１． 有機金属化学の基礎 ２． パラジウムの化学 - Allyl Palladium の反応 Mizoroki-Heck反応 Migita-Kosugi-Stille カップリング反応 Miyaura-Suzuki カップリング反応 (Tamao-Kumada-Corriu カップリング反応) ３． カルベンの化学 Schrock carbene Fischer carbene Grubbs catalyst RCM （閉環メタセシス） ４． 不斉合成 光学活性化合物の入手方法 不斉還元 不斉酸化 不斉アルキル化 不斉1,4付加 1 酸化と還元、元素の酸化数および原子価 元素の酸化数：ある元素が関与する結合中の電子対を電気陰性度の大きい元素に 割り当てたとき、その元素の原子上に残る電荷の数 _ Ph3P CH3 Ph3P Pt Ph3P CH3 Pt2+ Ph3P CH3 _ CH3 アニオン 中性分子 白金の酸化数は＋２ Pt2+, PtII, Pt(II) 実際の酸化数と違うので、形式酸化数と呼ぶ formal oxidation number 2 酸化的付加と還元的脱離 oxidative addition and reductive elimination _ A M + M2+ M B A A 酸化的付加 還元的脱離 _ B B _ H M + M2+ M H 還元的脱離 H H 酸化的付加 H _ H 3 配位子のハプト数 hapticity M M M M 3-ally 1-ally H2C CH2 HC H CH M M M 2-alkene 2-alkyne 4-diene M M 5-cyclopentadienyl 6-benzene H M 2-hydrogen 4 形式酸化数、ｄ電子数、総電子数 Ph3P CH3 白金の形式酸化数： 2 Pt(II) Pt Ph3P CH3 金属のｄ電子数： d8 総電子数： 16e _ 2 (CH3) d8 = 8e 2x2e = 4e 2 PPh3 2x2e = 4e Pt(II) _ Ph3P Ph3P 中性分子 Pt2+ CH3 _ 16e CH3 アニオン 5 配位子のハプト数、形式電荷、供与電子数 ハプト数 形式電荷 供与電子数 M R alkyl 1 -1 2 M H hydride 1 -1 2 M X halide 1 -1 2 M OR alkoxide 1 -1 2 acyl 1 -1 2 1-alkynyl 1 -1 2 1-allyl-allyl) 1 -1 2 acetylide 1 -1 2 O M M C C R C M M R 6 配位子のハプト数、形式電荷、供与電子数 ハプト数 形式電荷 供与電子数 R M C carbene (Fischer) 1 0 2 carbene (Schrock) 1 -2 4 M C R carbyne 1 -3 6 M CO carbonyl 1 0 2 2-alkene 2 0 2 2-alkyne 2 0 2 R' R M C R' C M C C M C 7 配位子のハプト数、形式電荷、供与電子数 ハプト数 形式電荷 供与電子数 M 3-allyl 3 -1 4 M 4-diene 4 0 4 5-cyclopentadienyl 5 -1 6 6 0 6 M 5 -Cp 6-arene M 8 配位子のハプト数、形式電荷、供与電子数 M M M H X R O ハプト数 形式電荷 供与電子数 M -hydride 1 -1 2 M -halide 1 -1 4 -alkoxide 1 -1 4 -carbonyl 1 0 2 -alkylidene 1 -2 4 3-carbonyl 1 0 2 3-alkylidyne 1 -3 6 M O M M C R2 C M M O M C M M M R C M M 9 ハプト数 M X X M M M H H M M 供与電子数 halide 1 -1 2 -halide 1 -1 4 hydride 1 -1 2 -hydride 1 -1 2 X M 形式電荷 X M M M 10 金属の形式酸化数、ｄ電子、錯体の電子数 Ni(PPh3)2(CH3)Cl ニッケル１０族元素 2 x PPh3 d8 2 x 2e 8e = 4e CH3 1 x 2e = 2e Cl 1 x 2e = 2e Ni(II) ニッケルの形式酸化数２ Ni(II), d8, 16e 16e OC Fe OC _ 鉄８族元素 2 x CO d8 2 x 2e 8e = 4e Cp 1 x 6e = 6e Fe(0) 18e 鉄の形式酸化数０ Fe(0), d8, 18e 11 １８電子則、有効原子番号則 18-electron rule, effective atomic number rule N CO N Cr Co Ph3P PPh3 H PPh3 Ni OC CO CO RuH2(PPh3)4 [Co(H2O)6]2+ V(CO)6 RuCl2(PPh3)3 12 Quiz 1. _ Ph3P Ir Ph3P CO イリジウム９族元素 I Rh OC I CO CH3 イリジウム９族元素 2- I I Ir+ Ti CH2 CO ロジウム９族元素 チタン４族元素 13 O H2C CH2CH3 H CH2CH2CH3 O H C L2Rh HRh(CO)L2 H d8, 16e L2Rh CH2CH2CH3 H CO CHCH3 CO CH2 d8, 18e d6, 18e Hydroformylation H2 CH2CH2CH3 O C L2Rh L2Rh CO CH2CH2CH3 CO 8 d , 16e d8, 16e CO L2Rh CO CH2CH2CH3 CO d8, 18e 14 酸化的付加 oxidative addition A 酸化的付加 LnM A + B L nM 還元的脱離 B 低原子価 配位不飽和 H Ph3P Cl Ir CO PPh3 Ph3P + H H cis-addition Cl Ir H PPh3 CO Vaska complex Ir(III), d6, 18e Ir(I), d8, 16e + H3C I trans-addition CH3 Ph3P CO Ir Cl PPh3 I Ir(III), d6, 18e 15 水素の酸化的付加 L L Pt + H L L H Pt Pt H L キ H H H L Pt(II), d8, 16e 10 Pt(0), d , 14e L H Pt Pt H L LUMO L L H L H H Pt Pt H L HOMO H L L H 16 ハロゲン化アルキルの酸化的付加 - + LnM SN2 LnM + R キ X LnM R + _ X R X R キ R L nM LnM X X 三中心遷移状態 Ph3P D H C Pd Ph3P Br Ph Pd(0), d10, 14e Pd(II), d8, 14e (PCy3)2Pd Pd(0), d10, 16e H D Ph3P Pd C Ph Ph3P X HR + _ Br Ph3P H D Br Pd C Ph Ph3P Pd(II), d8, 16e J. K. Stille, J. Am. Chem. Soc., 98, 5832 (1976). R R (PCy3)2Pd+ XPd H X Cy3P H Pd(II), d8, 16e 17 ハロゲン化アルキルの酸化的付加 S N2 LnM LnM R X キ LnM R + _ X R + X R キ R LnM LnM X X 三中心遷移状態 Pd キ Ph3P Ph3P + X Pd + X Ph3P Ph3P _ Pd(0), d10, 14e Ph3P X X Pd Pd Ph3P Pd(II), d8, 16e PPh3 Ph3P X: I > Br >> Cl 18 PhEt2P CH3 CH3 Pd + Pd PhEt2P キ PhEt2P PhEt2P _ Pd(II), d8, 16e Ph3P Pd + H3C Ph3P Pd(0), d10, 14e 19 還元的脱離 reductive elimination A 酸化的付加 LnM + A B L nM 還元的脱離 L R 解離経路 M B R R' + ML R R' + ML2 R R' + ML3 R' -L +L L R 直接経路 M L R' -L +L L L R M L R' 会合経路 20 ＣＯ挿入 CO insertion ? alkyl migration ? O CO L nM LnM R キ O C L nM R C R Ｒの立体化学は保持 ＲとＣＯはシス CH3 OC OC Mn CO OC CO OC Mn COCH3 CO L L OC OC Mn COCH3 CO CO CO CO Mn(I), d6, 18e Mn(I), d6, 16e Mn(I), d6, 18e 21 ＣＯ挿入 CO insertion CH3 OC - CO CH3 OC OC OC Mn OC CO OC Mn CO CO CO CO CO Mn CH3 CO 25% CO CO CH3 CO CH3 CO - CO OC Mn CO CO CO OC OC Mn CO cis CO CO 75% 22 ＣＯ挿入 CH3 migration CH3 OC - CO OC CO CO OC Mn CO OC Mn CH3 CO CO CO 25% OC OC CH3 CH3 CO CO Mn CO CO - CO OC CO Mn CO CO H3C CO OC Mn CO CO cis CO CO 50% CH3 OC - CO CO CO Mn CO CO OC CO H3C Mn CO trans CO CO 25% 23 CO Ph3P Cl Rh K R PPh3 ROC Ph3P Cl Rh Cl PPh3 Cl R K C2H5, C6H5CH2 > 50 C6H5CH2CH2 17 CH3 3.4+0.2 - p-ClC6H4CH2 0.07 C6H5 < 0.05 ClCH2, H <0.02 24 アルケン、アルキン挿入反応、 脱離反応 B A C LnM A C L nM C D 挿入反応 B A 脱離反応 L nM R 挿入反応 A B 脱離反応 LnM R C R D C C B R PMe3 Co Co CD3 CD3 Co CD3 CD3 CD3 H - CD3H CD3 Co PMe3 D3C 25 トランス影響、トランス効果 trans influence, trans effect 配位子置換反応 解離機構（配位飽和18電子錯体） HCo(CO)4 8 - CO + CO Co(I), d , 18e HCo(CO)3 X Co(I), d8, 18e d8 平面正方形16電子錯体 Y L M HCo(CH2=CH2)(CO)3 Co(I), d8, 16e 会合機構（配位不飽和16電子錯体） T H2C CH2 Y L L L T M L -X X T M L Y 立体保持 トランス効果の序列 CO, CN-, CH2=CH2 > PR3, H- > CH3- > C6H5-, I- > Br-, Cl- > NH3, H2O 26 トランス効果の序列 CO, CN-, CH2=CH2 > PR3, H- > CH3- > C6H5-, I- > Br-, Cl- > NH3, H2O 置換反応に及ぼす配位子Ｔの動的効果 トランス影響の序列 H-, CH3-, C6H5- > PR3, CN- > CO, CH2=CH2 > I-, Br- > Cl- > NH3, H2O 配位子ＴによってＭ－Ｘ結合がどの程度弱められているかを示す静的効果 Ｍ－Ｘ結合距離のＸ線構造解析 Ｍ－Ｘ結合のＩＲ伸縮振動 Ｍ－Ｘ結合のＮＭＲ結合定数 27 供与と 逆供与 Dewar-Chatt-Duncanson モデル C M C M C C (d M ) 供与 C (d 供与の寄与大 C ) 逆供与 C M 供与の寄与大 C IR 伸縮振動波数 C=C 50-60 cm-1 低波数シフト C=C 150-160 cm-1 低波数シフト 28 供与と 逆供与 O M n 供与 dM M dM _ M C C + O _ + M C O C O 逆供与 M C O IR 伸縮振動波数 CO 2143 cm-1 末端カルボニル 2125-1850 cm-1 29 ホスフィン配位子 酸性度定数 (pKa) 11.40 P(t-Bu)3 P(c-C6H11)3 9.65 PEt3 PMe3 8.69 8.65 PMePh2 4.59 PPh3 2.73 受容性 NO > CO > RNC > PF3 > PCl3 > P(OR)3 > PR3 > RCN > RNH2 > NH3 X M P X d X 