Pseudo-equatorial Position Research Articles

Competition between Hetero-Diels−Alder and Chelotropic Addition of Sulfur Dioxide. Theoretical and Experimental Substituent Effects on the Relative Stability of 3,6-Dihydro-1,2-oxathiin-2-oxides (Sultines) and 2,5-Dihydrothiophene-1,1-dioxides (Sulfolenes). Anomeric Effects in Sultine and 6-Substituted Derivatives

At low temperature and in the presence of CF3COOH, SO2 undergoes Diels-Alder additions with (E)-1-acetoxybutadiene (8d) giving a 1:10 mixture of diastereomeric 6-acetoxysultines (9d + 10d). The Van't Hoff plot for equilibria 8d + SO2 reversible arrow 9d + 10d led to Delta H-r = -7.0 +/- 0.3 kcal/mol, Delta S-r = -42 +/- 3 cal . mol(-1) . K-1. At 20 degrees C, 8d underwent a slow cheletropic addition with SO2 giving 2-acetoxysulfolene (11d, Delta Hr congruent to -11.5 kcal/mol), the structure of which was established by single-crystal X-ray diffraction studies. (E)-Chloro (8e) and (E)-bromobutadiene (8f) did not undergo Diels-Alder additions with SO2, even in the presence of protic or Lewis acid promoters. Low yields of 2-chloro- (11e) and 8-bromosulfolene (11f) were obtained at 20 degrees C. The structure of 11e was confirmed by single-crystal X-ray diffraction. The potential energy hypersurfaces of the Diels-Alder and cheletropic additions of SO2 to butadiene (8a), (E)-piperilene (8b), (E)-1-methoxy- (8c), (E)-1-acetoxy- (8d), and (E)-1-chlorobutadiene (8e) were studied by ab initio quantum calculations at the MP2/6-31G* level. In agreement with the experiment, 6-substituted sultines 9X and 10X were less stable than the corresponding 2-substituted sulfolenes 11X for X = Me, OAc, Cl. With X = OMe, the two diastereomeric 6-methoxysultines (9c, 10c) and 8-methoxysulfolene (11c) were calculated to have similar stabilities. This is attributed to a stabilizing thermodynamic anomeric effect or gem-sulfinate/methoxy disubstitution effect in 9c, 10c. Such effects were not detected for sulfinate/acetoxy (9d, 10d) and sulfinate/chloro (9e, 10e) disubstitutions. The relative instability of 8-acetoxy- (11d) and 2-chlorosulfolene (11e) compared with their cycloaddents is attributed to repulsive interactions between the SO2 moieties and the 2-substituents. The Alder endo of [4 + 2] cycloaddition of SO2 is predicted to be faster than the anti-Alder mode of additions for dienes 8X, X = Me, OMe, OAc, Cl. The resulting diastereomeric sultines 9X and 10X, respectively, exist as equilibria (energy barrier: ca. 5-6 kcal/mol) of two conformers 9X reversible arrow 9X, 10X reversible arrow 10X. In general, the conformers 9X, 10X with pseudoaxial S=O group are preferred (conformational anomeric effect of the sulfinate moiety). Repulsive interactions between pseudoaxial S=O and polar cis-6-substituents (e.g.: X = OMe, OAc) in 9X may render conformers 9X (with the S-O and 6-X groups in pseudoequatorial positions) as stable as conformers 9X. The calculations predict the existence of conformational anomeric effects of 2-3 kcal/mol for the gem-sulfinate/methoxy (9c, 10'c) and gem-sulfinate/acetoxy disubstitution (9d, 10'd).

Crystal and molecular structure of 3-chloro-3,6-dinitro-2,2-dimethyl-4-chromanone, C11H9N2O6Cl

3-Chloro-3,6-dinitro-2,2-dimethyl-4-chromanone is the first 3-chloro-3-nitro-4-chromanone to be synthesized by nitrating its corresponding 4-chromanone at the 3 position and then chlorinating the nitration product. Its structure was determined by IR, NMR, MS and x-ray crystallography. It crystallizes as a pair of enantiomers with 2 molecules in the primitive triclinic space group P $$\overline 1$$ (#2) with a = 9.476(2), b = 10.906(3), c = 6.578(5) A, and α = 101.08(3), β = 90.13(3), γ = 73.23(1)°, V = 637.7500 A3, and Z = 2. The nitro group at the 6 position conjugates with the benzene ring. The pyranone ring has a half-chair conformation; the chloro group occupies the pseudoequatorial position, and the nitro group occupies the pseudoaxial position. The 2 and 3 positions are essentially antiperiplanar, minimizing steric interaction.

