Baran Group Meeting Hai Dao Shu Kobayashi 04/20/2013 1959 Born in Tokyo, Japan Publications 1983 B.Sc.; The University of Tokyo (UT); Prof. T. Mukaiyama >600 Publications (c.a 60 Reviews) 1988 Ph.D.; The University of Tokyo; Prof. T. Mukaiyama Science (1); JACS (66); Angew (34) 1987 Assistant Professor; Tokyo University of Science 1991 Lecturer; Tokyo University of Science Web of Knowledge data(03/2013): 1992 Associate Professor; Tokyo University of Science average citations: 52.32 1998 Professor; UT; Graduate School of Pharmaceutical Sciences H-index: 86 2007 Professor; UT; Department of Chemistry, School of Science Most cited works: Important Honors and Awards Chem. Rev. 1999, 1069: 1061 times 1991 The Chemical Society of Japan Award for Young Chemists Synlett. 1994, 689: 601 times 1997 Springer Award in Organometallic Chemistry 2001 IBM Science Award Major Research Interests: 2002 Nagoya Silver Medal Novel Chiral catalysis 2005 Mitsui Chemical Catalysis Science Award Organic reaction in water 2006 Arthur C. Cope Scholar Awards Polymer supported catalysis Prof. Shu Kobayashi 2006 C.S. Hamilton Award Organic reaction in microreactors Doctoral years at UT with Prof. Mukaiyama OBn OBn Lewis acid catalysts: TrClO4; TrCl-SnCl2, O + TrClO4 (stoichiometric) BnO O O 3β-Cholestanol BnO O SbCl4-Sn(OTf)2; SnCl4-Sn(OTf)2 BnO BnO (Tr = Ph3C) O Cholestanyl OBn OBn − for various catalytic C−C bond formations: CH2Br Aldol reactions, Michael Reaction... His first publication Chem. Lett. 1984, 907. N Sn(OTf)2, TBAF, N Me Among the first examples of asymmetric OTMS (stoichiometric) OH O CHO + aldol reactions between prochiral silyl Ph SEt DCM, -78 oC; 78%, 82% ee Ph SEt enol ethers and prochiral aldehydes His first asymmetric reaction Chem. Lett. 1989, 297. JACS, 1991, 4247. First Independent publication O Lanthanide trifluoromethanesulfonates OSiMe3 (CH O)aq, THF 2 as stable Lewis acids in aqueous Ph OH Ph Yb(OTf) (1 mol%) media. Recovery and reuse of catalysts 3 Me 90% from aqueous layer. Chem. Lett. 1991, 2187. Baran Group Meeting Hai Dao Shu Kobayashi 04/20/2013 OH Part 1. Chiral Catalysis HO OSiMe Chiral Lewis Acid Catalysis for Activation of Electrophiles 3 catalyst (10 mol%) + NH O N OMe Tin Catalyst: (CLAC synthesis: chiral Lewis acids controlled synthesis) NMI, DCM, −45 oC Ph OMe Ph H 70%, 87% ee Sn(OTf)2 OH O OH O OSiMe3 chiral amine NMI = N-methylimidazole (sub-stoichiometric) 1. MeI, K CO RCHO + + 2 3 R SEt R SEt Br Br 2. CAN TBSO SEt Bu2Sn(OAc)2 OTBS OTBS DCM, −78 oC 83% chiral amine = L1 chiral amine = L2 O O (stoichiometric) 86%, 98% ee Zr NH O 82%, 98% ee O O 2 syn:anti = 98:2 syn:anti = 99:1 Ph OMe N Br Br N R Me catalyst J. Am. Chem. Soc. 1997, 7153. L1 O H N Sn N Strecker reaction (dinuclear cat.): Angew. Chem. Int. Ed. 1998, 3186 Sn N N N Hetero D-A reaction: J. Am. Chem. Soc. 1999, 4220; J. Am. Chem. Soc. N Me O H Me 2003, 3793. Me Aldol reaction: J. Am. Chem. Soc. 2002, 3292. L2 R [3+2] cycloadition: J. Am. Chem. Soc. 2004, 11279. Isolable, air-stable, storable Zr catalyst: J. Am. Chem. Soc. 2006, 11232. J. Am. Chem. Soc. 1994, 9805 HO 100 gram-scale synthesis of Vancomycin's building block using Zirconium OH O O OH catalyst: Adv. Synth. Catal. 