The Anomeric Effect and Associated Stereoelectronic Effects

Chapter 11

Anomeric and Reverse Anomeric Effect in Acetals and Related Functions

Downloaded by NORTH CAROLINA STATE UNIV on June 5, 2013 | http://pubs.acs.org Publication Date: November 23, 1993 | doi: 10.1021/bk-1993-0539.ch011

F. Grein Department of Chemistry, University of New Brunswick, Bag Service 45222, Fredericton, New Brunswick E3B 6E2, Canada

Ab initio geometry optimizations were performed on various conformations of XHm-CH2-OH and XHm-CH2-NH2 and corresponding protonated systems with XHm = F , OH and NH2. By combining Fourier analysis with energy decomposition methods developed in a previous paper, the electronic part of the anomeric stabilization energy, e, could be extracted. For neutral systems, the values of eO are -2.0 for X = F , -1.0 for OH and -0.7 for NH2. The values of eN are -3.6 for F , -1.9 for OH and -1.0 for NH2. eO refers to stabilization due to Ο and eN due to N. For protonated systems the results for eO are -20.5* for FH+, -6.2 for OH2+, and -3.5 for NH3+. eN values are -30.6* for FH+, -17.3* for OH2+, and -5.7 for NH3+. The units are kcal/mol. In the cases marked by asterisk, charge-dipole complexes are formed. Energy values for the reverse anomeric effect, operative in protonated systems, are vO = -7.5 for OH2+, -8.0 for NH3+, and vN = -7.5 for NH3+. In other cases, complexes are formed. The mechanism for electronic stabilization is explained by partial π-bonding in the CH2-OH or CH2-NH2 fragment of the molecule. Numerous theoretical studies on the anomeric effect have been published, with the first ab initio papers appearing in 1971 by Wolfe et al. (1) and Radom, Hehre and Pople (2,3). The energetic and structural changes, as observed experimentally and amply documented (4,5), are well reproduced by ab initio geometry optimizations, providing a basis for the more difficult task of interpreting the nature of this effect. A breakdown of the anomeric stabilization energy of model acetals into components was attempted in a recent paper by Grein and Deslongchamps (6), to be called paper I. The main purpose was to extract the underlying electronic energy of stabilization, and to separate it from other forms of energy, such as steric and electrostatic. Overall, this study was able to rationalize energy lowerings for systems X H - C H - Y H and their protonated counterparts X H - C H - Y H , where X and Y are Ν and O. Paper I will be reviewed in the main part of the present +

m

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0097-6156/93/0539-0205$06.50/0 © 1993 American Chemical Society

In The Anomeric Effect and Associated Stereoelectronic Effects; Thatcher, G.; ACS Symposium Series; American Chemical Society: Washington, DC, 1993.

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THE ANOMERIC EFFECT AND ASSOCIATED STEREOELECTRONIC EFFECTS

study under the heading "energy decomposition model". Results for systems with X = F will be added. In a second article, to be referred to as paper II (7), more detailed studies were performed on systems X F ^ - C H ^ O H , with X = N , O, F , C , where the O H hydrogen was rotated about the C - 0 bond. This is followed by a Fourier analysis of the energy as function of the rotation angle. Fourier analyses with the purpose of studying the anomeric effect were first performed by Radom et al. (8,9). Again, a decomposition of the energy into an electronic component ( V parameter), a steric component for the interaction of the rotating O H with the neighboring C H X group ( V parameter), and a steric/electrostatic component for the interaction of O H with X H (V parameter) was performed. The electronic component of the anomeric energy stabilization, considered to be the fundamental driving force of the anomeric effect, was related to the ability of the C H - O H portion of the molecule to form a partial double bond provided that OH carries a partial positive charge. The findings of paper II will be summarized under the heading "OH rotation model for X H CH -OH". The present work is based on the two previous papers. Additional systems, such as X H - C H - N H , with N H rotation, and protonated systems X H - C H - O H and X H - C H - N H , with O H rotation and N H rotation, respectively, will be presented and discussed. When applied to protonated systems, both the energy decomposition model and the O H or N H rotation model show the need for an additional energy parameter which is not encountered in neutral systems. This new parameter will be associated with the "reverse anomeric effect", as introduced by Lemieux and Morgan (10,11). Based on calculated energies and other properties of systems XR -CR 'YH and their protonated counterparts, with X = F , O, N , (C), and Υ = Ο and N , as function of the rotation angle of Y r ^ , the ideas presented in papers I and II will be combined, leading to much improved values for the electronic portion of the anomeric stabilization energy, as well as estimates of the reverse anomeric stabilization energy. The π-bonding model will be further developed. 2

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Energy Analysis for Neutral Systems On systems X H - C H - Y H , with X , Y = F , 0 , N , C , ab initio SCF calculations were performed using the GAUSSIAN 86 program (12) and 6-310** or 6-31+G* basis sets. For selected dihedral angles φ of one or two X H and Y H hydrogens, geometry optimizations of all bond distances, bond angles, and other dihedral angles were carried out. Structure 1 shows dihedral angles φ of 0 ° . In general, φ values were chosen to be 0 ° , 60°, 120° and 180° (and 90°, not reported here). Assuming lone pairs (£p) of electrons to be located in sp positions, and defining in a simpleminded way a lone pair in antiperiplanar position (app) (e.g. a lone pair on Y app to the C - X bond) to cause an anomeric effect (ae), then for structure 1 there is 0 ae, whereas structures 2, 3 and 4 have 1 ae(O), 1 ae(N), and 2 ae's, respectively, exemplified by N H - C H - O H . m

