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1 Vol. 9, o. 6 lefin Metathesis Features include: First Generation Grubbs Catalyst

2 2 Introduction Introduction Yves Chauvin obert. Grubbs ichard. Schrock erisson Chauvin 1971 Figure 2 1 Katz Schrock Grubbs Grubbs 5 CM CAMCM EM M CM ADMET [M] [M] William Sommer roduct Manager [M] eferences: (1) (a) Schrodi, Y.; ederson,. L. Aldrichimica Acta 2007, 40, 45. (b) Adv. Synth. Catal. 2007, 349, (lefi n Metathesis Special Issue). (c) Grubbs,.. Tetrahedron 2004, 60, (d) andbook of Metathesis; Grubbs,.., Ed.; Wiley-VC: Weinheim, 2003; Vols (e) Trnka, T. M.; Grubbs,.. Acc. Chem. es. 2001, 34, 18. (f ) Fürstner, A. Angew. Chem., Int. Ed. 2000, 39, (g) Schuster, M.; Blechert, S. Angew. Chem., Int. Ed. 1997, 36, (2) (a) erission, J. L.; Chauvin, Y. Makromol. Chem. 1971, 141, 161. (b) Chauvin, Y. Angew. Chem., Int. Ed. 2006, 45, (3) Katz T. J.; othchild,. J. Am. Chem. Soc. 1976, 98, (4) Schrock,.. et al. J. Am. Chem. Soc. 1990, 112, (5) guyen, S. T. et al. J. Am. Chem. Soc. 1992, 114, Figure 1 [M] Grubbs - M ADMET CM CM CAS MSDS sigma-aldrich.com/japan M, I aman, UV DF My rofile 1) Web language=japanese, 2) MSDS=English, 3) Country=Japan 3 Submit Web Tel: Fax: [email protected]

3 3 The Grubbs Catalysts Cy 3 Cy 3 Cy Grubbs 1 st generation catalyst Grubbs 2 nd generation catalyst Grubbs 3 rd generation catalyst Cy oveyda-grubbs 1 st generation catalyst oveyda-grubbs 2 nd generation catalyst Cy 3 Cy + 3 -BF iers-grubbs 1 st generation catalyst The Grubbs Catalysts Cy + 3 -BF 4 Cy 3 Cy 3 Cy iers-grubbs 2 nd generation catalyst Cy Discover ew Cross-Coupling Catalysts 2 d i-r Cy2 2 d Cy2 2 d i-r Cy2 i-r 2 d t-bu 2 i-r i-r i-r i-r i-r (from Xos) (from Sos) (from os) (from t-buxos) For more information, visit sigma-aldrich.com/buchwald sigma-aldrich.com Tel: Fax: [email protected]

4 4 ing-osing Metathesis ing-osing Metathesis C-C Villemin Grubbs 3 Grubbs Scheme 1 4 CM CM 2004 Wood Wood Scheme 2 2 mol Grubbs 25 mol Grubbs-oveyda 76 Grubbs oveyda-grubbs Grubbs iers iers Grubbs 0 Grubbs Scheme Grubbs 35 iers 50 M Scheme 4 7 IV Scheme 1 Scheme 2 Scheme 3 Et MB 76% Et Cy 3 Cy3 Cy 3 X (2-4 mol %) C66, 20 C X =, C 1-2 h 93% CF 3 X TBS 89% 85% Cy3 Cy3 (2 mol %) 2C=C2 C22, 25 C (25 mol %) toluene, Δ Cy3 BF4 (1 mol %) CD22, 0 C, 2h ingenol Et 98% Et >90% conversion 25% completion with Grubbs Catalyst (2 nd Generation) MB C C2 B(C 6F 5) 4 sigma-aldrich.com/japan Scheme 4 Tel: Fax: [email protected]

5 5 Stoltz Grubbs oveyda-grubbs CM Scheme 5 8 i-bu (5 mol %) benzene, 60 C i-bu 97% (+)-elatol = 22β - CM CM oveyda-grubbs Scheme 6 Donohoe CM oveyda-grubbs Grubbs TS TFA Scheme 7 Scheme (10 mol %) 1 toluene, 80 C 1 = TBS, 2 = Me, ; all combinations with 22α- and 22β- 1 =, 2 = Me, ; all combinations with 22α- and 22β- Scheme % ing-osing Metathesis Z - - Z - CM Grubbs 2 CM 72 Scheme 8 11 Et (10 mol %) toluene, 60 C then 1 eq TS 60% 3 C n-bu Cy 3 (10 mol %) toluene, reflux then 0.6 eq TFA 38% Scheme 7 Tel: Fax: [email protected]

