D. A. Evans The Anomeric Effect and Related Issues Chem 206 Infrared evidence for lone pair delocalization into vicinal antibonding orbitals The Anomeric effect The N-H stretching frequency of cis-methyl diazene is 200 cm-1 lower It is not unexpected that the methoxyl substituent on a cyclohexane ring than the trans isomer prefers to adopt the equatorial conformation H antibonding OMe AG°=+0.6 kcal/mol OMe vN-H= 2188 cm i What is unexpected is that the closely related 2-methoxytetrahydropyr prefers the axial conformation v N-H= 2317 cm-1 N-SP2 AG°=-06 kcal/mol OMe a The low-frequency N-H shift in the cis isomer is a result of N-H a That effect which provides the stabilization of the axial OR conformer which overrides the inherent steric bias of the substituent is referred to as bond weakening due to presence of the anti lone par on the vicinal the anomeric effect nitrogen which is interacting with the N-H antibonding orbital. Note that the orbital overlap is not nearly as good from the trans Principal HOMO-LUMO interaction from each conformation is llustrated N C. Craig& co-workers JACS 1979, 101, 2480 dehyde C-H Infrared Stretching Frequencies The IR C-H stretching frequency for aldehydes is lower than the closely related olefin C-H stretching frequency. For years this observation has i axial O lone paire>0*C-H axial o lone paire>0*C-o gone a Since the antibonding C-o orbital is a better acceptor orbital than the antibonding C-H bond, the axial OMe conformer is better stabilized by this interaction which is worth ca 1.2 kcal Other electronegative substituents such as cl, sr etc anomeric stabilization. H vC-H=3050 cm-1 1781A vC-H=2730 cm I We now conclude that this is another example of the vicinal lone pair effect This conformer 1819AC preferred by 1.8 kcal/mol Why is axial C-Cl bond longer?N N Me N N Me H N H N Me N N Me O H OMe O H OMe C H C R R R Cl O H O O H Cl H Cl H OMe OMe O H H OMe OMe H O H H C R O H Chem 206 ■ We now conclude that this is another example of the vicinal lone pair effect. D. A. Evans The Anomeric Effect and Related Issues filled N-SP2 Infrared evidence for lone pair delocalization into vicinal antibonding orbitals. n N–H = 2188 cm -1 n N–H = 2317 cm -1 filled N-SP2 antibonding s* N–H .. antibonding s* N–H The N–H stretching frequency of cis-methyl diazene is 200 cm-1 lower than the trans isomer. N. C. Craig & co-workers JACS 1979, 101, 2480. n C–H = 3050 cm -1 n C–H = 2730 cm -1 Aldehyde C–H Infrared Stretching Frequencies The IR C–H stretching frequency for aldehydes is lower than the closely related olefin C–H stretching frequency. For years this observation has gone unexplained. The Anomeric Effect It is not unexpected that the methoxyl substituent on a cyclohexane ring prefers to adopt the equatorial conformation. D G° = +0.6 kcal/mol D G° = –0.6 kcal/mol What is unexpected is that the closely related 2-methoxytetrahydropyran prefers the axial conformation: ■ That effect which provides the stabilization of the axial OR conformer which overrides the inherent steric bias of the substituent is referred to as the anomeric effect. axial O lone pair«s* C–H axial O lone pair«s* C–O Principal HOMO-LUMO interaction from each conformation is illustrated below: ■ Since the antibonding C–O orbital is a better acceptor orbital than the antibonding C–H bond, the axial OMe conformer is better stabilized by this interaction which is worth ca 1.2 kcal/mol. Other electronegative substituents such as Cl, SR etc. also participate in anomeric stabilization. This conformer preferred by 1.8 kcal/mol 1.819 Å 1.781 Å Why is axial C–Cl bond longer ? ●● ●● ●● ●● ●● ●● ■ The low-frequency N–H shift in the cis isomer is a result of N–H bond weakening due to presence of the anti lone par on the vicinal nitrogen which is interacting with the N–H antibonding orbital. Note that the orbital overlap is not nearly as good from the trans isomer