相互作用 30 ホスフィン配位子 立体因子 円錐角 (cone angle) P P 2/2 3/2 M 1/2 M 3 = (1/3)i i=1 P(o-MeC6H4)3 194 PBu3 136 P(t-Bu)3 182 P(c-C6H11)3 PPh3 179 145 PEt3 PMe3 132 118 P(OEt)3 107 31 ホスフィン配位子 立体因子 配位挟角 (bite angle) P Ph2 P Rh(cod)+ ClO4P Ph2 83.8 PPh2 Rh(ndb)+ ClO4PPh2 91.8 P M O PPh2 Rh(nbd)+ ClO4- O 98 PPh2 32 -Allyl Palladium Chemistry X Nu + Pd(0)Ln PdL2+ _ _ _ Nu + Pd(0)L + X n X X = OAc (most common), OCO2R, OP(O)(OR)2, OPh, OH, halide, SO2Ph, NO2, NR2, O NR3X, PPh3X, O COOEt EtOOC O _ Nu = malonate, O,N,S nucleophiles, R-M (M = Mg, Zn, B, Al, Sn, Si) catalyst = Pd(0) 33 Catalytic Cycle PdL4 18e - 2L Nu X PdL2 14e PdL2 16e PdL2 Nu 16e _ Nu PdL2+ 16e X _ X 34 R R R _ ligand attack Nu Nu Nu PdL2+ X LnPd _ _ Nu metal attack R R R reductive elimination Nu PdL2 Nu Nu LnPd ligand attack; soft carbanions suh as malonate, enolates, amines metal attack: RSnBu3, RZnX, Cp2Zr(R)Cl, RAlMe2, RMgX, RLi, NaBH4 35 Stereochemistry CO2Me CO2Me Pd(PPh3)4 _ + CO2Me CH(CO2Me)2 THF CO2Me OAc CO2Me PdL2+ OAc _ retention CO2Me CO2Me _ + CO2Me Pd(PPh3)4 CH(CO2Me)2 THF CO2Me OAc CO2Me PdL2+ OAc retention 36 _ Stereochemistry CO2Me CO2Me CO2Me Pd2(dba)3 + Cl benzene THF acetone DMF DMSO CO2Me PdCl PdCl retention inversion 100 : 0 95 : 5 75 : 25 29 : 71 3 : 97 CO2Me Pd(PPh3)4 benzene Cl PdCl inversion H. Kurosawa, J. Am. Chem. Soc., 114, 8417 (1992).37 NuH Pd-Catalyzed Reactions Involving -Allyl Palladium C, O, N nucleophiles Nu R M'R' transmetallation R M'Ar X Pd (0) transmetallation R R' Pd R R' R X Ar R M' X transmetallation R' R CO, ROH carbonylation CO2R R R'M'M'R' metallation H M'R' R _ R hydrogenolysis R -elimination R 38 Asymmetric Alkylation Review: B. M. Trost, Chem. Rev., 96, 395 (1996) CO2Me CO2Me SO2Ph + NaCH CO2CH3 OAc Pd(PPh3)4 / L* refluxing DME H (+)-cis _ O CO2CH3 PPh2 L* = PhO2S optical yield 46% PPh2 O H (+) DIOP CO2Me _ Nu Pd + *L L* B. M. Trost, J. Am. Chem. Soc., 99, 1649 (1977) 39 Ph Ph + OAc Ph NaCH(CO2CH3)2 [-C3H5PdCl]2 / L* THF, 25 °C Ph (CH3O2C)2HC Ph Ph optical yield 84% L* = Ph2P PPh2 S,S-Chiraphos Ph Ph + OAc NaCH(CO2CH3)2 [-C3H5PdCl]2 / L* THF, 25 °C Ph Ph (CH3O2C)2HC optical yield 22% B. Bosnich, J. Am. Chem. Soc., 107, 2033 (1985) B. Bosnich, J. Am. Chem. Soc., 107, 2046 (1985) 40 OAc OAc interconversion Pd(0) Pd(0) fast Pd P P * major P * Pd Pd Pd P P * P P P * minor _ _ Nu fast fast slow Nu major Nu slow Nu minor 41 Ph Ph + OAc NaCH(CO2CH3)2 [-C3H5PdCl]2 / L* Ph THF, 40 °C Ph CH(CO2CH3)2 90% ee OH Ph Ph H R P Me NuPd Fe CH C O H CR P N H2 H Ph Ph Me 1a: X = NMe OH X L* = OH Fe PPh2 PPh2 1b: X = N OH (R)-(S)-BPPF-X 1c: X = MeN OH T. Hayashi, Tetrahedron Lett., 27, 191 (1986) 42 Ph Ph + OAc CH2(CO2CH3)2 [-C3H5PdCl]2 / L* Ph CH2Cl2, rt CH(CO2CH3)2 KOAc / BSA L* = Ph 98% ee G. Helmchen, Tetrahedron Lett., 34, 1769 (1993) A. Pfaltz, Angew. Chem., 32, 566 (1993) J. M. J. Williams, Tetrahedron Lett., 34, 3149 (1993) O PPh2 N Pri Me Me H O N Ph P Pd Ph or Me Me H O N Ph Nu- Pd P Ph Nu- 43 Chiral Pocket Review: B. M. Trost, J. Org. Chem. 69, 5813 (2004) B. M. Trost, Aldchimica Acta, 40, 59 (2007) R R + OAc R [-C3H5PdCl]2 / L* CH2(CO2CH3)2 CH2Cl2 Cs2CO3 R CH(CO2CH3)2 O O NH HN L* = PPh2Ph2P When R = Ph, 9% yield along with 79% recovery of the starting material When R = Me, 98% with 92% ee B. M. Trost, J. Am. Chem. Soc., 118, 6520 (1996) 44 O O O Pd2(dba)3.CHCl3 / L* O THF, 0 °C N O NHTs TsHN O Ts 88% ee PPh2 O O O O NHTs TsHN L* H N L* = O Ph2P H N O Pd L* B. M. Trost, Angew. Chem., Int. Ed. Engl., 31, 228 (1992) 45 脱離 O O O NHTs TsHN L* O O O L* Pd O + Pd L* NHTs O Pd N Ts L* L* 攻撃 L* O O N 脱離 O O Ts O NHTs TsHN L* Pd L* O O O O O Pd L* TsHN 攻撃 N Pd L* Ts L* L* O O N Ts 46 O O CO2CH2Ph CO2CH2Ph OAc + [-C3H5PdCl]2 / L* toluene, 0 °C teramethylguanidine 86% ee O L* = O NH HN PPh2Ph2P O O CO2CH2Ph + OCO2CH3 [-C3H5PdCl]2 / L* toluene, 0 °C teramethylguanidine CO2CH2Ph H 88% dr 97% ee B. M. Trost, J. Am. Chem. Soc., 119, 7879 (1997) 47 O O + OAc [-C3H5PdCl]2 / L* LDA/Me3SnCl DME. rt 99% (88% ee) O L* = O NH HN PPh2 Ph2P B. M. Trost, J. Am. Chem. Soc., 121, 6759 (1999) nitoroalkane B. M. Trost, J. Am. Chem. Soc., 122, 6291 (2000) 48 O O O O O L* = Pd2(dba)3CHCl3/L* PPh2 N THF, 25 °C, 2 h But 85% (87% ee) B. M. Stoltz, J. Am. Chem. Soc. 126, 15044 (2004) O O O O Pd2(dba)3CHCl3/L* toluene, 23 °C, 20 h L* = PPh2 H N O Ph2P H N 78% (78% ee) O B. M. Trost, J. Am. Chem. Soc., 127, 2846 (2005) B. M. Trost, J. Am. Chem. Soc., 131, 18343 (2009) 49 O O O Pd(OAc)2/L*/HCOOH O dioxane, 40 °C, 10 h 88% (94% ee) O L* = PPh2 N O _ O But O _ O Pd+ Pd+ -CO2 B. M. Stoltz, J. Am. Chem. Soc., 128, 11348 (2006) 50 OBoc [-C3H5PdCl]2 / L* LiHMDS, BF3.OEt2 + dioxane, 25 °C N 86% (95%ee) unstabilized nucleophile L* = N O O NH HN PPh2 Ph2P B. M. Trost, J. Am. Chem. Soc., 130, 14092 (2008) 51 Asymmetric Inducion with Mono-substituted Allyl Systems R R Dynamic Kinetic Asymmetric Transformation + X X M(0) R X M(0) + R M B Nu- L* ent-A A + R M(0) + R M M enantiodiscrimination step L* Nu- R R Nu Nu Review: B.M. Trost, Aldrichimica Acta, 40, 59 (2007) 52 OH O O + [-C3H5PdCl]2 / L* HN O N O CH2Cl2, rt 99% (75:1) O 98%ee O L* = O NH HN PPh2Ph2P Nu H _ O Pd+ B. M. Trost, J. Am. Chem. Soc., 122, 5968 (2000) 53 [(C3H5)PdCl]2 / L* OAc + Ph Ph CH2(COOMe)2 Ph2P R CH2Cl2, 0 oC O Me S i L* = CH(COOMe)2 BSA, KOAc Pr Ph Ph2P Ph O Me S Pri L* = R R Ph 42 70 4-MeOC6H4 44 58 2,3,5,6-F4C6H 18 22 4-tBuC6H4 3,5-Me2C6H3 3,5-tBu2C6H3 1-Nap 2-Nap Bn Cy 70 63 33 60 56 89 91 77 85 51 74 76 75 81 t Bu 98 91 D. A. Evans, J. Am. Chem. Soc., 122, 7905 (2000) 54 [(C3H5)PdCl]2 / L* OAc CH2(COOMe)2 + Ph Ph Ph2P O BSA, KOAc