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Energy Decomposition Model. In Table I, relative energies and optimized C - X and C - Y distances are summarized for the 0 ae, 1 ae and 2 ae conformers of O H - C H O H , N H - C H - O H and N H - C H - N H (paper I). It is seen that the 1 ae conformers 2

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11. GREIN

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Anomeric and Reverse Anomeric Effect in Acetals

are more stable than their 0 ae counterparts, and that in turn the 2 ae conformers are more stable than the 1 ae ones, as expected. However, the energy lowerings in the N H - C H - N H system are marginal, and for N H - C H - O H , 2 ae is only slightly more stable than 1 ae. The only system where there is a distinct energy lowering from 0 ae to 1 ae to 2 ae is O H - C H - O H . 2

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In paper I, an energy analysis has been performed in order to explain qualitatively such different energetic behaviour. Energy differences between various conformers are described by an electronic component, labelled e; 1,3-diaxial H - H repulsions, labelled r; 1,3-diaxial fp-fp repulsions, called i\ and intramolecular "hydrogen bonding", labelled h, to be used for 1,3-diaxial H-£p interactions. Since in all conformations of Table I the 1,2-hydrogens and bonds are staggered, they need not be included in this analysis. Based on ab initio calculations, approximate values r = i = -h = 1 kcal/mol were obtained (paper I). Applying this model to the systems given in Table I leads to e = -2 kcal/mol, e = -2.5 kcal/mol, where e (e ) is the electronic energy due to an ae from Ο (Ν), when one of the £p's on Ο (Ν) is app to the C - X (or C-Y) bond. Surprisingly, the small energy differences between the conformers of N H - C H - N H , and between 1 ae and 2 ae of 0

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THE ANOMERIC EFFECT AND ASSOCIATED STEREOELECTRONIC EFFECTS

N H - C H - O H , ^ explained by steric and electrostatic effects, while still allowing for a sizeable electronic component e caused by the anomeric effect. The trends in calculated bond distances agree with qualitative models and many previous calculations. An ae from X causes the C - X bond to shorten and the C - Y bond to lengthen. 2

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Table I.

Relative energies ΔΕ in kcal/mol (first line) and optimized C-X/C-Y distances in Â (second line), obtained by 6-31G** geometry optimizations on systems X H - C H - Y H


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NH -CH -OH 2

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NH -CH -NH 2

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2 ae

1 ae(Y)

1 ae(X)

8.35 1.381

3.86 1.372/1.393

3.86 1.393/1.372

0.0 1.385

5.06 1.435/1.394

0.17 1.423/1.407

0.95 1.443/1.388

0.0 1.431/1.403

0.82 1.445

0.64 1.439/1.456

0.64 1.456/1.439

0.0 1.448

OH-rotation Model. In Table II, relative energies, bond distances and Mulliken charges are listed for rotating the O H hydrogen of X H - C H - O H around the C - 0 bond, while leaving the X H hydrogens at fixed dihedral angles. X H was chosen to be F , a-OH, s-NH and s-CH , with notations a (anti) and s (staggered) explained in structures 5 to 7. The dihedral angles of the X H hydrogens were held fixed at 0° for a-OH, ± 120° for s-NH , and 0, ± 120° for s-CH . In structures 5 to 7, the rotating O H is shown at a dihedral angle φ of 0 ° . C H - C H - O H was included as a reference system for which the anomeric effect is not operable. Results for φ values of 0 ° , 60°, 120° and 180° are given in Table II. Calculations were also performed for other angles, but they do not give additional insight, and have therefore been omitted. The dihedral angle φ = 0° corresponds to the 0 ae conformation in the case of the first two systems, and the 1 ae(N) conformation in m

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s-NH -CH -OH

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11. GREIN

Anomeric and Reverse Anomeric Effect in Acetals

Table II.

Relative energies ΔΕ in kcal/mol (first line), optimized C-O distances in À (second line), and Mulliken charges on O H (third line), obtained by 6-31G** geometry optimizations on X H - C H - O H for OH dihedral angles of 0 ° , 60°, 120° and 180° m

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X H - C H - OH m

0°

2

180°

120°

60°

F - C H OH

0.00 1.3749 -0.279

-1.63 1.3689 -0.273

-4.79 1.3630 -0.269

-2.37 1.3742 -0.288

a-OH-CH O H

0.00 1.3815 -0.280

-0.83 1.3787 -0.278

-4.49 1.3727 -0.279

-3.38 1.3802 -0.294

s-NH -CH - -OH

0.00 1.4082 -0.318

0.91 1.4090 -0.318

0.06 1.4029 -0.318

2.28 1.4087 -0.332

s-CH -CH - •OH

0.00 1.4035 -0.304

1.28 1.4074 -0.307

0.13 1.4026 -0.309

1.77 1.4053 -0.316

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the case of N H - C H - O H . For φ = 120°, one ae has to be added, leading to the 1 ae conformation of F - C H - O H and O H - C H - O H , and the 2 ae conformation of the NH -CH -OH. In Table III, Fourier constants V j to V are given for the systems X H - C H O H , obtained by fitting the energy values of Table II to the formula 2

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AE(0)=(V /2)(l-cos

The Anomeric Effect and Associated Stereoelectronic Effects

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