M.C. White, Chem 153 JE-Allyl chemistry -352 Week of December 2. 2002 Allylic carbonates OMe PPh3 10-20 mol% note: no external base is needed Meo,c CO,Me PPh: LmPd OMe LmPd OMe Chemoselectivity allylic carbonates are more reactive towards pd mediated oxidative addition than allylic acetates OCO,Me Pdxdbaa 2.5 mol% no product corresponding to attack Aco COMe PPh: 10-20 mol% at the allylic acetate was observed THF. rt Olefin geometry: anti/syn isomerization of the T-allyl intermediate occurs at a faster rate than nucleophilic attack Pd dba3 2.5 mol% 人人义 CO,M PPh3 10-20 mol% neryl acetate(2)oCO)Me THF. rt 54%,(5248E2)CO2Me review: Tsuji Acc. Chem. Res. 1987(
M.C. White, Chem 153 π-Allyl chemistry -352- Week of December 2, 2002 Allylic carbonates Ph O O OMe Pd2dba3 2.5 mol% PPh3 10-20 mol% THF, rt note: no external base is needed Ph LnPdII O OMe O CO2 Ph LnPdII OMe + O CO2Me PPh3 Ph LnPdII PPh3 OMe H Ph CO2Me O 90% O H CO2Me Me O MeO2C Me Chemoselectivity: allylic carbonates are more reactive towards Pd mediated oxidative addition than allylic acetates. AcO OCO2Me + O CO2Me H Pd2dba3 2.5 mol% PPh3 10-20 mol% THF, rt AcO O CO2Me 77% no product corresponding to attack at the allylic acetate was observed. Olefin geometry: anti/syn isomerization of the π-allyl intermediate occurs at a faster rate than nucleophilic attack. OCO2Me neryl acetate (Z) + O CO2Me Pd2dba3 2.5 mol% PPh3 10-20 mol% THF, rt O 54%, (52:48 E/Z) CO2Me Tsuji TL 1982 (23) 4809. review: Tsuji Acc. Chem. Res. 1987 (20) 140
M.C. White, Chem 153 JE-Allyl chemistry -353 Week of December 2. 2002 Mo-catalyeed allylic alkylation In Mo-catalyeed allylic alkylations, electronic factors and the steric demands of the metal effectively compete with steric req rements The high reactivity of the malonate anion and its modest steric requirements leads to attack at the electronically favored position which leads to the erically prefered Mo-olefin complex CO,Me sterically favored site COrM of Nu attack electronically favored CO,Me site of Nu attack OA Mo (Oac)Ln COrMe 89% COMe NaH.tol.110°C t-Bu ⊙O2 Why do electronic factors and/or steric demands of the metal play a greater role in influencing the regioselectivity of Mo-mediated allylic substitutions vs. Pd? A few possibilities Bn81% are: 1. Mo is an early metal therefore, it's bonding to C is more ionic in character than pd. the carbonium ion Increasing the steric bulk of the nucleophile resonance form may be more prevalent in the Mo T reverses the regioselectivity towards substitutio intermediate. The strong T-acceptor properties of the CO at the least sterically hindered position ligands on Mo may also serve to promote carbonium character, 2. Mo(CO) is octahedral, therefore it has greater steric requirements than a square planar Pd complex Trost JACS1983(105)3343. Stereoselectivity: dependent on the base used COmE O,Me O,Me Reaction monitoring by GC indicated CO)5 mol% acetate was occuring under either tol. 1 10PC COMe CO,Me COMe CO,Me COM COMe TMS NTMS Trost JACS 1982(104)5543
M.C. White, Chem 153 π-Allyl chemistry -353- Week of December 2, 2002 Mo-catalyzed allylic alkylation In Mo-catalyzed allylic alkylations, electronic factors and the steric demands of the metal effectively compete with steric requirements of the nucleophile: t-Bu OAc Mo0(CO)6 5 mol% NaH, tol, 110oC CO2Me CO2Me CO2Me CO2Me t-Bu CO2Me CO2Me 89% t-Bu MoII(OAc)Ln electronically favored site of Nu attack sterically favored site of Nu attack t-Bu Mo0Ln Nu t-Bu Mo0Ln Nu t-Bu 81% CO2Me CO2Me The high reactivity of the malonate anion and its modest steric requirements leads to attack at the electronically favored position which leads to the sterically prefered Mo-olefin complex. Increasing the steric bulk of the nucleophile reverses the regioselectivity towards substitution at the least sterically hindered position. Why do electronic factors and/or steric demands of the metal play a greater role in influencing the regioselectivity of Mo-mediated allylic substitutions vs. Pd? A few possibilities are: 1. Mo is an early metal therefore, it's bonding to C is more ionic in character than Pd. The carbonium ion resonance form may be more prevalent in the Mo π-allyl intermediate. The strong π-acceptor properties of the CO ligands on Mo may also serve to promote carbonium ion character, 2. Mo(CO)6 is octahedral, therefore it has greater steric requirements than a square planar Pd complex. Trost JACS 1983 (105) 3343. Stereoselectivity: dependent on the base used? CO2Me OAc Mo0(CO)6 5 mol% base, tol, 110oC CO2Me CO2Me CO2Me CO2Me CO2Me CO2Me CO2Me CO2Me : NaH 50:50 NTMS OTMS >95:<5 Reaction monitoring by GC indicated that no isomerization of the starting acetate was occuring under either condition. Trost JACS 1982 (104) 5543