1658 Bond angle variations in XCY fragments and their relationship to the anomeric effect B. Mario Pinto! Department of Chemistry, Simon Fraser University, Burnaby. B.C., Canada VSA 186 H. BERNHARD ScHLEGEL Depariment of Chemistry, Wayne State University, Detroit, MI 48202, U.S.A ‘SAUL WoLFe Department of Chemistry. Queen's University. Kingston, Ont., Canada K7L 3N6 Received March 11, 1986 B. Mano Piro, H. BERNHARD ScHILEGEL, and SAUL WOLFE. Can. J. Chem. 68, 1658 (1987) The crystal structures of 2-substituted heterocyclohexanes containing exocyclic X and endocyclic Y exhibit systematic variations in their XCY bond angles. When X is in the more stable axial orientation, corresponding to the anomeric effect, the XCY angle is larger than tetrahedral; when X is in the equatorial orientation the XCY angle is smaller than tetrahedral, ‘These geometrical effects are predicted by the perturbational molecular orbital analysis employed previously t account forthe existence of the anomeric effect and its Variation with changes in X and Y. Ab initio molecular orbital calculations, with full _Beometty opimization, of selected conformations of XCH;YH molecules also reproduce this geometrical effec. B, Mano Pinto, H. BERNHARD SCHLEGEL et SAUL WOLFE. Can. J. Chem. 68, 1658 (1987). Les structures cristallines d’hétérocyclohexanes substitués en positon 2 et contenant un groupement X exocyelique et un {groupement ¥ endocyclique présentent des variations systématiques de leurs angles de liaisons XCY.. Lorsque X se trouve dans orientation axiale la plus stable, correspondant 3 leffet anomére, I'angle XCY est plus grand que celui d'un tétraédre: par ailleurs, lorsque X est dans orientation équatoriale, angle XCY est plus petit que celui d'un tétraédre. On peut prédire ces effets péometriques en faisant ape I'analyse des orbitales moléculaites perturbationnelle qui wt utiliséeantérieurement pour expliguerI'existence de effet anomére ainsi que sa variation avec des changements dans X et Y. On peut auss reproduire cet effet géomérique en faisant appel A des calculsd’oritales moléculaires ab iniio,impliquant une optimisation complete de éométrie, de conformations choisies de molécules XCH:YH. Introduction Molecules of the type XYCAB, in which X and Y are heteroatoms, exhibit interesting geometries. When AB is a double bond (XYC=CH;), the XCY angle is substantially smaller than the 120° angle associated with sp?-hybridized carbon: X = Y = F, ZXCY = 109.4, X = F, Y= Cl, ZXCY = 112.0X Cl, 2XCY = 114.4°(1).? For A= B = H, a shortening (strengthening) of the C—X and C—Y bonds, compared to CH,X and CHsY, is normally observed (2, 3). The magnitude of this shortening is attenuated by torsion, about the C—X and (or) C—Y bonds when X and (or) Y are rotors (XR, YR) and is a manifestation of the Edward-Lemieux (anomeric) effect (4) ‘The bond strengthening observed in XYCH, is an electro static (coulombic) effect in which one substituent causes a change in the charge density at the central carbon and this, in ‘um, causes change in the length of the bond to the second substituent (5-7), The XCY bond angles in XYC—=CHp and the torsional behaviour and bond length variations in RXCHYR’ hhave been rationalized, both qualitatively (1, 6, 8) and quantitatively (1, 6, 9), by a perturbational molecular orbital (PMO) treatment that focuses on the two-orbital two-electron stabilizing orbital interactions that contribute to the HOMO of XYCAB. In this treatment the relevant interaction involves a doubly occupied nonbonding orbital on X and an unoccupied acceptor orbital on YCAB or, alternatively, a doubly occupied rnonbonding orbital on Y and an unoccupied acceptor orbital on XCAB (1, 9). The magnitude ofthis interaction is proportional ‘Author t whom conespondence may be addressed 2Revisin received January 6, 1987 “Alo, 8. Wolfe and M. H. Whangbo, unpublished results (Traduit pa la revue] Nef & “e Fic. |. The stabilizing orbital interaction that contributes to the HOMO ofa 1, L-disubstituted ethylene tothe square of the overlap between the interacting orbitals, and is inversely proportional to their energy difference. Figure 1 illustrates the application of this procedure to X’XC=CHs, with the interaction taken as X's" CX=CH. ‘The acceptor orbital of CX=CH, has nodal planes between X and C,, and between C, and Cy, and the coefficient of Cy is larger than the coefficient at X (1). For X'CX—=CH: to be formed from the interaction of X’ with CX=CHs, the primary overlap, of X' with C, (-::), must be in-phase (positive). With this requirement, it can be seen that the secondary