6 6 ing-osing Metathesis CAM Schrock C-C Fürstner 14 CAM Scheme 9 eferences: (1) icolaou, K. C. et al. Angew. Chem., Int. Ed. 2005, 44, (2) (a) Villemin, D. Tetrahedron Lett. 1980, 21, (b) Tsuji, J. et al. Tetrahedron Lett. 1980, 21, (3) Fu, G. C. et al. J. Am. Chem. Soc. 1993, 115, (4) Fu, G. C. et al. J. Am. Chem. Soc. 1993, 115, (5) ickel, A. et al. J. Am. Chem. Soc. 2004, 126, (6) omero,. E. et al. Angew. Chem. Int. Ed. 2004, 43, (7) omero,. E. iers, W. E. J. Am. Chem. Soc. 2005, 127, (8) White, D. E. et al. J. Am. Chem. Soc. 2008, 130, 810. (9) Matsuya, Y. et al. rg. Lett. 2009, 11, (10) (a) Donohoe, T. J. et al. Eur. J. rg. Chem. 2005, (b) Donohoe, T. J. et al. Tetrahedron 2008, 64, 809. (c) Donohoe, T. J. et al. rg. Lett. 2006, 8, 543. (d) Donohoe, T. J. et al. Chem. Eur. J. 2008, 14, (11) Donohoe, T. J. et al. Angew. Chem. Int. Ed. 2008, 47, (12) Schrock,.. Chem. ev. 2002, 102, 145. (13) (a)fürstner, A. et al. Chem. Commun. 2005, (b) Schrock,.. et al. Adv. Synth. Catal. 2007, 349, 55. (14) Bindl, M. et al. J. Am. Chem. Soc. 2009, 131, Me TIS Et TS Et Et Me TIS Cy3 (7.5 mol %) C22, Δ Et TIS then TS TIS (85% yield over two steps) Me Me C2Me C 2Me Cy3 (15 mol %) toluene, Δ 72% ( )-(Z)-deoxypukalide Scheme 8 3Si Mo Si3 3Si (20 mol %) sigma-aldrich.com/japan Scheme 9 87% 54% Tel: Fax: [email protected]

7 7 Cross Metathesis Corey 3 Scheme 1 Cy3 Cy3 (10 mol %) C2C2, rt Me Me Me Me Cross Metathesis Grubbs o- - oveyda-grubbs 4 Scheme 2 Grubbs oveyda-grubbs 5 mol Grubbs owell β - α- -β - oveyda- Grubbs Grubbs 5 Scheme 3 6 Botta β Grubbs CuS Scheme 4 7 eferences: (1) Connon, S. J. et al. Angew. Chem. Int. Ed. 2003, 42, (2) Chatterjee, A. K. et al. J. Am. Chem. Soc. 2003, 125, (3) (a) Xiong, Z. et al. J. Am. Chem. Soc. 2000, 122, (b) Xiong, Z. et al. J. Am. Chem. Soc. 2000, 122, (4) Stewart, I. C. et al. rg. Lett. 2008, 10, 441. (5) Liang, Y.et al. Tetrahedron Lett. 2009, 50, (6) Diver, S. T. et al. Chem. ev. 2004, 104, (7) Castagnolo, D. et al. J. rg. Chem. 2009, 74, Scheme 1 Et Et Ac 89%, >20:1 dr Scheme 2 + Scheme Et Et (5 mol %) C22, Δ 91%, >20:1 dr Et (3 x 2 mol %) C22, Δ Cy3 (10 mol %) 2 eq. CuS 4 t-bu/2 1:1 μw, 80 C then, I 2 Bz Et Bz 98%, >20:1 dr MB Et 66%, 3:2 dr 85% E:Z = 1:1 Bz 51% 68% 39% 63% Scheme 4 Tel: Fax: [email protected]