First example of the solvent effect on absolute conformation of chiral 3,3-disubstituted 1,4-benzodiazepin-2-ones

Chiral 3,3-disubstituted 1,4-benzodiazepin-2-ones (3S)- 7 and (3S)- 8 reveal solvent dependent conformational equilibria. The conformer with absolute P-conformation, with CH 2X (X = p-tosyl, Cl) group in a pseudoaxial (ψa) position and CH 2OAc group in a pseudoequatorial (ψe) position, prevails in nonpolar solvents, as shown by 1H-NMR and CD spectra. For (3S)- 7 only a small shift of the conformational equilibrium in a polar solvent (DMSO) is observed, whereas compound (3S)- 8 inverts to a prevailing M-conformer. The inversion barrier for M P equilibrium is estimated on the bases of TDNMR data. For compounds (3R)- 5 and (3S)- 7, 8 the relative stability of the M P conformers in the ground state is calculated by the MM2 method; comparison of these results with CD and 1H-NMR data reveal that nonpolar solvents invert the relative stability calculated for the two conformers.

Competition between Hetero-Diels−Alder and Cheletropic Addition of Sulfur Dioxide. Theoretical and Experimental Substituent Effects on the Relative Stability of 3,6-Dihydro-1,2-oxathiin-2-oxides (Sultines) and 2,5-Dihydrothiophene-1,1-dioxides (Sulfolenes). Anomeric Effects in Sultine and 6-Substituted Derivatives

At low temperature and in the presence of CF3COOH, SO2 undergoes Diels−Alder additions with (E)-1-acetoxybutadiene (8d) giving a 1:10 mixture of diastereomeric 6-acetoxysultines (9d + 10d). The Van't Hoff plot for equilibria 8d + SO2 ⇄ 9d + 10d led to ΔHr = −7.0 ± 0.3 kcal/mol, ΔSr = −42 ± 3 cal·mol-1·K-1. At 20 °C, 8d underwent a slow cheletropic addition with SO2 giving 2-acetoxysulfolene (11d, ΔHr ≅ −11.5 kcal/mol), the structure of which was established by single-crystal X-ray diffraction studies. (E)-Chloro (8e) and (E)-bromobutadiene (8f) did not undergo Diels−Alder additions with SO2, even in the presence of protic or Lewis acid promoters. Low yields of 2-chloro- (11e) and 2-bromosulfolene (11f) were obtained at 20 °C. The structure of 11e was confirmed by single-crystal X-ray diffraction. The potential energy hypersurfaces of the Diels−Alder and cheletropic additions of SO2 to butadiene (8a), (E)-piperilene (8b), (E)-1-methoxy- (8c), (E)-1-acetoxy- (8d), and (E)-1-chlorobutadiene (8e) were studied by ab initio quantum calculations at the MP2/6-31G* level. In agreement with the experiment, 6-substituted sultines 9X and 10X were less stable than the corresponding 2-substituted sulfolenes 11X for X = Me, OAc, Cl. With X = OMe, the two diastereomeric 6-methoxysultines (9c, 10c) and 2-methoxysulfolene (11c) were calculated to have similar stabilities. This is attributed to a stabilizing thermodynamic anomeric effect or gem-sulfinate/methoxy disubstitution effect in 9c, 10c. Such effects were not detected for sulfinate/acetoxy (9d, 10d) and sulfinate/chloro (9e, 10e) disubstitutions. The relative instability of 2-acetoxy- (11d) and 2-chlorosulfolene (11e) compared with their cycloaddents is attributed to repulsive interactions between the SO2 moieties and the 2-substituents. The Alder endo mode of [4 + 2] cycloaddition of SO2 is predicted to be faster than the “anti-Alder mode” of additions for dienes 8X, X = Me, OMe, OAc, Cl. The resulting diastereomeric sultines 9X and 10X, respectively, exist as equilibria (energy barrier: ca. 5−6 kcal/mol) of two conformers 9X ⇄ 9‘X, 10X ⇄ 10‘X. In general, the conformers 9X, 10X with pseudoaxial SO group are preferred (conformational anomeric effect of the sulfinate moiety). Repulsive interactions between pseudoaxial SO and polar cis-6-substituents (e.g.: X = OMe, OAc) in 9X may render conformers 9‘X (with the SO and 6-X groups in pseudoequatorial positions) as stable as conformers 9X. The calculations predict the existence of conformational anomeric effects of 2−3 kcal/mol for the gem-sulfinate/methoxy (9c, 10‘c) and gem-sulfinate/acetoxy disubstitution (9d, 10‘d).

