Ryoji Noyori Baran Group Meeting Masato Saito 10/3/20 Education and Appointment Awards (selected) 1938 Born, Sep. 3 1993 Tetrahedron Prize (UK) 1967 Ph.D., Hitoshi Nozaki, Kyoto University 1997 Arthur C. Cope Award (ACS) 1968 Associate Professor, Nagoya University 1998 Person of Cartural Merit (Japan) PPh2 1969 Post-doc, E. J. Corey, Hervard University 1999 King Faisal International Prize PPh 1972 Full Professor, Nagoya University for Science (Saudi Arabia) 2 2003 University Professor, Nagoya University 2000 The Order of Culture (Japan) 2003 President, RIKEN 2001 Wolf Prize in Chemistry (Israel) 2015-present Director-General, Center for Research 2001 Roger Adams Award (ACS) and Development Strategy 2001 Nobel Prize in Chemistry (Sweden) Hisashi Yamamoto Kazuhiro Takai Tamejiro Hiyama R Ph Ph O NiCl2 R O X CrCl O CrCl OH O X 2 X X 2 N S R R Al O O S R H H X R H R R Ph V Ph O Ph O S N S [CrIII] R X Pd0 Ph O Si X H [CrIII] F- R Koichiro Oshima Keiji Maruoka Today”s topic Me Me F · His supervised work. O Me B Me H 2 F Sn Sn · Works before the asymmetric hydrogenation Me F Me reaction Me Me Me Me · BINAP synthesis and the asymmetric N Br CoCl2(dpph) (3 mol %) hydrogenation reaction Br Me TMSCH2MgCl (2 equiv.) F Ar · Asymmetric transfer hydrogenation reaction [Cobalt catalyzed Ar Heck reaction] F and isomerization reaction F · Miscellenious Ryoji Noyori Baran Group Meeting Masato Saito 10/3/20 Supervised Work (Ph. D.) Supervised Work (Post-doc) MeO MeO Li SMe COOEt COOEt O SMe 5 steps SMe O + O O 1 (20 mol%) N2 SMe OEt O 25 25 OH 22% ([α] ; +0.065 ) 50% ([α]D ; +0.644 ) Me O D obs obs MeO Hydrolysis Ph Ph Ph Ph MeO O + O CHO N Me O O Me Cu COOEt COOEt Li O OH O Me N 25 25 28% ([α]D obs ; +0.054 ) 28% ([α]D obs; +0.098 ) Ph 1 OH COOH Tetrahedron. Lett. 1966, 43, 5239. OH COO HO Ph3P Ni0 chemistry with highly strained molecules (±) Prostaglandin F CN 2α Ni HO Me COOMe COOMe NC NiII Tetrahedron. Lett. 1970, 11, 311. HO COOMe (12.5 mol %) COOMe R Benzene MeOOC 60 °C, 45h COOMe R CN 89% 11% Ni J. Am. Chem. Soc. 1971, 93, 4948. COOMe NC COOMe Me Me Me Me CN MeOOC COOMe COOMe MeOOC Ni Me COOMe Me Me NC 1 1,3 and ~30%D Me 2 COOMe 2,3 fission D D COOMe 4 ~30%D ~30% D Me 3 D Ni D D COOMe + R MeOOC Me Me Me Me [Hydrogen scrambling] Me Me > 90% D R D D COOMe Me Me Me COOMe NiII II 1,4 and D Ni 2,3 fission COOMe COOMe Tetrahedron Lett. 1978, 19, 4823. J. Am. Chem. Soc. 1971, 93, 5894. Ryoji Noyori Baran Group Meeting Masato Saito 10/3/20 Iron carbonyl metal complex C-Nucleotide synthesis O O O R1 R1 O 1) Bromination R1 R1 O O 1) Zn/Cu Fe2(CO)9 2) Elimination Br O R1 R1 O Fe2(CO)9 2) OsO4, H2O2 R2 Br Br Br O Br Br R2 3) protection R2 R2 Br Br O R2 R2 O Me Me Me O Me O O Me Me O Me Me O Me CF3COOOH Me Me O Me Me HN NH O OtBu Me Me O O N Me Me O Me HO Me N N O Me O Urea Me Me O Cyclization; 84% 47% 77% 36% O O 2nd Step; 64% 50% 63% 50% Me Me O HO OH 1) Ozonolysis O 2) Wittig reaction Me J. Am. Chem. Soc. 1971, 93, 1272. Me Thiourea Guanidine S NH2 BINOL derived aluminum hydride reagent O HN HN NH N NH O O HO HO O HO O O OH O O O H (S) R Al O OEt THF R HO OH –78 °C, 2h HO OH HO OH Li (S) (~ 3 equiv.) Chemistry of TMSOTf O TMSOTf (1 mol%) O O OH OH OH * O R OTMS O Al Li TMSO TMS TMS Me Me O DCM D O –78° Me H O R · Super mild reaction condition O O 75%, 82% ee 62%, 95% ee 68%, 71% ee · No equiblium between starting O O TMS TMS material and product, which enable + the kinetic controled protection J. Am. Chem. Soc. 1979, 101, 3129. · Applicable to the protection of ketone in the presence of aldehyde Tetrahedron, 1981, 37, 3899. Ryoji Noyori Baran Group