D.A. Evans Conformational Analysis: Part-4 Chem 206 Other Reading Material http://www.courses.fasharvardedu/-chem206/ The Curtin-Hammett Principle Chemistry 206 J I. Seeman, J. Chem. Ed. 1986, 63, 42-48 Advanced Organic Chemistry J 1. Seeman Chem Rev. 1983. 83. 83-134 Leading References Eiel,p.647-655 Lecture Number 7 Carey& Sundberg, Part A, CH 4, pp 187-250 Conformational Analysis-4 a Problems of the Day:(To be discussed) Conformational Analysis of C6 >Cg Rings continued Predict the stereochemical outcome of this reaction. The Transition State torsional effects diastereoselection is 99: 1 Curtin-Hammett Principle mCPBA a Reading Assignment for week Eliel& Wilen, Stereochemistry of Carbon Compounds Chapter 11 (on reserve in CCB library Martinelli et al. Tett. Lett. 1989. 30. 3935 A. Carey Sundberg: Part A; Chapter 4 Study Descrption of Reaction Mechanisms Rationalizethe stereochemical outcome of this reaction K.Houk, Science.1986,231,1108-1117 Theory& Modeling of Stereoselective Organic Reactions(Handout) I COmE LiNE eo、coMe J I Seeman, chem Ed. 1986. 63. 42-48 The Curtin-Hammett Principle( Handout Matthew d shair October 2. 2002 Ladner, et al. Angew. Chemie, Int. Ed 1982, 21, 449-450
http://www.courses.fas.harvard.edu/~chem206/ J. I. Seeman, J. Chem. Ed. 1986, 63, 42-48 The Curtin-Hammett Principle (Handout) O Me O Me Me CO2Me N Ph O H LiNR2 Me-I N Ph O O H O Me O Me Me CO2Me Me D. A. Evans Chem 206 Matthew D. Shair Wednesday, October 2, 2002 ■ Reading Assignment for week A. Carey & Sundberg: Part A; Chapter 4 "Study & Descrption of Reaction Mechanisms" Conformational Analysis: Part–4 Chemistry 206 Advanced Organic Chemistry Lecture Number 7 Conformational Analysis-4 ■ Problems of the Day: (To be discussed) K. Houk, Science. 1986, 231, 1108-1117 Theory & Modeling of Stereoselective Organic Reactions (Handout) ■ Conformational Analysis of C6 ® C8 Rings continued ■ Transition State Torsional Effects ■ Curtin–Hammett Principle Leading References: The Curtin-Hammett Principle J. I. Seeman, J. Chem. Ed. 1986, 63, 42-48. J. I. Seeman, Chem Rev. 1983, 83, 83-134. Eliel, pp. 647-655 Carey & Sundberg,Part A, CH 4, pp 187-250 ■ Other Reading Material mCPBA Martinelli, et.al. Tett. Lett. 1989, 30, 3935 Predict the stereochemical outcome of this reaction. The diastereoselection is 99:1 Rationalizethe stereochemical outcome of this reaction. Ladner, et.al. Angew. Chemie, Int. Ed 1982, 21, 449-450 Eliel & Wilen, Stereochemistry of Carbon Compounds" Chapter 11 (on reserve in CCB library) diastereoselection is 8:1
D.A. Evans Ground state Torsional effects Chem 206 Torsional Effects Relevant Orbital Interactions: Torsional Strain: the resistance to rotation about a bond Torsional energy: the energy required to obtain rotation about a bond Torsional Angle: also known as dihedral angle Torsional steering: Stereoselectivity originating from transition stat torsional energy considerations GC-H& T electrons are C-H's properly aligned for T* overlap AG =+3 kcal mol destabilizing Dorigo, A E Pratt, D W; Houk, K N. JACS 1987, 109, 6591-6600 Conformational Preferences: Acetaldehyde Torsional Strain(Pitzer Strain): Ethane The eclipsed conformation(conformation A)is preferred Polarization of the carbonyl decreases the 4 electron destabilizing Houk. JACS 5,59805988 +2.0 kcal/mol eclipsed Conformational Preferences conformation 1-Butene(X= CH2); Propanal (X=O) Wiberg K B. Martin, E.J. Amer. Chem. Soc. 1985, 107, 5035-5041 A M H X+Me B See Lecture 5 for previous discussion Conformation A is preferred. There is little steric repulsion between the
Torsional Angle: also known as dihedral angle H H H H H O H Me X H H C C H H H H C C H H H H H H C C H H H C C H H H H H O H H H H H H X H H H Me H H B A B C H H H CH2 CH2 H A B A H C H H H D. A. Evans Ground State Torsional Effects Chem 206 Torsional Strain: the resistance to rotation about a bond Torsional energy: the energy required to obtain rotation about a bond Torsional steering: Stereoselectivity originating from transition state torsional energy considerations DG = +3 kcal mol-1 Torsional Strain (Pitzer Strain): Ethane staggered eclipsed Relevant Orbital Interactions: Dorigo, A. E.; Pratt, D. W.; Houk, K. N. JACS 1987, 109, 6591-6600. Wiberg K. B.; Martin, E. J. Amer. Chem. Soc. 1985, 107, 5035-5041. s C–H's properly aligned for p* overlap hence better delocalization s C–H & p electrons are destabilizing Conformational Preferences: Acetaldehyde The eclipsed conformation (conformation A) is preferred. Polarization of the carbonyl decreases the 4 electron destabilizing Rotational barrier: 1.14 kcal/mol Houk, JACS 1983, 105, 5980-5988. Conformational Preferences 1-Butene (X = CH2); Propanal (X = O) Conformation A is preferred. There is little steric repulsion between the methyl and the X-group in conformation A. Torsional Effects eclipsed conformation staggered conformation +2.0 kcal/mol See Lecture 5 for previous discussion
