D.A. Evans Acyclic Conformational Analysis-2 Chem 206 Problems of the Day: (To be discussed) http://www.courses.fas.harvard.edu/-chem206/ Can you predict the stereochemical outcome of this reaction? OTs OTS Chemistry 206 LINR Advanced Organic Chemistry n-C4Hg n-C4H9 982 Lecture Number 5 ■ Relevant enolate conformations Acyclic Conformational Analysis-2 n-CAHg Conformations of Simple Olefinic Substrates Introduction to Allylic Strain (CH2)4OTS TSO(H2C)4 Introduction to Allylic Strain-2: Amides and enolates SoLi Me-LC-CmOR Bu\ / CH2lS H OLi A1 Reading Assignment for week critical conformations A. Carey& Sundberg: Part A; Chapters 2&3 R. W. Hoffmann. Chem. Rev. 1989. 89. 1841-1860 Allylic 1-3-Strain as a Controlling Element in Stereoselective Transformations TSO(2C)4 R. W. Hoffmann, Angew. Chem. Int. Ed. Engl. 2000, 39, 2054-2070 CH2)lOTs Conformation Design of Open-Chain Compounds A2 B2 F. Weinhold, Angew. Science 2001, 411, 539-541 'A New Twist on Molecular Shape Frida EtOC.E Carl a. morales September 27, 2002 minor n-C4Hg
http://www.courses.fas.harvard.edu/~chem206/ EtO Me O n-C4H9 OTs H EtO Me OLi n-C4H9 OTs H C Bu H (CH2 )4OTs C OLi OR C Me H Bu TsO(H2C)4 C OLi OR Me C H Bu (CH2)4OTs C OLi OR Me C H Bu (CH2)4OTs C OLi OR Me C H Bu (CH2)4OTs C OLi OR C Me TsO(H2C)4 H Bu C OLi OR Me H n-C4H9 EtO2C Me H n-C4H9 O Me EtO A1 B1 C1 A2 B2 C2 LiNR2 D. A. Evans Chem 206 Carl A. Morales Friday, September 27, 2002 Chemistry 206 Advanced Organic Chemistry Lecture Number 5 Acyclic Conformational Analysis-2 ■ Conformations of Simple Olefinic Substrates ■ Introduction to Allylic Strain ■ Introduction to Allylic Strain-2: Amides and Enolates ■ Reading Assignment for week Acyclic Conformational Analysis-2 A. Carey & Sundberg: Part A; Chapters 2 & 3 R. W. Hoffmann, Chem. Rev. 1989, 89, 1841-1860 Allylic 1-3-Strain as a Controlling Element in Stereoselective Transformations R. W. Hoffmann, Angew. Chem. Int. Ed. Engl. 2000, 39, 2054-2070 Conformation Design of Open-Chain Compounds F. Weinhold, Angew. Science 2001, 411, 539-541 "A New Twist on Molecular Shape" 98:2 Can you predict the stereochemical outcome of this reaction? ■ Problems of the Day: (To be discussed) 2 1 critical conformations 1 + 2 ■ Relevant enolate conformations major minor
D.A. Evans Useful Destabilizing Interactions to Remember Chem 206 Hierarchy of Vicinal Eclipsing Interactions It may be concluded that in-plane 1, 3(Mee Me) interactions are Ca +4 kcal/mol while 1, 2 (Me+Me) interactions are destablizing by ca +3 kcal/mol X—Y8Ekca|mol-1 H-H +10 H H-Me +14 Me-Me +3.1 Estimates of In-Plane 1.2 1, 3-Dimethyl Eclipsing Interactions 7.6
~ 3.1 ~ 3.7 ~3.9 ~ 7.6 Estimates of In-Plane 1,2 & 1,3-Dimethyl Eclipsing Interactions Me Me Me Me Me Me Me Me Hierarchy of Vicinal Eclipsing Interactions d E kcal mol -1 +1.0 +1.4 +3.1 C C X Y H H H H X Y H H H Me Me Me Useful Destabilizing Interactions to Remember It may be concluded that in-plane 1,3(Me«Me) interactions are Ca +4 kcal/mol while 1,2(Me«Me) interactions are destabliizing by Ca +3 kcal/mol. minimized structure D. A. Evans Chem 206
D. A. Evans Stabilized Eclipsed Conformations in Simple Olefins Chem 206 Simple olefins exhibit unusal conformational a The Propylene Barrier 人 staggered properties relative to their saturated counterparts Butane versus 1-Butene +20 kcal/mol eclipsed conformation conformation a Acetaldehyde exhibits a similar conformational bias angered RCH2 conformation The low-energy conformation in each of above cases is eclispec △G°=-083 kcal mol1 Propane versus The Torsional Energy Profile d=50 ①=180 H New destabilizing effect emulsive interaction between .33 I-C-X&o-C-H 1.32 kcal +049 kcal =120 =0 Conforms to ab initio (3-21G)values H Wiberg, K B; Martin, E.J. Am. Chem. Soc. 1985, 107, 5035 K Wiberg,JACS1985.107,5035-5041 K. Houk,JAcS1987,109,6591-6600
