Lewis Base Catalysis: the Aldol Reaction (Scott Denmark) Tom Blaisdell Friday, January 17th 2014 Topic Talk Scott E. Denmark 1975 -‐ S.B. in Chemistry – MIT (Richard H. Holm and Daniel S. Kemp) 1980 -‐ D.Sc in Chemistry -‐ ETH Zurich (Albert Eschenmoser) 1980 -‐ Assistant Professor -‐ University of Illinois 1986 -‐ Associate Professor -‐ University of Illinois 1987 -‐ Professor -‐ University of Illinois 1991 -‐ Reynold C. Fuson Professor of Chemistry -‐ UIUC Main Research Interests: •  Lewis Base Activation of Lewis Acids •  Palladium-‐Catalyzed Cross-‐Coupling of Organosilicon Compounds •  Tandem Cycloaddition Chemistry of Nitroalkenes •  Asymmetric Phase Transfer Catalysis/Chemoinformatics Aldol Chemistry: Mid-‐1990s to mid-‐2000s The Aldol Reaction •  One of the most ubiquitous reactions in organic chemistry •  Provides numerous selectivity challenges (chemo-‐, site-‐, enantio-‐ and diastereoselectivity) •  “…continues to serve as a platform for the demonstration of conceptual advances in the ^ield [of organic chemistry]” The Aldol Reaction OTMS O OH H TiCl 4 82% Ph 3:1 syn:anti PhCHO Mukiyama, T. Chem. Lett. 1973, 9, 1011 O OB(nBu)2 O O OH Me PhCHO N N Ph >500:1 syn:anti O O Me Evans, D. J. Am. Chem. Soc. 1981, 103, 2127 Formation of Enoxyborinates and Enoxysilanes OB(nBu) OTMS 2 R R 1 1 R R 2 2 Enoxyborinates Enoxysilanes •  Most stable and widely used enolates •  Allowed for identi^ication of which carbonyl was acting as the nucleophile (site and chemoselectivity) •  Both have unique reactivity (diastereo-‐ and enantioselectivity) Enoxyborinates •  Coordination of the aldehyde to the boron is necessary •  Proceeds through a predictable chair-‐like transition state PhCHO OB(nBu) O OH 2 CH Cl 2 2 Me 77% yield Et Et Ph Et O >97:3 syn/anti H 2 Me -78-0 °C >97:3 Z/E Et nBu H B O nBu H O Ph Me nHex B O PhCHO O OH CH Cl 2 2 Ph 4:96 syn/anti Et O 2 -78-0 °C cPent H B O nHex O Ph H Evans, D. J. Am. Chem. Soc. 1981, 103, 3099-‐3111 Enoxysilanes •  Unlike boron, the silicon atom is not lewis acidic enough to bind and activate the aldehyde. •  Cannot form a six-‐membered transition state •  Requires a secondary Lewis acid for activation and therefore undergo an open transition state PhCHO OTMS O OH BF -OEt 3 2 Me 62% yield Et Et Ph CH Cl 60:40 syn/anti H 2 2 Me -78 °C >99:1 Z/E OTMS PhCHO O OH SnCl 2 82% yield Ph 70:30 anti/syn TMSCl CH Cl 2 2 -78 °C Heathcock, C. Tetrahedron Le7. 1984, 25, 5973-‐5976 Mukiyama, T. Chem. Le7., 1987, 463-‐466 Enoxysilanes OTMS NH PhChO O OTMS NH Sn(OTf)2 (20 mol %) EtS + EtS Ph EtCN Me Me 77% 92:8 syn/anti 20 mol % 95:5 e.r. Ph O CO H OTMS 2 O OTMS O O PhChO Me + nBu nBu Ph O O EtCN Me B H 97% 20 mol % 93:7 syn/anti 97:3 e.r. Mukiyama, T. Chem. Le7., 1990, 1455-‐1458 Yamamoto. J. Am. Chem. Soc. 1991, 113, 1041-‐1042 Nelson, Tetrahedron Asymmetry, 1998, 9, 357-‐389 Denmark’s Approach •  Combining the inherient properties of both enoxyborinates and enoxysilanes –  Enoxyborinates: Predictable six-‐membered TS to control diasteroselectivity –  Enoxysilanes: Able to establish asymmetric control 1.  Enoxysilacyclobutanes Si O tBu R Me 2.  Lewis base catalysis as a means of activating the metal center LB* ML n O R Me

Lewis Base Catalysis: the Aldol Reaction (Scott Denmark) PDF

45 Pages

2014

3 MB

English

by Thomas Blaisdell

Checking for file health...