N-(2-Dimethoxymethyl-3-hydroxy-2-methyl-6-nitro-3,4-dihydro-2H-1-benzopyran-4-yl)acetamide

The benzopyran-based title compound, C15H20N2O7, is a potential potassium-channel opener with cardiovascular therapeutic activities. The 2-dimethoxy­methyl and 3-hydroxyl groups are in axial positions while the 4-acetamide group is in a pseudo-equatorial position. The 4-acetamide group is nearly perpendicular to the benzopyran plane. There are two inter­molecular hydrogen bonds; one between the hydroxyl O and acetamide O atoms [2.725 (5) Å], and the other between the acetamide N and methoxy O atoms [3.139 (5) Å].

Synthesis and stereochemistry of the spin adducts of a new chiral spin trap, 3,5-diphenyl-5-methylpyrroline-1-oxide

The synthesized spin trap 3,5-diphenyl-5-methylpyrroline-1-oxide (3), its derivatives and spin adducts were studied using NMR, ESR and ENDOR spectroscopic methods. The structure of 3 was determined using x-ray analysis. The nitrone 3 was found to have a rigid structure. Two species were observed in the EPR and ENDOR spectra of the spin adducts of 3, but not in the NMR spectra of its diamagnetic derivatives. These two species were attributed to those formed when the addends attack carbon-2 from both the re and si sides, resulting in trans (I) and cis (II) adducts in relation to the phenyl substituent in position 3. Therefore, these two species differ only through the substitution on carbon-2, whereby there are different steric interactions of the substituents within both species. The lack of observation of these two species in NMR spectra could be interpreted in terms of unfavourable relaxation times on the NMR time-scale. These species are observed in EPR and ENDOR spectra mainly because of their different β-C—H dihedral angles, which do not play a role in NMR spectroscopy. Both species have the ability to trap stereoselectively carbon- and oxygen-centred radicals, which occupy pseudo-equatorial and pseudo-axial positions, respectively. The occupation of oxygen-centred addends in the pseudo-axial positions is stabilized by the ‘anomeric effects.’ This nitrone 3 was found to have the ability to scavenge short-lived free radicals in both aqueous and non-aqueous solutions. © 1998 John Wiley & Sons, Ltd.

Structure and conformation of the procyanidin B-2 dimer

The structure of the proanthocyanidin B-2 dimer was proved to be (—)epicatechin-(4β-8)-(—)epicatechin by two-dimensional heteronuclear NMR spectroscopy. The compound adopts two conformations in solution, in which the interflavan dihedral angles are roughly ±90°. The preferred conformation of the pyran ring is a half-chair with the 3′,4′-dihydroxyphenyl substituents in pseudo-equatorial positions. © 1997 John Wiley & Sons, Ltd.

Structure and conformation of the procyanidin B-2 dimer

The structure of the proanthocyanidin B-2 dimer was proved to be (—)epicatechin-(4β-8)-(—)epicatechin by two-dimensional heteronuclear NMR spectroscopy. The compound adopts two conformations in solution, in which the interflavan dihedral angles are roughly ±90°. The preferred conformation of the pyran ring is a half-chair with the 3′,4′-dihydroxyphenyl substituents in pseudo-equatorial positions. © 1997 John Wiley & Sons, Ltd.

Ab Initio and Nonlocal Density Functional Study of 1,3,5-Trinitro-s-triazine (RDX) Conformers

Geometry optimizations and normal-mode analyses of three conformers of 1,3,5-trinitro-s-triazine (RDX) are performed using second-order Moller−Plesset (MP2) and nonlocal density functional theory (DFT) methods. The density functional used in this study is B3LYP. The three conformers of RDX are distinguished mainly by the arrangement of the nitro groups relative to the ring atoms of the RDX molecule. NO2 groups arranged in either pseudo-equatorial or axial positions are denoted with (E) or (A), respectively. The AAE conformer has Cs symmetry and is the structure in the room-temperature stable crystal (α-RDX). The AAA and EEE conformers have C3v symmetry, a symmetry consistent with vapor and β-solid infrared spectra. The AAE and AAA conformers are studied at the MP2/6-31G*, B3LYP/6-31G*, and B3LYP/6-311+G** levels, and the EEE conformer is studied using the B3LYP density functional and the 6-31G* and 6-311+G** basis sets. The geometric parameters and infrared spectra of the AAA conformer are in good agreement with experimental gas-phase and β-solid data, supporting the hypotheses derived from experiment that the AAA structure is the most probable conformer in vapor-phase and β-solid RDX. The B3LYP/6-311+G** structures and simulated infrared spectra are in closest overall agreement with experimental data. The MP2/6-31G* structures and spectra are in poorest overall agreement with experiment.