CH2Cl2, -20 oC R' L* = R' S CH(COOMe)2 Ph Ph2P i Ph O R' S Pri L* = Pr But But Me 91 98 Ph 75 91 i 75 69 Pr Ph2P O L* = S But R1 R2 Pri R1 R2 H Me H Me H H Me Me 67%ee 91%ee 98%ee 85%ee 55 Me + SbF6- Me O Me Ph P S But Ph Pd H H Ph Me 2.3 : 1 Me O Me Ph P S But Ph Pd Ph Ph Ph H H Nu- Nufast slow Me Me Me O Me Nu Ph P S H Ph Pd Ph H t Bu Ph + SbF6- H Me O Me Ph P S t Ph Ph Pd H Bu Ph H Nu H 56 [-C3H5PdCl]2 / L* Li2CO3 OCOOMe + CH2(COOEt)2 CH(COOEt)2 H2O, 40 oC, 12 h O 94% yield 98%ee H O PS O O n HN C (CH2)3 N N M PPh2 recyclable amphiphilic resin-supported catalyst M = PdCl(3-C3H5) recyclable by filtration 1st run 2nd run 3rd run 60% 91%ee 70% 90%ee 65% 90%ee OCOOMe at 25 oC Y. Uozumi, J. Am. Chem.Soc., 123, 2919 (2001) 57 Ruthenium-Catalyzed Reaction CO2Me _ + CH(CO2CH3)2 OC(O)OMe decane, 60 oC CO2Me 立体反転 + CO2Me CpRu(cod)Cl NH4PF6 CH(CO2CH3)2 99% (trans/cis = 97/3) 立体反転 Ru(cod)Cp T. Mitsudo, Organometallics, 18, 4742 (1999) 58 Ruthenium-Catalyzed Reaction O t Bu O Me Ru Ph AN AN Ph + OAc NaCH(CO2CH3)2 P Ar2 THF, 20 °C Ph Ph CH(CO2CH3)2 98% (97%ee) S. Takahashi, J. Am. Chem. Soc., 123, 10405 (2001) 59 Rhodium-Catalyzed Reaction OCO2Me + NaCH(CO2Me)2 Me S RhCl(PPh3)3 P(OMe)3 CH(CO2Me)2 Me S 30 oC 95%ee 97%ee Me Me OCO2Me + CH(CO2Me)2 Me CH(CO2Me)2 99% (42 : 1) Me 83% (2 : 1) OCO2Me D CH(CO2Me)2 OCO2Me + Me D Me Me D Me Me CH(CO2Me)2 Me 92% (>19 : 1) P. A. Evans, J. Am. Chem. Soc., 120, 5581 (1998) 60 Iridium-Catalyzed Reaction [IrCl(cod)]2 Ph O P N O OPh Ph Ph OCO2Me + Ph PhOLi THF, 50 oC, 20 h 86% (96%ee) 96 : 4 + Ph OPh minor J. F. Hartig, J. Am. Chem. Soc., 125, 3426 (2003) 61 Allylic C-H Alkylation O H COOMe O S S Ph Pd(OAc)2 Ph + Ph NO2 Pd(II)X2 dioxane/DMSO DMBQ/AcOH 45 °C, 24 h oxidant _ PdX/2 COOMe Ph NO2 83% Pd(0) COOMe NO2 Ph M. C. White, J. Am. Chem. Soc., 130, 14090 (2008) 62 Mizoroki-Heck Reaction Reviews: de Meijere, Angew. Chem., Int. Ed. Engl., 33, 2379 (1994) I. P. Beletskaya, Chem. Rev., 100, 3009 (2000) R1 X + cat. Pd (0) R2 amine R1 R 2 + amineH+ X- R1 = Ar, ArCH2, CH2=CH O X = Br, I, OTf, N2+, Cl catalyst = Pd(0) 63 Mechanism d10, 18e PdL4 HBr + - 2L Ar Ar Br PdL2 L H Pd 8 d10, 14e Br d , 16e L Ar Pd Ar d8, 16e L -elimination Ar Br Pd(L)Br L d8, 14e Ar Pd olefin insertion (syn addition) Br L d8, 16e 64 Regioselectivity R1 2 Br (I) R R2 cat. Pd (0) + R1 100% 100% 100% 100% 1% Me CO2Me Me CN CO2Me 99% 100% 7% 21% 21% 20% Me OMe Me OMe MeO 79% 93% 79% Me steric and electronic factors direct Ar to least hindered carbon Bu 80% 65 The First Report Ph PdCl2 0.5 mmol PhI + 50 mmol Ph 100 mmol CH3COOK 60 mmol CH3OH 1 mol 120 oC, 2 h Ph Ph + Ph 90% 12% T. Mizoroki, Bull. Chem. Soc. Jpn., 44, 581 (1971) Pd(OAc)2 0.2 mmol PhI 20 mmol + Ph 25 mmol Bu3N 20 mmol 100 oC, 2 h Ph Ph 75% "Mizoroki and coworkers have recently reported a palladium-catalyzed arylation reaction of olefinic compounds with aryl iodides and potassium acetate in methanol at 120 oC. We have independently discovered this reaction and find that it can be carried out under much more convenient laboratory conditions than were used by Mizoroki and that the reaction provides an extremely convenient method for preparing a variety of olefinic compounds." R. F. Heck, J. Org. Chem., 37, 2320 (1972) 66 H CO2Et EtO2C Pd(OAc)2, PPh3 Br R3SiO H K2CO3, MeCN OSiR3 H CO2Et PdX EtO2C H R3SiO PdX H OSiR3 - HPdX H syn addition syn elimination R3SiO OSiR3 R3SiO OSiR3 I. Shimizu, J. Org. Chem., 58, 2523 (1993) 67 OMe DBS N Pd(OCOCF3)2/PPh3 H OBn toluene, 120 oC MeO I Me Me OBn N Me DBS Me Me N OMe PdX DBS H syn addition syn elimination O OH N (-)-morphine Me N L. E. Overman, J. Am. Chem. Soc., 115, 11028 (1993) 68 N N I OTBS Pd(OAc)2 N 2N HCl THF Bu4NCl, DMF, K2CO3 70 °C H O H H O N isostrychine N N O H OH 71% N O N H Pd+ H H H H O strychine OH V. H. Rawal, J. Org. Chem., 59, 2685 (1994) 69 Asymmetric Mizoroki-Heck Reaction: Intramolecular Ref: M. Shibasaki, J. Am. Chem. Soc., 118, 7108 (1996) and references cited therein. pioneer works COOMe I Pd(OAc)2 / (R)-BINAP Ag2CO3 O 60 °C NMe COOMe PdI COOMe H 46% ee COOMe H H PdI M. Shibasaki, J. Org. Chem., 54, 4738 (1989) 70 OTf Pd(OAc)2 / DIOP benzene, rt O Pd + O 45% ee Pd+ O O L. E. Overman, J. Org. Chem., 54, 5846 (1989) cf. L. E. Overman, J. Am. Chem. Soc., 125, 6261 (2003) 71 Asymmetric Mizoroki-Heck Reaction: Intermolecular Pd(OAc)2 / (R)-BINAP 6 mol% 3 mol% OTf + O X + O i Pr2NEt (3 equiv) X X 30-40 °C 1 equiv O 5 equiv 71-89% >90%ee 29-11% 50-60%ee TfO is necessary, racemic products observed for idodide Reaction are very slow, 22-72 h F. Ozawa, T. Hayashi, J. Am. Chem. Soc., 113, 1417 (1991) 72 + P * P Pd Pd P + P P H Pd P O Ar O * + * O Ar Ar Ar O O + * P P OTf Pd _ Ar O + P Pd O Ar P * Pd P * + P P H O + * Pd P 1. Insert 2. -H 3. dissociate O Ar Ar O Ar thermodynamic 73 product (R) Asymmetric Mizoroki-Heck Reaction: Intermolecular OTf Pd(dba)2 (3 mol%) + O i Pr2NEt (2 equiv) O C6H6, 30 °C, 3 days 1 equiv 3.9 equiv 92% yield >99%ee O No 2,3-isomer detected Slow reactions (3-7 days) PPh2 N But A. Pfaltz, Angew. Chem., Int. Ed. Engl. 35, 200 (1996) 74 Ph Cl + Ph cat. Pd2(dba)3 / PBut3 Ph Cs2CO3 dioxane, 120 °C, 120 h Ph 80% TON = 400 MeO P MeO OMe 3 not effective (<2%) similar cone angle, pKa G. C. Fu, J. Org. Chem., 64, 10 (1999) 75 A Fluorescence-based Assay O O O + X O O O O O Pd(dba)2 / L NaOAc 1. TFA 2. TMSCHN2, MeOH MeO O DMF, 100 °C L = PBut3 O O X: Br, Cl L: 40 different P-ligand X = Br O O PBut2 Fe X = Cl L= PBut2 Fe J. H. Hartwig, J. Am. Chem. Soc., 121, 2123 (1999) 76 Screening of Homogeneous Catalysts by Fluorescence