Preview Lewis Base Catalysis: the Aldol Reaction (Scott Denmark)

Lewis Base Catalysis: the Aldol Reaction (Scott Denmark) Tom Blaisdell Friday, January 17th 2014 Topic Talk Scott E. Denmark 1975 -‐ S.B. in Chemistry – MIT (Richard H. Holm and Daniel S. Kemp) 1980 -‐ D.Sc in Chemistry -‐ ETH Zurich (Albert Eschenmoser) 1980 -‐ Assistant Professor -‐ University of Illinois 1986 -‐ Associate Professor -‐ University of Illinois 1987 -‐ Professor -‐ University of Illinois 1991 -‐ Reynold C. Fuson Professor of Chemistry -‐ UIUC Main Research Interests: •  Lewis Base Activation of Lewis Acids •  Palladium-‐Catalyzed Cross-‐Coupling of Organosilicon Compounds •  Tandem Cycloaddition Chemistry of Nitroalkenes •  Asymmetric Phase Transfer Catalysis/Chemoinformatics Aldol Chemistry: Mid-‐1990s to mid-‐2000s The Aldol Reaction •  One of the most ubiquitous reactions in organic chemistry •  Provides numerous selectivity challenges (chemo-‐, site-‐, enantio-‐ and diastereoselectivity) •  “…continues to serve as a platform for the demonstration of conceptual advances in the ^ield [of organic chemistry]” The Aldol Reaction OTMS O OH H TiCl 4 82% Ph 3:1 syn:anti PhCHO Mukiyama, T. Chem. Lett. 1973, 9, 1011 O OB(nBu)2 O O OH Me PhCHO N N Ph >500:1 syn:anti O O Me Evans, D. J. Am. Chem. Soc. 1981, 103, 2127 Formation of Enoxyborinates and Enoxysilanes OB(nBu) OTMS 2 R R 1 1 R R 2 2 Enoxyborinates Enoxysilanes •  Most stable and widely used enolates •  Allowed for identi^ication of which carbonyl was acting as the nucleophile (site and chemoselectivity) •  Both have unique reactivity (diastereo-‐ and enantioselectivity) Enoxyborinates •  Coordination of the aldehyde to the boron is necessary •  Proceeds through a predictable chair-‐like transition state PhCHO OB(nBu) O OH 2 CH Cl 2 2 Me 77% yield Et Et Ph Et O >97:3 syn/anti H 2 Me -78-0 °C >97:3 Z/E Et nBu H B O nBu H O Ph Me nHex B O PhCHO O OH CH Cl 2 2 Ph 4:96 syn/anti Et O 2 -78-0 °C cPent H B O nHex O Ph H Evans, D. J. Am. Chem. Soc. 1981, 103, 3099-‐3111 Enoxysilanes •  Unlike boron, the silicon atom is not lewis acidic enough to bind and activate the aldehyde. •  Cannot form a six-‐membered transition state •  Requires a secondary Lewis acid for activation and therefore undergo an open transition state PhCHO OTMS O OH BF -OEt 3 2 Me 62% yield Et Et Ph CH Cl 60:40 syn/anti H 2 2 Me -78 °C >99:1 Z/E OTMS PhCHO O OH SnCl 2 82% yield Ph 70:30 anti/syn TMSCl CH Cl 2 2 -78 °C Heathcock, C. Tetrahedron Le7. 1984, 25, 5973-‐5976 Mukiyama, T. Chem. Le7., 1987, 463-‐466 Enoxysilanes OTMS NH PhChO O OTMS NH Sn(OTf)2 (20 mol %) EtS + EtS Ph EtCN Me Me 77% 92:8 syn/anti 20 mol % 95:5 e.r. Ph O CO H OTMS 2 O OTMS O O PhChO Me + nBu nBu Ph O O EtCN Me B H 97% 20 mol % 93:7 syn/anti 97:3 e.r. Mukiyama, T. Chem. Le7., 1990, 1455-‐1458 Yamamoto. J. Am. Chem. Soc. 1991, 113, 1041-‐1042 Nelson, Tetrahedron Asymmetry, 1998, 9, 357-‐389 Denmark’s Approach •  Combining the inherient properties of both enoxyborinates and enoxysilanes –  Enoxyborinates: Predictable six-‐membered TS to control diasteroselectivity –  Enoxysilanes: Able to establish asymmetric control 1.  Enoxysilacyclobutanes Si O tBu R Me 2.  Lewis base catalysis as a means of activating the metal center LB* ML n O R Me

See more

The list of books you might like

Most books are stored in the elastic cloud where traffic is expensive. For this reason, we have a limit on daily download.