Conformation of 5-Amino-5-deoxypentonolactams

Four configuration isomers of 5-amino-5-deoxy-D-pentonolactam 1a-4a and their tri-O-acetyl derivatives 1b-4b were studied using NMR and CD spectroscopy. For all compounds chemical shifts of the 1H and 13C nuclei as well as of vicinal coupling constants were obtained. Comparison of the observed 3J(H,H) with those calculated for various conformations by a modified Karplus relationship led to the assignment of predominant conformation 3H4(D) or 4H3(D) to the lactams 1a-4a and 1b-4b in solution. The most important factor for determining the conformation seems to be the pseudoequatorial position of the substituent on the carbon next to the carbonyl group. The results of the CD spectra of the lactams 1a-4a in water, interpreted according to the currently used rules, agreed with the NMR results.

Tetrahydrofuran Derivatives from Epoxides via Group Transfer Cyclization or Reductive Radical Cyclization of Organotellurium and Organoselenium Intermediates

Monosubstituted epoxides were regiospecifically ring-opened from the sterically least hindered side by benzenetellurolate and benzeneselenolate reagents to afford aryl beta-hydroxyalkyl tellurides and selenides, respectively. These materials were O-allylated by treatment with allylic bromides/sodium hydride in tetrahydrofuran and O-prop-2-ynylated when reacted with propargyl bromide/sodium hydride. On photolysis in benzene containing 40 mol % of hexabutylditin, the beta-(allyloxy)alkyl aryl tellurides were found to undergo group transfer cyclization to afford 2-substituted 4-[(aryltelluro)methyl]tetrahydrofurans (cis/trans = 1/3-1/10). The aryl beta-(prop-2-ynyloxy)alkyl tellurides similarly afforded 2-substituted 4-[(aryltelluro)methylene]tetrahydrofurans with an E/Z-ratio close to unity. The beta-(allyloxy)alkyl aryl selenides and aryl beta-(prop-2-ynyloxy)alkyl selenides failed to undergo group transfer cyclization. In the presence of tributyltin hydride and 2,2'-azobisisobutyronitrile, the former compounds were found to undergo reductive radical cyclization in high yields to afford 2-substituted 4-methyltetrahydrofurans (cis/trans = 1/3-1/10). Aryl beta-(prop-2-ynyloxy)alkyl selenides similarly afforded 2-substituted 4-methylenetetrahydrofurans. 2-Alkoxy-2-(allyloxy)ethyl phenyl selenides, prepared by allyloxyselenenation of vinyl ethers, were found to undergo reductive radical cyclization to afford 2-alkoxy-4-methyltetrahydrofurans (cis/trans = 1/3-1/4). The preference for formation of trans-2,4-disubstituted tetrahydrofurans in the group transfer and reductive radical cyclizations was rationalized assuming a chairlike transition state with a preferred adoption of a pseudoequatorial position of the 2-substituent. By carrying out the reactions at lower temperatures (ambient or -45 degrees C), using triethylborane as an initiator, it was possible to further increase the trans selectivity in the reductive cyclizations.

Crystal and molecular structures of two unsaturated monosaccharides: methyl 6-(N-benzenesulfonylamino)-N,O-isopropylidene-2,3,6,8-tetradeoxy-α-D-erythrooct-2-enopyranos-4-uloside, and 1,1-O,O-ethylidene-3,4-dideoxy-D,L-hex-3-enoz-2-ulopyranos-5-ulose