Resonance Energy Transfer Me O2S N N N + N Me O2S NMe2 Br Boc N strong fluorescence Pd(dba)2/ 70 different ligand Boc N NMe2 N weak fluorescence N J. F. Hartwig, J. Am. Chem. Soc., 123, 2677 (2001) 77 78 O Recovery of Catalyst O KN Me O O O OMs n Me O O DMF reflux, 5 h n = 110 N n 87% O SPh H N HO H2NNH2, EtOH Me reflux, 20 h O O NH2 n O O Pd Cl SPh DMF, rt, 14 h SPh Me O O H N H N Pd Cl n O O SPh 98% D. E. Bergbreiter, J. Am. Chem. Soc., 121, 9531 (1999) 79 cat. 1 mol% PhI + Ph DME, Et3N 115 oC, 6.5 h Ph Ph 1st cycle 91% 2nd cycle 95% 3rd cycle 92% cat. 1 mol% PhI + COOMe DME, Et3N 115 oC, 2.5 h Ph COOMe 1st cycle 85% 2nd cycle 87% 3rd cycle 95% 触媒はジエチルエーテルを加えて沈殿させ、回収 80 Migita-Kosugi-Stille Coupling Reviews: J. K. Stille, Angew. Chem., Int. Ed. Engl., 25, 508 (1986) V. Farina, V. Krishnamurthy, W. J. Scott, Org. React., 50, 1 (1998) P. Espinet, A. M. Echavarren, Angew. Chem. Int. Ed., 43, 4704 (2004) R X + R' SnR"3 cat. Pd (0) R R' + X SnR"3 R = aryl, RC(O), allyl, benzyl, vinyl, Ar, RCXH(COOR') X = halogen, OTf R' = H, aryl, Alkenyl, allyl, benzyl, alkynyl, alkyl catalyst = Pd(0) 81 Mechanism L4Pd (0) R' oxidative addition Ar Br L transmetallation Ar Pd Br -2 L SnR"3 L _ X L Ar Pd R' SnR"3 L isomerization Ar Pd L L R' reductive elimination L2Pd R R' cf. P. Espinet, J. Am. Chem. Soc., 128, 14571 (2006). Reactivity R C C > RCH CH > Ar > RCH CHCH2 ArCH2 > CH3(CO)CH2 > alkyl 82 The first paper Br SnBu3 + cat. Pd(PPh3)4 + Bu3SnBr benzene 100 °C, 20 h 96% M. Kosugi, T. Migita, Chem. Lett., 301 (1977) O + Ph Cl Me4Sn O cat. Pd(PPh3)4 benzene 140 °C, 5 h Ph + Me Me3SnCl 54% M. Kosugi, T. Migita, Chem. Lett., 1423 (1977) O + Ph Cl Me4Sn O cat. PhCH2Pd(PPh3)2Cl HMPA, 65 °C, 10 min + Ph Me3SnCl Me 89% J. K. Stille, J. Am. Chem. Soc., 100, 3636 (1978) 83 CO2Me CO2Me Pd(dba)2 / 2PPh3 + Bu3Sn CO2CH2Ph CO2CH2Ph THF 50 °C Cl CO2Me 87% inversion J. K. Stille, J. Am. Chem. Soc., 106, 4833 (1984) PdClL2 ButHNOC N TMS N Br + Me3Sn ButHNOC TMS N N S S 65% benzene S S Pd(PPh3)2Cl2 micrococcinic acid T. R. Kelly, Tetrahedron Lett., 32, 4263 (1991) 84 SnBu3 + I OH PdCl2(MeCN)2 DMF 25 °C OH 73% J. K. Stille, J. Am. Chem. Soc., 109, 813 (1987) OMe N N TBDMSO N N O I + SnBu3 OMe PdCl2(MeCN)2 N N TBDMSO TBDMSO N toluene OTBDMS O TBDMSO V. Nair, J. Am. Chem. Soc., 109, 7223 (1987) N OTBDMS >90% 85 TIPSO MeO OMe O O N O TESO O TBSO O O TIPSO Bu3Sn O MeO OMe OMe O I O N O TESO A. B. Smith, III, J. Am. Chem. Soc., 117, 5407 (1995) O TBSO O O MeO O Rapamycin 86 OH (-)-Macrolactine A O O HO A. B. Smith, III, J. Am. Chem. Soc., 120, 3935 (1998) HO OTBS SnBu3 OTBS O Bu3Sn I I OH OH O OH OPiv OH TBSO TBSO TBSO Bu3Sn I TBSO 87 OMe Me TBSO TIPSO OMe NH Me OMe O I I 1) Pd(MeCN)2Cl2 Bu3Sn SnBu3 Me DMF/THF NH Me TBSO OMe OMe O OMe TIPSO O 2) CAN THF/H2O 3) aq. HF/CH3CN Me HO TIPSO NH Me (+)-Mycontrienol O O OMe J. S. Panek, J. Am. Chem. Soc., 120, 4123 (1998) 88 HO OH O OH NH O O OH H NH O O N N NH O O Sanglifehrin A (SFA) O K. C. Nicolau, J. Am. Chem. Soc., 122, 3830 (2000) OH I O O HO SnBu3 O OH NH + O O H NH O O N N NH O O OH 89 I O O O I O H N NH O O N NH O I O Bu3Sn O NH O O NH2 N NH O O + HO O OH OH 90 91 R' B R X Pd oxidative addition R Pd X B X transmetallation R Pd R' - Pd reductive elimination R R' _ role of base R Pd R' B R Pd _ _ OR X OR OR R' B R' B OR R Pd ate complex OR R' B cf. B. P. Carrow, J. F. Hartwig, J. Am. Chem. Soc., 133, 2116 (2011). C. Amatore, Chem. Eur. J., 18, 6616 (2012). OH Et3P O B PEt3 (4 equiv) Rh Ph C6D12, 70 °C Et3P PEt3 Et3P Ph Rh Et3P PEt3 J. F. Hartwig, J. Am. Chem. Soc., 129, 1876 (2007). 92 The first paper cat. Pd(PPh3)4 O Br B + benzene NaOEt / EtOH reflux, 2 h O 81% N. Miyaura, A. Suzuki, Tetradedron Lett., 3437 (1979) Carbonylative coupling I Pd(PPh3)4 + CO + B K3PO4 dioxane rt, 5 h O 90% N. Miyaura, A. Suzuki, Bull. Chem. Soc. Jp., 64, 1999 (1991) 93 Alkyl-Alkyl coupling NC I Pd(PPh3)4 + B K3PO4 dioxane 60 °C CN 61% N. Miyaura, A. Suzuki, Chem. Lett., 691 (1992) 94 Scope of Palladium-Catalyzed Miyaura-Suzuki Cross-Coupling Reaction Alkyl Alkyl B CH2=CHCH2 I CH2=CHCH2 B X RCH=CH B RCH=CH X B X RC C B RC C X 95 Industrial Application TESO TESO H H CN OTf N O + (HO)2B Pd2(dba)3 aq. KOH, THF -78 °C → rt CO2PNB CN H H N O CO2PNB 95% Yasuda, N.; Xavier, L.; Rieger, D. L.; Li, Y.; DeDamp, A. E.; Dolling, U. H. Tetrahedron Lett. 1993, 34, 3211. TESO O H H Me OSiMe3 Pd(dba)2 N O OTf CO2PNB + THF, H2O, Et3N 30 °C, 2-3 h (HO)2B 996 g TESO H H Me N O Yasuda, N.; Huffman, M. A. et al J. Org. Chem. 1998, 63, 5438. O OSiMe3 CO2PNB 2.00 kg (70%) 96 O O X O OY O Me O YO OMe OY OY OY OY O OY Me OY YO OAc OY OY OY O OY OY Palytoxin caboxylic acid YO OY O YO Y. Kishi, J. Am. Chem. Soc., 111, 7525 (1989) MeO MeO P O OY OY O 97 Recent Advances in Cross-Coupling Reactions Cl Use of Design of Ligand OTs bulky and electron-rich phosphine N-heterocyclic carbene For a review on Pd-catalyzed coupling reactions of aryl chlorides: G. C. Fu, Angew. Chem. Int. Ed., 41, 4176 (2002). For a review on monoligated Pd species: U. Christmann, R. Vilar, R. Angew. Chem. Int. Ed., 44, 366 (2005). 