2006, 1831. H3C(H2C)9 O CO2H Yb catalysts for (aza)-Diels-Alder reactions: Synlett, 1994, 689. OH Nb catalysts for stereoselective ring opening of meso-epoxides and meso- khafrefungin aziridines: J. Am. Chem. Soc. 2007, 8103. application to enantioselective total synthesis of D-erythro-Sphingosine (Tetrahedron Lett. 1994, 9573.); sphingofungin B (synlett 1996, 672.); Copper Catalysts khafrefungin (J. Am. Chem. Soc. 2001, 1372)... O Nu O X Ph Ph Zirconium Catalysts for Addition to Imines R R N Challenges in Lewis acids catalyzed enantioselective reaction with imines Cu cat. N NH HN X = OR; NHR - Lewis acids are trapped by the basic nitrogen atoms of EtO * R R Sc, Y, EtO CuL nucleophiles the starting materials/products => difficult to make it catalytic Ln, Zr, Nb O O diamine ligands N-acyliminoesters O - Lewis acid - imine interaction is not regid => difficult to H Mannich type: Org. Lett. 2002, 143; make it enantioselective O n J. Am. Chem. Soc. 2003, 2507; C11H23 NH OH LA J. Am. Chem. Soc. 2004, 6558. R LA LA R HO Aldol-type: Angew. Chem. Int. Ed. 2004, 3258; Ph N N N Allylation: Angew. Chem. Int. Ed. 2006, 1615. Review: Acc. Chem. Res. 2008, 292. HPA-12 R1 R2 R1 R2 R1 R2 (3 steps, 82.9 % yield) Baran Group Meeting Hai Dao Shu Kobayashi 04/20/2013 O O Activation of Nucleophiles: "Catalytic Carbanion Reaction" Ca(OAr)2 (10 mol%) O O ligand (10 mol%) NO2 + MeO OMe + - OML* Ph O M B BH OH O MeO OMe toluene, −20 oC 1 NO2 H + R CHO 80%, 96% ee Ph OR OR R1 * OR BH M+B- + - Pyridinebisoxazoline (Pybox) Ligands: direct aldol reaction: M B = catalyst O N - neutral coordinative ligands: stronger Ph Ph Alkaline Earth Metal Catalysts N N Bronsted bacicity of the complexes Ca - three coordination number => more Ph Ph RO OR rigid complexes = high ee Pybox-calcium alkoxide complexes Angew. Chem. Int. Ed. 2009, 9117. Mannich reaction: J. Org. Chem. 2010, 963. Michael reaction: J. Am. Chem. Soc. 2010, 7890. Strontium Catalysis: J. Am. Chem. Soc. 2008, 2430. Picture from Harder, S. Chem. Rev. 2010, 3852. Barium Catalysis: J. Am. Chem. Soc. 2006, 8704. Alkaline Earth Metal Compounds: Review for Alkaline Earth Metal Catalysis: Acc. Chem. Res. 2010, 58. - low electronegativity = stronger Bronsted basicity of counter anion => Silver Catalysis: silver amide with phosphine ligand for [3+2] cycloadditions: based-catalyzed reactions Angew. Chem. Int. Ed. 2011, 4893. J. Am. Chem. Soc. 2012, 20049. - Highl nucleophilicity (as of group 1) - Significant Lewis Acidity (as of group 3) => substrate binding for high ee Modification of Nucleophiles - Large ionic radius (Ca2+, 1.00Å; Sr2+, 1.18Å; Ba2+, 1.35Å; ) => large number of coordination sites => challenges in chiral modification for high ee Fluorenone Schiff Base O R R Asymmetric Calcium Catalysis N N i O O Ca(O Pr)2 (10 mol%) Ph N base O ligand (10 mol%) Ph N OMe + Ph N OMe OMe o Ph OMe −30 C, THF Ph COOMe Ph quant., 83% ee Schiff base * N fluorenone imines 14π-e aromatic anions O O low pKa N Ca O Mannich-type reaction: (R = COOMe) Angew. Chem. Int. Ed. 2008, 5613. N N Ph N (R = alkyl, aryl) J. Am. Chem. Soc. 2010, 3244. OMe Ph Ph a Box ligand O O O O Ph Sulfonylimidates as Nucleophiles N N N N * Ca Ca N Ca(OR)2 Ph Ph Ph Ph Mannich-type reaction, Michael-type reaction: OR OR N Ca O (DBU) J. Am. Chem. Soc. 2008, 1804. (alkaline earth Ph N base). Angew. Chem. Int. Ed. 2009, 6041. Box-calcium alkoxide complexes OMe (organosuperbase). Angew. Chem. Int. Ed. 2012, Bisoxazoline (Box) Ligands: Ph 9525. Tsuji-Trost Reaction: Chem. Commun. 2008, 6354. pros: covalence/ionic bond = strong interaction Review: Chem. Eur. J. 2009, 10694. cons: decrease in Bronsted basicity of chiral calcium enolate the complexes J. Am. Chem. Soc. 2007, 5364 picture from Chem. Eur. J. 2009, 10694. Baran Group Meeting Hai Dao Shu Kobayashi 04/20/2013 Other Chiral Catalysis - Allylation Part 2. Organic Reaction in Aqueous Media Neutral Coordinate Organocatalysts (NCOs) Initial Finding O S Ln(OTf)3 and Sc(OTf)3 = Stable Lewis Acids in Aqueous Media Me ptolyl NHBz NHBz HN Aldol reaction N (3 equiv.) OSiMe3 OH O + SiCl3 Yb(OTf)3 (10 mol%) DCM, 78 oC Ph Ph H − PhCHO + Ph 73%, 93% ee THF-H2O (4:1) J. Am. Chem. Soc. 2003, 6610. Adv. Synth. Catal. 2004, 1023. 91% - HOTf (various pH): low conversions Both Yb and water Enantioselective Transfer Aminoallylation - In THF only or water only: low conversions are important OH Mannich-type reaction EtOH NH3 + OMe Yb(OTf)3 (10 mol%) O NH2 p HOOC OH rt, 5min OOC HCHO + ClC6H4NH2 + O p 72%, 87% ee Me THF-H2O (9:1) ClC6H4 Me 92% B(pin) J. Chem. Soc., Chem. Commun., 1995, 1379. NH3 first ex. in aqueous media: NH NH Michael reaction, allylation, Diels-Alder reaction: Synlett, 1994, 689 O COO COO O O Interesting finding: Cu(OTf) = Excellent Catalyst for Aldol Reaction and Allylation in Aqueous Media O 2 J. Am. Chem. Soc. 2006, 11038. Chem. Lett. 1997, 959. How about other metals? Transmetallation(TM) (In, Zn, Ag) Systematic Studies of Various Lewis Acid Catalysis in Water I NHBz In I(5 mol%) NHBz * HN Sc N B(pin) L (5 mol%) + 4.3 hydrolysis constant (pKh) PhMe, MeOH, 0 oC 7 Ph H Ph 4.8 10 inner-sphere water ligands 99%, 96% ee exchange rate constant (WERC) base CN L*−InI B(pin) O O Ph Ph N HN L*−InI transmetallation Ph Ph L* E L*−In the active nucleophile Angew. Chem. Int. Ed. 2010, 1838. Acc. Chem. Res. 2012, 1331. 6 -1 -1 pKh = 4.3−10.08; WERC > 3.2 10 M s J. Am. Chem. Soc. 1998, 8287. Baran Group Meeting Hai Dao Shu Kobayashi 04/20/2013 Catalytic Asymmetric Reaction in Aqueous Media Catalyzed by Ln(OTf) Hydrolysis constant 3 + + 2 - large ionic radius, large number of coordination sites = challenging 3+ + + [M(OH) ] [H ] M + 2H2O M(OH)2 + 2H Kh = [M2+] Challenges in designing a chiral ligand for Ln(OTf)3 : pKh = -logKh - too strong coordinating ability => reduction of Lewis acidity WERC: measured by NMR, sound absorption, or multidentate legand method - too weak coordinating ability => low ee due to achiral free L.A pathways Martell, A.