overlap (depicted by double-headed arrows), between X’ and Cy. and between X’ and X, is out-of-phase (negative). Maximum1659 Pee eee oe oe ee ae aa F aaa aea eat eae ea oc 7 ae epee wn Se . emameee irs oan Peery iy co ri Pe oreaas as . eee foes ene oh i ie cee : ef eel aera ota ee ee en eae i peer pian Gon eee i eens oat 7 he i aeons : cere’ i oe a : ia i Pent go bucprne : i ina if ee eye aoe ae : fa : Se eee : i ee i: a i a : leona (ee : on oe [ aa ee ' eee preuees f a hineeeeant el ‘Tri-O-acetyl-B-p-xylopyranosylfuoride H iF 105.7 18 ‘Tri-O-benzoyl-B-p-xylopyranosylRuoride F 4 110.7, 109.9 Is “Compounds have been numbered according © the convention Zor carbobydate derivatives, Fic, 2. The stabilizing orbital interaction that contributes 10 the HOMO of XCH.YR. A, antiperiplanar conformation: B, perpendi- cular conformation. overlap between X’ and CX—CHs will therefore be achieved by an increase in the CCX’ angle, and a concomitant decrease inthe X’C,X angle. Figure 2 illustrates the application of the PMO procedure to CY torsion in XCH.YR, with the interaction taken as RY-"-CH;X. In each conformation shown, the doubly occu- Pied orbital is np, the p-type nonbonding orbital on Y. and the acceptor orbital is the unoccupied orbital of CH:X that has the proper symmetry for non-zero primary overlap with rp. In the antiperiplanar conformation, this is 7cy,x. and in the perpen- Fic. 3. The primary (+++) and secondary () overlap in the stabilizing orbital interactions of Fi dicular conformation, the acceptor orbital is o*cu.x. Since the © orbital les lower than the =r* orbital (6, 10), there is greater stabilization in the nc interaction than in the n—* inter- action. This analysis accounts for the greater stability of the ‘gauche conformations of XCH2YR molecules in comparison to the 5) or antiperiplanar conformations (4, 6); it also predicts @ longer CX bond in the more stable gauche conformation, because there is greater charge transfer to the antibonding C—X region in this case. Furthermore, if the CYR moiety of XCHZYR is incorporated into a heterocyelohexane, the analysis ‘can account forthe existence of the anomeric and relaed (11) effects, and for the tends in these effects as both X and Y are varied (8). Results and discussion ‘The purpose ofthis manuscript isto point out thatthe analysis of Fig. I can be incorporated into Fig. ? co predict that the XCY bond angles of XCH,YR molecules will differ systematically in the gauche and antiperiplanar conformations. Figure 3is similar to Fig, 2, but now emphasizes the primary (+++) and secondary1660 (CAN J.-CHEM. VOL. 65, 1987 ‘Tante 2. Relative energy, C—X and C—Y bond lengths, and X—C—Y bond angles in selected conformations of XCH;YH molecules” Teunecwegy Bowden Bondage) (kcal mol") rey (A) xX—C—Y 200 tos 106 nes 1s 16. x te 00 ony LBD gas) 631.29 40142 on" x 00 ae unit re 402 Las 1052 X=OY=S x 90 0" 185011800" sr sate re 295015)" 1e31810% op joe. X=OWY=0 4 00 vat 23 feast Lat ws X=HY=O gy 00 1 m0 fe 386 1a wos x oo sos ns fe 402 103 1090 xo shy 00 om? Les, us zis fe tmowey Fee ABBE, osaunae XM 20%, 90 1 uss be oon ais vio KENT =S6, 90 1 wie fe tos ss ns X=RYOMH ggg 1s usa te 90 12 ws x 00 ae uss te 03 12s wos.sPINTO ETAL 1661 ‘TapLe 2 (concluded) Relative energy Compound (keal mot") OH Y=NHg, 9.0 Be 7.89 Bond tength Bond angle (°) re—y (Ay X—C-Y ron 1419 reno 1440 a ron 1440 ren 1422 eg “From ab initio MO calculations employing full geometry optimization and the 4-316 basis et. ‘Values i parentheses ate those obtain with the $216 Fic. 4. ‘The hyperconjugative interaction propesed for a I-axilly substituted pyranoside (>) overt in the nom interaction of the antiperiplanar conformation and the na" interaction of the perpendicular conformation. Inthe antiperiplnar conformation, although the interaction is tabilzing and atractive with respect to the CHX soup asa whole, the secondary overlap interactions 1 and 2are both outof-phas, ang result ina repulsive force. If the CHaX groups assimed tobe rigid, the YCH and YCX anges cannot ‘both increase.* Because the hydrogen atoms of 7*cy,x have larger coefficients than X (6,10), 1s more epulsive tan 2: the YCH angles increase, and the YCX ange decreases. Maximum overlap between RY and CHX is achieved by a decrease in the angle from the idealized tetrahedral angle depicted in Fig. 3. This decrease reduces the secondary overlap | atthe expense ofa small ingrease inthe secondaty overlap 2 In the perpendicular conformation, the secondary overlaps 3 and 4 fe both negative but 4 is more repulsive than 3 “Maximum overlap between RY and CH;X in this conformation can be achieved by msnimizing overlap al the expense ofan increase in 3.