D. A. Evans Stabilized Eclipsed Conformations in Simple Olefins Chem 206 Butane versus 1-Butene eclipsed conformation staggered conformation D G° = +4 kcal mol-1 Me C H C H H Me H Me H H H H Me eclipsed conformation staggered conformation D G° = –0.8.3 kcal mol-1 Me C C H H CH2 CH2 H H Me +1.33 kcal +1.32 kcal +0.49 kcal F = 180 F = 120 F = 50 F = 0 F = 0 F = 180 The Torsional Energy Profile Conforms to ab initio (3-21G) values: Wiberg, K. B.; Martin, E. J. Am. Chem. Soc. 1985, 107, 5035. H C H C H H H H C H C H H H H C H C H H H Me Me H H C C H H H Me Me Simple olefins exhibit unusal conformational properties relative to their saturated counterparts ■ The Propylene Barrier C H CH2 H H H C H CH2 H eclipsed conformation staggered conformation +2.0 kcal/mol ■ Acetaldehyde exhibits a similar conformational bias O H H H H O Me H H H O H Me H H O Me Me H H The low-energy conformation in each of above cases is eclisped H Me H H H H 109° H CH2 H H H 120° Propane versus Propene Hybridilzation change opens up the C–C–C bond angle K. Wiberg, JACS 1985, 107, 5035-5041 X C H H H H repulsive interaction between p–C–X & s–C–H X C H H H K. Houk, JACS 1987, 109, 6591-6600 New destabilizing effect H H
Evans, Duffy Ripin Conformational Barriers to Rotation: Olefin A-1, 2 Interactions Chem 206 1-butene 2-propen-1-o/ 2 180 Co Deg) ΦDeg) The Torsional Energy Profile The Torsional Energy Profile Φ=50 =180H Φ=12 2.00 +133 kcal ①=0 +1.32 kcal 1.18 kcal +0.49 kcal Φ=120 +0. 37 kcal Conforms to ab initio( 3-21G)values iberg, K B; Martin, E.J. Am. Chem. Soc. 1985, 107, 5035
0 1 2 3 4 5 -180 -90 0 90 180 0 1 2 3 4 5 -180 -90 0 90 180 C H C H H OH H H C H C H H Me H H C C H H H Me H H Me H H C C H H H Me H H C H C H H Me H H C H C H H HO H H C C H H H OH H H C H C H H HO H H C C H H H OH H H C C H H H F F F = 0 F = 180 F = 0 F = 60 F = 120 F = 180 +1.18 kcal +0.37 kcal +2.00 kcal +1.33 kcal +1.32 kcal +0.49 kcal F = 180 F = 120 F = 50 F = 0 F = 0 F = 180 E (kcal/mol) The Torsional Energy Profile The Torsional Energy Profile Evans, Duffy, & Ripin Conformational Barriers to Rotation: Olefin A-1,2 Interactions Chem 206 (Deg) E (kcal/mol) 1-butene 2-propen-1-ol Conforms to ab initio (3-21G) values: Wiberg, K. B.; Martin, E. J. Am. Chem. Soc. 1985, 107, 5035. (Deg)
Evans, Duffy, Ripin Conformational Barriers to Rotation Olefin A-1, 2 Interactions-2 Chem 206 2-methyl-1-butene 2-methyl-2-propen-1-0/ 2 ,4 ΦqDeg) The Torsional Energy Profile The Torsional Energy Profile ①=180 d: 60 =120 ①=110 +2.68 +2.01 Φ=0 +1. 39 kcal +1.16 kcal 0.21 kcal +0.06 kcal Φ=180
0 1 2 3 4 5 -180 -90 0 90 180 0 1 2 3 4 5 -180 -90 0 90 180 Evans, Duffy, & Ripin Conformational Barriers to Rotation: Olefin A-1,2 Interactions-2 Chem 206 (Deg) 2-methyl-1-butene E (kcal/mol) +2.68 kcal +1.39 kcal +0.06 kcal F = 180 F = 110 F = 50 F = 0 F = 0 F = 180 The Torsional Energy Profile (Deg) 2-methyl-2-propen-1-ol E (kcal/mol) The Torsional Energy Profile F = 0 F = 180 F = 0 F = 60 F = 120 F = 180 +0.21 kcal +1.16 kcal +2.01 kcal H C H C Me H H H C H C Me H H H C H Me H H C C Me H H C Me H H Me Me H H C C Me H H Me Me H C H C Me H H OH OH HO H C H H C Me H OH HO H H C C Me H H H H C C Me H H H H C C Me H H F F