Methyl 6-(N-benzenesulfonylamino)-N,O-isopropylidene-2,3,6,8-tetradeoxy-α-d-erythrooct-2-enopyranos-4-uloside, C18H23N1O6S1, (3) crystallizes in the orthorhombic space groupP212121. The unit cell parameters are:a=7.839(2),b=10.111(2),c=24.217(5) A. The dihydropyranone ring adopts a deformed sofa conformation with the O5 atom deviating 0.586(2) A from the least-squares plane and the β-face of the carbonyl group shielded by the terminal (C8) methyl group. 1,1-O,O-Ethylidene-3,4-dideoxy-d,l-hex-3-enoz-2-ulopyranos-5-ulose, C8H10O5, (6) crystallizes in the monoclinic space groupP21/n. The unit cell parameters are:a=6.310(1),b=18.656(3),c=7.604(1) A, β=106.01(1)°. The dihydropyranone ring adopts a deformed sofa conformation with O6 atom deviating 0.482(1) A from the leastsquares plane and the hydroxy and dioxolanyl substituents are in pseudoaxial and pseudoequatorial positions, respectively. The average planes of six-membered and five-membered rings are approximately coplanar.

The differing modes of reaction of 1-(8-dimethylamino-1-naphthyl)-1-hydrodisilane and 1-(1-naphthyl)-1-hydrodisilane in nickel-catalyzed reactions with acetylene: formation of a pseudo-pentacoordinate silole via SiSi bond cleavage vs. hydrosilation without SiSi bond cleavage

Pseudo-pentacoordinate 1-(8-dimethylamino-1-naphthyl)-1-hydrodisilanes 1 and 2 and the tetracoordinate counterpart 3 have been prepared. In the presence of an Ni(0) complex as catalyst, 1 and 2 undergo degradation to generate a silylene species and a hydrosilane. The complex with Ni of the silylene species from 1 has been trapped with an excess of diphenylacetylene to give a pseudo-pentacoordinate silole 4. The X-ray structure of 4 indicates that this silole occupies two pseudo-equatorial positions. In contrast, the tetracoordinate hydrodisilane 3 undergoes hydrosilation without SiSi bond cleavage.

A Lactone Derived from an Amino Acid with a Cyclohexyl Skeleton: (1S,6R,9S)-6-Benzamido-9-hydroxymethyl-8-oxabicyclo[4.3.0]non-3-en-7-one

In the title compound, C16H17NO4, the five-membered lactone ring is trans-fused to the cyclohexene ring. The cyclohexene ring exhibits a half-chair conformation with the benzamido group in an axial position. The γ-butyrolactone adopts an envelope conformation with the hydroxymethyl substituent in a pseudo-equatorial position. The crystal structure is stabilized by two intermolecular hydrogen bonds (O—H⋯O and N—H⋯O) involving the benzamido and hydroxy groups.

Cis,trans-4,5-Diphenyl-1,3,2-dioxathiolane 2-Oxide, cis,cis-4,5-Diphenyl-1,3,2-dioxathiolane 2-Oxide and 4,4-Diphenyl-1,3,2-dioxathiolane 2-Oxide

All three title compounds, C14H12O3S, adopt half-chair (envelope) conformations with the S=O group and the phenyl groups in pseudoaxial and pseudoequatorial positions, respectively. The steric effects of the phenyl groups are discussed in terms of S—O/C—O bond lengths and ring torsion angles.

Conformational studies of depurinating DNA adducts from syn-dibenzo[a,l]pyrene diolepoxide.

One of the major DNA adducts from the extremely potent aromatic carcinogen dibenzo[a,l]pyrene (DB[a,l]P) is the depurinating adduct syn-DB[a,l]P diolepoxide-14-N7Ade. Low-temperature fluorescence spectra of this adduct (and related derivaties bound to N3-adenine and N7-guanine) showed two distinct (0,0) origin bands with different excited-state vibrational frequencies, as measured by means of fluorescence line narrowing spectroscopy. The relative intensity of the two origin bands was solvent dependent. The hypothesis that this phenomenon could be due to a conformational equilibrium was tested using molecular mechanics, dynamical simulations and semi-empirical quantum-mechanical calculations. The hydrolyzed metabolite DB[a,l]P tetraol was also studied for comparison. It was found that the syn-DB[a,l]P diolepoxide-14-N7Ade adduct is formed via trans addition to the epoxide. Exploration of the conformational space indeed produced two potential energy minima; both corresponding to structures in which the aromatic ring system is severely distorted. In conformation I the proximity of the distal ring forces the adenine base into a pseudo-axial position and the cyclohexenyl ring adopts a half-boat structure. In conformation II the distal ring is bent in the opposite direction, allowing the cyclohexenyl ring to adopt a half-chair structure with the base in a pseudo-equatorial position, partially stacked over the distal ring. THe difference in (0,0) transition energy calculated for the two conformers agrees very well with the spectroscopic data, and the relative orientations of the hydrogens bound to the cyclohexenyl ring in the major (half-boat) conformation I are in full agreement with the experimentally observed proton NMR coupling constants.