98 Room-temperature Miyaura-Suzuki Coupling of Unactivated Aryl Chlorides Me Cl cat. Pd(OAc)2 / L + B(OH)2 Me CsF dioxane, rt, 94% PCy2 S. L. Buchwald, JACS, 120, 9722 (1998) JACS, 121, 9550 (1999) L= Me2N Me Cl + cat. Pd2(dba)3 / PBut3 B(OH)2 Me Cs2CO3 dioxane, 80 °C, 5 h 86% active Pd species bears a single PBut3 steric bulk and electron-richness G. C. Fu, Angew. Chem., Int. Ed., 37, 3387 (1998) JACS, 122, 4020 (2000) cf. A review of Pd-catalyzed coupling reactions of aryl chlorides G. C. Fu, Angew. Chem. Int. Ed., 41, 4176 (2002) 99 Me Me Cl + (HO)2B K3PO4 toluene 90 °C, 12 min Me increases steric bulk MeO PCy2 OMe prevents cyclometalation Br Me Me 98% oxygen lone pair may stabilize Pd complex increases electron density in biaryl backbone Me Me Me Me Me Me Me 0.2 mol% Pd(OAc)2 + (HO)2B Me Pd(OAc)2 K3PO4 toluene 110 °, 18 h Me Me Me 82% S. L. Buchwald, Angew. Chem. Int. Ed., 43, 1871 (2004). J. Am. Chem. Soc., 127, 4685 (2005). J. Am. Chem. Soc., 129, 3358 100(2007). PCy2 Pri iPr XPhos MeO t Bu OMs + Pd(OAc)2 (HO)2B Pri MeO t Bu THF, K3PO4 80 °C, 3 h 91% H. N. Nguyen, X. Huang, S. L. Buchwald, J. Am. Chem. Soc., 125, 11818 (2003). MeO OTs Ni(cod)2/PCy3 + (HO)2B MeO THF, K3PO4 rt, 8 h 86% Z.-Y. Tang, Q.-S. Hu, J. Am. Chem. Soc., 126, 3058 (2004). Z.-Y. Tang, Q.-S. Hu, J. Org. Chem., 71, 2167 (2006). MeO OMs + NiCl2(dppe)/PPh3 (HO)2B toluene, K3PO4 80 °C, 14 h MeO 80% 101 V. Percec, G. M. Golding, J. Smidrkal, J. Weichold, J. Org. Chem., 69, 3447 (2004). cf. Me Cl + HN cat. Pd2(dba)3 / PBut3 NH Me N NH o-xylene, 120 °C 88% Y. Koie (Tosoh Co.), Tetrahedron Lett., 39, 617 (1998) imidazol-2-ylidene ligand For a review on N-Heterocyclic Carbenes, see: W. A. Herrmann, Angew. Chem. Int. Ed. 41, 1290 (2002) M. G. Organ, Angew. Chem. Int. Ed. 46, 2768 (2007) N N S. P. Nolan, J. Org. Chem., 64, 3804 (1999) 102 Cl B(OH)2 80% + N N Pd CsF dioxane rt, 2 h Me N N Me 573 the highest TON [(mol product)(mol Pd)-1(h)-1] at rt Gstottmayr, C. W. K.; Bohm, V. P. W.; Herdtweck, E.; Grosche, M.; Herrmann, W. A. Angew. Chem. Int. Ed. 2002, 41, 1363. + Cl 12 Me Pd(OAc)2 K3PO4 THF/toluene 110 °C, 16 h Me Me Me 96% O N (HO)2B Me Me O Me Me Me Me N 12 Altenhoff, G.; Goddard, R.; Lehmann, C. W.; Glorius, F. J. Am. Chem. Soc. 2004, 126, 15195. 103 Me Me Me Me Cl (HO)2B + NaOBut i PrOH rt, 75 min Me Me 88% ArN NAr Pd Cl NMe2 Ar = 2,6-(iPr)2C6H3 NMe2 O Pd Cl NMe2 IPr IPr IPr i PrOH Pd O NMe2 H Pd H NMe2 [IPrPd(0)] Navarro, O.; Kelly, R. A.; Nolan, S. P. J. Am. Chem. Soc. 2003, 125, 16194. 104 Alkyl-Alkyl Coupling R R PdLn R' H H H H R H H PdLn R H H R' X PdLn X undesired -hydride elimination H M X R' M R + PdLn X 105 Alkyl-Alkyl Coupling Hex Br + 9-BBN Dec Pd(OAc)2/PCy3 K3PO4.H2O Hex Dec THF, rt, 16 h 85% Netherton, M. R.; Dai, C.; Neuschutz, K.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 10099. Hex Cl + 9-BBN Dec Pd2(dba)3/PCy3 CsOH.H2O o dioxane, 90 C 48 h Hex Dec 83% Kirchhoff, J. H.; Dai, C.; Fu, G. C. Angew. Chem. Int. Ed. 2002, 41, 1945. O NC 5 Br + BrZn 3 O c Pd2(dba)3/P( C5H9)3 OEt THF/NMP, NMI 80 °C, 14 h NC 3 5 OEt 65% Zhou, J.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 12527. 106 O EtO 4 + Br Ph Si(OMe)3 PdBr2 PMetBu2 Bu4NF THF, r.t. O EtO 4 Ph 79% Lee, J.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 5616. [(-ally)PdCl]2 Ph PCy(pyrrolidinyl)2 O EtO 4 Br + Bu Sn 3 Me4NF THF, rt O Ph EtO 4 89% Tang, H.; Menzel, K.; Fu, G. C. Angew. Chem. Int. Ed. 2003, 42, 5079. O EtO O 4 Br + Cp2ClZr Ph Pd(acac)2 LiBr THF/NMP 55 °C, 24 h ligandless EtO Ph 4 99% Wiskur, S. L.; Korte, A.; Fu, G. C. J. Am. Chem. Soc. 2004, 126, 82. 107 O O N s N Bu-Pybox N Bus Bus Ni(cod)2 Br + OPh BrZn OPh DMA, r.t., 20 h 62% Zhou, J.; Fu. G. C. J. Am. Chem. Soc. 2003, 125, 14726. Ph Br + Ni(cod)2 Ph B(OH)2 Ph N butanol, KOBut 60 oC, 5 h N Ph s 91% Zhou, J.; Fu, G. C. J. Am. Chem. Soc. 2004, 126, 1340. Gonzalez-Bobes, F.; Fu, G. C. J. Am. Chem. Soc. 2006, 128, 5360. Si: Powell, D. A.; Fu, G. C. J. Am. Chem. Soc. 2004, 126, 7788. 108 510. Sn: Powell, D. A.; Maki, T.; Fu, G. C. J. Am. Chem. Soc. 2005, 127, 109 Cross-Coupling of Secondary Nucluophiles with Secondary Propargylic Electrophiles at RT TIPS TIPS NiCl2 . glyme / + IZn Cl Et THF, rt N N N N N Et 75% G. C. Fu, Angew. Chem. Int. Ed., 47, 9334 (2008) 110 Sonogashira Coupling NC Br + Cl [(-ally)PdCl]2 CuI, Cs2CO3 DMF/Et2O, 45 °C, 16 h NC Cl 74% G. C. Fu, J. Am. Chem. Soc., 125, 13642 (2003) cf. A review: H. Doucet and J.-C. Hierso, Angew. Chem., Int. Ed. 46, 834 (2007) 111 Negishi Coupling R X + Pd(0) R' ZnX R = Ar, vinyl, alkyl X = I, Br generaion of Zn reagents R'MgX + ZnCl2 R'Li + ZnCl2 R'3Al + ZnCl2 R R' + ZnX2 R' = Ar, vinyl, alkyl inert to ketone, esters, amino and cyano goups A recent review: E. Negishi, Aldrichimica Acta, 38, 71 (2005). R' I + Zn(Cu) D. Cardenas, Chem. Soc. Rev. 38, 1598 (2009). iodine-zinc exchange Mechanism: J. A. Casares, P. Espinet, J. Am. Chem. Soc. 129, 3508 (2007). 112 Pd(0) R X + R' SiY3 R R' + Y3Si X Y = Cl, F, H, OMe, cyclobutyl, thienyl, OH ..... R = Ar, vinyl, alkynyl, allyl R' = Ar, vinyl, allyl, alkynyl X = I, Br, OTf review: Hiyama, T. Topp. Curr. Chem. 2002, 219, 61. D. R. Spring, Chem. Soc. Rev., 41, 1845 (2012). [( 3-C3H5)PdCl]2 (Et2N)3S+Me3SiF2- (TASF) I + SiMe3 HMPA, 50 °C, 2 h 98% Hatanaka, Y.; Hiyama, T. J. Org. Chem. 1988, 53, 918. Review: Denmark, Regens, C. S. Acc. Chem, Res. 2008, 41, 1486. Nakano, Y.; Hiyama, T. J. Am. Chem. Soc. 2005, 127, 6952. 113 Tamao-Kumada-Corriu Coupling + R X R' MgX NiCl2(dppp) R R' + MgX2 PPh2 R = Ar, vinyl, benzyl R' = Ar, vinyl, ally, alkyl X = I, Br, Cl RX L2Ni L2Ni L2NiR'2 2MgX2 PPh2 oxidative addition 2R'MgX L2NiX2 dppp = R'MgX R' R' reductive elimination R X transmetalation R R' L2Ni R R' MgX2 114 The first reports Cl Et + EtMgBr NiCl2(dppe) Et2O reflux, 20 h 98% Tamao, K.; Sumitani, K.; Kumada, M. J. Am. Chem. Soc. 1972, 94, 4374. Ph Br + PhMgBr Ni(acac)2 Et2O, rt Ph Ph 70% Corriu, R. J. P.; Masse, J. P. J. Chem. Soc., Chem. Commun. 1972, 144. 