D.A. Evans Directed Reactions: An Introduction Chem 206 Stereochemical control elements for all reactions Heteroatom-directed Reactions Steric Electronic Factors Mechanism-based(HO&C=C must be allylic Stereoelectronic Considerations I Associative Substrate-Reagent Interactions ■ Steric control: A-B disfavored favored product A-B vored Nonbonding Interactions disfavor the syn diastereoface Simmons-Smith Reaction Directed Reactions Hydroxyl-directed Reactions Review. Hoveyda, Evans, Fu Chem. Reviews 1993, 93, 1307 tio 92: 8 Associative Substrate-Reagent Interactions A-B A-B -BUOoH Sharpless vo(acac)2 JACS95,6136,(1 favored product disfavored Noncovalent Interaction favors the syn diastereoface A-B Directed Oxidations OH JACS 91, 6892. (1969) ratio 90: 10 Directed Reductions Hydrogenation Hydride reduction AcS105,1072(1983) Directed c-c Bond constructions Acs1063866(1984X R A B A B X A B R B A X B A A B C C H H H C C H H H A B A B A B OH OH R R OH MCPBA Et2Zn Cl CO3H t-BuOOH Et2Zn CH2I2 OH Me CH2 I2 R O CH2 R O Zn CH2 I R H OH O Me OH CH2 OH R R O CH2 OH R (Ir+ ) Stork JACS 105, 1072 (1983) (Rh+ ) Evans JACS 106, 3866 (1984) M(I) + H2 Mechanism-based: (HO & C=C must be allylic) Simmons-Smith Reaction Claisen Rearrangement [3,3] via Reagent Ligation Heteroatom-directed Reactions ratio 90 : 10 Winstein JACS 91, 6892, (1969) Henbest J. Chem. Soc. 1958, (1957) Sharpless VO(acac) JACS 95, 6136, (1973) 2 ratio 98 : 2 ratio 92 : 8 Hydroxyl-directed Reactions Directed C–C Bond Constructions Directed Reductions Hydrogenation Hydride reduction Epoxidation Hydroboration Directed Oxidations Agenda Directed Reactions favored disfavored favored product ■ Associative Substrate-Reagent Interactions Noncovalent Interaction favors the syn diastereoface Review: Hoveyda, Evans, Fu Chem. Reviews 1993, 93, 1307 ■ Steric control: Stereochemical Control Elements for all reactions ■ Steric & Electronic Factors ■ Stereoelectronic Considerations ■ Associative Substrate-Reagent Interactions favored product favored disfavored Nonbonding Interactions disfavor the syn diastereoface D. A. Evans Directed Reactions: An Introduction Chem 206