Experiments Directed Towards the Synthesis of Anthracyclinones. XXIX. Fluoro-Substituted Tetracycles

Diastereoselective formation of 9-fluoro-9-methylanthracyclinones has been achieved by treating ortho-methallyl-substituted anthraquinonyl homochiral dioxans with boron trifluoride etherate . The demethoxy anthraquinonyl dioxan (16) underwent slow reaction to give exclusively the (7S,9R) fluoro tetracycle (21) in 58% yield. The dimethoxy anthraquinonyl dioxan (15) was less reactive, allowing other reactions to compete, but boron trifluoride -acetic acid complex effected rapid cyclization of (15) with high diastereoselectivity. Short reaction times with this reagent circumvented the formation of the alkenes (25) and the naphthacenedione (9). Boron trifluoride-nitromethane gave the (7S,9R) fluoro tetracycle (19) in 36% yield. Although the yields of the fluoro tetracycles were modest, they compare favourably with a 4% yield reported for the fluorination of daunomycinone. The 6-demethoxy tetracycle (21) has been shown to exist in the expected half-chair conformation, with the bulky C7 side chain in a pseudo-equatorial position. In contrast, the 6,11-dimethoxy fluoro tetracycle (19) exists in a significantly perturbed half-chair conformation with a pseudo-axial side chain.

On the Funicolides, Briaranes of the Pennatulacean Coral Funiculina quadrangularis from the Tuscan Archipelago: Conformational preferences in this class of diterpenes

AbstractKinetic and equilibrium NMR studies of briarane diterpenes isolated from the pennatulacean coral Funiculina quadrangularis showed that funicolide A (1), funicolide D (5), and brianthein W (6), with R2 = Hβ, undergo slow flipping by rotation of the C(1)C(2)C(3)C(4) dihedral angle, giving rise to two observable conformers in a 4:96 population ratio, both having an axial AcOC(14) and C(16) pointing ‘downwards’, but differing for pseudoaxial or pseudoequatorial position of R1O, respectively. δ(C) for the minor conformers could be quickly assigned by an original emulation methodology. Similar studies revealed that funicolide B (2), 7‐epifunicolide A (4), funicolide E (7), and unnatural epibrianthein W (8) undergo similar motions, where, however, the nature of the α‐positioned substituent R2 determines which conformer predominates: axial R1O for R2 = Hβ (4 and 8) or equatorial R1O for R2 α‐OH, (2 and 7). In contrast, funicolide C (3) proved to undergo slow conformational motions that involve also the cyclohexene ring, resulting in two observable conformers characterized by either an equatorial AcOC(14) and trans‐diaxial C(2)/C(9) or an axial AcOC(14) and trans‐diequatorial C(2)/C(9) in a 9:1 population ratio, respectively. These observations, and molecular‐mechanics calculations for briaranes known to exhibit broad NMR signals, lead to general views on the conformational preferences of diterpenes of this class.

(1R*,3S*,4R*)-4-tert-Butyldiphenylsilyloxy-6,7-dimethoxy-1-methyl-3-phenyl-1,2,3,4-tetrahydroisoquinoline

The crystal structure of the title compound, C 34 H 39 NO 3 Si, shows that the heterocyclic fragment of the molecule exhibits a half-chair conformation. The structural data also confirm the earlier configurational assignments and show that the solid-state conformation has the methyl and phenyl substituents in pseudoequatorial and equatorial positions, respectively, and that the group linked to C2 is in a trans configuration with respect to the phenyl substituent.

Conformational analysis of 3,4-dihydropyridine and its alkyl derivatives

The geometry of dihydropyridine and its alkyl derivatives was studied by the molecular mechanics method. The dihydrocycle was found to be mobile; however, substituents exert little effect on its distorted sofa conformation. The alkyl groups attached to the saturated carbon atoms occupy pseudo-equatorial position in monosubstituted and pseudo-axial positions in disubstituted 3,4-dihydropyridines. Unusually high barriers to inversion of the dihydrocycle were observed incis-3,4-dialkyl-3,4-dihydropyridines caused by the eclipse of the substituents in the transition state.