115 BuBr + Mg Cl + Cl 29.5 g BuMgBr Mg (12.2 g, 0.50 mol) Et2O (200 mL) 1-bromobutane (68.5 g, 0.5 mol) in Et2O (50 mL) NiCl2(dppp) Bu Et2O 0 °C → reflux 6h Bu 79-83% (30.0-31.5 g) NiCl2(dppp) (0.25 g, 0.5 mmol) 1,2-dichlorobenzene (29.5 g, 0.21 mol) Et2O (150 mL) Kumada, M.; Tamao, K.; Sumitani, K. Org. Synth. 1988, Coll. Vol. 6, 407. cf. Buck, J. R.; Park, M.; Wang, Z.; Prudhomme, D. R.; Rizzo, C. J. Org. Synth. 1999, Vol. 77, 153. Organic Synthesis Website: http://www.orgsyn.org/ 116 NiCl2/L* + Ph Br MgCl PPh2 H O O Fe PPh2 PPh2 NMe2 R H Me2N PPh2 R = iPr R = tBu 81% ee 94% ee H Me H (-)-DIOP <16% ee Ph Ph * Et2O 0 °C, 2 d (S)-(R)-PPFA 63% ee MgCl (R) Ph Valphos t-Leuphos MgCl (S) Hayashi, T.; Konishi, M.; Fukushima, M.; Kanehira, K.; Hioki, T.; Kumada, M. J. Org. Chem. 1983, 48, 2195. 117 i Pr H Me2N MgCl PPh2 NiCl2 * H2C CHBr Et2O, 0 °C [O] * COOH ibuprofen 81%ee Hayashi, T.; Konishi, M.; Fukushima, M.; Mise, T.; Kagotani, M.; Tajika, M.; Kumada, M. J. Am. Chem. Soc. 1982, 104, 180. 118 PhCH2 H Me2N TfO OTf PPh2 Pd Cl2 PhMgBr/LiBr Et2O/toluene - 30 °C, 40 h Ph OTf Ph Ph + 87% (93%ee) Ph 13% PPh2 Hayashi, T.; Niizuma, S.; Kamikawa, T.; Suzuki, N.; Uozumi, Y. J. Am. Chem. Soc. 1995, 117, 9101. 119 Ph OMe + PhMgBr NiCl2(PPh3)2 C6H6 rt, 72 h 70% Wenkert, E.; Michelotti, E. L.; Swindell, C. S.; Tingoli, M. J. Org. Chem. 1984, 49, 4894. Ph OMe + PhMgBr NiCl2(PPhCy2)2 t AmOMe/Et2O 23 °C, 15 h 91% Dankwardt, J. W. Angew. Chem., Int. Ed. 2004, 43, 2428. 120 Iron-Catalyzed Grignard Cross-Coupling O OMe THF/NMP 0 °C → rt, 5 min X X = Cl: C6H13MgBr (91%) C6H13MgBr: N N O Fe(acac)3 RMgBr OMe R PhMgBr (28%) MgBr MgBr X = Cl (91%) OTf (87%) OTs (83%) Br, I (<40%) Cl Fe(acac)3 RMgBr THF/NMP 0 °C → rt, 5 min N R N MgBr (82%) RMgBr: C14H29MgBr (95%) PhMgBr (73%) N S MgBr (69%) Furstner, A.; Leitner, A.; Mendez, M.; Krause, K. J. Am. Chem. Soc. 2002, 124, 13856. Furstner, A.; Leitner, A. Angew. Chem. Int. Ed. 2002, 41, 609. 121 NiCl2(dppp) C4H9MgBr TfO N Cl Et2O reflux, 6 h C4H9 N C4 H9 63% Fe(acac)3 C6H13MgBr TfO N Cl THF/NMP 0 °C, 5 min C6H13 N C6H13 73% Fe(acac)3 1) Me2CHCH2MgBr 2) C14H29MgBr TsO N Cl N THF/NMP, 0 °C 1) 3 min 2) 5 min 71% 122 RCH2CH2CH2CH2R Fe 4 RCH2CH2MgX + RCH CH2 + RCH2CH3 MgX2 RX [R Fe(MgX)] [Fe(MgX)2] FeCl2 cf. A. Furstner, J. Am. Chem. Soc., 130, 8773 (2008) R R' R'MgX R' [R Fe(MgX)2] RX Ni 2R'MgX L2NiX2 L2Ni L2Ni L2NiR'2 2MgX2 R X R'MgX R' R' R R' L2Ni R R' MgX2 123 MeOOC O MgCl. LiCl PCy 2 NMe 2 Pd(dba)2 MeOOC + O toluene/THF, -20 °C I N Boc 86% N Boc Cl Cl Cl N O Cl S Cl O S O F 3C 55% O 73% 86% Buchwald, S. L.; Martin, R. J. Am . Chem . Soc. 2007, 129, 3844. 124 Generation of Ar-Pd-X Species Pd(0) Ar X Ar O Ar PdX PdX2 Ar OH + HX + CO2 PdX A. G. Myers, J. Am. Chem. Soc., 124, 11250 (2002). J. Am. Chem. Soc. 127, 10323 (2006). O MeO MeO OH OMe + Ph Pd(O2CCF3)2, Ag2CO3 DMSO-DMF, 120 °C 1h MeO MeO Ph OMe DFT study: L. Liu, J. Am. Chem. Soc., 132, 638 (2010). 125 Generation of Ar-Pd-X Species O Ar P OH P O Ar PdX + OH O Ar PdX2, F- OH O- - F Ar P OH F OH PdX2 OH - X- F P OH OH H. Shinokubo, K. Oshima, J. Am. Chem. Soc., 125, 1484 (2003) XPd O Ar P F OH OH O Ar PdX + F P OH OH O P OH OH MeO + Ph Ph Pd(OAc)2, M3NO, TBAF dioxane, 100 oC 24 h MeO 100% 126 O O2N Cu2O, PdI2 1,10-phenanthroline, Tol-BINAP OK + NMP, 170 °C, 24 h TfO CuX2Phen Pd(0) O2N O O2N OCuX 72% Pd OTf -CO2 O2N CuX L. J. Goossen, J. Am. Chem. Soc., 130, 15248 (2008) 127 Carbene Complex M C (1) Schrock carbenes But Ta t Bu But O O + Ph t Ta Me Bu Ph Me O Ta Ph Me + But But R. R. Schrock, J. Am. Chem. Soc., 98, 5399 (1976) (2) Fischer carbenes OMe (OC)5Cr C Me BuLi _ (OC)5Cr OMe C OMe O (OC)5Cr C O- O (OC)5Cr C CH2 C. P. Casey, J. Organomet. Chem., 102, 175 (1975) 128 (3) Grubbs catalyst Cl Cl PCy3 Ru RCM = Ring-Closing Metathesis ROMP = Ring-Opening Metathesis Polymerization Ph PCy3 Ph (4) Carbenoid R COOMe LnRh(II) or LnCu(I) N2 - N2 R R COOMe R COOMe COOMe MLn R' H R' H Review: A. Padwa, Angew. Chem., Int. Ed., 33, 1797 (1994) J. Adamas, Tetrahedron, 47, 1765 (1991) M. A. McKervey, Chem. Rev., 94, 1091 (1994) 129 R1 R1 M2+ M C Schrock Carbenes 2- R2 R2 R1, R2 = H, alkyl PMe3 CH2 Cp2TaV But CH3 t Bu W But PMe3 Tebbe Olefination Cp2TiCl2 + 2 AlMe3 Review: Schrock, Acc. Chem. Res., 19, 342 (1986) H2 C Cp2Ti Cl py AlMe2 Cp2Ti CH2 + py AlMe2Cl O toluene, -15 °C → rt Tebbe's reagent F. N. Tebbe (du Pont), J. Am. Chem. Soc., 100, 3611 (1978) CH2 65% 130 O Cp2Ti CH2 + X R O R Cp2Ti X X = Cl X R R. H. Grubbs, J. Am. Chem. Soc., 102, 3270 (1980) O TiClCp2 R CH2 X = H, R, OR, NR2 OH R'CHO O R' R R. H. Grubbs, J. Am. Chem. Soc., 105, 1664 (1983) 131 O BnO O BnO OBn BnO O OBn BnO OBn OBn T. V. Rajanbabu (du Pont), J. Org. Chem., 51, 5458 (1986) OTBS OBn OTBS EtO2C OTBS OBn 1. Swern oxidation CH2OH 2. Tebbe's reagent OTBS OBn OTBS EtO2C OTBS S. L. Schreiber, J. Am. Chem. Soc., 112, 9657 (1990) OTBS OBn OTBS Hizikamcin 132 Petasis reagent O Cp2TiCl2 + 2 MeLi Cp2TiMe2 toluene or THF 60-65 °C O Ph O O C H2 + CH2 H + CH4 O O O Ph OMe Ph O O TiCp2 Cp2 Ti O CH3 O O O N. A. Petasis, J. Am. Chem. Soc., 112, 6392 (1990) mechanistic evidence for discrete carbene mechanism -elimination Cp2TiMe2 Cp2Ti CH2 133 CH2Br2 + TiCl4 + Zn-Pb O CH2Br2 TiCl4/Zn THF 25 °C 89% K. Oshima, Tetrahedron Lett., 2417 (1978) O COOMe CH2Br2 TiCl4/Zn COOMe THF THPO THPO OTHP OTHP 80% S. Ikegami, Tetrahedron Lett., 24, 3493 (1983) 134 O CH2I2 TiCl4/Zn THF 25 °C, 15 min 88% K. Takai, Tetrahedron Lett., 26, 5579 (1985) Ph Bu BuCHBr TiCl4/Zn/TMEDA O OEt THF 25 °C Ph OEt 82% (Z/E = 93/7) K. Takai, J. Org. Chem., 52, 4410 (1987) 135 OMe Fischer Crabene (OC)5Cr C R Preparation _ Cr(CO)6 + RLi _ (OC)5Cr O O (OC)5Cr C R C _ Me3O+ BF4 OMe (OC)5Cr C R R E. O. Fischer, Angew. Chem., 3, 580 (1964) 136 Elaboration BF3.OEt2 OMe (OC)5Cr C _ BuLi (OC)5Cr OMe C OMe O (OC)5Cr _ O O C (OC)5Cr C CH2 Me pKa = 8 C. P. Casey, J. Organomet. Chem., 102, 175 (1975) OMe (OC)5Cr C Et (CO)5Cr BuLi Et2O -78 °C PhCHO, TiCl4 CH2Cl2 -78 °C, 1 h (CO)5Cr OH MeO Ph OH + MeO Me Ph Me 55% (86 : 14) W. Wulff, J. Am. Chem. Soc., 107, 503 (1985) 137 Elaboration OMe (OC)5W C _ Ph (OC)5W C OMe PhLi Ph HCl (OC)5W C Ph Ph Ph Casey carbene C. P. Casey, J. Am. Chem. Soc., 99, 2127 (1977) (also amines, mercaptanes, etc) cf. E. O. Fischer, Chem. Ber., 106, 1277 (1973) OLi OMe (OC)5Cr + OMe (OC)5Cr O 82% C. P. Casey, J. Organomet. Chem., 77, 345 (1974) 138 Elaboration OMe + (OC)5Cr 25 °C 3 min OMe MeO Cr(CO)5 78% (endo/exo = 94/6) much faster than O (104) W. Wulff, J. Am. Chem. Soc., 105, 6726 (1983) OMe (OC)5Cr TMSO TMSO + OMe Me benzene 25 °C 10 min Me Cr(CO)5 OMe OMe 100% W. Wulff, J. Am. Chem. Soc., 106, 7565 (1984) 139 Review: K. H. Dötz, Angew. Chem., 23, 587 (1984) Dötz Reaction OH OMe (OC)5Cr RL + RL RS RS (OC)3Cr OMe A first report OMe (OC)5Cr OH OH Ph Ph Ph Bu2O 45 °C Ph CO (40 atm) Ph Ph (OC)3Cr OMe 62% OMe 80% K. H. Dötz, Angew. Chem., 14, 644 (1975) 140 Cr(CO)5 MeO R - CO R' Cr(CO)4 MeO MeO R (CO)4 Cr CO Cr(CO)4 R' O MeO C O MeO R R O (OC)3Cr OMe R' R' Cr(CO)3 OH R' R' R R (OC)3Cr OMe 141 Natural Product Synthesis 1. OMe (OC)5Cr OMe O THF, 45 °C OH O 2. [Fe(DMF)3Cl2][FeCl4] O O O O OMe O OH OMe O OH O O OH OH OMe O O O COH OMe O OMe W. Wulff, J. Am. Chem. Soc., 106, 434 (1984) 142 Ring-Closing Metathesis (RCM) Catalyst Review: R. H. Grubbs, Acc. Chem. Res., 28, 446 (1995) S. K. Armstrong, J. Chem. Soc., Perkin I, 371 (1998) A. Fürstner, Angew. Chem. Int. Ed., 39, 3013 (2000) Y. Schrodi, Aldrichimica Acta, 40, 45 (2007) F. Verpoort, Chem. Rev., 110, 4865 (2010) Pri Cl N (F3C)2MeCO i Pr Mo (F3C)2MeCO Cl PCy3 Ru Ph PCy3 Cl Cl PCy3 Ru PCy3 Ph Ph CHCMe2Ph 2 3 1 1 Schrock, J. Am. Chem. Soc., 112, 3875 (1990) 2 R. H. Grubbs, J. Am. Chem. Soc., 115, 9858 (1993) 3 R. H. Grubbs, Angew. Chem., Int. Ed. Engl.34, 2039 (1995) 143 Pri O Ph (F3C)2MeCO N Pri Mo (F3C)2MeCO CHCMe2Ph O Ph H3CHC CHCH3 + benzene, 20 °C, 15 min O O + _ M O M M O O - CH2=CH2 M CH2=CH2 M R. H. Grubbs, J. Am. Chem. Soc., 114, 5426 (1992) 144 N COOBut PCy3 Cl Ru Cl PCy3 Ph Ph N COOBut benzene, 20 °C, 1 h 93% O O Ph Ph O 5h O O Ph 1h O 87% 86% Cl+ N H NaOH Ph N CH2Cl2 20 °C, 36 h Ph 79% R. H. Grubbs, J. Am. Chem. Soc., 115, 9856 (1993) 145 Ph O O OH H H O O O O OR H O O H ( -)-gloeosporone OR O O H OR O O H A. Fürstner, J. Am. Chem. Soc., 119, 9130 (1997) A review on metathesis in total synthesis: A. Fürstner, Chem. Commum., 47, 6505 (2011). 146 NHTf OMe O3, MeOH, p-TsOH H MeO NaHCO3, Me2S NHTf O Ti(OPri)4 (1.2 eq.) 82% OMe OH Zn(pent)2 4-pentenoyl chloride MeO DMAP, pyridine 88% (>98%ee) O OMe O O CF3COOH O O H MeO 91% 90% 147 SnBu3 OH (S)-BINOL (20 mol%) O O TBDMSCl, imidazole Ti(OPri)4 (10 mol%) Cl Cl 77% (>98% de) PCy3 O (3 mol%) Ru PCy3 Ph H i Ti(OPr )4 (30 mol%) OR O O KMnO4, Ac2O O OR CH2Cl2, 40 oC H 80% (Z:E = 2.7:1) O H O O H OH aq. HF MeCN H O 54% O O (-)-gloeosporone H 148 BnO BnO BnO O O TiCl4, Zn TMEDA, CH2Br2 PbCl2 (cat.) BnO BnO BnO Pri N Pri (F3C)2MeCO Mo (F3C)2MeCO CHCMe Ph 2 O BnO BnO BnO O 68% M. H. D. Postema, J. Org. Chem., 64, 1770 (1999) cf. R. H. Grubbs, J. Org. Chem., 59, 4029 (1994) 149 PCy3 Cl Ru Cl R. H. Grubbs, Angew. Chem., Int. Ed. Engl.34, 2039 (1995) PCy3 Ph 1st generation catalyst Pri N Cl N Pri W. A. Herrmann, Angew. Chem. Int. Ed. 37, 2490 (1998) Ru Cl Pr i Ph i N Pr N Mes N Cl N Mes 1,3-dimesityl-4,5-dihydroimidazol-2-ylidene ligand Ph R. H. Grubbs, Org. Lett., 1, 953 (1999) R. H. Grubbs, J. Am. Chem. Soc., 122, 3783 (2000) Ru Cl PCy3 2nd generation catalyst A recent review: R. H. Grubbs, Chem. Rev., 110, 1746 (2010) 150 ROMP (Ring-Opening Metathesis Polymerization) O O NMe PCy3 Cl Ru Cl PCy3Ph O CH2Cl2, H2O DTAB O O N Me O n R. H. Grubbs, J. Am. Chem. Soc., 118, 784 (1996) water-soluble Ruthenium alkylidene complexes Me2+ ClN NMe3+Cl- P Cl catalyzed ROMP of strained, cyclic olefins in water P Cl Ru Cl P R. H. Grubbs, J. Am. Chem. Soc., 122, 6601 (2000) Ru Cl Ph NMe3+Cl- P Ph N Me2+ Cl- J. Am. Chem. Soc., 123, 3187 (2001) 151 Recyclable Catalyst Me Me Me Me Cl O Me N2 O H CH2Cl2 90% OBn O H CH2Cl2 -78 °C Me Cl Cl Me O Ru PCy3 H Me Cl Ru PCy3 PCy3 RuCl2(PPh3)3 H Cl Cl Ru PPh3 OBn 75% recovered catalyst 89% by silica gel chromatography A. M. Hoveyda, J. Am. Chem. Soc., 121, 791 (1999) CH2Cl2, 22 °C, 2 h 95% 152 Recyclable Catalyst Me Cl Me O Cl Ru H Mes N N Mes O O commercial CH2Cl2 at 22 oC in air O 59% conversion SiMe2 ring-opening/cross metathesis glass-bound metathesis catalyst J. T. Fourkas, A. M. Hoveyda, Angew. Chem., Int Ed. 40, 4251 (2001) 153 permanently immobilized metathesis catalyst M. R. Buchmeiser, Angew. Chem. Int. Ed., 40, 3839 (2001) 154 Sustainable Concepts in Olefin Metathesis Mes N N Mes Mes N Mes N N Mes N Mes Cl Ru Cl Cl Ru Cl Cl Ru Cl O O O _ SO3 + NEt2H _ +N PF6 N A review: S.P. Nolan, Angew. Chem. Int. Ed., 46, 6786 (2007) cf. Polymer-Supported Well-Defined Metathesis Catalyst M. R. Buchmeiser, Chem. Rev. 109, 303 (2009). 