2.5 mol%) RuCO3 cO reductive elimination The authors propose that the o, -chelate ruthenium complex reacts with ethylene to form a metallacycle in which the Ru-s bond remains intact Murai,S.JACS1999,7160-7161
M.C. White/Q. Chen, Chem 153 Q&A -343- Week of December 2, 2002 N S O Me N S O Me N S Me OCRu O OC CO N S O O Me N S O O Me CO Murai has described the synthesis of butanolides from a three component coupling shown below. Propose a mechanism for this process. Ru3CO12 (2.5 mol%) tol., 140 °C, 20h "RuCO3" Murai, S. JACS 1999, 7160-7161. ethylene (3 atm) CO (5 atm) S O N Me Ru "σ,σ-chelate ruthenium complex" The authors propose that the σ,σ-chelate ruthenium complex reacts with ethylene to form a metallacycle (CO)3 in which the Ru-S bond remains intact. S O N Me Ru (CO)3 S N Me Ru (CO)2 O O reductive elimination CO insertion O M M O
M.C. White, Chem 153 JE-Allyl chemistry -344 Week of December 2. 2002 Allylic substitutions via metal -allyl intermediates Highly regio-and stereoselective allylic substitutions are possible with metal mediated reactions LMcat X=OAc(most common Pd(most common) OCO,Me Moo wo FeO Nio halide, epoxide, sulfone I rh Nu= soft carbanions(malonate) roatom nucleophiles O, N organometallics(main group M" LUMO of allyl cation MIXL ML L HOMO of neutral ligand allyl cation ne representation of a metal T-allyl has the metal in its reduced form and the allyl ligand with a full positive charge ML Mo+2L NuMa+L Consideration of the LUMO of an allyl cation indicates that nucleophilic attack is most likely at the terminal positions of the allyl group
M.C. White, Chem 153 π-Allyl chemistry -344- Week of December 2, 2002 X X = OAc (most common) OCO2Me halide, epoxide, sulfone MnLm cat M = Pd0 (most common) Mo0, W0, Fe0, Ni0, IrI, RhI Nu Nu = soft carbanions (malonate) heteroatom nucleophiles O, N organometallics (main group) Nu Highly regio- and stereoselective allylic substitutions are possible with metal mediated reactions Allylic substitutions via metal π-allyl intermediates General mechanism: MnLm X Mn+2Lm X MnLm One representation of a metal π-allyl has the metal in its reduced form and the allyl ligand with a full positive charge. Consideration of the LUMO of an allyl cation indicates that nucleophilic attack is most likely at the terminal positions of the allyl group. HOMO of allyl cation LUMO of allyl cation Nu or Mn+2Lm X Nu MnLm Nu Nu Mn+2(X)Lm OA L neutral ligand Nu
M.C. White, Chem 153 JE-Allyl chemistry -345 Week of December 2. 2002 Mechanism Double inversion mechanism is thought to operate for Pd allylic substitutions that proceed with net retention. This mechanism operates with stabilized oft" C nucleophiles such as malonates, sulfonylacetates and may operate in part for amines MeO, Cr Pd(PPh, )cat. Merc MeOr CO,Me net retention THF reflux Pd(oac conaton MeO MeO,C- via SN2 VS SN2 b/c plated and shown to undergo COMe of Pd's sensitivity nucleophilic substitution with THF reflux Trost JOC. 1976(19)3215 vidence for double retention has been established in one case of Mo mediated allylic substitution RE (CH(CO, Me)) Kocovsky JACS 1995(117)6130 CO,Me
M.C. White, Chem 153 π-Allyl chemistry -345- Week of December 2, 2002 Substitution with net retention. Mechanism MeO2C OAc Pd(PPh3)4 cat. CO2Me CO2Me Na MeO2C CO2Me CO2Me PPh3 THF, reflux 92% net retention Trost JOC 1976 (19) 3215. OAc inert towards Pd0- catalyzed allylic substitution Mo(CO)6 15 mol% toluene, 100oC CO2Me CO2Me Na MoII(OAc)Ln OA CO2Me CO2Me Na NaOAc ligand exchange MoII(CH(CO2Me)2)Ln CO2Me CO2Me 96% RE Kocovsky JACS 1995 (117) 6130. Evidence for double retention has been established in one case of Mo mediated allylic substitution. MeO OAc 2C OAc MeO2C SN2 MeO2C LnPdII (OAc) OAc MeO2C LnPd0 Pd(PPh3)4 cat. CO2Me CO2Me Na MeO2C CO2Me CO2Me PPh3 MeO2C LnPdII (-OAc) CO2Me CO2Me PPh3 PPh3 Double inversion mechanism is thought to operate for Pd allylic substitutions that proceed with net retention. This mechanism operates with stabilized "soft" C nucleophiles such as malonates, sulfonylacetates and may operate in part for amines. = Thought to proceed via SN2 vs. SN2' b/c of Pd's sensitivity towards sterics. THF, reflux 92% net retention ionization Pd0Ln Pd π-allyl intermediates have been isolated and shown to undergo nucleophilic substitution with inversion
M.C. White, Chem 153 JT-Allyl chemistry -346 Week of December 2. 2002 Mechanism Substitution with immersion CO,Me Pd(dba) THF. 50C CO,B leOC LaPd(cn CO2Bn Meo2C lmPd CO,Bn Stille!S198410483 BuaSnCI Amine nucleophiles: CO,M Pd(PPh3)43-8 mol% COmE CO,Me THF rt 2N NHR NHR 81%(2: 3 identity of major isomer is not specified) MeO,C Meog -OAc) MeO2c F +(-OAc NpD(OAc) L.Pall Trost JOC 1979(44)3451
M.C. White, Chem 153 π-Allyl chemistry -346- Week of December 2, 2002 CO2Me Cl Pd(dba)2 n-Bu3Sn CO2Bn THF, 50oC CO2Me CO2Bn Pd0Ln LnPdII MeO (Cl) 2C n-Bu3Sn CO2Bn n-Bu3SnCl LnPdII MeO2C CO2Bn RE 87% OA via SN2 Mechanism Substitution with inversion: Stille JACS 1984 (106) 4833. CO2Me OAc H2N OMe OMe Pd(PPh3)4 3-8 mol% THF, rt CO2Me NHR CO2Me NHR + 81% (2:3 identity of major isomer is not specified) (OAc) MeO2C LnPdII Pd0Ln MeO2C (-OAc) LnPdII + NH2R MeO2C (-OAc) LnPdII (+NH2R) Amine nucleophiles: Trost JOC 1979 (44) 3451