Meeting Masato Saito 10/3/20 Prostaglandins Three component approach for the synthesis of Prostaglandins O Exhibit diverse pharmalogical properties. O More than 450 publications and 5000 1,4-addition O Trap the enolate R analogues have appeared up to 1982 R I O Me PGO H R Me HO Me HO PGO HO HO Difficulty of three component approach Cu O CuO I O MO MO Me O Li fast PGO 2 Me Me PGO PGO OGP PGO OGP PGO PGO J. Am. Chem. Soc. 1973, 95, 7788. Three component synthesis of Prostagladin Me O COOMe COOH O COOMe H HO O O O 1) Dehydroxylation Me 2) reduction Me Dehydro-PGE2 3) Deprotection HO Me OTHP 4) Hydrolysis OH HO THPO THPO HO PGE1 Tetrahedron Lett. 1982, 23, 5563. Cu Me (Bu P) x 4 O MeOOC Prostacyclin OTHP 1O O 2 Pd(PPh3)4 (10 mol%) O O Tetrahedron Lett. 1983, 24, 1187. tBuLi (2 equiv.), CuI (1equiv.) Introduction of Phosphine Me Me nBu P (2.6 equiv.) 4 ligand suppressed the HO enolization of opposite site and Me I Me reduce the use of chiral building O Me O OH block. Me O HO OTHP O (1equiv) OH Ph Ph H O P O O OMe Pyridinium tosylate 97% ee Rh Tetrahedron Lett. 1982, 23, 4057. HO OMe P Ph H O I Me O Ph O ClO O O H 4 I Me (S) Al O OEt O O 27%, 91% ee OH THF 65%, 94% ee HO 97%, 95% ee Li Tetrahedron Lett. 1987, 28, 4719. Ryoji Noyori Baran Group Meeting Masato Saito 10/3/20 Synthesis of BINAP Ph Ph t Me Me BuLi Ph recrystallization Br P Ph N Me Br Ph Br then Ph2PCl PPh 1 P then LAH PPh2 PPh2 OH 2 Pd Br PPh P PPh2 PPh2 OH neat, 300 °C THF, –95 °C 2 quant. Ph R; 39% >99% ee 78% Ph S; 36% >99% ee J .Am. Chem. Soc. , 1980, 102, 7932. Me BzO COOH Me O Ph 2 O Ph N Mg, then Ph2POCl P Ph recrystallization P Ph HSiCl3, Et3N Me Pd Cl BzO COOH P Ph P Ph 2 O Ph O Ph 1 (–) 2 J. Org. Chem 1986, 51, 629. Rh catalyzed hydrogenation of olefin Ru catalyzed hydrogenation Ph Ph Ph H OH 4 (< 1 mol %) OH 3 (1 mol %) Ph P 1 1 P H L R COOR H (4 atm) R COOR OMe R1 2 R1 2 Rh Ru L OMe P R2 NHBz EtOH, r.t. R2 NHBz P R2 R2 48h Ph H Ph Ph Ph ClO4 Me Me Me Me Me Me OH Me OH Me OH Me COOH COOH COOMe COOH 99%, 98% ee (from E olefin) 99%, 98% ee (from Z olefin) 96%, 92% ee (from E olefin) NHBz NHBz Me NHBz TBSO Me NHBz Me Me Me OH Me 99%, 99 % ee Me OH H from exo-olefin 96%, 96% ee 93%, 87% ee 97%, 98% ee 98%, 93% ee Me (From Z olefin) (From E olefin) (From Z olefin) NH using (R)-TolBINAP 99%, 99% ee (from E olefin) O J. Am. Chem. Soc. 1987, 109, 1597. J .Am. Chem. Soc. , 1980, 102, 7932. 4 (< 1 mol %) O OH OH O OH O H2 Me Me Me Me X X Cl 3, various condition R R Me SEt OEt Me OH Me OH OH OH O 93% ee (R)BINAP 97% ee O less than 70 % ee OH O O OH Me Me OMe Me Me NMe Chem. Lett. 1985, 14, 1007. 92 % ee 96% ee (R)BINAP 96% ee 2 99% ee J. Am. Chem. Soc. 1988, 110, 629. Ryoji Noyori Baran Group Meeting Masato Saito 10/3/20 Mechanism of Ru catalyzed reduction Ligand-Metal bifunctional catalysis Ar Ar P O OH Ci Hetero atom is required for 5 : amine : KOH = 1: 1 : 2 Ru this reduction Cl Me Me P H , alcohol 2 Ar Ar 5 H2N NH2 Phosphine Amine ee (%) (S)-BINAP (S,S)-DPEN 97% (S)-BINAP (R,R)-DPEN 14% DPEN Me OH MeO OH Me OH Me Me OMe Me Me NH2 NH (S)-BINAP/ (S)-TolBINAP/ (S)-XylBINAP/ 2 (S)-DAIPEN (S)-DAIPEN (S)-DAIPEN 90% ee 99% ee 95% ee DAIPEN Catalyst for Base-Free condition · Selective reduction of ketone BH3 O OH Ar Ar H (10 atm) 6 (0.2 mol%) H2 Ph 2 H (S)-BINAP/(S)-DAIPEN H (8 atm) P N 2 O (0.000001 mol%) OH O Me Me Ru i K2CO3 PrOH N P H Ph Me Me Me [without base] H MeOH Ar Ar H 99%, 97% ee 6 quant, 97% ee 0% OH OH O OH · Role of strong base O Me Me N Me Me Me Ar Ar Ar Ar H2 Strong base H2 P Cl P H 99%, 99% de 100%, 94% ee 95%, 99% ee N H2 N Ru Ru J. Am. Chem. Soc. 2002, 124, 6508.