155 Asymmetric Ring-Closing Metathesis Me OTES Me Me Me Me i t Pr Bu O N Pri Mo O CHCMe2Ph But Me SETO OTES H Me H + + Me benzene, 22 °C, 10 min Me 43% 93%ee dimer 38% 19% >99%ee krel = 58 R. R. Schrock, J. Am. Chem. Soc., 120, 4041 (1998) cf. R. R. Schrock, J. Am. Chem. Soc., 118, 2499 (1996) 156 O O C6H6, 50 oC, 4 h 87% 96%ee A. H. Hoveyda, J. Am. Chem. Soc., 123, 3139 (2001) 157 AROM R O RCM R A MoLn R R O O R RCM AROM O LnMo O ent-A MoLn R O A or ent-A 158 Enyne Metathesis OAc A recent review: C. Bolm, Chem. Soc. Rev., 6, 55 (2007) PCy3 Cl Ru Cl PCy3 OAc Ph Ph TsN TsN benzene, rt, 40 min 86% M. Mori, Synlett, 1020 (1994) O PCy3 Cl Ru Cl PCy3 Ph CH2Cl2, rt, Ph O Ph 6 % (under Ar) 96% (under ethylene) M. Mori, J. Org. Chem., 63, 6083 (1998) 159 Alkyne Metathesis O O A review: A. Fürstner, Chem. Commun. 2307 (2005) O O O O W( CCMe3)(OCMe3)3 O O + C6H5Cl, 80°C 73% O O O 97% A. Fürstner, Angew. Chem., Int. Ed.,37, 1734 (1998) A. Fürstner, Chem. Eur. J., 7, 5299 (2001) O 160 O O Mo( O CH)(NBut(3,5-Me2C6H3)3 O O TBSO CH2Cl2, 80 °C O TBSO cis-alkene 1) H2, Lindler O 2) HF, CH3CN O O PGE2 TBSO A. Fürstner, Angew. Chem., Int. Ed., 39, 1234 (2000) J. Am. Chem. Soc., 122, 11799 (2000) 161 O O [Cp*Ru(MeCN)]PF6 O O O HSi(OEt)3 O O CH2Cl2, rt O O O O AgF O O THF/MeOH rt O O O trans-alkene Si(OEt)3 93% (Z/E = 95/5) A. Fürstner, Tetrahedron, 60, 7315 (2004) 162 163 O O Ph O O HN Ph3SiO Mo OSiPh3 OEt2 Ph3SiO MeO OMOM toluene, rt 79% O O A. Furstner, J. Am. Chem. Soc., 132, 11045 (2010). 164 An Endless Route to Cyclic Polymer N N Cl n Ru Cl PCy Ph 3 直鎖高分子 n n 水素化 N N Cl Ru Cl PCy3 n n-1 n-1 環状高分子 R. H. Grubbs, Science, 297, 2041 (2002) J. Am. Chem. Soc. 131, 2670 (2009) 165 ROMP Ar N N Cl Ru Cl Ar Ar N PCy3 N Ar Ar N Ru Ar Ru Ru Ar N N N Ar Ar N N Ar Ru 166 N N Cl Ar Ru Cl n PCy3 N N Ar N N Ru Ru n n n Ar N N Ru n Ar N N n Ru n-1 167 Carbenoid Reactions Review: M. A. KcKervey, Chem. Rev., 94, 1091 (1994) A. Padawa, Angew. Chem., Int. Ed. Engl., 33, 1797 (1994) C. A. Merlic, Synthesis, 1137 (2003) M. S. Sanford, Tetrahedron, 62, 2439 (2006) H. M. L. Davies, Chem. Soc. Rev., 40, 1857 (2011) R1 RO2C R' RO2C N2 LnRh(II) or LnCu(I) - N2 RO2C R1 MLn R2 H OR3 RO2C RO2C R2 R1 OR3 168 R1 H Rh(II)-Catalyzed C-H Insertion Reactions O O OO Rh Rh O EtO2C H O O O [Rh(OAc)2]2 EtO2C N2 O O CO2Et N2 R CO2Et R D. F. Taber, J. Org. Chem., 47, 4808 (1982) D. F. Taber, J. Am. Chem. Soc., 107, 196 (1985) 169 Rh2L4 N2 Ph H + O O O L = OAc L = C3F7CO2 (pfb) 67 33 0 100 100 0 O L= N A. Padawa, J. Am. Chem. Soc., 115, 8669 (1993) (cap) 170 Regioselectivity [Rh(OAc)2]2 O N2 O O O J. Adams, Tetrahedron Lett., 28, 4773 (1987) O O N2 [Rh(OAc)2]2 OMe OMe n n = 1 : 83% n = 2: 81% n O O G. Stork, Tetrahedron Lett., 29, 2283 (1988) O O O N2 O COMe [Rh(OAc)2]2 O O OH O COMe T. Durst, J. Chem. Soc., Chem. Commun., 1150171 (1987) Insertion into Heteroatom-H Bonds O [Rh(OAc)2]2 O O N2 CO2Et OH CO2Et C. J. Moody, J. Chem. Soc., Perkin 1, 721 (1989) OH H H O NH N2 O [Rh(OAc)2]2 CO2Bn OH H H O N Tienamycin O CO2Bn P. J. Reider, Tetrahderon Lett., 23, 2293 (1982) O O H Ph N2 [Rh(OAc)2]2 + HSiEt3 Ph SiEt3 M. P. Doyle, J. Org. Chem., 53, 6158 (1988) 172 Enantioselective O-H Insertion O O Ph OMe + Cu(OTf)2, (+)-1 Me3Si OH ClCH2CH2Cl, H2O rt, 1 h N2 Ph OMe Me3SiCH2CH2O H 94% (90%ee) Me Me Me Me Fe Me N Fe Me Me N O Me Me Me BF3.Et2O CH2Cl2, rt (+)-1 Ph OMe HO H G. C. Fu, J. Am. Chem. Soc. 128, 4594 (2006). BocNH2: G. C. Fu. J. Am. Chem. Soc., 129, 12066 (2007). Phenol/bisoxazoline: Q.-L. Zhou, J. Am. Chem. Soc. 129, 12616 (2007). 173 Intramolecular Asymmetric Cyclopropanation R1 R1 2 R N2 Rh2(MEPY)4 O H H 2 R O R1 = H, R2 = H, Ar, alkyl R1 = H, R2 = H O >94%ee 65-75%ee 5-MEPY = O _ N CO2Me M. P. Doyle, S. F. Martin, and P. Muller, J. Am. Chem. Soc., 113, 1423 (1991) S. F. Martin, Tetrahedron, 49, 3521 (1993) M. P. Doyle, Tetrahedron, 50, 1665 (1994) 174 Asymmetric C-H Insertion O O N2 O Rh2(MEPY)4 R = OMe R = Ph O 91%ee 46%ee R R M. P. Doyle, J. Am. Chem. Soc., 113, 8982 (1991) H N2 H O n O O nH O + O nH Rh2(MEPY)4 3-4 : 1 Rh2(MACIM)4 99 : 1 (96-97%ee) O MeOC N 4S-MACIM = O _ N CO2Me M. P. Doyle and P. Muller, J. Am. Chem. Soc., 116, 4507 (1994) 175 CO2Me + N2 Ph CO2Me + N2 Ph O + Ar, degassed 10 oC Ph Ar, degassed -10 oC CO2Me Ph Ar, degassed -50 oC, hexane H O Rh O Rh 4 N SO2Ar 80% (95%ee) Ar = p-(C11H23)C6H4 Rh2(S-DOSP)4 CO2Me Rh2(S-DOSP)4 1 mol% Rh2(S-DOSP)4 1 mol% N2 CO2Me Rh2(S-DOSP)4 1 mol% Ph 20% (75%ee) CO2Me O Ph (97%ee) H. M. L. Davies, J. Am. Chem. Soc., 122, 3063 (2000) 176(2003) cf. H. M. L. Davies, J. Am. Chem. Soc., 125, 6462 Boc O N 1 0.66 2700 1700 Ph2ButSi 28,000 0.011 0.078 H 24,000 Relative Rates of Reaction with Various Substrates approach from front H MeO2C Ar NBoc + H Ar MeO2C Rh H NBoc Rh MeO2C Ar H 177 cf. DFT calculation: E. Nakamura, Adv. Synth. Catal., 345, 1159 (2003). [2,3]-Sigmatoropic Rearrangement O O COOMe O N2 Rh2(S-PTTL)4 toulene, 0 °C COOMe O 70 %, 74%ee O O O t Bu COOMe N H O O O Rh Rh Rh2(S-PTTL)4 O Rh + O COOMe _ Rh S. Hashimoto, Tetrehedron Lett., 42, 6361 (2001). 178 C-H Amination H N H2N Rh2(OAc)4 O O PhI(OAc)2, MgO CH2Cl2, 40 °C, 12 h O PhI 86% (AcO)4Rh2 N O N O O O O J. Du Bois, Angew. Chem., Int. Ed., 40, 598 (2001). Ts O O S H2N O HN O COOMe J. Du Bois J. Am. Chem. Soc., 123, 6935 (2001) O no PhI(OAc)2 H. Lebel. J. Am. Chem. Soc., 127, 14198 (2005). 179 Enantioselective C-H Amination Ts H O H2N O S O N O Rh H N Rh O HN O S O PhI=O, CH2Cl2 85% (92%ee) D. N. Zalatan, J. Du Bois, J. Am. Chem. Soc., 130, 9220 (2008). 180 Asymmetric C-H Amination O H N O O NTs S + _ (+) NH2 O Rh O Rh O (R) NTs S NH p-Tol PhI(OCOBut )2 Cl2CHCHCl2/MeOH -35 °C 77% (98%de, 98%ee) P. Mullerm R. H. Dodd, P. Dauban, J. Am. Chem. Soc., 130, 343 (2008). Review: P. Dauban, Chem. Soc. Rev., 40, 1926 (2011). Y. Shi, Chem. Soc. Rev., 41, 931 (2012). 181 182
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