8 8 ing-pening Metathesis olymerization M ing-pening Metathesis olymerization M M Ziegler atta M Grubbs M 2 M M M Grubbs Synthesis of ush-like olymers via M Cheng M - Cheng Grubbs DI Scheme 1 3 eferences: (1) (a) Ziegler,. et al. Angew. Chem. 1955, 67, 541.(b) atta, G. Angew. Chem. 1956, 68, 393. (2) guyen, S. T. et al. J. Am. Chem. Soc. 1992, 114, (3) Lu,. et al. J. Am. Chem. Soc., 2009, 131, TMS 1.0 eq Scheme eq (5 mol %) x TMS n brush-like polymer TF: C22 (9:1) y TMS x y polymerization of amino acid -carboxyanhydride CMU sigma-aldrich.com/japan + C F6 - For more information, visit sigma-aldrich.com/comu sigma-aldrich.com ATU Tel: Fax: Ethyl(hydroxyimino)cyanoacetate (XYMA) Bt, At C At [email protected]

9 9 Catalysts andbook of Metathesis, 3 volume set ISB Z EA 1 ea 69,600 2,6-Diiso pro pyl phenyl imido-neoph yl idene[( S )-( )-BIE] molybdenum(vi), 97.0% (C) [ ] C Mo 2 FW purum, ring-closing metathesis catalyst 3C 3C 3C 3C i-r t-bu Mo t-bu i-r C3 C MG-F 100 mg 53,500 Tris(triphenylsilyloxy)molybdenum nitride pyridine complex, 95% C Mo 2 3 Si 3 FW contains up to 10 wt. % toluene Si Mo Si Si mg 18,000 oveyda-grubbs Catalyst 1 st Generation [ ] C FW ,111,121 sigma-aldrich.com/materialicense MG 100 mg 10, MG 500 mg 41, G 2 g 124,100 Dichloro(3-methyl-2-butenylidene)bis(tricyclohexylphosphine) ruthenium(ii) [ ] C FW C C 3 C3 C3 Catalysts Grubbs Catalyst, 2 nd Generation [ ] C FW C 3C C3 C3 3C 6,111,121 7,329,758 sigma-aldrich.com/materialicense [email protected] Materia MG 100 mg 12, MG 500 mg 40, G 2 g 112,100 oveyda-grubbs Catalyst 2 nd Generation [ ] C FW C 3C C3 C3 3C 6,921,735 sigma-aldrich.com/materialicense MG 100 mg 13, MG 500 mg 54, G 2 g 159,000 3C C3 C3 C3 5,969,170 sigma-aldrich.com/materialicense G 1 g 21, G 5 g 74,500 Dichloro(3-methyl-2-butenylidene)bis(tricyclopentylphosphine) ruthenium(ii) [ ] C FW ,969,170 sigma-aldrich.com/materialicense G 1 g 21, G 5 g 69,700 Grubbs Catalyst, 1 st generation [ ] C FW C 3 C3 6,111,121 sigma-aldrich.com/materialicense G 1 g 20, G 5 g 74,000 Tel: Fax: [email protected]

10 10 [1,3-Bis(2-methylphenyl)-2-imidazolidinylidene]dichloro- (benzylidene) (tricyclohexylphosphine)ruthenium(ii) [ C FW C3 C3 [1,3-Bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene]dichloro- [3-(2-pyridinyl-κ )propylidene-κc]ruthenium(ii) [ ] 3C C3 C C C FW C C3 Catalysts 6,111,121 7,329,758 sigma-aldrich.com/materialicense [email protected] Materia MG 100 mg 11, MG 500 mg 42, G 2 g 137,400 [1,3-Bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene] dichloro(benzylidene)bis(3-bromopyridine)ruthenium(ii) C C FW C C 3 3C C3 C 3 11/094,102 sigma-aldrich.com/materialicense MG 100 mg 11, MG 500 mg 44, G 2 g 135,500 the nium Metathesis Catalysts Kit I sigma-aldrich. com/materialicense [email protected] Materia [email protected] 6,759,537 sigma-aldrich.com/materialicense MG 100 mg 10, MG 500 mg 43, G 2 g 130,800 [1,3-Bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene]dichloro- (3-methyl-2-butenylidene) (tricyclohexylphosphine)ruthenium(ii) C C C3 FW C C 3 3C 5,969,170 7,529,758 sigma-aldrich.com/materialicense [email protected] Materia MG 100 mg 8, MG 500 mg 31, G 2 g 98,700 C 3 C3 C 3 thenium Metathesis Catalysts Kit I Components Grubbs Catalyst, 1 st Generation (Aldrich ) 1 G Grubbs Catalyst, 2 nd Generation (Aldrich ) 100 MG oveyda-grubbs Catalyst 2 nd Generation (Aldrich ) 100 MG oveyda-grubbs Catalyst 1 st Generation (Aldrich ) 100 MG Dichloro(3-methyl-2-butenylidene)bis(tricyclohexylphosphine)ruthenium(II) (Aldrich ) 1 G Dichloro(3-methyl-2-butenylidene)bis(tricyclopentylphosphine)ruthenium(II) (Aldrich ) 1 G [1,3-Bis(2-methylphenyl)-2-imidazolidinylidene]dichloro(benzylidene) (tricyclohexylphosphine)ruthenium(ii) (Aldrich ) 100 MG [1,3-Bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene]dichloro(benzylidene)bis(3- bromopyridine)ruthenium(ii) (Aldrich ) 100 MG [1,3-Bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene]dichloro(3-methyl-2- butenylidene) (tricyclohexylphosphine)ruthenium(ii) (Aldrich ) 100 MG [1,3-Bis(2-methylphenyl)-2-imidazolidinylidene]dichloro(2- isopropoxyphenylmethylene)ruthenium(ii) (Aldrich ) 100 MG [1,3-Bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene]dichloro[3-(2-pyridinyl-κ ) propylidene-κ C ]ruthenium(ii) (Aldrich ) 100 MG KT 1 kit 133,800 sigma-aldrich.com/japan [1,3-Bis(2-methylphenyl)-2-imidazolidinylidene]dichloro- (2-isopropoxyphenylmethylene)ruthenium(II) C FW C3 Tel: Fax: C 3 6,921,735 sigma-aldrich.com/materialicense MG 100 mg 11, MG 500 mg 44, G 2 g 135,500 3C C3 [email protected]