D.A. Evans Transition State Torsional Effects According to Houk Chem 206 Houk: Torsional effects in transition states are more important than in ground states H Transition states H H-radical and H-anion: antiperiplanar o*C-R orbital stabilized the ts H illustrated for Nu additio H2C=C-+H H2C R C-RL C-RL 0°30°60°90°120 +16 Forming bond Same trends are observed for H+ addition Forming bond Houk, Science1981,231,1108-1117 "The Theory and Modeling of Stereoselective Organic Reactions 2 Carmol Transition state a*C-RL 53 N 0°30°60°90°120 Houk,JACS1981,103,2438 Ground state F*C-RL Houk,JACs1982,104,7162 RL
D. A. Evans Transition State Torsional Effects According to Houk Chem 206 H2C C H* H2C C H* H2C C H* 60° 90° 0° 120° 30° 60° 90° 120° 2 Kcalmol-1 +4.7 0 0 H 0 H H +1.6 H H H 0° H 30° H H +5.3 +2.4 no H* Transition states Houk, JACS 1981, 103, 2438 Houk: "Torsional effects in transition states are more important than in ground states" C Nu C RL H-radical and H-anion: antiperiplanar s*C–R orbital stabilized the TS illustrated for Nu addition Houk, Science 1981, 231, 1108-1117 "The Theory and Modeling of Stereoselective Organic Reactions" Same trends are observed for H+ addition sC-Nu s*C-RL sC-Nu homo s*C-RL lumo Forming bond Forming bond Houk, JACS 1982, 104, 7162 H H H C C H H H RL H H Nu sC-Nu s*C-RL Transition state C R H RL H H Nu sC-Nu s*C-RL Ground state H - H • H +
D.A. Evans Transition State Torsional Effects: Olefin Additions Chem 206 Olefin Addition Reactions: Case one Olefin Addition Reactions: Case two How do we account for the high exo selectivities in addition How do we account for the high selectilvities in the oxidation of ctions to norbornene? the indicated olefin? exo Highly exo selective for electrophilic, Oso nucleophilic and cycloaddition reactions mCPBA Rate enhancement due to strain ndo 98:2 diastereoselectivity diastereoselectivity The Controversy over origin of high exoselectivities Steric effects Nitrogen protecting group does not affect selectivities Least nuclear motion A Orbital distortion Schleyer: torsional steering Favored Schleyer, P. R.J. Amer. Chem. Soc. 1967, 89, 701 Martinelli et al. Tett. Lett. 1989. 30. 3935 Addition from exo face avoids eclipsing A &B hydrogens Addition from indicated olefin face avoids eclipsing a&BHs tter hy perconjugative stabilization of transition state) (better hyperconjugative stabilization of transition state Martinelli has carried out further studies on related structures
Steric effects Least nuclear motion Orbital distortion Nitrogen protecting group does not affect selectivities H H N Ph O OH OH H OsO4 N Ph O H A B A N Ph O O H B D. A. Evans Transition State Torsional Effects: Olefin Additions Chem 206 ■ Olefin Addition Reactions: Case one How do we account for the high exo selectivities in addition reactions to norbornene? exo endo Highly exo selective for electrophilic, nucleophilic and cycloaddition reactions The Controversy over origin of high exoselectivities Schleyer: torsional steering Rate enhancement due to strain Schleyer, P. R. J. Amer. Chem. Soc. 1967, 89, 701. Addition from exo face avoids eclipsing A & B hydrogens (better hyperconjugative stabilization of transition state) 98 : 2 diastereoselectivity 99 : 1 diastereoselectivity Martinelli, et.al. Tett. Lett. 1989, 30, 3935 mCPBA ■ Olefin Addition Reactions: Case two Favored Addition from indicated olefin face avoids eclipsing A & B H's (better hyperconjugative stabilization of transition state) How do we account for the high selectilvities in the oxidation of the indicated olefin? Martinelli has carried out further studies on related structures
D. A. Evans Transition State Torsional Effects: Olefin Additions Chem 206 Martinelli. Torsional steering important in selectivity mCPBA 99: 1 diastereoselectivity mCPBA 50: 50 diastereoselectivity Authors propose that diastereoselection controlled by TS torsional effects Martinelli& Houk, J. Org. Chem. 1994, 59, 2204
63° 62° 74° 40° major Me O H Me O O H D. A. Evans Transition State Torsional Effects: Olefin Additions Chem 206 Martinelli: Torsional steering important in selectivity 99 : 1 diastereoselectivity 50 : 50 diastereoselectivity 99 : 1 diastereoselectivity Martinelli & Houk, J. Org. Chem. 1994, 59, 2204. mCPBA mCPBA mCPBA 89° major Authors propose that diastereoselection controlled by TS torsional effects