* This leads to an increase in the XCY angle from the idealized terahedal angle depicted in Fig. 3 Variations of the foregoing argument have beenemployed to account for methy] tilt angles in CH3X molecules (12), and for bond angle trends in lactones and lactams (13). To check the validity ofthe argument in the present cas, uanttative PMO analyses (6) were performed on FCH,OH in its antperiplanar and perpendicular conformations, with pat- cular reference to the interactions depicted in Fig. 3 and the charge cstibutions i the acceptor omial. Atte 4-31G level, the optimized perpendicular structure is 5.27 keal/mol more stale, and the optimized. geometrical parameters ate. pe pendicular: C—-F'1408 A. CO 1.383 A, CFCO Ti ZOCH, 107.7", ZOCH, 113.9; atiperiplanar: C—F 1.386 A, €—0 1.398 A, ZFCO 106.6", OCH 11.5" Tn the antipeniplanar conformation, the 2p atomic orbital coeficients on carbon and on fluorine in-2*cypp ae C. 1.49: 0.18, and the Is atomic orbital coefficients on the hydrogens “an alterate atgument supposes that the interaction of X with RYCH, tends to open the XCH angles. This interaction is the same in both conformations, and it wll eause the XHC angles to be the same in both conformations, ie.. rigid CHX group, For small changes in the XCY angle, the change in the primary overlap will be negligible 73.26 ant 0) are 1.61 (out-of-phase with Cap). In the perpendicular sirscture, the hybrid orbital depicted for carbon in Figs. 2 and 3 comprises Cas, 0.45, and Capa, 1.2% the hybrid orbital depicted for, ev. urine in Figs, 2and 3 comprises F,0.74, and Fipe. “0.42: the Ls coefiicients are Hy, ~0.73; Ha, 0.76. The secondary overlap associated with the 2s component of fluorine approximately cancels the secondary overlap asso- ciated with Hand H, because the fluorine is inthe plane of the oxygen donor orbital and the hydrogens are no. Interaction thetefore dominates because of the 2pr component of fluorine Tocarry this later point further, addtional quantitative PMO analyses were performed on the perpendicular structure, with the FCO angle decreased to 106.6%, the value inthe antperi- planar structure. At the smaller angle, the hydrogen atomic orbital coeicients increase, to Hy, 0.81; Hy, ~0.88; the 2s component of the fluorine decreases, to 0.72, and the total overlap between Ory, and 0 cusp decreases from 0.298 10 60.282. The changes in he atomic orbital coeicients on Hy, He, and on F reflect the adjustment of the charge distribution and secondary overlap to the smaller FCO angle. Table | summarizes experimental data, taken from X-ray and neutron diffraction erystal structures, of a~ and B:pyranoses and pyranosides (14-17), L-axially and I-equatorially oriented B-p-xylopyranosyl fluorides (18), and axial and equatorial fetrahydropyranyl acetals (16). In all of these structures the 0;—C,—X; valence bond angle is systematically larger than the tetrahedral value when X is axial, and systematically smaler than the tetrahedral value when X is equatorial The larger than tetrahedral X-C-—Y bond angle in -axially substituted pyranoses has been commented upon previously by Lemieux ef al. (15), and rationalized in terms of the greater trigonal character of the central carbon atom (C,) associated with the hyperconjugative interaction depicted in Fig. 4 However, such an argument would not account forthe decrease in the XC—Y bond angle that is observed in [-equatoially Substituted pyranoses. The PMO argument, on the other hand, anticipates both effects To probe these trends fither, the bond angle variations in X—C—Y fragments were examined computationally on the ‘model compounds XCHYH, in which X = NH, OH, SH, Cl, F, and Y = 0, S, NH. The calculations were performed using GAUSSIAN 80 (19) with the 431G basis set, and full eometry optimization of all structures. To facilitate the discussion, Fig. 5 shows the conformations of XCHsYH that correspond to local ‘minima on the potetil energy surface, and their relationship to the conformations of heterocyclohenanes. Table 2 summarizes the felative energies of the XCH3YH conformations, the optimized CX and C—Y bond lengths and the optimized X—C—Y bond angles. Although the individual values ofthese geometrical parameters are basis setAx 2 ke x Ky wy Roe > “a xe “ yyy DEY —_; WN aa teh Fic. 5. Conformations of XCH.YH molecules and their relation ship tothe conformations of 2-substituted heterocyelohexanes, dependent, the trends are not (20-22). 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