11 11 Dichloro(tricyclohexylphosphine)[(tricyclohexylphosphoranyl)- methylidene]ruthenium tetrafluoroborate, 95% C B 2 F 4 2 FW BF4 - [1,3-Bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene]dichloro- [(tricyclohexylphosphoranyl)methylidene]ruthenium tetrafluoroborate, 95% [ ] C 40 60B 2F4 2 FW C C3 3C C 3 C3 3C F F B F F UTI artnership 7,354,140 Materia sigma-aldrich.com/materialicense [email protected] Materia info@ materia-inc.com MG 100 mg 6, MG 500 mg 26, G 2 g 79,000 UTI artnership 7,354,140 Materia sigma-aldrich.com/materialicense [email protected] Materia info@ materia-inc.com MG 100 mg 11, MG 500 mg 43, G 2 g 130,000 Catalysts TurboGrignards for al/mg Exchange of Aryl and eteroaryl Compounds Knochel-auser-Base for Selective Deprotonations FG Mg Li = Mg Li (TurboGrignard) FG = alkyl, alkenyl, ', C 2 ', C, 2, halogen C 3 3 C Mg Li FG Mg Li Mg Li 3 C 3 C C 3 C 3 Mg Li TF Sold in partnership with Selective 1,2-Additions La 3 /Li TF For more information, visit sigma-aldrich.com/metalations sigma-aldrich.com Tel: Fax: [email protected]

12 Chem roduct Central Substructure Search Building Blocks rganic Building Blocks eterocyclic Building Blocks Amino Acid Derivatives Unnatural Amino Acid Derivatives Monosaccharides ucleosides Chiral Building Blocks rganometallic eagents Boronic Acids and Derivatives Grignard eagents ieke and rganozinc eagents rganolithium rganosilicon rganotin rganoaluminum thers Synthetic eagents Coupling Lewis Acids C-C Bond Formation rganic Acids C-X Bond Formation (alogen) Inorganic Acids C-X Bond Formation (onhalogen) osphazene Bases rganic Bases xidation Inorganic Bases eduction Inorganic Salts rotection and Derivatization Dehydrating eagents adical Chemistry Compressed and ase Transfer Catalysts Liquified Gases Chelation/Complexation Compounds Asymmetric Synthesis Chiral Catalysts, Ligands, and eagents Chiral Auxiliaries Chiral Building Blocks Chiral esolution eagents Ionic Liquids Ammonium Choline Imidazolium osphonium yrazolium yridinium yrrolidinium Sulfonium Specialty Synthesis igh Throughput Synthesis Chemical Ligation eptide Synthesis Carbohydrate Synthesis ligonucleotide Synthesis Enzyme-Mediated Synthesis Fluorous Synthesis Supported Synthesis